A 79-year-old woman comes to the office due to bleeding from an ulcerative lesion on her right nipple. The lesion is itchy, has been there for several months, and is slowly increasing in size. Examination shows a crusty, thickened, erythematous, and ulcerated nodule with evidence of hyperpigmentation. Changes extend to the surrounding areola. Excisional biopsy reveals relatively well-circumscribed aggregates of large, polygonal, pleomorphic cells with abundant mitotic activity and surrounding necrosis. S-100 and HMB-45 stains are diffusely positive. Which of the following is the most likely diagnosis?

Question

A 79-year-old woman comes to the office due to bleeding from an ulcerative lesion on her right nipple.  The lesion is itchy, has been there for several months, and is slowly increasing in size.  Examination shows a crusty, thickened, erythematous, and ulcerated nodule with evidence of hyperpigmentation.  Changes extend to the surrounding areola.  Excisional biopsy reveals relatively well-circumscribed aggregates of large, polygonal, pleomorphic cells with abundant mitotic activity and surrounding necrosis.  S-100 and HMB-45 stains are diffusely positive.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

This older patient has a crusted, ulcerated, hyperpigmented nodule on the nipple and areola. Biopsy was performed to differentiate Paget disease of the breast (Choice C), an adenocarcinoma of the areolar epithelium, from nodular malignant melanoma. Histopathology revealed poorly differentiated cells with abundant mitotic activity and necrosis. Subsequent immunostaining was positive for S-100 (a protein expressed in cells derived from the neural crest such as melanocytes) and HMB-45 (a monoclonal antibody that binds to immature melanosomes found in melanocytic tumors) indicating melanoma. Immunostaining is often used to assist the diagnosis of melanoma because histopathologic features are sometimes insufficient to confirm the diagnosis. Tumor cells that stain positive for multiple melanocyte markers (as in this case) are very likely to be melanoma. S-100 is positive in >95% of melanoma tumors, and HMB-45 is both highly sensitive (>95%) and highly specific (~100%) for the malignancy. (Choice A) Basal cell carcinoma usually appears on the face as a nodular, flesh colored papule. Although scaly trunk lesions can occasionally occur, this tumor is derived from basal epithelial cells and would not stain positive for melanocyte markers. (Choice D) Seborrheic keratosis is a benign skin lesion that is well demarcated (appears "stuck on") with a verrucous surface. These lesions are derived from immature keratinocytes and would not stain positive for multiple melanin markers. (Choice E) Squamous cell carcinoma is most common on the head and neck but can also occasionally arise on the trunk. It generally appears as hyperkeratotic plaque, nodule, or papule. Because it is derived from epithelial cells (not melanocytes), multiple melanin markers would not be positive. Educational objective: Melanoma is often diagnosed when immunostaining of biopsy samples reveals multiple melanocyte markers (eg, S-100, HMB-45, MART-1).

A 79-Year-Old Woman Comes to the Office Due to Bleeding