Article

To the Editor:

Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.¹ Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.² Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.^3-7

Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (T_H2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.^8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.

An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.

Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.

Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).^5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.

Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.^12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.¹⁴ We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.

Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.^15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.¹⁷ Diminishing pruritus is difficult and often aided by management of the underlying renal disease.¹⁸

In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.¹⁹ Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits T_H2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.²⁰ The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.¹⁰ The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.

To the Editor:

Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.¹ Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.² Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.^3-7

Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (T_H2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.^8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.

An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.

Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.

Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).^5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.

Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.^12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.¹⁴ We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.

Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.^15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.¹⁷ Diminishing pruritus is difficult and often aided by management of the underlying renal disease.¹⁸

In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.¹⁹ Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits T_H2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.²⁰ The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.¹⁰ The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.

To the Editor:

Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.¹ Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.² Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.^3-7

Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (T_H2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.^8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.

An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.

Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.

Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).^5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.

Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.^12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.¹⁴ We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.

Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.^15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.¹⁷ Diminishing pruritus is difficult and often aided by management of the underlying renal disease.¹⁸

In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.¹⁹ Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits T_H2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.²⁰ The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.¹⁰ The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC. 

The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat. 

In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC. 

In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.

The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.

The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.

Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.

Click here to read more

Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.

Click here to read more

Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.

Click here to read more

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermatopathology was consistent with a diagnosis of cutaneous myxoma (CM). There are very few dermoscopic descriptions of CM in the literature, so diagnostic features are not established. However, the absence of more diagnostic features of basal cell carcinoma or squamous cell carcinoma (SCC) increases the likelihood of a rare diagnosis, such as CM.

CMs are rare benign neoplasms that manifest most commonly in young adults as small (< 1 cm) flesh-colored to blue papules on the head, neck, and trunk. The size of this particular CM was an outlier. CMs may be associated with Carney Complex (CNC), a rare inherited syndrome that has been linked to multiple endocrine neoplasias—namely, pituitary adenomas, testicular Sertoli cell tumors, thyroid tumors, and cardiac atrial myxomas.¹ Additionally, in CNC, lentigines and multiple blue nevi develop on the skin and mucosal surfaces.

The differential diagnosis for a large, pink to flesh-colored nodule of this size includes benign histiocytoma, SCC, CM, and dermatofibrosarcoma protuberans. Benign histiocytomas and SCCs are much more common than CM. Clinical features only hint at the correct diagnosis, which must be made histologically.

Patients with CMs benefit from ongoing dermatology surveillance to monitor for the development of atypical nevi or new CMs. In this case, a wide excision with generous margins was planned with plastic surgery. (CMs have been reported to recur after surgery, which is why wide margins are essential.)

Additionally, 2 factors prompted an echocardiogram: the association between CMs and possible cardiac tumors and the patient’s need to undergo future orthopedic surgery under general anesthesia. No cardiac tumors were visible on echocardiogram. Thyroid imaging and genetic evaluation were planned but not completed.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

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In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
 

Read More

In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
 

Read More

In this supplement to Cardiology News, John R. Nelson, MD, FACC, FNLA, FASNC, and Matthew J. Budoff, MD, discuss results from RESPECT-EPA and the existing evidence that purified eicosapentaenoic acid significantly reduces residual CV risk in patients with CVD.
 

Read More

In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction. 

Read More


 

In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction. 

Read More


 

In this supplement to Cardiology News, Payal Kohli, MD, FACC, and Nihar Desai, MD, MPH, discuss the PROMINENT trial and the debate on avoiding the use of fibrates for cardiovascular risk reduction. 

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The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of breast cancer with metastatic spread to the chest wall and lungs. 

Globally, breast cancer is the most frequently diagnosed life-threatening cancer and the leading cause of cancer death among women. In the United States, an estimated 287,850 new cases of invasive breast cancer will be diagnosed in 2022; in addition, 43,250 deaths because of breast cancer are expected to occur. Despite advances in adjuvant treatment strategies, such as tamoxifen for patients with ER-positive breast cancer, many patients with early breast cancer still experience disease recurrence after primary therapy. Because of its systemic nature and inevitable resistance to therapy, metastatic breast cancer is largely incurable.

