RESUMO
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.
Assuntos
Citodiagnóstico/métodos , Citoplasma/química , Lipofuscina/urina , Pigmentos Biológicos/urina , Urina/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cor , Diagnóstico Diferencial , Feminino , Hemossiderina/urina , Humanos , Masculino , Melaninas/urina , Melanoma/diagnóstico , Melanoma/urina , Melanose/diagnóstico , Melanose/urina , Pessoa de Meia-Idade , Pigmentação , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/urinaAssuntos
Fosfatase Alcalina/sangue , Falência Hepática Aguda/diagnóstico , Neoplasias Hepáticas/diagnóstico , Melaninas/urina , Melanoma/diagnóstico , Neoplasias Cutâneas/patologia , Adulto , Colangiopancreatografia por Ressonância Magnética , Evolução Fatal , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/urina , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/urina , Masculino , Melanoma/complicações , Melanoma/secundário , Melanoma/urina , Ressuscitação , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/urina , UltrassonografiaRESUMO
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.
Assuntos
Melanoma/complicações , Melanose/etiologia , Neoplasias Cutâneas/complicações , Biópsia , Evolução Fatal , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Masculino , Melaninas/urina , Melanoma/patologia , Melanoma/secundário , Melanose/patologia , Melanose/urina , Pessoa de Meia-Idade , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundárioRESUMO
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.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/complicações , Melanoma/complicações , Melanose/etiologia , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Biópsia , Evolução Fatal , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Melaninas/urina , Melanoma/patologia , Melanoma/secundário , Melanose/urina , Melanose/patologiaAssuntos
Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias Ósseas/complicações , Neoplasias Hepáticas/complicações , Neoplasias Pulmonares/complicações , Melanoma/complicações , Melanose/etiologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/secundário , Antineoplásicos/uso terapêutico , Axila , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Humanos , Indóis/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Masculino , Melaninas/urina , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/secundário , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/uso terapêutico , VemurafenibAssuntos
Melaninas/urina , Melanoma/diagnóstico , Melanoma/secundário , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Cisteinildopa/sangue , Humanos , Masculino , Melanoma/sangue , Melanoma/urina , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/sangue , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/urinaRESUMO
We report a case of a 70-year-old Hawaiian man with an exophytic black nodule on the left suprascapular region of several years' duration. Histopathologic examination of the excised lesion showed a nodular melanoma with 17-mm Breslow thickness. The patient had firm fixed lymph nodes circumferentially around his neck. He underwent palliative cervical lymph node dissection to remove the compressive nodes but declined further therapy. One year later, the patient's skin was noted to have a generalized uniformly gray-brown color. Physical examination showed ulcerated masses on his trunk, right arm, and both axillae. A urine specimen initially was dark yellow but turned black after exposure to air at room temperature and ambient light for several minutes. Black urine, termed melanuria, is a rare finding in patients with disseminated melanoma. In melanogenuria, the urine is yellow and darkens as the colorless melanin precursors oxidize in the presence of air. Detection of these urinary melanin precursors may someday help determine the prognosis of melanoma and monitor response to treatment.
Assuntos
Indóis/urina , Melaninas/urina , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Diagnóstico Diferencial , Evolução Fatal , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/patologia , Pescoço , Metástase Neoplásica , Neoplasias Cutâneas/patologiaRESUMO
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.
Assuntos
Melanoma/diagnóstico , Melanoma/urina , Melanose/etiologia , Doenças da Esclera/diagnóstico , Neoplasias Cutâneas/diagnóstico , Feminino , Humanos , Melaninas/urina , Melanoma/complicações , Melanoma/secundário , Melanoma/terapia , Melanose/diagnóstico , Melanose/urina , Pessoa de Meia-Idade , Indução de Remissão , Doenças da Esclera/complicações , Doenças da Esclera/urina , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/terapiaAssuntos
Melaninas/urina , Melanoma/complicações , Melanose/etiologia , Neoplasias Cutâneas/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/administração & dosagem , Difosfonatos/administração & dosagem , Humanos , Imidazóis/administração & dosagem , Masculino , Melanoma/tratamento farmacológico , Melanose/patologia , Melanose/urina , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/tratamento farmacológico , Ácido ZoledrônicoRESUMO
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.
Assuntos
Benzotiazóis/urina , Melaninas/urina , Melanoma/urina , Melanose/urina , Adulto , Cromatografia Líquida/métodos , Humanos , Isomerismo , Masculino , Pessoa de Meia-Idade , Espectrofotometria UltravioletaRESUMO
Melanoma is most rapidly increasing in the white population and people with pheomelanin skin type are at high risk to develop melanoma. However, little is known about the pheomelanin structure and function, and further elucidation of this melanin is therefore an important task. A GC/MS method was developed based on hydriodic acid hydrolysis of pheomelanin in the urine. Derivatization was performed with ethyl chloroformate and ethanol:pyridine (4:1, v/v). N,O-Ethoxycarbonyl-ethyl esters were extracted with chloroform and analyzed by GC/MS. 4-Amino-3-hydroxyphenylalanine and 3-amino-4-hydroxyphenylalanine together with one benzothiazinone and two benzothiazole compounds were detected and identified in hydrolyzed samples of synthetic pheomelanin and melanin from the urine of a patient with melanoma. These findings strongly suggest that heterocyclic pheomelanin-type units are incorporated in the pigment structures.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Melaninas/química , Melanoma/diagnóstico , Humanos , Hidrólise , Masculino , Melaninas/urina , Pessoa de Meia-IdadeRESUMO
Diffuse melanosis with melanuria is a rare complication of metastatic malignant melanoma that is associated with a very poor prognosis. Acute kidney injury secondary to melanuria has not been reported previously. We describe a patient with malignant melanoma, diffuse melanosis, and melanuria who developed acute kidney injury that was clinically indicated by an increase in urinary excreted metabolites in the serum. Histopathologic examination of kidney tissue revealed damage to tubules associated with disseminated intra-tubular melanin deposits. Diffuse melanosis with melanuria may lead to morphologic and functional kidney changes and warrants careful monitoring of kidney function in affected malignant melanoma patients.
