Primary cutaneous malignant melanoma with lipolast-like cells

Archives of Pathology & Laboratory Medicine, Mar 2003 by Cruz, Joao, Reis-Filho, Jorge S, Lopes, Jose Manuel

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A 74-year-old woman presented with a dome-shaped, ulcerated, hyperpigmented lesion on the anterior aspect of her right arm. Physical examination revealed a 1.5 x 1.2-cm, hyperpigmented, and partially ulcerated lesion with irregular borders and color variegation. No other cutaneous or subcutaneous lesions were detected on physical examination. A clinical diagnosis of polypoid nevus was considered. A spindle-shaped surgical excision with wide margins was performed, and the specimen was submitted for pathologic examination.

The specimen consisted of a 3.5 X 2.2 X 2.0-cm skin ellipse with an elevated, partially ulcerated, pigmented lesion with irregular borders, measuring 1.5 x 1.2 x 0.8 cm, localized in the central area. Histologic examination disclosed a dome-shaped, asymmetric, partially ulcerated melanocytic lesion extending from the epidermis to the deep dermis (Figure, A). The functional component of the neoplasm was asymmetric and composed of atypical epithelioid melanocytes arranged in noncohesive nests in the dermal-epidermal junction; these nests were associated with a remarkable number of variably pigmented malignant cells arranged in a pagetoid fashion among epidermal cells (Figure, A, inset). The intradermal component of the neoplasm was composed of medium-sized to large epithelioid cells with eosinophilic to vacuolated well-defined cytoplasm, large and irregular nuclei, clumped chromatin, and 1 to multiple prominent amphophilic to eosinophilic nucleoli. These cells were arranged in solid or noncohesive sheets. Pleomorphic cells with a single, large, intracytoplasmic vacuole displacing the nuclei to the periphery, similar to signet ring cells, were observed (Figure, B). An eye-catching feature was the presence of neoplastic cells with multiple cytoplasmic vacuoles of varying sizes; the vacuoles had an empty appearance, scalloping the atypical nuclei, remarkably resembling lipoblasts (Figure, C and inset). Scattered cells with finely spider-webbed cytoplasm, balloon cells (Figure, B, arrow), as well as cells with dusty Masson-Fontana-positive pigment and multinucleated cells were detected. The tumor was rated Clark level IV and was 5.75 mm thick. The mitotic index was 15.2 per 10 high-power fields (10/mm^sup 2^). Immunohistochemistry with antibodies for 5100 protein, gp100 (HMB-45), vimentin, and cytokeratins (CAM5.2 and AE1/AE3) was performed. Neoplastic cells were strongly and diffusely decorated by S100 protein and vimentin, multifocally stained by gp100 (HMB-45), and negative for cytokeratins. Lipoblast-like cells and signet ring cells also showed immunoreactivity for S100 protein (Figure, D) and focal immunoreactivity for HMB-45. A diagnosis of malignant melanoma with signet ring and lipoblast-like cells was established. The patient was discharged and remains free of disease 3 months after diagnosis.

Malignant melanoma (MM) is well known for its protean morphologic appearance1-3 Besides the common cytomorphologic types (epithelioid and spindle cell), several histopathologic variants have been reported, including desmoplastic, balloon cell, pleomorphic (fibrohistiocytic), hemangiopericytic, myxoid, small cell, and nevoid MM.1,3 Interestingly, the most unusual morphologic appearances are more frequently observed in metastatic than in primary lesions,1-3 which may lead even experienced pathologists to misdiagnoses of poorly differentiated carcinoma, lymphoma, or sarcoma.1-3 Anecdotal cases of metastatic MM mimicking several types of sarcomas, including fibrosarcoma, monophasic synovial sarcoma, malignant peripheral nerve sheath tumor, malignant fibrous histiocytoma, leiomyosarcoma, and liposarcoma, have been reported.1-3

Among the trickiest variants is signet ring melanoma, which is frequently confounded with signet ring carcinoma or signet ring lymphoma.1-3 Two distinctive types of signet ring cells may be observed in this variant: (1) the usual type, composed of polygonal cells with accumulation of vimentin filaments in the cytoplasm, which displace the nucleus to the periphery of the cell and also confer a semilunar shape, and (2) a rarer variant, composed of cells with intracytoplasmic vacuoles and scalloped eccentric nuclei.2,4 In such situations, the neoplastic cells may resemble monovacuolated lipoblasts.2 Lipoblast-- like cells are very unusual features of metastatic MMs and may be observed in metastatic deposits of signet ring and in balloon cell melanomas.1-3 Owing to their rarity the prognostic significance of lipoblast-like cells in either primary or metastatic malignant melanomas remains elusive.3 To the best of our knowledge, no report on primary cutaneous MMs with both lipoblast-like and signet ring cells has been published to date.

The present case illustrates an epithelioid primary MM with signet ring cells and several foci composed of univacuolated and multivacuolated cells with scalloped nuclei, which confer a remarkable resemblance to the epithelioid variant of pleomorphic liposarcoma (PL).1-5 Pleomorphic liposarcoma is the rarest variant of liposarcoma; it usually affects deep soft tissues of the proximal extremities of elderly patients (median age, seventh decade); up to 20% of the cases may be superficial, and there are rare reports of PLs affecting children..5 Pleomorphic liposarcoma is characterized by the presence of adipocytic differentiation, better exemplified by lipoblasts.5 The epithelioid variant of PL is composed of epithelioid cells with eosinophilic to vacuolated cytoplasm, round nuclei, and prominent nucleoli.5 In this variant, the presence of bona fide lipoblasts may be very scanty, posing diagnostic difficulties to differentiate it from other epithelioid neoplasms with lipoblast-like cells.5 The differentiation between an epithelioid PL and an MM can be achieved by the presence of a functional component, as well as the expression of S100 protein and melanocytic markers, such as gp100, NKI-C3, MARTI, and MiTF in the latter. A few cases of S100 protein-negative signet ring cell melanomas have been reported.2,4