Diffuse melanosis after chemotherapy-induced tumor lysis syndrome in a patient with metastatic melanoma.

Diffuse melanosis is a rare event associated with advanced metastatic malignant melanoma. A 35-year-old woman with stage IV melanoma is presented, who developed slate bluish-gray to brown discoloration of her skin after chemotherapy-induced tumor lysis syndrome. A number of studies were performed to re-evaluate possible mechanisms of melanosis. Skin tissue was examined on routine hematoxylin-and-eosin-stained sections, Fontana stains, immunohistochemical studies with antibodies for Melan-A, gp100, tyrosinase, FXIIIa, and CD68, and by electron microscopy. The main cell types found to contain melanin pigment were histiocytes and dendritic cells. In the dermis, they were distributed mainly around venules. In the subcutaneous fat, they were scattered throughout the fat lobule. Melanin pigment was not only seen within cells but also extracellularly. No melanoma cells were seen in the skin. No increase in melanin pigment or number of melanocytes was seen in the epidermis. A bone marrow biopsy contained melanophages but no melanoma cells. Ultrastructural examination of the patient's serum revealed the presence of melanosomes. Sequence analysis of the tumor's cDNA failed to identify any mutations in the tyrosinase gene, and no tyrosinase protein was detected in non-melanocytic cells, indicating that it was unlikely that a mutation had resulted in a secretory form of the protein. These findings document that diffuse melanosis may result from tumor lysis, with release of melanosomes into the bloodstream.