Diagnosis: malignant metastatic melanoma presenting with generalized melanosis and melanuria

European Journal of Dermatology. Volume 11, Number 5, 477-8, September - October 2001, Votre diagnostic !

Author(s) : Luigi IULIANO, Angela GURGO, Guglielmo PRANTEDA, Institute of Clinical Medicine I, Università "La Sapienza", Via del Policlinico Umberto I, 165, 00185 Rome, Italy.

Summary : A 62-year-old man was admitted to the Clinic because of a two month history of increasingly weakness. Two weeks before, the patient had developed a progressive gray-blue skin discoloration (Fig. 1). He had also recently noticed darkening of his urine which appeared amber in colour when freshly voided but turned in black on exposure to air (Fig. 2).

Pictures

ARTICLE

Diagnosis: malignant metastatic melanoma presenting with generalized melanosis and melanuria

Microscopic examination of the pigmented lesion located on the forearm revealed a superficial spreading melanoma (Clark level IV, Breslow thickness 3.1 mm) with melanoma cells (positive for S-100 protein) within the dermis and invading the epidermis. The histopathological examination of the eyelid lesion showed aggregates of melanoma cells within the upper part of the dermis but not invading the epidermis, consistent with cutaneous metastasis.

A total-body computed tomography showed multiple metastatic lesions involving brain, mediastinal lymph nodes, liver, spleen and adrenal glands.

Support therapy and chemotherapy with Dacarbazine (800 mg/m² i.v.) was started. However, the patient's general condition dramatically deteriorated and he eventually died after 40 days. Autopsy confirmed the presence of widespread metastases and revealed additional involvement of the larynx, trachea and heart.

Comments

The patient presented with an advanced stage of widespread metastatic melanoma, a very small primary lesion (0.5 cm in diameter) on the forearm, and with a rare complication, melanosis and melanuria [1-6]. Melanosis is caused by the melanin precursor 5-6 dihydroxyindole that is produced and secreted in an increased amount by malignant cells, and then deposited within macrophages throughout the body, where it is oxidised to melanin [3]. Alternatively, it has been hypothesised that melanosis results from the deposition into the skin of melanosomes (granules of melanin and its precursors) synthesised by distant malignant melanoma cells [1]. Other authors suggested that melanosis is secondary to unlimited spread of individual, discrete melanoma cells to and throughout the entire skin [2]. Melanuria is caused by the passage in urine of melanogens (melanin and other specific metabolites) produced in large amounts by melanoma cells. Air-oxidation of these pigments causes the characteristic coffee-like discoloration of urine [4]. *

Article accepted on 22/11/00

REFERENCES

1. Silberger I, Kopf AW, Gumport SL. Diffuse melanosis in malignant melanoma. Report of a case and of studies by light and electron microscopy. Arch Dermatol 1968; 97: 671-7.

2. Konrad K, Wolff K. Pathogenesis of diffuse melanosis secondary to malignant melanoma. Br J Dermatol 1974; 91: 635-55.

3. Fitzpatrick TB, Montgomery H, Lerner AB. Pathogenesis of generalized dermal pigmentation secondary to malignant melanoma and melanuria. J Invest Dermatol 1954; 22: 163-72.

4. Matons B, Bubnova E, Budesinska A, Kostirova M. Markers of melanogenesis in malignant melanoma. Sb Lek 1994; 95: 333-8.