Cutis

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on self-tanners. Consideration must be given to:

• Anthelios 50 Mineral Tinted
  La Roche-Posay Laboratoire Dermatologique
  Recommended by Gary Goldenberg, MD, New York, New York

• St. Tropez Self Tan products
  PZ Cussons Beauty LLP
  “It helps to produce an even and natural-looking skin tone.”—Anthony M. Rossi, MD, New York, New York

• Sun-Free Self-Tanning Formula
  Kiehl’s
  Recommended by Gary Goldenberg, MD, New York, New York

• Sunless Tanning Towelette
  Sun Bum
  “This product is easy to use. Make sure to use it in conjunction with a broad-spectrum sunscreen.”—Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening products, and athlete’s foot treatments will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

The Diagnosis: Blaschkoid Graft-vs-host Disease

The patient had a history of myelodysplastic syndrome and underwent a bone marrow transplant 1 year prior to presentation. She had acute graft-vs-host disease (GVHD) 6 weeks following the transplant, which resolved with high-dose prednisone followed by UVB phototherapy. Skin biopsy demonstrated lichenoid dermatitis with vacuolar degeneration, dyskeratosis, and prominent pigment incontinence (Figure). Based on these findings and her clinical presentation, a diagnosis of blaschkoid GVHD was made.

Although acute GVHD is the result of immunocompetent donor T cells recognizing host tissues as foreign and initiating an immune response, the pathophysiology of chronic GVHD is not well understood.^1,2 Theories for disease pathogenesis in chronic GVHD suggest an underlying autoimmune and/or alloreactive process.^2-5 The skin often is the first organ affected in acute GVHD, and patients generally present with a pruritic morbilliform eruption that begins on the trunk and spreads to the rest of the body.^1,2 Cutaneous manifestations of chronic GVHD may be protean. Lesions can resemble systemic sclerosis or morphea, lichen planus, psoriasis, ichthyosis, and many other conditions.²

The differential diagnosis of linear dermatoses includes herpes zoster, contact dermatitis, lichen striatus (blaschkitis), nevus unius lateris, inflammatory linear verrucous epidermal nevus, and incontinentia pigmenti.^6,7 Lichen planus-like chronic GVHD occurring in a linear distribution has been described.^6-14 Distinction between dermatomal and blaschkoid processes is diagnostically important. In the case of GVHD, dermatomal distribution may suggest an association between GVHD and prior herpes simplex virus or varicella-zoster virus infection.^6,8 Herpesvirus may alter surface antigens of keratinocytes, rendering them targets of donor lymphocytes, and antibodies to viral particles may cross-react with host keratinocyte HLA antigens. It also is possible that dermatomal GVHD may simply be a type of isomorphic response (Köbner phenomenon).⁸

When cutaneous GVHD follows Blaschko lines, other mechanisms appear to be at play.^9-14 It is plausible that these patients have an underlying genetic mosaicism, perhaps the result of a postzygotic mutation, that results in a daughter cell population that expresses surface antigens different from those of the primary cell population found elsewhere in the skin. Donor lymphocytes may selectively react to this mosaic population, leading to the clinical picture of chronic GVHD oriented along Blaschko lines.^10,11,13,14 

In conclusion, lichenoid linear GVHD following Blaschko lines is an uncommon presentation of chronic GVHD that highlights the heterogeneity of this disease and should be considered in the appropriate clinical setting.

The Diagnosis: Blaschkoid Graft-vs-host Disease

The patient had a history of myelodysplastic syndrome and underwent a bone marrow transplant 1 year prior to presentation. She had acute graft-vs-host disease (GVHD) 6 weeks following the transplant, which resolved with high-dose prednisone followed by UVB phototherapy. Skin biopsy demonstrated lichenoid dermatitis with vacuolar degeneration, dyskeratosis, and prominent pigment incontinence (Figure). Based on these findings and her clinical presentation, a diagnosis of blaschkoid GVHD was made.