Assuntos
Rim/patologia , Melaninas/urina , Melanoma/patologia , Melanose/patologia , Neoplasias Cutâneas/patologia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Ultraviolet-B (UVB) radiation due sunlight can result in sunburns and/or suntans. Sunburn occurs only several hours after solar UVB radiation, while a suntan requires several days to several weeks to develop. In the present study, we measured serum and urine levels of melanin-related metabolites, 5-S-cysteinyldopa (5-S-CD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in nine subjects exposed to normal sunlight over the course of 12 months. We collected samples in the middle of each month and examined the variation of the markers, the correlation between them, and their correlation with solar UVB radiation. Those markers exhibited a seasonal variation with lower values in the winter and higher values in the summer. Levels of 5-S-CD and 6H5MI2C in the serum showed 48% and 54% increases in the summer compared with those in the winter, respectively. Comparison of 5-S-CD in the serum and urine showed the highest correlation (r2 = 0.344), followed by the pair of 5-S-CD and 6H5MI2C in the serum. Levels of 5-S-CD in the serum showed the highest correlation (r2 = 0.729) with the mean solar UVB radiation during the first 10 d of the month, while 6H5MI2C in the serum was highly correlated (r2 = 0.483) with solar UVB radiation during the previous month. Levels of 5-S-CD and 6H5MI2C in the serum appear to reflect the degrees of skin injury and pigmentation in the skin, respectively.
Assuntos
Cisteinildopa/sangue , Cisteinildopa/urina , Indóis/sangue , Indóis/urina , Melaninas/sangue , Melaninas/urina , Estações do Ano , Raios Ultravioleta , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/lesões , Pele/metabolismo , Pigmentação da Pele/efeitos da radiaçãoRESUMO
Normal and malignant melanocytes produce melanins and melanin-related metabolites, most of which are retained in the cells but some are secreted into the blood and then excreted in the urine. In this study, we developed a method to measure levels of eumelanin in urine samples and evaluated its clinical significance in comparison with the melanin-related metabolites 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) and 5-S-cysteinyldopa (5-S-CD), and with pheomelanin, measured after degradation as 4-amino-3-hydroxyphenylalanine (4-AHP). The method is based on the production of pyrrole-2,3,5-tricarboxylic acid (PTCA) on permanganate oxidation of eumelanin, followed by quantification by liquid chromatography. For 118 urine samples from 10 control subjects, mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD and 4-AHP were 19, 67, 37 and 59 micromol/mol creatinine respectively. In melanoma patients (n = 45), the mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD, and 4-AHP were 91, 926, 4070 and 3530 micromol/mol creatinine respectively. Median level of PTCA in melanoma patients was elevated 2.1-fold compared with control subjects. The degrees of elevation for 6H5MI2C, 5-S-CD, and 4-AHP were 1.8-, 22- and 6.2-fold respectively. Thus, although urinary PTCA is of little clinical value in following the progression of melanoma, urinary 4-AHP appears to be of considerable value in this respect.
Assuntos
Melaninas/urina , Melanoma/urina , Neoplasias Cutâneas/urina , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Cutâneas/patologiaAssuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Melanoma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias Cutâneas , Neoplasias das Glândulas Suprarrenais/secundário , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Melaninas/urina , Melanoma/secundário , Tomografia por Emissão de Pósitrons , Encaminhamento e Consulta , Tomografia Computadorizada por Raios XAssuntos
Melanoma/patologia , Melanose/patologia , Invasividade Neoplásica/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Melaninas/urina , Melanoma/complicações , Melanose/complicações , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Estudos de Amostragem , Neoplasias Cutâneas/complicações , Taxa de Sobrevida , Doente TerminalRESUMO
The color of hair, skin, and eyes in animals mainly depends on the quantity, quality, and distribution of the pigment melanin, which occurs in two types: black to brown eumelanin and yellow to reddish pheomelanin. Microanalytical methods to quantify the amounts of eumelanin and pheomelanin in biological materials were developed in 1985. The methods are based on the chemical degradation of eumelanin to pyrrole-2,3,5-tricarboxylic acid and of pheomelanin to aminohydroxyphenylalanine isomers, which can be analyzed and quantitated by high performance liquid chromatography. This review summarizes and compares eumelanin and pheomelanin contents in various pigmented tissues obtained from humans, mice, and other animals. These methods have become valuable tools to study the functions of melanin, the control of melanogenesis, and the actions and interactions of pigmentation genes. The methods have also found applications in many clinical studies. High levels of pheomelanin are found only in yellow to red hairs of mammals and in red feathers of birds. It remains an intriguing question why lower vertebrates such as fishes do not synthesize pheomelanin. Detectable levels of pheomelanin are detected in human skin regardless of race, color, and skin type. However, eumelanin is always the major constituent of epidermal melanin, and the skin color appears to be determined by the quantity of melanin produced but not by the quality.