Cutis

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

The Diagnosis: Paraneoplastic Pemphigus

A workup for infectious organisms and vasculitis was negative. The patient reported unintentional weight loss despite taking oral steroids prescribed by her pulmonologist for severe obstructive lung disease that appeared to develop around the same time as the mouth ulcers.

Computed tomography of the abdomen revealed an 8.1-cm pelvic mass that a subsequent biopsy revealed to be a follicular dendritic cell sarcoma. Biopsies of the mouth ulcers showed a mildly hyperplastic mucosa with acantholysis and interface change with dyskeratosis. Direct immunofluorescence of the perilesional mucosa showed IgG and complement C3 in an intercellular distribution (Figure 1). The pathologic findings were consistent with a diagnosis of paraneoplastic pemphigus (PNP). Serologic testing via enzyme-linked immunosorbent assay, immunoblotting, and indirect immunofluorescence were not performed. The patient died within a few months after the initial presentation from bronchiolitis obliterans, a potentially fatal complication of PNP.

Paraneoplastic pemphigus is an autoimmune blistering disease associated with neoplasia, particularly lymphoproliferative disorders and thymoma.¹ Oral mucosal erosions and crusting along the lips commonly is seen along with cutaneous involvement. The main histologic features are interface changes with dyskeratosis and a lichenoid infiltrate and variable acantholysis.²

Direct immunofluorescence of perilesional skin classically shows IgG and complement C3 in an intercellular distribution, usually in a granular or linear distribution along the basement membrane. This same pattern of direct immunofluorescence is seen in pemphigus erythematosus; however, pemphigus erythematosus is clinically distinct from PNP, lacking mucosal involvement and affecting the face and/or seborrheic areas with an appearance more similar to seborrheic dermatitis or lupus erythematosus, depending on the patient.³ Indirect immunofluorescence with rat bladder epithelium typically is positive in PNP and can be a helpful feature in distinguishing PNP from other autoimmune blistering diseases (eg, pemphigus erythematosus, pemphigus vulgaris, pemphigus foliaceus).²

Immunoblotting assays via serology often detect numerous antigens in patients with PNP, including but not limited to plectin, desmoplakin, bullous pemphigoid antigens, envoplakin, desmoplakin II, and desmogleins 1 and 3.⁴ Some of these autoantibodies have been identified in tumors associated with paraneoplastic pemphigus, particularly Castleman disease and follicular dendritic cell sarcoma.

Acute graft-versus-host disease (GVHD) can have a similar histologic appearance to PNP with prominent dyskeratosis and characteristically shows satellite cell necrosis consisting of dyskeratosis with surrounding lymphocytes (Figure 2). Unlike PNP, acantholysis is not a feature of GVHD. Direct immunofluorescence typically is negative; however, nonspecific IgM and complement C3 deposition at the dermoepidermal junction and around the superficial vasculature has been reported in 39% of cases.⁵ Early chronic GVHD often shows retained lichenoid interface change, but late chronic GVHD has a sclerodermoid morphology that is easily distinguished histologically from PNP. Patients also have a history of either a bone marrow or solid organ transplant.⁶

Lichen planus also shows interface change with dyskeratosis and a lichenoid infiltrate; however, acantholysis typically is not seen and, there often is prominent hypergranulosis (Figure 3). Mucosal lesions often show more subtle features with decreased hyperkeratosis, more subtle hypergranulosis, and decreased interface change with plasma cells in the inflammatory infiltrate.⁶ Additionally, direct immunofluorescence is either negative or shows IgM-positive colloid bodies and/or an irregular band of fibrinogen at the dermoepidermal junction. The characteristic intercellular and granular/linear IgG positivity at the dermoepidermal junction of PNP is not seen.

Lupus erythematosus is an interface dermatitis with histologic features that can overlap with PNP, in addition to positive direct immunofluorescence, which has been seen in 50% to 94% of cases and can vary depending on previous steroid treatment and timing of the biopsy in the disease process.⁷ Unlike PNP, lupus erythematosus has a full-house pattern on direct immunofluorescence with IgG, IgM, IgA, and complement C3 deposition in a granular pattern at the dermoepidermal junction. While PNP also typically shows granular deposition of IgG and complement C3 at the dermoepidermal junction, there also is intercellular positivity without a full-house pattern. While both conditions show interface change, histologic features that distinguish lupus erythematosus from PNP are a superficial and deep perivascular lymphocytic infiltrate, basement membrane thickening, follicular plugging, and increased dermal mucin (Figure 4). Subacute lupus erythematosus and discoid lupus erythematosus can have similar histologic features, and definitive distinction on biopsy is not always possible; however, subacute lupus erythematosus shows milder follicular plugging and milder to absent basement membrane thickening, and the inflammatory infiltrate typically is sparser than in discoid lupus erythematosus.⁷ Subacute lupus erythematosus also can show anti-Ro/Sjögren syndrome antigen A antibodies, which typically are not seen in discoid lupus eythematosus.⁸

Stevens-Johnson syndrome (SJS) is on a spectrum with toxic epidermal necrolysis, with SJS involving less than 10% and toxic epidermal necrolysis involving 30% or more of the body surface area.⁵ Erythema multiforme also is on the histologic spectrum of SJS and toxic epidermal necrolysis; however, erythema multiforme typically is more inflammatory than SJS and toxic epidermal necrolysis. Stevens-Johnson syndrome typically affects older adults and shows both cutaneous and mucosal involvement; however, isolated mucosal involvement can be seen in children.⁵ Drugs, particularly sulfonamide antibiotics, usually are implicated as causative agents, but infections from Mycoplasma and other pathogens also may be the cause. There is notable clinical (with a combination of mucosal and cutaneous lesions) as well as histologic overlap between SJS and PNP. The density of the lichenoid infiltrate is variable, with dyskeratosis, basal cell hydropic degeneration, and occasional formation of subepidermal clefts (Figure 5). Unlike PNP, acantholysis is not a characteristic feature of SJS, and direct immunofluorescence generally is negative.

The Diagnosis: Paraneoplastic Pemphigus

A workup for infectious organisms and vasculitis was negative. The patient reported unintentional weight loss despite taking oral steroids prescribed by her pulmonologist for severe obstructive lung disease that appeared to develop around the same time as the mouth ulcers.

Computed tomography of the abdomen revealed an 8.1-cm pelvic mass that a subsequent biopsy revealed to be a follicular dendritic cell sarcoma. Biopsies of the mouth ulcers showed a mildly hyperplastic mucosa with acantholysis and interface change with dyskeratosis. Direct immunofluorescence of the perilesional mucosa showed IgG and complement C3 in an intercellular distribution (Figure 1). The pathologic findings were consistent with a diagnosis of paraneoplastic pemphigus (PNP). Serologic testing via enzyme-linked immunosorbent assay, immunoblotting, and indirect immunofluorescence were not performed. The patient died within a few months after the initial presentation from bronchiolitis obliterans, a potentially fatal complication of PNP.

Paraneoplastic pemphigus is an autoimmune blistering disease associated with neoplasia, particularly lymphoproliferative disorders and thymoma.¹ Oral mucosal erosions and crusting along the lips commonly is seen along with cutaneous involvement. The main histologic features are interface changes with dyskeratosis and a lichenoid infiltrate and variable acantholysis.²

Direct immunofluorescence of perilesional skin classically shows IgG and complement C3 in an intercellular distribution, usually in a granular or linear distribution along the basement membrane. This same pattern of direct immunofluorescence is seen in pemphigus erythematosus; however, pemphigus erythematosus is clinically distinct from PNP, lacking mucosal involvement and affecting the face and/or seborrheic areas with an appearance more similar to seborrheic dermatitis or lupus erythematosus, depending on the patient.³ Indirect immunofluorescence with rat bladder epithelium typically is positive in PNP and can be a helpful feature in distinguishing PNP from other autoimmune blistering diseases (eg, pemphigus erythematosus, pemphigus vulgaris, pemphigus foliaceus).²

Immunoblotting assays via serology often detect numerous antigens in patients with PNP, including but not limited to plectin, desmoplakin, bullous pemphigoid antigens, envoplakin, desmoplakin II, and desmogleins 1 and 3.⁴ Some of these autoantibodies have been identified in tumors associated with paraneoplastic pemphigus, particularly Castleman disease and follicular dendritic cell sarcoma.