Although acute GVHD is the result of immunocompetent donor T cells recognizing host tissues as foreign and initiating an immune response, the pathophysiology of chronic GVHD is not well understood.^1,2 Theories for disease pathogenesis in chronic GVHD suggest an underlying autoimmune and/or alloreactive process.^2-5 The skin often is the first organ affected in acute GVHD, and patients generally present with a pruritic morbilliform eruption that begins on the trunk and spreads to the rest of the body.^1,2 Cutaneous manifestations of chronic GVHD may be protean. Lesions can resemble systemic sclerosis or morphea, lichen planus, psoriasis, ichthyosis, and many other conditions.²

The differential diagnosis of linear dermatoses includes herpes zoster, contact dermatitis, lichen striatus (blaschkitis), nevus unius lateris, inflammatory linear verrucous epidermal nevus, and incontinentia pigmenti.^6,7 Lichen planus-like chronic GVHD occurring in a linear distribution has been described.^6-14 Distinction between dermatomal and blaschkoid processes is diagnostically important. In the case of GVHD, dermatomal distribution may suggest an association between GVHD and prior herpes simplex virus or varicella-zoster virus infection.^6,8 Herpesvirus may alter surface antigens of keratinocytes, rendering them targets of donor lymphocytes, and antibodies to viral particles may cross-react with host keratinocyte HLA antigens. It also is possible that dermatomal GVHD may simply be a type of isomorphic response (Köbner phenomenon).⁸

When cutaneous GVHD follows Blaschko lines, other mechanisms appear to be at play.^9-14 It is plausible that these patients have an underlying genetic mosaicism, perhaps the result of a postzygotic mutation, that results in a daughter cell population that expresses surface antigens different from those of the primary cell population found elsewhere in the skin. Donor lymphocytes may selectively react to this mosaic population, leading to the clinical picture of chronic GVHD oriented along Blaschko lines.^10,11,13,14 

In conclusion, lichenoid linear GVHD following Blaschko lines is an uncommon presentation of chronic GVHD that highlights the heterogeneity of this disease and should be considered in the appropriate clinical setting.

The Diagnosis: Blaschkoid Graft-vs-host Disease

The patient had a history of myelodysplastic syndrome and underwent a bone marrow transplant 1 year prior to presentation. She had acute graft-vs-host disease (GVHD) 6 weeks following the transplant, which resolved with high-dose prednisone followed by UVB phototherapy. Skin biopsy demonstrated lichenoid dermatitis with vacuolar degeneration, dyskeratosis, and prominent pigment incontinence (Figure). Based on these findings and her clinical presentation, a diagnosis of blaschkoid GVHD was made.

Although acute GVHD is the result of immunocompetent donor T cells recognizing host tissues as foreign and initiating an immune response, the pathophysiology of chronic GVHD is not well understood.^1,2 Theories for disease pathogenesis in chronic GVHD suggest an underlying autoimmune and/or alloreactive process.^2-5 The skin often is the first organ affected in acute GVHD, and patients generally present with a pruritic morbilliform eruption that begins on the trunk and spreads to the rest of the body.^1,2 Cutaneous manifestations of chronic GVHD may be protean. Lesions can resemble systemic sclerosis or morphea, lichen planus, psoriasis, ichthyosis, and many other conditions.²

The differential diagnosis of linear dermatoses includes herpes zoster, contact dermatitis, lichen striatus (blaschkitis), nevus unius lateris, inflammatory linear verrucous epidermal nevus, and incontinentia pigmenti.^6,7 Lichen planus-like chronic GVHD occurring in a linear distribution has been described.^6-14 Distinction between dermatomal and blaschkoid processes is diagnostically important. In the case of GVHD, dermatomal distribution may suggest an association between GVHD and prior herpes simplex virus or varicella-zoster virus infection.^6,8 Herpesvirus may alter surface antigens of keratinocytes, rendering them targets of donor lymphocytes, and antibodies to viral particles may cross-react with host keratinocyte HLA antigens. It also is possible that dermatomal GVHD may simply be a type of isomorphic response (Köbner phenomenon).⁸

