Morphological and immunophenotypic variations in malignant melanoma

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet-ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi- or multi-nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro-/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB-45, Melan-A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.