Acute graft-versus-host disease (GVHD) can have a similar histologic appearance to PNP with prominent dyskeratosis and characteristically shows satellite cell necrosis consisting of dyskeratosis with surrounding lymphocytes (Figure 2). Unlike PNP, acantholysis is not a feature of GVHD. Direct immunofluorescence typically is negative; however, nonspecific IgM and complement C3 deposition at the dermoepidermal junction and around the superficial vasculature has been reported in 39% of cases.⁵ Early chronic GVHD often shows retained lichenoid interface change, but late chronic GVHD has a sclerodermoid morphology that is easily distinguished histologically from PNP. Patients also have a history of either a bone marrow or solid organ transplant.⁶

Lichen planus also shows interface change with dyskeratosis and a lichenoid infiltrate; however, acantholysis typically is not seen and, there often is prominent hypergranulosis (Figure 3). Mucosal lesions often show more subtle features with decreased hyperkeratosis, more subtle hypergranulosis, and decreased interface change with plasma cells in the inflammatory infiltrate.⁶ Additionally, direct immunofluorescence is either negative or shows IgM-positive colloid bodies and/or an irregular band of fibrinogen at the dermoepidermal junction. The characteristic intercellular and granular/linear IgG positivity at the dermoepidermal junction of PNP is not seen.

Lupus erythematosus is an interface dermatitis with histologic features that can overlap with PNP, in addition to positive direct immunofluorescence, which has been seen in 50% to 94% of cases and can vary depending on previous steroid treatment and timing of the biopsy in the disease process.⁷ Unlike PNP, lupus erythematosus has a full-house pattern on direct immunofluorescence with IgG, IgM, IgA, and complement C3 deposition in a granular pattern at the dermoepidermal junction. While PNP also typically shows granular deposition of IgG and complement C3 at the dermoepidermal junction, there also is intercellular positivity without a full-house pattern. While both conditions show interface change, histologic features that distinguish lupus erythematosus from PNP are a superficial and deep perivascular lymphocytic infiltrate, basement membrane thickening, follicular plugging, and increased dermal mucin (Figure 4). Subacute lupus erythematosus and discoid lupus erythematosus can have similar histologic features, and definitive distinction on biopsy is not always possible; however, subacute lupus erythematosus shows milder follicular plugging and milder to absent basement membrane thickening, and the inflammatory infiltrate typically is sparser than in discoid lupus erythematosus.⁷ Subacute lupus erythematosus also can show anti-Ro/Sjögren syndrome antigen A antibodies, which typically are not seen in discoid lupus eythematosus.⁸

Stevens-Johnson syndrome (SJS) is on a spectrum with toxic epidermal necrolysis, with SJS involving less than 10% and toxic epidermal necrolysis involving 30% or more of the body surface area.⁵ Erythema multiforme also is on the histologic spectrum of SJS and toxic epidermal necrolysis; however, erythema multiforme typically is more inflammatory than SJS and toxic epidermal necrolysis. Stevens-Johnson syndrome typically affects older adults and shows both cutaneous and mucosal involvement; however, isolated mucosal involvement can be seen in children.⁵ Drugs, particularly sulfonamide antibiotics, usually are implicated as causative agents, but infections from Mycoplasma and other pathogens also may be the cause. There is notable clinical (with a combination of mucosal and cutaneous lesions) as well as histologic overlap between SJS and PNP. The density of the lichenoid infiltrate is variable, with dyskeratosis, basal cell hydropic degeneration, and occasional formation of subepidermal clefts (Figure 5). Unlike PNP, acantholysis is not a characteristic feature of SJS, and direct immunofluorescence generally is negative.

The Diagnosis: Paraneoplastic Pemphigus

A workup for infectious organisms and vasculitis was negative. The patient reported unintentional weight loss despite taking oral steroids prescribed by her pulmonologist for severe obstructive lung disease that appeared to develop around the same time as the mouth ulcers.

Computed tomography of the abdomen revealed an 8.1-cm pelvic mass that a subsequent biopsy revealed to be a follicular dendritic cell sarcoma. Biopsies of the mouth ulcers showed a mildly hyperplastic mucosa with acantholysis and interface change with dyskeratosis. Direct immunofluorescence of the perilesional mucosa showed IgG and complement C3 in an intercellular distribution (Figure 1). The pathologic findings were consistent with a diagnosis of paraneoplastic pemphigus (PNP). Serologic testing via enzyme-linked immunosorbent assay, immunoblotting, and indirect immunofluorescence were not performed. The patient died within a few months after the initial presentation from bronchiolitis obliterans, a potentially fatal complication of PNP.

Paraneoplastic pemphigus is an autoimmune blistering disease associated with neoplasia, particularly lymphoproliferative disorders and thymoma.¹ Oral mucosal erosions and crusting along the lips commonly is seen along with cutaneous involvement. The main histologic features are interface changes with dyskeratosis and a lichenoid infiltrate and variable acantholysis.²

Direct immunofluorescence of perilesional skin classically shows IgG and complement C3 in an intercellular distribution, usually in a granular or linear distribution along the basement membrane. This same pattern of direct immunofluorescence is seen in pemphigus erythematosus; however, pemphigus erythematosus is clinically distinct from PNP, lacking mucosal involvement and affecting the face and/or seborrheic areas with an appearance more similar to seborrheic dermatitis or lupus erythematosus, depending on the patient.³ Indirect immunofluorescence with rat bladder epithelium typically is positive in PNP and can be a helpful feature in distinguishing PNP from other autoimmune blistering diseases (eg, pemphigus erythematosus, pemphigus vulgaris, pemphigus foliaceus).²

Immunoblotting assays via serology often detect numerous antigens in patients with PNP, including but not limited to plectin, desmoplakin, bullous pemphigoid antigens, envoplakin, desmoplakin II, and desmogleins 1 and 3.⁴ Some of these autoantibodies have been identified in tumors associated with paraneoplastic pemphigus, particularly Castleman disease and follicular dendritic cell sarcoma.

Acute graft-versus-host disease (GVHD) can have a similar histologic appearance to PNP with prominent dyskeratosis and characteristically shows satellite cell necrosis consisting of dyskeratosis with surrounding lymphocytes (Figure 2). Unlike PNP, acantholysis is not a feature of GVHD. Direct immunofluorescence typically is negative; however, nonspecific IgM and complement C3 deposition at the dermoepidermal junction and around the superficial vasculature has been reported in 39% of cases.⁵ Early chronic GVHD often shows retained lichenoid interface change, but late chronic GVHD has a sclerodermoid morphology that is easily distinguished histologically from PNP. Patients also have a history of either a bone marrow or solid organ transplant.⁶

Lichen planus also shows interface change with dyskeratosis and a lichenoid infiltrate; however, acantholysis typically is not seen and, there often is prominent hypergranulosis (Figure 3). Mucosal lesions often show more subtle features with decreased hyperkeratosis, more subtle hypergranulosis, and decreased interface change with plasma cells in the inflammatory infiltrate.⁶ Additionally, direct immunofluorescence is either negative or shows IgM-positive colloid bodies and/or an irregular band of fibrinogen at the dermoepidermal junction. The characteristic intercellular and granular/linear IgG positivity at the dermoepidermal junction of PNP is not seen.

Lupus erythematosus is an interface dermatitis with histologic features that can overlap with PNP, in addition to positive direct immunofluorescence, which has been seen in 50% to 94% of cases and can vary depending on previous steroid treatment and timing of the biopsy in the disease process.⁷ Unlike PNP, lupus erythematosus has a full-house pattern on direct immunofluorescence with IgG, IgM, IgA, and complement C3 deposition in a granular pattern at the dermoepidermal junction. While PNP also typically shows granular deposition of IgG and complement C3 at the dermoepidermal junction, there also is intercellular positivity without a full-house pattern. While both conditions show interface change, histologic features that distinguish lupus erythematosus from PNP are a superficial and deep perivascular lymphocytic infiltrate, basement membrane thickening, follicular plugging, and increased dermal mucin (Figure 4). Subacute lupus erythematosus and discoid lupus erythematosus can have similar histologic features, and definitive distinction on biopsy is not always possible; however, subacute lupus erythematosus shows milder follicular plugging and milder to absent basement membrane thickening, and the inflammatory infiltrate typically is sparser than in discoid lupus erythematosus.⁷ Subacute lupus erythematosus also can show anti-Ro/Sjögren syndrome antigen A antibodies, which typically are not seen in discoid lupus eythematosus.⁸