Approximately 5%-35% of patients with breast cancer develop locoregional recurrence either alone or with distant metastases. The lung is a frequent site of breast cancer metastasis. In addition, approximately 11% of patients have persistent chest wall progression. Recurrent breast cancer in the chest wall is considered a marker of poor prognosis and is normally accompanied by or a precursor to distant metastases. 

Risk factors for chest wall recurrence include primary tumor size, primary stage, and lymph node involvement; in addition, the risk is increased in patients aged 40 years or younger and in those with gross multifocal or multicentric disease. Histopathological risk factors include positive margin status, DCIS, extensive intraductal component, high grade, lymphovascular invasion, tumor oncogene, and tumor suppressor gene expression (eg, p53 and HER2), and ER status. 

According to the National Comprehensive Cancer Network (NCCN) 2022 guidelines, the staging evaluation of patients who present with recurrent or stage IV breast cancer should include:

•    History and physical exam
•    Complete blood count and liver function tests
•    Chest diagnostic CT
•    Bone scan
•    Radiographs of any long or weight-bearing bones that are painful or appear abnormal on bone scan
•    Diagnostic CT of the abdomen (with or without diagnostic CT of the pelvis) or MRI of the abdomen
•    Biopsy documentation of first recurrence, when possible

The use of sodium fluoride PET or PET-CT for the evaluation of patients with recurrent disease is largely discouraged. 

Determination of hormone receptor status (ER and progesterone receptor [PR]) as well as HER2 status should be repeated because ER and PR assays may be falsely negative or falsely positive and there may be discordance between the primary and metastatic tumors.

In the metastatic setting, genetic testing results may have therapeutic implications; specifically, germline mutations in BRCA1/BRCA2 have demonstrated clinical utility and therapeutic impact. Thus, the NCCN panel recommends that germline BRCA1/BRCA2 mutations be evaluated in all patients with recurrent or metastatic breast cancer to identify candidates for appropriate targeted therapies (eg, poly adenosine diphosphate ribose polymerase–inhibitor therapy).

In patients with recurrence of breast cancer to the chest wall, complete chest wall resection and appropriate reconstruction may prolong overall survival, although appropriate patient selection is essential for optimal outcomes. Patients with tumors that display a more aggressive phenotype (eg, triple-negative or HER2-positive disease) may not benefit from this approach and supportive care may be more appropriate.

Avan J. Armaghani, MD, Assistant Member, Department of Breast Oncology, Moffitt Cancer Center, University of South Florida, Tampa, FL. 

Avan J. Armaghani, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.

The Diagnosis: Pseudoangiomatous Squamous Cell Carcinoma

Pseudoangiomatous squamous cell carcinoma (PSCC), a variant of acantholytic squamous cell carcinoma (SCC), is a rare epithelial neoplasm that can mimic angiosarcoma.¹ Clinically, PSCC presents as a white-gray ulcer or nodular pink tumor on sun-exposed areas, typically on the head and neck. Due to its increased potential for metastasis, this variant of SCC is considered particularly aggressive. Histologically, PSCC shows nests of acantholytic atypical keratinocytes arranged in anastomosing arrays that form pseudovascular or pseudoglandular structures.² Acantholytic spaces frequently are filled with erythrocytes. Immunohistochemically, PSCC tumor cells express classic squamous markers such as cytokeratin (CK) 5 and p63 but not vascular markers such as CD31, CD34, and von Willebrand factor.³ In our patient, histopathology of the lesion revealed invasive nests, lobules, and interconnected columns of well-differentiated squamous tumor cells that emanated from the base of the epidermis. The tumor exhibited acantholysis forming ectatic and slitlike spaces, some of which contained erythrocytes. The neoplastic cells, including those lining pseudovascular spaces, positively stained for CK5 (Figure 1A) and nuclear p63 but lacked reactivity to CD31 (Figure 1B) and CD34, corroborating squamous and not vascular differentiation. Current treatment guidelines include Mohs micrographic surgery, excisional surgery, or radiation.⁴ Our patient’s lesion was completely removed by Mohs micrographic surgery. Three months later, there was no evidence of recurrence.