When cutaneous GVHD follows Blaschko lines, other mechanisms appear to be at play.^9-14 It is plausible that these patients have an underlying genetic mosaicism, perhaps the result of a postzygotic mutation, that results in a daughter cell population that expresses surface antigens different from those of the primary cell population found elsewhere in the skin. Donor lymphocytes may selectively react to this mosaic population, leading to the clinical picture of chronic GVHD oriented along Blaschko lines.^10,11,13,14 

In conclusion, lichenoid linear GVHD following Blaschko lines is an uncommon presentation of chronic GVHD that highlights the heterogeneity of this disease and should be considered in the appropriate clinical setting.

The Diagnosis: Chronic Hyperplastic Candidiasis (Nodular Form)

Chronic hyperplastic candidiasis (CHC) is a rare form of oropharyngeal candidiasis. The most frequent clinical presentation is a white plaque that cannot be detached (also known as candidal leukoplakia). It usually involves the anterior buccal mucosa, mainly the commissural area, though the palate and tongue also can be affected. The nodular type of CHC is even less common. Our patient exhibited the typical clinical presentation of the nodular type of CHC.^1-3 The differential diagnosis includes leukoplakia, premalignant and malignant epithelial lesions, granular cell tumor, and florid oral papillomatosis.^1,3 A biopsy usually is required for diagnostic confirmation. Histologically, CHC is characterized by parakeratosis and a hyperplastic epithelium invaded by Candida hyphae.⁴ Because Candida species are commensal in up to 50% of the healthy population, superficial colonization of tissues is not enough to indicate notable disease.¹ In our patient, the histopathology revealed a hyperplastic mucosa without atypia and numerous hyphae (Figure). Both lingual swab and tissue cultures revealed high growth of Candida albicans. 

Infection by C albicans depends on pathogen virulence and host factors such as wearing dentures, reduced salivary production, smoking habit, or immunosuppression.^1,4 Apart from wearing dentures, our patient did not present with other predisposing factors. It is possible that the immunosuppressive status related to old age and associated oral changes contributed to Candida infection in this case. 

Topical or systemic antifungal agents together with the elimination of predisposing factors are usual first-line treatments. Because of the relationship with atypia and the possibility of evolving into carcinoma in untreated or persistent lesions, follow-up is necessary to verify complete resolution after treatment.^1,3,4 In the case reported herein, the lesions disappeared after 15 days of oral fluconazole treatment.

The Diagnosis: Chronic Hyperplastic Candidiasis (Nodular Form)

Chronic hyperplastic candidiasis (CHC) is a rare form of oropharyngeal candidiasis. The most frequent clinical presentation is a white plaque that cannot be detached (also known as candidal leukoplakia). It usually involves the anterior buccal mucosa, mainly the commissural area, though the palate and tongue also can be affected. The nodular type of CHC is even less common. Our patient exhibited the typical clinical presentation of the nodular type of CHC.^1-3 The differential diagnosis includes leukoplakia, premalignant and malignant epithelial lesions, granular cell tumor, and florid oral papillomatosis.^1,3 A biopsy usually is required for diagnostic confirmation. Histologically, CHC is characterized by parakeratosis and a hyperplastic epithelium invaded by Candida hyphae.⁴ Because Candida species are commensal in up to 50% of the healthy population, superficial colonization of tissues is not enough to indicate notable disease.¹ In our patient, the histopathology revealed a hyperplastic mucosa without atypia and numerous hyphae (Figure). Both lingual swab and tissue cultures revealed high growth of Candida albicans. 

Infection by C albicans depends on pathogen virulence and host factors such as wearing dentures, reduced salivary production, smoking habit, or immunosuppression.^1,4 Apart from wearing dentures, our patient did not present with other predisposing factors. It is possible that the immunosuppressive status related to old age and associated oral changes contributed to Candida infection in this case. 