Stevens-Johnson syndrome (SJS) is on a spectrum with toxic epidermal necrolysis, with SJS involving less than 10% and toxic epidermal necrolysis involving 30% or more of the body surface area.⁵ Erythema multiforme also is on the histologic spectrum of SJS and toxic epidermal necrolysis; however, erythema multiforme typically is more inflammatory than SJS and toxic epidermal necrolysis. Stevens-Johnson syndrome typically affects older adults and shows both cutaneous and mucosal involvement; however, isolated mucosal involvement can be seen in children.⁵ Drugs, particularly sulfonamide antibiotics, usually are implicated as causative agents, but infections from Mycoplasma and other pathogens also may be the cause. There is notable clinical (with a combination of mucosal and cutaneous lesions) as well as histologic overlap between SJS and PNP. The density of the lichenoid infiltrate is variable, with dyskeratosis, basal cell hydropic degeneration, and occasional formation of subepidermal clefts (Figure 5). Unlike PNP, acantholysis is not a characteristic feature of SJS, and direct immunofluorescence generally is negative.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

The Diagnosis: Superficial Migratory Thrombophlebitis

On initial presentation, the differential diagnosis included livedoid vasculopathy, cutaneous polyarteritis nodosa, erythema ab igne, cholesterol embolism, and livedo reticularis. Laboratory investigation included antiphospholipid antibody syndrome (APS), antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, serum protein electrophoresis, and coagulation tests. Pertinent findings included transient low total complement activity but normal complement protein C2, C3, and C5 levels and negative cryoglobulins. Additional laboratory testing revealed elevated antiphosphatidylserine IgG, which remained elevated 12 weeks later.

New lesions continued to appear over the next several months as painful, erythematous, linear, pruritic nodules that resolved as hyperpigmented linear patches, which intersected to form a livedo reticularis-like pattern that covered the lower legs. Biopsy of an erythematous nodule on the right leg revealed fibrin occlusion of a medium-sized vein in the subcutaneous fat. Direct immunofluorescence was not specific. Venous duplex ultrasonography demonstrated chronic superficial thrombophlebitis and was crucial to the diagnosis. Ultimately, the patient's history, clinical presentation, laboratory results, venous studies, and histopathologic analysis were consistent with a diagnosis of superficial migratory thrombophlebitis (SMT) with resultant postinflammatory hyperpigmentation presenting in a reticular pattern that mimicked livedoid vasculopathy, livedo reticularis, or erythema ab igne.

Superficial migratory thrombophlebitis, also known as thrombophlebitis migrans, is defined as the recurrent formation of thrombi within superficial veins.¹ The presence of a thrombus in a superficial vein evokes an inflammatory response, resulting in swelling, tenderness, erythema, and warmth in the affected area. Superficial migratory thrombophlebitis has been associated with several etiologies, including pregnancy, oral contraceptive use, APS, vasculitic disorders, and malignancies (eg, pancreas, lung, breast), as well as infections such as secondary syphilis.¹

When SMT is associated with an occult malignancy, it is known as Trousseau syndrome. Common malignancies found in association with Trousseau syndrome include pancreatic, lung, and breast cancers.² A systematic review from 2008 evaluated the utility of extensive cancer screening strategies in patients with newly diagnosed, unprovoked venous thromboembolic events.³ Using a wide screening strategy that included computed tomography of the abdomen and pelvis, the investigators detected a considerable number of formerly undiagnosed cancers, increasing detection rates from 49.4% to 69.7%. After the diagnosis of SMT was made in our patient, computed tomography of the chest, abdomen, and pelvis was performed, but the findings were unremarkable.

Because occult malignancy was excluded in our patient, the likely etiology of SMT was APS, an acquired autoimmune condition diagnosed based on the presence of a vascular thrombosis and/or pregnancy failure in women as well as elevation of at least one antiphospholipid antibody laboratory marker (eg, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein I antibody) on 2 or more occasions at least 12 weeks apart.⁴ Other antibodies such as those directed against negatively charged phospholipids (eg, antiphosphatidylserine [which was elevated in our patient], phosphatidylinositol, phosphatidic acid) have been reported in patients with APS, although their diagnostic use is controversial.⁵ For example, the presence of antiphosphatidylserine antibodies has been considered common but not specific in patients with APS.⁴ However, a recent observational study demonstrated that antiphosphatidylserine antibodies are highly specific (87%) and useful in diagnosing clinical APS cases in the presence of other negative markers.⁶

In our patient, diagnosis of SMT with resultant postinflammatory hyperpigmentation in a reticular pattern was based on the patient's medical history, clinical examination, and histopathologic findings, as well as laboratory results and venous studies. However, it is important to note that a livedo reticularis-like pattern also is a very common finding in APS and must be included in the differential diagnosis of a reticular network on the skin.⁷ Moreover, differentiating livedo reticularis from SMT has prognostic importance since SMT may be associated with underlying malignancies while livedo reticularis may be associated with Sneddon syndrome, a disorder in which neurologic vascular events (eg, cerebrovascular accidents) are present.⁸ While this distinction is important, there are no pathognomonic histologic findings seen in livedo reticularis, and consideration of the clinical picture and additional testing is critical.^4,8

Livedo vasculopathy was excluded in our patient due to the lack of diagnostic histopathologic findings, such as fibrin deposition and thrombus formation involving the upper- and mid-dermal capillaries.⁹ Furthermore, characteristic direct immunofluorescence findings of a homogenous or granular deposition in the vessel wall consisting of immune complexes, complement, and fibrin were absent in our patient.⁹ Our patient also lacked common clinical findings found in livedo vasculopathy such as small ulcerations or atrophic, porcelain-white scars on the lower legs. Erythema ab igne also was excluded in our patient due to the absence of heat exposure and presence of fibrin occlusion in the superficial leg veins. Physiologic livedo reticularis, defined as a livedoid pattern due to physiologic changes in the skin in response to cold exposure,¹⁰ also was excluded, as our patient's cutaneous changes included an alteration in pigmentation with a brown reticular pattern and no blanching, erythematous or violaceous hue, warmth, or tenderness.

In conclusion, SMT is a disorder with multiple associations that may clinically mimic livedo reticularis and livedoid vasculopathy when postinflammatory hyperpigmentation has a lacelike or livedoid pattern. While nontraditional antibodies may be useful in diagnosis in patients suspected of having APS with otherwise negative markers, standardized assays and further studies are needed to determine the specificity and value of these antibodies, particularly when used in isolation. Our patient's elevated antiphosphatidylserine IgG may have been the cause of her hypercoagulable state causing the SMT. A livedoid pattern is a common finding in APS and also was seen in our patient with SMT, but the differentiation of the brown pigmentary change and more active erythema was critical to the appropriate clinical workup of our patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

Penile squamous cell carcinoma (SCC) with considerable urethral extension is uncommon and difficult to manage. It often is resistant to less invasive and nonsurgical treatments and frequently results in partial or total penectomy, which can lead to cosmetic disfigurement, functional issues, and psychological distress. We report a case of penile SCC in situ with considerable urethral extension with a focus of cells suspicious for moderately well-differentiated and invasive SCC that was treated with Mohs micrographic surgery (MMS).

Mohs micrographic surgery with distal urethrectomy and reconstruction is a valuable treatment technique for cases of SCC involving the glans penis and distal urethra. It offers equivalent or better overall cure rates compared to more radical interventions. Additionally, preservation of the penis with MMS spares patients from considerable physical and psychosocial morbidity. Our case, along with growing body of literature,^1-4 calls on dermatologists and urologists to consider MMS as a treatment for penile SCC with or without urethral involvement.

Case Report

A 61-year-old man presented to the dermatology department with a pruritic lesion on the penis that had been present for 6 years. Shave biopsy demonstrated SCC in situ with a focus of cells suspicious for moderately well-differentiated and invasive SCC. Physical examination revealed an ill-defined, 2.2×1.9-cm, pink, eroded plaque involving the tip of the penis and surrounding the external urinary meatus (Figure 1). There was no palpable inguinal lymphadenopathy.

Distal penectomy and lymph node biopsy was recommended following evaluation by the urologic oncology department, but the patient declined these interventions and presented to our dermatology department (A.H.) for a second opinion. The tumor, including the invasive perineural portion, was removed using MMS several weeks after initially presenting to urologic oncology. Ventral meatotomy allowed access to the SCC in situ portion extending proximally up the pendulous urethra (Figure 2). Clear margins were obtained after the eighth stage of MMS, which required removal of 4 to 5 cm of the distal urethra (Figure 3). Reconstruction of the wound required urethral advancement, urethrostomy, and meatoplasty. A positive outcome was achieved with preservation of the length and shape of the penis as well as the cosmetic appearance of the glans penis (Figure 4). The patient was satisfied with the outcome. At 49 months’ follow-up, no evidence of local recurrence or disease progression was noted, and the distal urethrostomy remained intact and functional.

