Diffuse melanosis arising from metastatic melanoma: Pathogenetic function of elevated melanocyte peptide growth factors

The origin of diffuse melanosis resulting from metastatic melanoma is unkno wn. We examined the light microscopic and ultrastructural changes in the sk in of an affected 35-year-old woman and determined the peripheral blood lev els of melanocyte growth factors. A total of 7 biopsy specimens were examin ed by light and electron microscopy and immunohistology (S-100, HMB45, MART 1, CD68, MAC387). Serum/plasma levels of melanocyte growth factors of the p atient were determined by enzyme-linked immunosorbent assays and compared w ith those of normal volunteers (n = 10) and amelanotic patients with metast atic melanoma (n = 10), matched to the UICC stage of the affected patient. Hyperpigmented but otherwise apparently normal skin of the patient displaye d epidermal melanocyte hyperplasia, increased melanogenesis, and dermal pig ment stored in histiocytes and other cells along with extracellular deposit s. Blood levels of alpha -melanocyte stimulating hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated in the affected patie nt. Aberrant production of these factors may not only be responsible for ac tivation of the pigment system in diffuse melanosis of metastatic melanoma, but also for increased proliferation, motility, and pigment incontinence o f normal and malignant melanocytes.