The color of urine: then and now-a comprehensive review of the literature with emphasis on intracytoplasmic pigments encountered in urinary cytology.

The color of urine, once considered by uroscopists to give the most important clues to the diagnosis, still can provide some diagnostic clues in modern medicine. Pigmented cells are an uncommon and surprising find in urine cytology and can at the same time provide important diagnostic clues or represent a dangerous pitfall. We present a review of the significance of pigmented cells in urine cytology. The presence of intracellular pigment granules; their color, size, shape, and variation in size and shape; as well as their staining reactions with special stains can provide useful diagnostic insight, especially when interpreted in the cytologic context (type of pigmented cell and its degree of atypicality) and patient's clinical context. The main differential diagnosis of cytoplasmic pigmented granules includes hemosiderin, lipofuscin, and melanin, each having a different pathogenesis and significance. The goal of this paper is to describe the morphological, histochemical, and ultrastructural characteristics of the pigments seen in urinary cytology, and to review the benign and malignant conditions associated with them.

Diffuse cutaneous melanosis: rare complication of metastatic melanoma.

Diffuse cutaneous melanosis is a rare complication of metastatic melanoma related to a worse prognosis. There are few cases reported in the literature. Its pathogenesis has not been completely elucidated, although studies have suggested certain mechanisms for its occurrence. It is clinically manifested as a blue-gray discoloration of the skin and mucous membranes in a cephalo caudal progression and usually associated with melanuria. Skin and mucosa histopathology reveals only the presence of melanophages in the dermis, mainly perivascular, and free interstitial melanin. We report the case of a 68-year-old male with metastatic melanoma, diffuse hyperpigmentation of the skin and melanuria.

Diffuse cutaneous melanosis: rare complication of metastatic melanoma

Abstract Diffuse cutaneous melanosis is a rare complication of metastatic melanoma related to a worse prognosis. There are few cases reported in the literature. Its pathogenesis has not been completely elucidated, although studies have suggested certain mechanisms for its occurrence. It is clinically manifested as a blue-gray discoloration of the skin and mucous membranes in a cephalo caudal progression and usually associated with melanuria. Skin and mucosa histopathology reveals only the presence of melanophages in the dermis, mainly perivascular, and free interstitial melanin. We report the case of a 68-year-old male with metastatic melanoma, diffuse hyperpigmentation of the skin and melanuria.

Giant congenital melanocytic nevi: selected aspects of diagnostics and treatment.

BACKGROUND: Treatment of giant melanocytic nevi (GMN) remains a multidisciplinary challenge. We present analysis of diagnostics, treatment, and follow- up in children with GMN to establish obligatory procedures in these patients. MATERIAL/METHODS: In 24 children with GMN, we analyzed: localization, main nevus diameter, satellite nevi, brain MRI, catecholamines concentrations in 24-h urine collection, surgery stages number, and histological examinations. The t test was used to compare catecholamines concentrations in patient subgroups. RESULTS: Nine children had "bathing trunk" nevus, 7 had main nevus on the back, 6 on head/neck, and 2 on neck/shoulder and neck/thorax. Brain MRI revealed neurocutaneous melanosis (NCM) in 7/24 children (29.2%), symptomatic in 1. Among urine catecholamines levels from 20 patients (33 samples), dopamine concentration was elevated in 28/33, noradrenaline in 15, adrenaline in 11, and vanillylmandelic acid in 4. In 6 NCM children, all catecholamines concentrations were higher than in patients without NCM (statistically insignificant). In all patients, histological examination of excised nevi revealed compound nevus, with neurofibromatic component in 15 and melanoma in 2. They remain without recurrence/metastases at 8- and 3-year-follow-up. There were 4/7 NCM patients with more than 1 follow-up MRI; in 1 a new melanin deposit was found and in 3 there was no progression. CONCLUSIONS: Early excision with histological examination speeds the diagnosis of melanoma. Brain MRI is necessary to confirm/rule-out NCM. High urine dopamine concentration in GMN children, especially with NCM, is an unpublished finding that can indicate patients with more serious neurological disease. Treatment of GMN children should be tailored individually for each case with respect to all medical/psychological aspects.

[Diffuse brown discoloration of skin, mucosa and urine]. / Diffuse Braunfärbung von Haut, Schleimhaut und Urin.

A 45-year-old woman presented with diffuse melanosis, icteric sclera and melanuria. Physical examination revealed a massive nodular melanoma with ulceration and satellite metastases on the back. Further investigation showed distant cutaneous and visceral metastasis. After palliative debulking along with postoperative multidrug chemotherapy, the patient has shown objective disease regression for more than 11 months. However, it remains to be seen if disease regression will translate into increased survival.

Pheomelanin-related benzothiazole isomers in the urine of patients with diffuse melanosis of melanoma.

BACKGROUND: Currently used as structural markers for pheomelanin identification and quantitation, benzothiazole compounds derived from isomers of cysteinyldopa have been indicated by recent in vitro studies as new potential pheomelanogenesis intermediates. The presence of benzothiazole compounds in the urine of patients with melanoma with or without diffuse melanosis was investigated. METHODS: Hydrophilic interaction liquid chromatography with zwitterionic stationary phase (ZIC-HILIC) and photo-diode array (PDA) detection was used for analysis of 6-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-5), and 7-(2-amino-2-carboxyethyl)-4-hydroxybenzothiazole-2-carboxylic acid (BTCA-2), derived from 5-S-cysteinyldopa (5-S-CD) and 2-S-cysteinyldopa (2-S-CD) isomers, respectively. After minimal sample preparation, isocratic chromatography allowed efficient separation of the compounds, which were safely identified by their typical absorption features. RESULTS: Three patients with diffuse melanosis, 16 patients with melanoma (stages III and IV) and three healthy subjects were investigated. The urinary BTCAs were found to be highly associated with melanosis but more loosely to excreted 5-S-CD. Analysis of the pigmented fraction of urine following alkaline hydrogen peroxide degradation and quantitation of BTCAs provided evidence for the presence of pheomelanins at high levels in patients with melanosis. CONCLUSION: Identification of free BTCA isomers in urine provides a significant contribution in the field of urinary melanogens, and has important implications for biosynthetic activity of normal and pathologic melanocytes.

Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning: a randomized placebo-controlled study.

BACKGROUND: Millions of people in Bangladesh, India, Taiwan, and Chile are consuming high concentration of arsenic through drinking water, and thousands of them have already developed chronic arsenic poisoning. There is no specific treatment. Some authors suggest the use of vitamins and minerals for more than 6 months. The present placebo-controlled double-blind study was conducted to evaluate effectiveness of spirulina extract plus zinc in the treatment of chronic arsenic poisoning. METHODS: Forty-one patients of chronic arsenic poisoning were randomly treated orally by either placebo (17 patients) or spirulina extract (250 mg) plus zinc (2 mg) (24 patients) twice daily for 16 weeks. Each patient was supplied with arsenic-safe drinking water by installing a locally made water filter at household level. Effectiveness of spirulina extract plus zinc was evaluated by comparing changes in skin manifestations (clinical scores), arsenic contents in urine and hair, between the placebo- and spirulina extract plus zinc-treated groups. RESULTS: The concentrations of total arsenic in water (without filtration) of placebo- and spirulina extract plus zinc-treated groups were 150.1 +/- 18.3 and 161.7 +/- 23.9 microg/l, respectively. Intake of these high concentrations of arsenic lead to increased excretion of arsenic in urine (72.1 +/- 14.5 microg/l in placebo-treated group and 78.4 +/- 19.1 microg/l in spirulina plus zinc-treated group). After 2 weeks of using filtered water, there were significant reduction of both arsenic intake through water and urinary arsenic excretion (8.3 +/- 3.6 microg/l and 18.4 +/- 7.3 microg/l in placebo group; 9.7 +/- 5.4 microg/l and 21.6 +/- 5.8 microg/l) in spirulina extract plus zinc-treated group. There was a sharp increase in urinary excretion of arsenic (138 +/- 43.6 microg/l) at 4 weeks following spirulina plus zinc administration and the effect was continued for another 2 weeks. Spirulina extract plus zinc removed 47.1% arsenic from scalp hair. Spirulina extract had no major adverse effect that required physician's attention. The clinical scores (median) for melanosis before and after treatment with placebo was not statistically significant (p > 0.05), whereas in spirulina extract plus zinc-treated group it was statistically significant (p < 0.01). In cases of keratosis, the median clinical scores before and after treatment was not statistically significant (p > 0.05) in placebo-treated group. In spirulina extract plus zinc-treated group, the clinical scores for keratosis before and after treatment was statistically significant (p < 0.05). CONCLUSIONS: Results show that spirulina extract (250 mg) plus zinc (2 mg) twice daily for 16 weeks may be useful for the treatment of chronic arsenic poisoning with melanosis and keratosis.

[Toxic melanoderma in chronic intoxication with trinitrotoluene]. / Toksicheskaia melanodermiia pri khronicheskoi intoksikatsii trinitrotoluolom.

Hyperkinetic atactic syndrome, an atypical neurologic disorder of a chemical origin, was reported in connection with trinitrotoluene-induced melanoderma. Decreased level of urinary 17-hydroxycorticoids stresses the failure of one biochemical link in melanin synthesis, but proves the same pathogenic origin of both melanopathy manifestations. Antioxidant therapy in the pathogenesis treatment of melanoderma is considered valuable.

Trichochromuria in melanosis of melanoma.

Two patients with metastasizing melanoma and diffuse melanosis have previously been reported to excrete large quantities of trichochromes in the urine. The present study describes 2 further melanoma patients with diffuse melanosis and trichochromuria. The hair of one of the patients which had been red in childhood and turned brown in adult age returned to red with the appearance of melanosis. Normal excretion of a methylated melanocytic metabolite, 6-hydroxy-5-methoxyindole-2-carboxylic acid, was observed in this patient, possibly indicating exhaustion of the methylating system. The other patients excreted large quantities of 6-hydroxy-5-methoxyindole-2-carboxylic acid. Both patients showed highly increased excretion of 5-S-cysteinyldopa. Both patients with melanosis exhibited fine electrone-dense granules in lysosomes of dermal histiocytes. The findings support the concept that trichochromes or similar pigments in dermal histiocytes are responsible for diffuse melanosis in melanoma patients.

[Malignant blue nevus]. / Naevus bleu malin.

Malignant blue naevi with an aggressive behaviour are rare tumours. To our knowledge, this is the first reported case who has developed generalized skin melanosis and melanuria in its terminal stage.

Diffuse melanosis and trichochromuria in malignant melanoma.

A previous finding of pronounced excretion of trichochromes in a patient with metastasizing melanoma and diffuse melanosis prompted this study on trichochromes in another patient with these two features. The patient now reported also excreted large amounts of trichochromes. Iit is suggested that diffuse melanosis in metastatic melanoma patients is due to deposition of trichochromes in the tissue.