Comment

Penile SCC is a rare malignancy that represents between 0.4% and 0.6% of all malignant tumors in the United States and occurs most commonly in men aged 50 to 70 years.⁴ The incidence is higher in developing countries, approaching 10% of malignancies in men. It occurs most commonly on the glans penis, prepuce, and coronal sulcus, and has multiple possible appearances, including erythematous and indurated, warty and exophytic, or flat and ulcerated lesions.⁵ Some reports indicate that more than 40% of penile SCCs are attributable to human papilloma virus,⁶ while lack of circumcision, chronic inflammation, poor hygiene, balanitis xerotica obliterans, penile trauma, human immunodeficiency virus, UVA treatment of penile psoriasis, and tobacco use are known risk factors.⁵

Invasive penile SCC generally is treated with penectomy (partial or total), radiation therapy, or MMS; SCC in situ can be treated with topical chemotherapy, laser therapy, and wide local excision (2-cm margins) including circumcision, complete glansectomy, or MMS.⁵ Squamous cell carcinoma in situ with urethral involvement treated with nonsurgical therapies is associated with higher recurrence rates, ultimately necessitating more aggressive treatments, most commonly partial penectomy.⁷ The high local recurrence rate of SCC in situ with urethral involvement treated with nonsurgical therapies reflects the fact that determining the presence of urethral extension is difficult and, if present, is inherently inaccessible to these local therapies because the urethra is not an outward-facing tissue surface; MMS represents one possible solution to these issues.

Across all treatment modalities, the most prognostic factor of cancer-specific survival in patients with penile SCC is pelvic lymph node involvement. Some reports cite 5-year survival rates as low as 0% in the setting of pelvic lymph node involvement,⁵ whereas others had cited rates of 29% to 40%⁴; 5-year survival rates of higher than 85% have been reported in node-negative patients.⁴ Recurrence rates vary widely by treatment modality, ranging from less than 10% with partial penectomy and long-term follow-up⁸ and up to 50% within 2 years with penile-preserving approaches (eg, topical chemotherapy, laser therapy, radiotherapy).⁵ Multiple case series of penile cancer (the most common of which was SCC/SCC in situ) treated with MMS report comparable and at times superior survival and recurrence data (Table).^1-4 Slightly higher recurrences of penile SCC treated with MMS compared to penectomy have been reported, along with considerably higher recurrence rates compared to nonpenile cutaneous SCC treated with MMS (reported to be less than 3%).⁴ The elastic and expansile nature of penile tissue may lead to distortion from swelling/local anesthesia when taking individual Mohs layers. Additionally, as a large percentage of penile SCCs are attributable to human papillomavirus, difficulty in detecting human papilloma virus–infected cells (which may have oncogenic potential) with the naked eye or histologically with typical staining techniques may help explain the higher recurrence rate of penile SCC treated with MMS compared to penectomy. Despite the higher recurrence rates, survival is comparable or higher in cases treated with MMS (Table).

Partial penectomy also has a negative impact on health-related quality of life. Kieffer et al⁹ compared the impact of penile-sparing surgery (PSS)(including MMS) versus partial or total penectomy on sexual function and health-related quality of life in 90 patients with penile cancer. Although the association between the extent of surgery (partial penectomy/total penectomy/PSS) surgery type and extent and most outcome measures was not statistically significant, partial penectomy was associated with significantly more problems with orgasm (P=.031), concerns about appearance (P=.008), interference in daily life (P=.032), and urinary function (P<.0001) when compared to patients treated with PSS.⁹ Although this study included only laser/local excision with or without circumcision or glans penis amputation with or without reconstruction as PSSs and did not explicitly include MMS, MMS is clearly a tissue-sparing technique and the study results are generalizable to MMS. The fact that MMS was not included as a PSS also may underscore the fact that MMS for penile cancer may not yet be available in certain regions; this study was conducted in the Netherlands.

Conclusion

Penile SCC with considerable urethral extension is uncommon, difficult to manage, and often is resistant to less invasive and nonsurgical treatments. As a result, partial or total penectomy is sometimes necessary. Such cases benefit from MMS with distal urethrectomy and reconstruction because MMS provides equivalent or better overall cure rates compared to more radical interventions.^1-4 Importantly, preservation of the penis with MMS can spare patients considerable physical and psychosocial morbidity. Partial penectomy is associated with more health-related quality-of-life problems with orgasm, concerns about appearance, interference in daily life, and urinary function compared to PSSs such as MMS.⁹ This case, and a growing body of literature, are a call to dermatologists and urologists to consider MMS as a treatment for penile SCC, even with involvement of the urethra.

Penile squamous cell carcinoma (SCC) with considerable urethral extension is uncommon and difficult to manage. It often is resistant to less invasive and nonsurgical treatments and frequently results in partial or total penectomy, which can lead to cosmetic disfigurement, functional issues, and psychological distress. We report a case of penile SCC in situ with considerable urethral extension with a focus of cells suspicious for moderately well-differentiated and invasive SCC that was treated with Mohs micrographic surgery (MMS).

Mohs micrographic surgery with distal urethrectomy and reconstruction is a valuable treatment technique for cases of SCC involving the glans penis and distal urethra. It offers equivalent or better overall cure rates compared to more radical interventions. Additionally, preservation of the penis with MMS spares patients from considerable physical and psychosocial morbidity. Our case, along with growing body of literature,^1-4 calls on dermatologists and urologists to consider MMS as a treatment for penile SCC with or without urethral involvement.

Case Report

A 61-year-old man presented to the dermatology department with a pruritic lesion on the penis that had been present for 6 years. Shave biopsy demonstrated SCC in situ with a focus of cells suspicious for moderately well-differentiated and invasive SCC. Physical examination revealed an ill-defined, 2.2×1.9-cm, pink, eroded plaque involving the tip of the penis and surrounding the external urinary meatus (Figure 1). There was no palpable inguinal lymphadenopathy.

Distal penectomy and lymph node biopsy was recommended following evaluation by the urologic oncology department, but the patient declined these interventions and presented to our dermatology department (A.H.) for a second opinion. The tumor, including the invasive perineural portion, was removed using MMS several weeks after initially presenting to urologic oncology. Ventral meatotomy allowed access to the SCC in situ portion extending proximally up the pendulous urethra (Figure 2). Clear margins were obtained after the eighth stage of MMS, which required removal of 4 to 5 cm of the distal urethra (Figure 3). Reconstruction of the wound required urethral advancement, urethrostomy, and meatoplasty. A positive outcome was achieved with preservation of the length and shape of the penis as well as the cosmetic appearance of the glans penis (Figure 4). The patient was satisfied with the outcome. At 49 months’ follow-up, no evidence of local recurrence or disease progression was noted, and the distal urethrostomy remained intact and functional.

Comment

Penile SCC is a rare malignancy that represents between 0.4% and 0.6% of all malignant tumors in the United States and occurs most commonly in men aged 50 to 70 years.⁴ The incidence is higher in developing countries, approaching 10% of malignancies in men. It occurs most commonly on the glans penis, prepuce, and coronal sulcus, and has multiple possible appearances, including erythematous and indurated, warty and exophytic, or flat and ulcerated lesions.⁵ Some reports indicate that more than 40% of penile SCCs are attributable to human papilloma virus,⁶ while lack of circumcision, chronic inflammation, poor hygiene, balanitis xerotica obliterans, penile trauma, human immunodeficiency virus, UVA treatment of penile psoriasis, and tobacco use are known risk factors.⁵

Invasive penile SCC generally is treated with penectomy (partial or total), radiation therapy, or MMS; SCC in situ can be treated with topical chemotherapy, laser therapy, and wide local excision (2-cm margins) including circumcision, complete glansectomy, or MMS.⁵ Squamous cell carcinoma in situ with urethral involvement treated with nonsurgical therapies is associated with higher recurrence rates, ultimately necessitating more aggressive treatments, most commonly partial penectomy.⁷ The high local recurrence rate of SCC in situ with urethral involvement treated with nonsurgical therapies reflects the fact that determining the presence of urethral extension is difficult and, if present, is inherently inaccessible to these local therapies because the urethra is not an outward-facing tissue surface; MMS represents one possible solution to these issues.