Topical or systemic antifungal agents together with the elimination of predisposing factors are usual first-line treatments. Because of the relationship with atypia and the possibility of evolving into carcinoma in untreated or persistent lesions, follow-up is necessary to verify complete resolution after treatment.^1,3,4 In the case reported herein, the lesions disappeared after 15 days of oral fluconazole treatment.

The Diagnosis: Chronic Hyperplastic Candidiasis (Nodular Form)

Chronic hyperplastic candidiasis (CHC) is a rare form of oropharyngeal candidiasis. The most frequent clinical presentation is a white plaque that cannot be detached (also known as candidal leukoplakia). It usually involves the anterior buccal mucosa, mainly the commissural area, though the palate and tongue also can be affected. The nodular type of CHC is even less common. Our patient exhibited the typical clinical presentation of the nodular type of CHC.^1-3 The differential diagnosis includes leukoplakia, premalignant and malignant epithelial lesions, granular cell tumor, and florid oral papillomatosis.^1,3 A biopsy usually is required for diagnostic confirmation. Histologically, CHC is characterized by parakeratosis and a hyperplastic epithelium invaded by Candida hyphae.⁴ Because Candida species are commensal in up to 50% of the healthy population, superficial colonization of tissues is not enough to indicate notable disease.¹ In our patient, the histopathology revealed a hyperplastic mucosa without atypia and numerous hyphae (Figure). Both lingual swab and tissue cultures revealed high growth of Candida albicans. 

Infection by C albicans depends on pathogen virulence and host factors such as wearing dentures, reduced salivary production, smoking habit, or immunosuppression.^1,4 Apart from wearing dentures, our patient did not present with other predisposing factors. It is possible that the immunosuppressive status related to old age and associated oral changes contributed to Candida infection in this case. 

Topical or systemic antifungal agents together with the elimination of predisposing factors are usual first-line treatments. Because of the relationship with atypia and the possibility of evolving into carcinoma in untreated or persistent lesions, follow-up is necessary to verify complete resolution after treatment.^1,3,4 In the case reported herein, the lesions disappeared after 15 days of oral fluconazole treatment.

Review the PDF of the fact sheet on common hair disorders with board-relevant, easy-to-review material. This fact sheet reviews information about the most common hair disorders, including clinical and histopathological features, trichoscopy, and management of these diseases.

Practice Questions

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

Answers to practice questions provided on next page

Practice Question Answers

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

Review the PDF of the fact sheet on common hair disorders with board-relevant, easy-to-review material. This fact sheet reviews information about the most common hair disorders, including clinical and histopathological features, trichoscopy, and management of these diseases.

Practice Questions

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

Answers to practice questions provided on next page

Practice Question Answers

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

Review the PDF of the fact sheet on common hair disorders with board-relevant, easy-to-review material. This fact sheet reviews information about the most common hair disorders, including clinical and histopathological features, trichoscopy, and management of these diseases.

Practice Questions

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

Answers to practice questions provided on next page

Practice Question Answers

1. A 40-year-old woman presents to the clinic with a burning sensation and tenderness on the scalp. At physical examination you notice erythematous papules and pustules on the vertex scalp. The most likely diagnosis is:

a. alopecia areata
b. CCSA
c. folliculitis decalvans
d. lichen planopilaris
e. traction alopecia

2. A 60-year-old woman presents with receding hair loss on the frontal and bitemporal scalp. She has noticed hair loss on her eyebrows. She has a history of oral ulcers. On physical examination there is mild erythema and perifollicular scales on the frontal hairline. A hair pull test is positive in this area. The most likely diagnosis is:

a. androgenetic alopecia
b. chronic cutaneous lupus erythematosus
c. frontal fibrosing alopecia
d. telogen effluvium
e. trichotillomania

