Relation Between Animal-Type Melanoma and Reduced Nuclear Expression of Glutathione S-Transferase π

Background: Animal-type melanoma (ATM) is a rare variant of the tumor showing diffuse, heavily pigmented neoplastic cells in the dermis. Despite the high mean thickness of the lesions, reports seem to indicate a less aggressive behavior and a better survival rate for ATM compared with conventional melanoma, but the underlying pathways related to this favorable outcome are still unknown. Observations: Five women and 2 men aged 20 to 92 years presented with pigmented skin nodules (n = 5) or plaques (n = 2), varying in size from 1.0 to 4.5 cm. Findings from microscopic examination showed monotypic-appearing melanocytes with abundant intracytoplasmic melanin in a nodular or fascicular arrangement (mean Breslow thickness, 4.97 mm). Immunohistochemical analysis of ATM cells demonstrated the typical positive staining for S-100, vimentin, HMB-45, and melan-A. The investigation of the pi isoform of glutathione S-transferase, a family of enzymes involved in tumor progression, revealed that nuclear expression is reduced in ATMs compared with control melanomas, whereas results from cytoplasmic staining did not vary. One patient died of cardiac failure without evidence of disease progression; the remaining patients are disease-free at 3 (n = 4) and 5 years (n = 3). Conclusions: Our findings confirm that ATM is a variant of melanoma with distinctive clinical and histological features. Low nuclear expression of glutathione S-transferase pi expression is a characteristic of ATM and could add new insight to better understand the unusual biological behavior of this rare neoplasm.