Across all treatment modalities, the most prognostic factor of cancer-specific survival in patients with penile SCC is pelvic lymph node involvement. Some reports cite 5-year survival rates as low as 0% in the setting of pelvic lymph node involvement,⁵ whereas others had cited rates of 29% to 40%⁴; 5-year survival rates of higher than 85% have been reported in node-negative patients.⁴ Recurrence rates vary widely by treatment modality, ranging from less than 10% with partial penectomy and long-term follow-up⁸ and up to 50% within 2 years with penile-preserving approaches (eg, topical chemotherapy, laser therapy, radiotherapy).⁵ Multiple case series of penile cancer (the most common of which was SCC/SCC in situ) treated with MMS report comparable and at times superior survival and recurrence data (Table).^1-4 Slightly higher recurrences of penile SCC treated with MMS compared to penectomy have been reported, along with considerably higher recurrence rates compared to nonpenile cutaneous SCC treated with MMS (reported to be less than 3%).⁴ The elastic and expansile nature of penile tissue may lead to distortion from swelling/local anesthesia when taking individual Mohs layers. Additionally, as a large percentage of penile SCCs are attributable to human papillomavirus, difficulty in detecting human papilloma virus–infected cells (which may have oncogenic potential) with the naked eye or histologically with typical staining techniques may help explain the higher recurrence rate of penile SCC treated with MMS compared to penectomy. Despite the higher recurrence rates, survival is comparable or higher in cases treated with MMS (Table).

Partial penectomy also has a negative impact on health-related quality of life. Kieffer et al⁹ compared the impact of penile-sparing surgery (PSS)(including MMS) versus partial or total penectomy on sexual function and health-related quality of life in 90 patients with penile cancer. Although the association between the extent of surgery (partial penectomy/total penectomy/PSS) surgery type and extent and most outcome measures was not statistically significant, partial penectomy was associated with significantly more problems with orgasm (P=.031), concerns about appearance (P=.008), interference in daily life (P=.032), and urinary function (P<.0001) when compared to patients treated with PSS.⁹ Although this study included only laser/local excision with or without circumcision or glans penis amputation with or without reconstruction as PSSs and did not explicitly include MMS, MMS is clearly a tissue-sparing technique and the study results are generalizable to MMS. The fact that MMS was not included as a PSS also may underscore the fact that MMS for penile cancer may not yet be available in certain regions; this study was conducted in the Netherlands.

Conclusion

Penile SCC with considerable urethral extension is uncommon, difficult to manage, and often is resistant to less invasive and nonsurgical treatments. As a result, partial or total penectomy is sometimes necessary. Such cases benefit from MMS with distal urethrectomy and reconstruction because MMS provides equivalent or better overall cure rates compared to more radical interventions.^1-4 Importantly, preservation of the penis with MMS can spare patients considerable physical and psychosocial morbidity. Partial penectomy is associated with more health-related quality-of-life problems with orgasm, concerns about appearance, interference in daily life, and urinary function compared to PSSs such as MMS.⁹ This case, and a growing body of literature, are a call to dermatologists and urologists to consider MMS as a treatment for penile SCC, even with involvement of the urethra.

Penile squamous cell carcinoma (SCC) with considerable urethral extension is uncommon and difficult to manage. It often is resistant to less invasive and nonsurgical treatments and frequently results in partial or total penectomy, which can lead to cosmetic disfigurement, functional issues, and psychological distress. We report a case of penile SCC in situ with considerable urethral extension with a focus of cells suspicious for moderately well-differentiated and invasive SCC that was treated with Mohs micrographic surgery (MMS).

Mohs micrographic surgery with distal urethrectomy and reconstruction is a valuable treatment technique for cases of SCC involving the glans penis and distal urethra. It offers equivalent or better overall cure rates compared to more radical interventions. Additionally, preservation of the penis with MMS spares patients from considerable physical and psychosocial morbidity. Our case, along with growing body of literature,^1-4 calls on dermatologists and urologists to consider MMS as a treatment for penile SCC with or without urethral involvement.

Case Report

A 61-year-old man presented to the dermatology department with a pruritic lesion on the penis that had been present for 6 years. Shave biopsy demonstrated SCC in situ with a focus of cells suspicious for moderately well-differentiated and invasive SCC. Physical examination revealed an ill-defined, 2.2×1.9-cm, pink, eroded plaque involving the tip of the penis and surrounding the external urinary meatus (Figure 1). There was no palpable inguinal lymphadenopathy.

Distal penectomy and lymph node biopsy was recommended following evaluation by the urologic oncology department, but the patient declined these interventions and presented to our dermatology department (A.H.) for a second opinion. The tumor, including the invasive perineural portion, was removed using MMS several weeks after initially presenting to urologic oncology. Ventral meatotomy allowed access to the SCC in situ portion extending proximally up the pendulous urethra (Figure 2). Clear margins were obtained after the eighth stage of MMS, which required removal of 4 to 5 cm of the distal urethra (Figure 3). Reconstruction of the wound required urethral advancement, urethrostomy, and meatoplasty. A positive outcome was achieved with preservation of the length and shape of the penis as well as the cosmetic appearance of the glans penis (Figure 4). The patient was satisfied with the outcome. At 49 months’ follow-up, no evidence of local recurrence or disease progression was noted, and the distal urethrostomy remained intact and functional.

Comment

Penile SCC is a rare malignancy that represents between 0.4% and 0.6% of all malignant tumors in the United States and occurs most commonly in men aged 50 to 70 years.⁴ The incidence is higher in developing countries, approaching 10% of malignancies in men. It occurs most commonly on the glans penis, prepuce, and coronal sulcus, and has multiple possible appearances, including erythematous and indurated, warty and exophytic, or flat and ulcerated lesions.⁵ Some reports indicate that more than 40% of penile SCCs are attributable to human papilloma virus,⁶ while lack of circumcision, chronic inflammation, poor hygiene, balanitis xerotica obliterans, penile trauma, human immunodeficiency virus, UVA treatment of penile psoriasis, and tobacco use are known risk factors.⁵

Invasive penile SCC generally is treated with penectomy (partial or total), radiation therapy, or MMS; SCC in situ can be treated with topical chemotherapy, laser therapy, and wide local excision (2-cm margins) including circumcision, complete glansectomy, or MMS.⁵ Squamous cell carcinoma in situ with urethral involvement treated with nonsurgical therapies is associated with higher recurrence rates, ultimately necessitating more aggressive treatments, most commonly partial penectomy.⁷ The high local recurrence rate of SCC in situ with urethral involvement treated with nonsurgical therapies reflects the fact that determining the presence of urethral extension is difficult and, if present, is inherently inaccessible to these local therapies because the urethra is not an outward-facing tissue surface; MMS represents one possible solution to these issues.

Across all treatment modalities, the most prognostic factor of cancer-specific survival in patients with penile SCC is pelvic lymph node involvement. Some reports cite 5-year survival rates as low as 0% in the setting of pelvic lymph node involvement,⁵ whereas others had cited rates of 29% to 40%⁴; 5-year survival rates of higher than 85% have been reported in node-negative patients.⁴ Recurrence rates vary widely by treatment modality, ranging from less than 10% with partial penectomy and long-term follow-up⁸ and up to 50% within 2 years with penile-preserving approaches (eg, topical chemotherapy, laser therapy, radiotherapy).⁵ Multiple case series of penile cancer (the most common of which was SCC/SCC in situ) treated with MMS report comparable and at times superior survival and recurrence data (Table).^1-4 Slightly higher recurrences of penile SCC treated with MMS compared to penectomy have been reported, along with considerably higher recurrence rates compared to nonpenile cutaneous SCC treated with MMS (reported to be less than 3%).⁴ The elastic and expansile nature of penile tissue may lead to distortion from swelling/local anesthesia when taking individual Mohs layers. Additionally, as a large percentage of penile SCCs are attributable to human papillomavirus, difficulty in detecting human papilloma virus–infected cells (which may have oncogenic potential) with the naked eye or histologically with typical staining techniques may help explain the higher recurrence rate of penile SCC treated with MMS compared to penectomy. Despite the higher recurrence rates, survival is comparable or higher in cases treated with MMS (Table).

