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MALIGNANT SKIN LESIONS

Nava Siegelmann-Danieli, Hector Isaac Cohen, Ofer Ben-Izhack

Rambam Medical Center and Western Galilee Hospital, Haifa, Israel

CASE 1: NEVOID MALIGNANT MELANOMA OF THE BREAST PRESENTING AS A CONTRALATERAL BREAST METASTASIS

A 47-year-old Ashkenazi woman presented with an 8-mm lobular density in the lower inner aspect of her left breast on her first screening mammography (Fig 1). A breast tissue specimen measuring 4 x 2.5 x 1 cm was surgically removed. Microscopic sections revealed a 7-mm nodule containing malignant epitheloid cells that stained positive for HMB-45 and S-100 and was surrounded by a rich lymphocytic tissue, consistent with metastaic malignant melanoma to the breast, possibly to an intramammary lymph node¹ (Fig 2). On physical examination (including skin and membrane survey and gynecology and ophthalmology examinations), the only putative source for the metastatic melanoma was a 7-mm benign-appearing nevus located on the lower outer aspect of the right breast. This lesion was removed to reveal a 7-mm wide and 0.72-mm deep papillary melanocytic lesion confined to the upper and medial dermis and structured by solid groups of cohesive atypical epithelioid melanocytic cells similar to those found in the metastatic contralateral breast nodule. No maturation at the base of the lesion was evident, consistent with T1 malignant nevoid melanocytic melanoma^2-4 (Fig 3). The patient had no other evidence of metastatic disease. She was treated with a series of allogeneic vaccine injections and oral cimetidine and is currently without evidence of disease 19 months after diagnosis.

View larger version (81K): [in this window] [in a new window]   Fig 1.

View larger version (78K): [in this window] [in a new window]   Fig 2.

View larger version (143K): [in this window] [in a new window]   Fig 3.

A lesion in the breast is a rare manifestation of a nonmammary malignant neoplasm. In a series reported from the Memorial hospital in New York, NY, of 4,000 adult patients who underwent breast biopsy for an operable breast tumor, only 1.2% were found to have nonprimary, nonleukemic, metastatic tumors.⁵ More recent series show metastatic lesions to account for 2.7% to 5.1% of breast malignancies diagnosed by fine-needle cytology, with hematologic malignancies, lung carcinoma, and malignant melanoma being the most common sources.^6,7 Metastatic lesions to the breast are far more common in women compared with men, and in 10% to 40%, they represent the initial manifestation of an extramammary neoplasm.^5-8 The clinical presentation is often of a painless, solitary, well-circumscribed lesion in breast regions rich in glandular tissue (upper outer quadrants), but local tenderness and multiple nodules involving one or both breasts have been described as well.^5,8-10 Lesions show a notable tendency for a superficial location in the subcutaneous and immediate adjacent breast; axillary or supraclavicular adenopathy occurs in 25% to 55% of patients.^5,8,10 The most common occult primary tumor is small-cell lung carcinoma, with carcinoids and carcinoma originating in the kidney, stomach, and ovary being reported as well.^10,11 The most common previously diagnosed solid tumor is malignant melanoma, with sarcomas, non–small-cell lung carcinoma, prostate carcinoma, and various other malignancies reported as well.^5,10,11 The majority of patients with breast metastases originating in malignant melanoma are premenopausal women whose disease presented 2 to 3 years earlier on the upper extremity or trunk (although melanoma in this age group mostly originates in lower extremities).^1,9 Several types of malignant lymphoma have sometimes been included under the heading of metastases to the breast, although they are best regarded as primary breast lymphoma or as part of a systemic disease affecting the lymphoid system.^12-15 According to the Working Formulation, the most common primary breast lymphomas are diffuse large-cleaved, diffuse small-cleaved, and diffuse or mixed-cell non-Hodgkin's lymphomas with B-cell immunophenotype. Hodgkin's disease and T-cell lymphoma of the breast are extremely rare. Breast lymphoma occurs mainly in women in their 50s or early 60s; the majority of patients present with stage IE or IIE disease, and tumor size of 4 cm or larger is not uncommon. Diffuse bilateral lymphoma, mostly of Burkitt's type, has been reported in young women in association with pregnancy or breastfeeding.

Mammographically, metastatic lesions tend to be discrete, round shadows without spiculation and are similar to circumscribed primary breast carcinomas, such as papillary, medullary, or colloid tumors.^8,10 Microcalcifications are extremely rare but have been described in metastatic ovarian carcinoma containing psammoma bodies.¹⁶ Breast lymphoma may present as a discrete, well-defined nodule or with diffuse parenchymal and cutaneous infiltration and multiple ill-defined lesions (the latter mostly in association with systemic lymphoma affecting the breast).^8,17,18 Histologically, metastatic carcinoma or melanoma is often surrounded by normal-appearing breast parenchyma that shows little or no hyperplasia and no in situ carcinoma.^5,11 Lymphatic spread in the breast can occur with metastatic tumor or with primary breast carcinoma. Breast lymphoma typically shows dense diffuse infiltrates of tumor cells into the mammary parenchyma or adipose tissue, with ducts and lobules being obliterated at the central portion of the lesions; reactive small lymphocytes and germinal centers may present at the periphery of the tumor.^12,14,15 When the primary tumor is known, fine-needle aspiration can often be used for diagnosis.^6,7,9,15 With occult tumors, however, diagnosis can be a challenge and may require excisional biopsy and special studies, such as immunohistochemical stains and electron microscopy.

The prognosis depends on the histologic type of the tumor involving the breast. With metastatic carcinoma or melanoma, metastases at other organs develop within a short period of time, and the majority of patients die within a year.^1,5,8,10 The median survival time is 10 to 11 months, although a few long-term metastatic melanoma survivors have been reported (one at 2 years and one at 4 years). With primary breast lymphoma, the 5-year survival rate ranges from 51% to 85%, depending on stage, grade, age at diagnosis, and treatment.^12-15 Late relapses have been reported, however, and the 10-year survival rate ranges from 42% to 73%.

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