3. A 5-year-old girl with a history of seasonal allergies and eczema presents with recurrent patchy hair loss on the scalp of 6 months’ duration. Her mother has noticed rapidly progressive hair loss affecting the whole scalp. On trichoscopy, you find yellow dots, broken hairs, and tapering hairs. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. telogen effluvium
d. traction alopecia
e. trichotillomania

4. A 30-year-old white woman with history of obsessive-compulsive disorder presents to the clinic with hair loss for the last 3 years. She says she has noticed worsening of the hair loss when she is under stress. She also bites her nails. On physical examination you identify an irregular patch of alopecia with broken hairs on the occipital scalp. The most likely diagnosis is:

a. alopecia areata
b. androgenetic alopecia
c. lichen planopilaris
d. traction alopecia
e. trichotillomania

5. A 45-year-old black woman who has a family history of hair loss in her mother presents with tenderness and burning sensation on the vertex scalp. She reports the hair loss was worse after she got a hair relaxer 6 months prior. She uses braids on her scalp and she has not had a relaxer since then. The most likely diagnosis is:

a. CCSA
b. chronic cutaneous lupus erythematosus
c. folliculitis decalvans
d. lichen planopilaris
e. trichotillomania

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz provided an update on dermoscopy as a first-line noninvasive imaging modality for skin cancer screening and diagnosis along with reflectance confocal microscopy and dynamic optical coherence tomography. She explained how noninvasive imaging offers a more complete picture of lesions along with what is seen clinically and on pathology and discussed how it can help catch aggressive melanomas and other skin cancers at earlier stages. For these reasons, she emphasized that increased use of dermoscopy can be used to justify the need for regular skin cancer screenings. Finally, she discussed how noninvasive imaging can be used to guide dermatologists in performing optimal biposies of suspicious lesions.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz provided an update on dermoscopy as a first-line noninvasive imaging modality for skin cancer screening and diagnosis along with reflectance confocal microscopy and dynamic optical coherence tomography. She explained how noninvasive imaging offers a more complete picture of lesions along with what is seen clinically and on pathology and discussed how it can help catch aggressive melanomas and other skin cancers at earlier stages. For these reasons, she emphasized that increased use of dermoscopy can be used to justify the need for regular skin cancer screenings. Finally, she discussed how noninvasive imaging can be used to guide dermatologists in performing optimal biposies of suspicious lesions.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz provided an update on dermoscopy as a first-line noninvasive imaging modality for skin cancer screening and diagnosis along with reflectance confocal microscopy and dynamic optical coherence tomography. She explained how noninvasive imaging offers a more complete picture of lesions along with what is seen clinically and on pathology and discussed how it can help catch aggressive melanomas and other skin cancers at earlier stages. For these reasons, she emphasized that increased use of dermoscopy can be used to justify the need for regular skin cancer screenings. Finally, she discussed how noninvasive imaging can be used to guide dermatologists in performing optimal biposies of suspicious lesions.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz addressed some common questions physicians have about dermoscopy, including what kind of dermatoscope to buy, how to incorporate dermoscopy into a dermatology practice, and how to efficiently perform skin examinations using a dermatoscope. She also emphasized the importance of attending courses and workshops to learn how to utilize dermoscopy and other noninvasive imaging devices effectively.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz addressed some common questions physicians have about dermoscopy, including what kind of dermatoscope to buy, how to incorporate dermoscopy into a dermatology practice, and how to efficiently perform skin examinations using a dermatoscope. She also emphasized the importance of attending courses and workshops to learn how to utilize dermoscopy and other noninvasive imaging devices effectively.

At the 19th Annual Mount Sinai Winter Symposium, Dr. Orit Markowitz addressed some common questions physicians have about dermoscopy, including what kind of dermatoscope to buy, how to incorporate dermoscopy into a dermatology practice, and how to efficiently perform skin examinations using a dermatoscope. She also emphasized the importance of attending courses and workshops to learn how to utilize dermoscopy and other noninvasive imaging devices effectively.