Partial penectomy also has a negative impact on health-related quality of life. Kieffer et al⁹ compared the impact of penile-sparing surgery (PSS)(including MMS) versus partial or total penectomy on sexual function and health-related quality of life in 90 patients with penile cancer. Although the association between the extent of surgery (partial penectomy/total penectomy/PSS) surgery type and extent and most outcome measures was not statistically significant, partial penectomy was associated with significantly more problems with orgasm (P=.031), concerns about appearance (P=.008), interference in daily life (P=.032), and urinary function (P<.0001) when compared to patients treated with PSS.⁹ Although this study included only laser/local excision with or without circumcision or glans penis amputation with or without reconstruction as PSSs and did not explicitly include MMS, MMS is clearly a tissue-sparing technique and the study results are generalizable to MMS. The fact that MMS was not included as a PSS also may underscore the fact that MMS for penile cancer may not yet be available in certain regions; this study was conducted in the Netherlands.

Conclusion

Penile SCC with considerable urethral extension is uncommon, difficult to manage, and often is resistant to less invasive and nonsurgical treatments. As a result, partial or total penectomy is sometimes necessary. Such cases benefit from MMS with distal urethrectomy and reconstruction because MMS provides equivalent or better overall cure rates compared to more radical interventions.^1-4 Importantly, preservation of the penis with MMS can spare patients considerable physical and psychosocial morbidity. Partial penectomy is associated with more health-related quality-of-life problems with orgasm, concerns about appearance, interference in daily life, and urinary function compared to PSSs such as MMS.⁹ This case, and a growing body of literature, are a call to dermatologists and urologists to consider MMS as a treatment for penile SCC, even with involvement of the urethra.

Intralymphatic histiocytosis was first described in 1994.¹ To date, at least 70 cases have been reported in the English-language literature, the majority being associated with systemic or local inflammatory conditions such as rheumatoid arthritis (RA), malignancy, and metal prostheses. The remaining cases arose independent of any detectable disease process.² The clinical lesion localizes to areas around surgical scars or inflamed joints and generally presents with erythematous livedoid papules and plaques. Because of its rarity, pathologists and clinicians may be unfamiliar with this entity, leading to delayed or missed diagnoses.

Although the pathogenesis of intralymphatic histiocytosis remains unclear, it may be related to dysregulated immune signaling. The condition follows a chronic, relapsing-remitting course that has shown variable response to topical and systemic treatments. We present a rare case of intralymphatic histiocytosis associated with joint replacement/metal prosthesis^3-14 that was responsive to a novel treatment with intralesional steroid injection and pressure bandage.

Case Report

An 89-year-old woman presented with a relapsing and remitting rash on the right calf and popliteal fossa of 11 months’ duration. It was becoming more painful over time and recently began to hurt when walking. Her medical history was remarkable for deep vein thromboses of the bilateral legs, Factor V Leiden deficiency, osteoarthritis, and a popliteal (Baker) cyst on the right leg that ruptured 22 months prior to presentation. Her surgical history included bilateral knee replacements (10 years and 2 years prior to the current presentation for the right and left knees, respectively). Her international normalized ratio (2.0) was therapeutic on warfarin.

Initially, swelling, pain, and redness developed in the right calf, and recurrent right-leg deep venous thrombosis was ruled out by Doppler ultrasound. The findings were considered to be secondary to inflammation from a popliteal cyst. Symptoms persisted despite application of warm compresses, leg elevation, and compression stockings. Treatment with doxycycline prescribed by the patient’s primary care physician 9 months prior for presumed cellulitis produced little improvement. Physical examination revealed a well-healed vertical scar on the right calf from an incisional biopsy within an 8-cm, tender, erythematous, indurated, sclerotic plaque with erythematous streaks radiating from the center of the plaque (Figure 1). There also was red-brown, indurated discoloration on the right shin.

Fine-needle aspiration of the lesion revealed red blood cells and histiocytes. Laboratory studies showed an elevated erythrocyte sedimentation rate of 74 mm/h (reference range, 0–30 mm/h) and a C-reactive protein level of 39 mg/L (reference range, 0–10 mg/L). An incisional biopsy including the muscular fascia showed dense dermal fibrosis with chronic inflammation and scarring. A dermatopathologist (G. A. S.) reviewed the case and confirmed variable fibrosis and chronic inflammation associated with edema in the dermis and epidermal acanthosis. Inspection of vessels in the mid to upper dermis in one area revealed stellate, thin-walled, vascular structures that contained bland epithelioid cells lining the lumen as well as packed within the vessels. The epithelioid cells did not show atypia or mitotic figures, and they did not show intracytoplasmic vacuoles (Figure 2). Immunocytochemical staining for D2-40 was strongly positive in cells lining the vessels, consistent with lymphatics (Figure 3). CD68 immunohistochemistry for histiocytes stained the cells within the lymphatics (Figure 4). A diagnosis of intralymphatic histiocytosis was made.

Intralesional triamcinolone acetonide 10 mg/cc×1.6 cc was injected into the plaque once monthly for 2 consecutive months, and daily compression with a pressure bandage of the right lower leg was initiated. Four months after the first treatment with this regimen, the plaque was smaller and no longer sclerotic or painful, and the erythema was markedly reduced (Figure 5). Clinical and symptomatic improvement continued at 1-year follow-up.

Comment

Intralymphatic histiocytosis is a rare cutaneous disorder defined histologically by histiocytes within the lumina of lymphatics. In addition to the current case, our review of PubMed articles indexed for MEDLINE using the search term intralymphatic histiocytosis yielded more than 70 total cases. The condition has a slight female predominance and typically is seen in individuals over the age of 60 years (age range, 16–89 years).¹² Many cases are associated with RA/elevated rheumatoid factor.^2,4,8,15-30 At least 9 cases of intralymphatic histiocytosis were associated with premalignant or malignant conditions (ie, adenocarcinoma of the breasts, lungs, and colon; Merkel cell carcinoma; melanoma; melanoma in situ; Mullerian carcinoma, gammopathy).^4,15,31-34 Primary disease, defined as occurring in patients who are otherwise healthy, was noted in at least 10 cases.^{1,2,4,12,35,36} Finally, intralymphatic histiocytosis was identified in areas adjacent to metal implants and joint replacements or exploration in approximately 15 cases (including the current case).^3-14,29,37

The condition presents with papules, plaques, and nodules in the setting of characteristic livedoid discoloration; however, some patients present with nonspecific nodules or plaques. Lesions may be symptomatic (eg, pruritic, tender) or asymptomatic. The histologic features of intralymphatic histiocytosis are distinctive but may be focal, as in our case, and the diagnosis is easily missed. The histologic differential diagnosis includes diseases in which intravascular accumulations of cells may be seen, including intravascular B-cell lymphoma, which can be excluded with stains that detect B cells (CD20/CD79a), and reactive angioendotheliomatosis, a benign proliferation of endothelial cells, which may be excluded with stains against endothelial markers (CD31/CD34). The course typically is chronic, and treatment with topical steroids,^3,9,15,22,26 cyclophosphamide,¹⁵ local radiation,¹ thalidomide,³⁵ pentoxifylline,⁷ and RA medications (eg, prednisolone, methotrexate, nonsteroidal anti-inflammatory drugs, hydroxychloroquine) generally are ineffective.^2,16,20,25 Symptoms may improve with joint replacement,⁴ excision of the involved lesion, treatment of an associated malignancy/infection,^33,36,38,39 nonsteroidal anti-inflammatory drugs, intra-articular steroid injection,¹⁸ amoxicillin and aspirin,¹⁹ infliximab,²⁵ pressure bandage application,²⁶ steroid-containing adhesive application,¹⁸ arthrocentesis,^3,27 oral pentoxifylline,²¹ tacrolimus,²⁹ CO₂ laser,⁴⁰ prednisolone,⁴¹ and tocilizumab.²⁸ Treatment of associated RA is beneficial in rare cases.^{2,15,20,25,26}

The pathogenesis of intralymphatic histiocytosis has not been elucidated with certainty but may represent an abnormal proliferative response of histiocytes and vessels in response to chronic systemic or local inflammation. Lymphangiectasis caused by lymphatic obstruction secondary to trauma, surgical manipulation, or chronic inflammation can promote lymphostasis and slowed clearance of antigens producing an accumulation of histiocytes and subsequent local immunologic reactions, thus an “immunocompromised district” is formed.⁴² It also is thought that rheumatic or prosthetic joints produce inflammatory mediator–rich (namely tumor necrosis factor α) synovial fluid that drains and collects within the dilated lymphatics, creating a nidus for histiocytes.^1,5 In one case, treatment with an anti–tumor necrosis factor antibody (infliximab) improved the skin presentation and rheumatoid joint pain.²⁵ Bakr et al² noted an association with increased intralymphatic macrophage HLA-DR expression. This T-cell surface receptor typically is upregulated in cases of chronic antigen stimulation and autoimmune conditions.