Angiosarcoma is an aggressive neoplasm associated with a poor prognosis and 5-year survival rate of 30% to 40%. The etiology of angiosarcoma still is unclear, but identified risk factors include prior radiation therapy, lymphedema (Stewart-Treves syndrome), and genetic predisposition.⁵ In the skin, angiosarcoma often occurs in the head and neck region, accounting for 60% of cutaneous cases.^5,6 Early in the disease, most patients present with a bruiselike lesion on the scalp or forehead, often delaying the diagnosis.⁶ As the cancer progresses, tissue infiltration, edema, and hemorrhage contribute to the formation of violaceous nodules, which eventually prompt for biopsy. Angiosarcoma spans a broad histologic spectrum depending on the cytology of malignant cells (eg, spindle, small round, epithelioid) and their capacity for vasoformation. Welldifferentiated angiosarcoma shows retiform slitlike spaces in between collagen bundles that are lined by hyperchromatic hobnailing endothelial cells (Figure 2).⁷ Epithelioid angiosarcoma can be mistaken for SCC.⁸ Immunohistochemically, angiosarcoma stains positively for CD31, CD34, ETS-related gene 1, D2-40, and factor VIII.9 In our patient, the neoplasm was negative for vascular markers CD31 and CD34.

Bacillary angiomatosis (BA), caused by Bartonella henselae, is a rare disease that first was identified in HIV patients with diminished CD4+ T-cell counts. In the skin, BA often manifests as centrally ulcerated, single or clustered, reddish-purple nodules.¹⁰ Histologically, it is characterized by highly vascularized, histiocyterich infiltrates with admixed neutrophils and plasma cells (Figure 3). Capillaries often proliferate in a lobular fashion.¹¹ Atypical cytology with areas of necrosis may mimic angiosarcoma.¹² The pathognomonic feature of BA is the presence of enlarged histiocytes with pink-purplish cytoplasm corresponding to intracytoplasmic aggregates of bacteria, which can be revealed by Warthin-Starry or Grocott-Gomori methenamine-silver staining. Immunohistochemically, proliferative benign capillaries are highlighted by CD34 and CD31, and histiocytes are decorated by CD68.¹² This diagnosis was excluded based on the patient’s history, clinical presentation, and positive staining for CK5 and p63.

Squamoid eccrine ductal carcinoma is an exceedingly rare subtype of eccrine carcinoma that mimics SCC both clinically and histologically.¹³ It most often occurs on the head and neck of elderly patients. This neoplasm can look similar to SCC and its variants, including PSCC. Histologically, squamoid eccrine ductal carcinoma exhibits a biphasic growth pattern.¹⁴ Well-differentiated squamous dysplasia transitions to carcinoma with eccrine duct formation as the tumor percolates deep into the dermis (Figure 4). As a result, superficial skin biopsies often lead to an incorrect diagnosis.¹⁵ Unlike SCC, the risk for locoregional and widespread metastasis is elevated. Identifying ducts in the deep aspect of the tumor is critical, thus immunohistochemical staining for carcinoembryonic antigen and epithelial membrane antigen is paramount for the diagnosis.¹⁵ Pseudoangiomatous SCC will stain negative for carcinoembryonic antigen, as was the case in our patient.

Pseudoepitheliomatous hyperplasia is a benign histologic reaction that can result from trauma, chronic inflammation (ie, pyoderma gangrenosum), tattoo placement, underlying neoplasia or fungal infection, or a spider bite reaction.^14,15 It most commonly is seen as a well-demarcated nodule or plaque associated with scaling or crusting. Papules vary in size from less than 1 cm to several centimeters. Histologically, it is defined by an acanthotic proliferation of the adnexal epithelium and epidermis (Figure 5).^16,17 Irregular strands, cords, and nests of squamoid cells can extend into the dermis.¹⁸ It can closely mimic SCC, but there are a few key differences. Pseudoepitheliomatous hyperplasia will not display atypical mitotic figures or atypical nuclei and will never invade lymphatics or vascular systems.¹⁹ Pseudoepitheliomatous hyperplasia shows identical histology to well-differentiated SCC, and thus clinicopathologic correlation and mindful histologic evaluation are crucial. The presence of an increased influx of neutrophils and histiocytes should prompt for microbial stains or deeper sectioning. A superficial biopsy should be followed by a deep biopsy. In our patient, microorganismal stains were negative.