Generalized melanosis with malignant melanoma metastasizing to skin-a pathological study with S-100 protein and HMB-45

Abstract

A patient with primary malignant melanoma localized to the right gluteal region is described. Four years later and after intercurrent influenza, disseminated metastases of malignant melanoma to the skin occurred. After a further 6 months melanodermia developed and lasted until the death of the patient (6 months later). Autopsy revealed melanosis of the visceral organs. Histology taken from internal organs using S-100 protein and HMB-45 melanoma methods confirmed metastases of malignant melanoma to the skin, oral cavity, palatal tonsils, nasal and nasopharyngeal mucosae, lungs, myocardium and brain. The authors discuss the mechanism of melanosis--a rare sign in patients with metastasizing malignant melanoma.

Diffuse Melanosis cutis in Disseminated Malignant Melanoma

“…Further speculative mechanisms were alterations in dermal lymphatics that lead to deposition of pigment or dermal invasion of pigmented single-cell metastases [13,16]. However, these observations, could not be confirmed [2,5,6]. An important finding is the involvement of growth factors such as ·-melanocyte-stimulating hormone, which in combination with hepatocyte growth factor and endothelin 1 stimulates the proliferation of normal and malignant melanocytes.…”

“…The most often described histological finding, as also found in case 1, was the presence of pigmented granules but not of malignant cells [2]. In most of the cases, biopsy specimens revealed that the hyperpigmentation resulted from a marked deposition of pigment in the dermis, and in only 1 case was increased epidermal pigmentation seen [11].…”

“…About 30 cases of generalized melanosis have been reported in the English literature so far [1]. Patients with melanosis cutis have a bleak prognosis with survival times of only weeks or months after the onset of melanosis [1,2]. Despite significant efforts to elucidate the pathogenesis of this phenomenon, the exact mechanisms are a matter of debate.…”

Localized Melanosis in an Immunocompromised Patient with Local Metastatic Melanoma

“…The first reported case of diffuse melanosis was described by Legg in 1884. 17,22,34,35 Others propose the breakdown of melanoma cells with transfer of melanosomes via the circulation either freely or intracellularly. Murray et al 36 report that the feature that distinguishes melanosis from conventional metastatic melanoma is the accumulation of melanin via the bloodstream throughout the body.…”

“…1 Typically, generalized melanosis is a late complication of metastatic melanoma and presents as widespread cutaneous and internal organ pigment deposition. 12,13,18,23,25,27,[32][33][34] Most authors agree that a combination of these mechanisms may be responsible for the clinical finding of melanosis; however, only a few have observed metastatic cells within a biopsy specimen of the pigmented area. This leads to progressive pigmentation of all internal organs and the skin.…”