Conclusion

Our patient had a history of a joint prosthesis and a popliteal cyst, which could have altered lymphatic drainage promoting abnormal immune cell trafficking contributing to the development of intralymphatic histiocytosis. The response to intralesional steroids supports this pathogenic hypothesis. Specifically, direct injection of the area suppressed the immune dysregulation, while compression lessened the degree of lymphostasis. In light of previously reported cases of intralymphatic histiocytosis in association with metal implants,^3-9 we suggest that the condition should be considered in patients with chronic painful livedoid nodules or plaques around an affected joint, even in the absence of RA. The dermatopathologist should be warned to search carefully for the subtle but distinctive histologic features of the disease that confirm the diagnosis. Treatment with intralesional triamcinolone acetonide with an overlying pressure wrap has minimal side effects and can work quickly with sustained benefits.

Intralymphatic histiocytosis was first described in 1994.¹ To date, at least 70 cases have been reported in the English-language literature, the majority being associated with systemic or local inflammatory conditions such as rheumatoid arthritis (RA), malignancy, and metal prostheses. The remaining cases arose independent of any detectable disease process.² The clinical lesion localizes to areas around surgical scars or inflamed joints and generally presents with erythematous livedoid papules and plaques. Because of its rarity, pathologists and clinicians may be unfamiliar with this entity, leading to delayed or missed diagnoses.

Although the pathogenesis of intralymphatic histiocytosis remains unclear, it may be related to dysregulated immune signaling. The condition follows a chronic, relapsing-remitting course that has shown variable response to topical and systemic treatments. We present a rare case of intralymphatic histiocytosis associated with joint replacement/metal prosthesis^3-14 that was responsive to a novel treatment with intralesional steroid injection and pressure bandage.

Case Report

An 89-year-old woman presented with a relapsing and remitting rash on the right calf and popliteal fossa of 11 months’ duration. It was becoming more painful over time and recently began to hurt when walking. Her medical history was remarkable for deep vein thromboses of the bilateral legs, Factor V Leiden deficiency, osteoarthritis, and a popliteal (Baker) cyst on the right leg that ruptured 22 months prior to presentation. Her surgical history included bilateral knee replacements (10 years and 2 years prior to the current presentation for the right and left knees, respectively). Her international normalized ratio (2.0) was therapeutic on warfarin.

Initially, swelling, pain, and redness developed in the right calf, and recurrent right-leg deep venous thrombosis was ruled out by Doppler ultrasound. The findings were considered to be secondary to inflammation from a popliteal cyst. Symptoms persisted despite application of warm compresses, leg elevation, and compression stockings. Treatment with doxycycline prescribed by the patient’s primary care physician 9 months prior for presumed cellulitis produced little improvement. Physical examination revealed a well-healed vertical scar on the right calf from an incisional biopsy within an 8-cm, tender, erythematous, indurated, sclerotic plaque with erythematous streaks radiating from the center of the plaque (Figure 1). There also was red-brown, indurated discoloration on the right shin.

Fine-needle aspiration of the lesion revealed red blood cells and histiocytes. Laboratory studies showed an elevated erythrocyte sedimentation rate of 74 mm/h (reference range, 0–30 mm/h) and a C-reactive protein level of 39 mg/L (reference range, 0–10 mg/L). An incisional biopsy including the muscular fascia showed dense dermal fibrosis with chronic inflammation and scarring. A dermatopathologist (G. A. S.) reviewed the case and confirmed variable fibrosis and chronic inflammation associated with edema in the dermis and epidermal acanthosis. Inspection of vessels in the mid to upper dermis in one area revealed stellate, thin-walled, vascular structures that contained bland epithelioid cells lining the lumen as well as packed within the vessels. The epithelioid cells did not show atypia or mitotic figures, and they did not show intracytoplasmic vacuoles (Figure 2). Immunocytochemical staining for D2-40 was strongly positive in cells lining the vessels, consistent with lymphatics (Figure 3). CD68 immunohistochemistry for histiocytes stained the cells within the lymphatics (Figure 4). A diagnosis of intralymphatic histiocytosis was made.

Intralesional triamcinolone acetonide 10 mg/cc×1.6 cc was injected into the plaque once monthly for 2 consecutive months, and daily compression with a pressure bandage of the right lower leg was initiated. Four months after the first treatment with this regimen, the plaque was smaller and no longer sclerotic or painful, and the erythema was markedly reduced (Figure 5). Clinical and symptomatic improvement continued at 1-year follow-up.

Comment

Intralymphatic histiocytosis is a rare cutaneous disorder defined histologically by histiocytes within the lumina of lymphatics. In addition to the current case, our review of PubMed articles indexed for MEDLINE using the search term intralymphatic histiocytosis yielded more than 70 total cases. The condition has a slight female predominance and typically is seen in individuals over the age of 60 years (age range, 16–89 years).¹² Many cases are associated with RA/elevated rheumatoid factor.^2,4,8,15-30 At least 9 cases of intralymphatic histiocytosis were associated with premalignant or malignant conditions (ie, adenocarcinoma of the breasts, lungs, and colon; Merkel cell carcinoma; melanoma; melanoma in situ; Mullerian carcinoma, gammopathy).^4,15,31-34 Primary disease, defined as occurring in patients who are otherwise healthy, was noted in at least 10 cases.^{1,2,4,12,35,36} Finally, intralymphatic histiocytosis was identified in areas adjacent to metal implants and joint replacements or exploration in approximately 15 cases (including the current case).^3-14,29,37

The condition presents with papules, plaques, and nodules in the setting of characteristic livedoid discoloration; however, some patients present with nonspecific nodules or plaques. Lesions may be symptomatic (eg, pruritic, tender) or asymptomatic. The histologic features of intralymphatic histiocytosis are distinctive but may be focal, as in our case, and the diagnosis is easily missed. The histologic differential diagnosis includes diseases in which intravascular accumulations of cells may be seen, including intravascular B-cell lymphoma, which can be excluded with stains that detect B cells (CD20/CD79a), and reactive angioendotheliomatosis, a benign proliferation of endothelial cells, which may be excluded with stains against endothelial markers (CD31/CD34). The course typically is chronic, and treatment with topical steroids,^3,9,15,22,26 cyclophosphamide,¹⁵ local radiation,¹ thalidomide,³⁵ pentoxifylline,⁷ and RA medications (eg, prednisolone, methotrexate, nonsteroidal anti-inflammatory drugs, hydroxychloroquine) generally are ineffective.^2,16,20,25 Symptoms may improve with joint replacement,⁴ excision of the involved lesion, treatment of an associated malignancy/infection,^33,36,38,39 nonsteroidal anti-inflammatory drugs, intra-articular steroid injection,¹⁸ amoxicillin and aspirin,¹⁹ infliximab,²⁵ pressure bandage application,²⁶ steroid-containing adhesive application,¹⁸ arthrocentesis,^3,27 oral pentoxifylline,²¹ tacrolimus,²⁹ CO₂ laser,⁴⁰ prednisolone,⁴¹ and tocilizumab.²⁸ Treatment of associated RA is beneficial in rare cases.^{2,15,20,25,26}

The pathogenesis of intralymphatic histiocytosis has not been elucidated with certainty but may represent an abnormal proliferative response of histiocytes and vessels in response to chronic systemic or local inflammation. Lymphangiectasis caused by lymphatic obstruction secondary to trauma, surgical manipulation, or chronic inflammation can promote lymphostasis and slowed clearance of antigens producing an accumulation of histiocytes and subsequent local immunologic reactions, thus an “immunocompromised district” is formed.⁴² It also is thought that rheumatic or prosthetic joints produce inflammatory mediator–rich (namely tumor necrosis factor α) synovial fluid that drains and collects within the dilated lymphatics, creating a nidus for histiocytes.^1,5 In one case, treatment with an anti–tumor necrosis factor antibody (infliximab) improved the skin presentation and rheumatoid joint pain.²⁵ Bakr et al² noted an association with increased intralymphatic macrophage HLA-DR expression. This T-cell surface receptor typically is upregulated in cases of chronic antigen stimulation and autoimmune conditions.

Conclusion

Our patient had a history of a joint prosthesis and a popliteal cyst, which could have altered lymphatic drainage promoting abnormal immune cell trafficking contributing to the development of intralymphatic histiocytosis. The response to intralesional steroids supports this pathogenic hypothesis. Specifically, direct injection of the area suppressed the immune dysregulation, while compression lessened the degree of lymphostasis. In light of previously reported cases of intralymphatic histiocytosis in association with metal implants,^3-9 we suggest that the condition should be considered in patients with chronic painful livedoid nodules or plaques around an affected joint, even in the absence of RA. The dermatopathologist should be warned to search carefully for the subtle but distinctive histologic features of the disease that confirm the diagnosis. Treatment with intralesional triamcinolone acetonide with an overlying pressure wrap has minimal side effects and can work quickly with sustained benefits.

Intralymphatic histiocytosis was first described in 1994.¹ To date, at least 70 cases have been reported in the English-language literature, the majority being associated with systemic or local inflammatory conditions such as rheumatoid arthritis (RA), malignancy, and metal prostheses. The remaining cases arose independent of any detectable disease process.² The clinical lesion localizes to areas around surgical scars or inflamed joints and generally presents with erythematous livedoid papules and plaques. Because of its rarity, pathologists and clinicians may be unfamiliar with this entity, leading to delayed or missed diagnoses.

Although the pathogenesis of intralymphatic histiocytosis remains unclear, it may be related to dysregulated immune signaling. The condition follows a chronic, relapsing-remitting course that has shown variable response to topical and systemic treatments. We present a rare case of intralymphatic histiocytosis associated with joint replacement/metal prosthesis^3-14 that was responsive to a novel treatment with intralesional steroid injection and pressure bandage.

Case Report

An 89-year-old woman presented with a relapsing and remitting rash on the right calf and popliteal fossa of 11 months’ duration. It was becoming more painful over time and recently began to hurt when walking. Her medical history was remarkable for deep vein thromboses of the bilateral legs, Factor V Leiden deficiency, osteoarthritis, and a popliteal (Baker) cyst on the right leg that ruptured 22 months prior to presentation. Her surgical history included bilateral knee replacements (10 years and 2 years prior to the current presentation for the right and left knees, respectively). Her international normalized ratio (2.0) was therapeutic on warfarin.

Initially, swelling, pain, and redness developed in the right calf, and recurrent right-leg deep venous thrombosis was ruled out by Doppler ultrasound. The findings were considered to be secondary to inflammation from a popliteal cyst. Symptoms persisted despite application of warm compresses, leg elevation, and compression stockings. Treatment with doxycycline prescribed by the patient’s primary care physician 9 months prior for presumed cellulitis produced little improvement. Physical examination revealed a well-healed vertical scar on the right calf from an incisional biopsy within an 8-cm, tender, erythematous, indurated, sclerotic plaque with erythematous streaks radiating from the center of the plaque (Figure 1). There also was red-brown, indurated discoloration on the right shin.

Fine-needle aspiration of the lesion revealed red blood cells and histiocytes. Laboratory studies showed an elevated erythrocyte sedimentation rate of 74 mm/h (reference range, 0–30 mm/h) and a C-reactive protein level of 39 mg/L (reference range, 0–10 mg/L). An incisional biopsy including the muscular fascia showed dense dermal fibrosis with chronic inflammation and scarring. A dermatopathologist (G. A. S.) reviewed the case and confirmed variable fibrosis and chronic inflammation associated with edema in the dermis and epidermal acanthosis. Inspection of vessels in the mid to upper dermis in one area revealed stellate, thin-walled, vascular structures that contained bland epithelioid cells lining the lumen as well as packed within the vessels. The epithelioid cells did not show atypia or mitotic figures, and they did not show intracytoplasmic vacuoles (Figure 2). Immunocytochemical staining for D2-40 was strongly positive in cells lining the vessels, consistent with lymphatics (Figure 3). CD68 immunohistochemistry for histiocytes stained the cells within the lymphatics (Figure 4). A diagnosis of intralymphatic histiocytosis was made.

Intralesional triamcinolone acetonide 10 mg/cc×1.6 cc was injected into the plaque once monthly for 2 consecutive months, and daily compression with a pressure bandage of the right lower leg was initiated. Four months after the first treatment with this regimen, the plaque was smaller and no longer sclerotic or painful, and the erythema was markedly reduced (Figure 5). Clinical and symptomatic improvement continued at 1-year follow-up.

Comment

Intralymphatic histiocytosis is a rare cutaneous disorder defined histologically by histiocytes within the lumina of lymphatics. In addition to the current case, our review of PubMed articles indexed for MEDLINE using the search term intralymphatic histiocytosis yielded more than 70 total cases. The condition has a slight female predominance and typically is seen in individuals over the age of 60 years (age range, 16–89 years).¹² Many cases are associated with RA/elevated rheumatoid factor.^2,4,8,15-30 At least 9 cases of intralymphatic histiocytosis were associated with premalignant or malignant conditions (ie, adenocarcinoma of the breasts, lungs, and colon; Merkel cell carcinoma; melanoma; melanoma in situ; Mullerian carcinoma, gammopathy).^4,15,31-34 Primary disease, defined as occurring in patients who are otherwise healthy, was noted in at least 10 cases.^{1,2,4,12,35,36} Finally, intralymphatic histiocytosis was identified in areas adjacent to metal implants and joint replacements or exploration in approximately 15 cases (including the current case).^3-14,29,37

The condition presents with papules, plaques, and nodules in the setting of characteristic livedoid discoloration; however, some patients present with nonspecific nodules or plaques. Lesions may be symptomatic (eg, pruritic, tender) or asymptomatic. The histologic features of intralymphatic histiocytosis are distinctive but may be focal, as in our case, and the diagnosis is easily missed. The histologic differential diagnosis includes diseases in which intravascular accumulations of cells may be seen, including intravascular B-cell lymphoma, which can be excluded with stains that detect B cells (CD20/CD79a), and reactive angioendotheliomatosis, a benign proliferation of endothelial cells, which may be excluded with stains against endothelial markers (CD31/CD34). The course typically is chronic, and treatment with topical steroids,^3,9,15,22,26 cyclophosphamide,¹⁵ local radiation,¹ thalidomide,³⁵ pentoxifylline,⁷ and RA medications (eg, prednisolone, methotrexate, nonsteroidal anti-inflammatory drugs, hydroxychloroquine) generally are ineffective.^2,16,20,25 Symptoms may improve with joint replacement,⁴ excision of the involved lesion, treatment of an associated malignancy/infection,^33,36,38,39 nonsteroidal anti-inflammatory drugs, intra-articular steroid injection,¹⁸ amoxicillin and aspirin,¹⁹ infliximab,²⁵ pressure bandage application,²⁶ steroid-containing adhesive application,¹⁸ arthrocentesis,^3,27 oral pentoxifylline,²¹ tacrolimus,²⁹ CO₂ laser,⁴⁰ prednisolone,⁴¹ and tocilizumab.²⁸ Treatment of associated RA is beneficial in rare cases.^{2,15,20,25,26}

The pathogenesis of intralymphatic histiocytosis has not been elucidated with certainty but may represent an abnormal proliferative response of histiocytes and vessels in response to chronic systemic or local inflammation. Lymphangiectasis caused by lymphatic obstruction secondary to trauma, surgical manipulation, or chronic inflammation can promote lymphostasis and slowed clearance of antigens producing an accumulation of histiocytes and subsequent local immunologic reactions, thus an “immunocompromised district” is formed.⁴² It also is thought that rheumatic or prosthetic joints produce inflammatory mediator–rich (namely tumor necrosis factor α) synovial fluid that drains and collects within the dilated lymphatics, creating a nidus for histiocytes.^1,5 In one case, treatment with an anti–tumor necrosis factor antibody (infliximab) improved the skin presentation and rheumatoid joint pain.²⁵ Bakr et al² noted an association with increased intralymphatic macrophage HLA-DR expression. This T-cell surface receptor typically is upregulated in cases of chronic antigen stimulation and autoimmune conditions.

Conclusion

Our patient had a history of a joint prosthesis and a popliteal cyst, which could have altered lymphatic drainage promoting abnormal immune cell trafficking contributing to the development of intralymphatic histiocytosis. The response to intralesional steroids supports this pathogenic hypothesis. Specifically, direct injection of the area suppressed the immune dysregulation, while compression lessened the degree of lymphostasis. In light of previously reported cases of intralymphatic histiocytosis in association with metal implants,^3-9 we suggest that the condition should be considered in patients with chronic painful livedoid nodules or plaques around an affected joint, even in the absence of RA. The dermatopathologist should be warned to search carefully for the subtle but distinctive histologic features of the disease that confirm the diagnosis. Treatment with intralesional triamcinolone acetonide with an overlying pressure wrap has minimal side effects and can work quickly with sustained benefits.