cysteinyldopa and Nevus--Pigmented

5-S-Cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are formed during biosynthesis of melanins. They are used as indicators of pigment formation and markers of melanoma progression in adults and could possibly be used as markers of activity, growth and even malignant transformation in large pigmented naevi in children. We investigated the urinary excretion of these pigment precursor metabolites from 136 children, 5 to 15 years of age. The mean 5SCD excretion was 38.1 mumol/mol creatinine. A significant age-related decrease from a mean of 60.4 mumol/mol creatinine at 5 years of age to 28.0 mumol/mol creatinine at age 15 was found. In a reference group (29 adults, 20-33 years of age) the mean excretion was 48.9 mumol/mol creatinine. The mean excretion of 6H5MI2C was 42.8 mumol/mol creatinine at 5 years of age and 26.1 mumol/mol creatinine at the age of 15. The mean value for the young adults was 33.4 mumol/mol creatinine. No correlation between the mean excretion of 5SCD and 6H5MI2C was demonstrated. We suggest an upper reference level of 90 mumol/mol creatinine for the excretion of 5SCD in the age group 5-11 years and of 60 mumol/mol creatinine in the age group 13-15 years. Corresponding figures for the indole 6H5MI2C are 70 and 60 mumol/mol creatinine. The establishment of reference values in children will make it possible to use 5SCD and 6H5MI2C measurements as diagnostic tools, indicating growth or malignant transformation in giant melanocytic naevi during childhood.

Topics: Adolescent; Adult; Age Factors; Biomarkers, Tumor; Child; Child, Preschool; Cysteinyldopa; Female; Humans; Indoles; Male; Melanins; Nevus, Pigmented; Sex Factors; Skin Neoplasms

The serum concentrations of 5-S-cysteinyldopa (5-S-CD) in pediatric patients with giant pigmented nevi (GPN) were investigated and compared with those of pediatric patients with small- or medium-sized congenital nevi (CN), or non-melanocytic benign skin tumor (control group). Serum 5-S-CD levels in the GPN group (N = 21), particularly in patients less than 5 years old, were significantly higher (highest concentration 38.4, mean +/- S.D. 16.6 +/- 9.4 nmol/L) than those in the CN (N = 22) or control groups (N = 26). Serum 5-S-CD levels in the CN group were not significantly different from those in the control group. There was a significant correlation between the serum 5-S-CD level and size (surface area) of the GNP. There was a significant inverse correlation between the serum 5-S-CD level and age in the CN and control groups, but not in the GPN group. Serum 5-S-CD levels were transiently elevated immediately after treatment of patients with GPN with a combination of skin abrasion and cryotherapy with solid carbon dioxide. These results suggest that serum 5-S-CD levels in the GPN group reflected the 5-S-CD derived from GPN, particularly in patients less than 5 years old. This indicates that melanogenesis may be accelerated in infant patients in the GPN group.

Topics: Adolescent; Age Factors; Carbon Dioxide; Child; Child, Preschool; Cryotherapy; Cysteinyldopa; Dermabrasion; Female; Humans; Infant; Male; Nevus; Nevus, Pigmented; Skin Neoplasms

This study reports our success in developing a murine monoclonal antibody (mAb) against phaeomelanin and its major precursor, 5-S-cysteinyldopa (5-S-CD). A competitive enzyme-linked immunosorbent assay was developed and demonstrated that the new mAb, designated as 6D4 (IgG1, kappa), reacted with both 5-S-CD and phaeomelanin, but not with eumelanin. The concentrations required for 50% inhibition of 5-S-CD and phaeomelanin were 65 ng/ml and 95 ng/ml respectively. The minimal amount of 5-S-CD and phaeomelanin which could be detected by mAb 6D4 was approximately 5 and 6 ng/ml, respectively. The immunohistochemical assay indicated that the antigenic epitope(s) recognized by mAb 6D4 was localized in the cytoplasm of certain types of melanocytic tumours, such as superficial spreading melanoma.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Binding, Competitive; Cysteinyldopa; Enzyme-Linked Immunosorbent Assay; Humans; Hybridomas; Immunoglobulin G; Melanins; Melanoma; Mice; Mice, Inbred BALB C; Neoplasms; Nevus, Pigmented; Rats; Skin Neoplasms; Tumor Cells, Cultured

On the basis of clinical and histopathological studies on 17 patients who had been diagnosed as having pigmented Spitz nevus (PSN), pigmented spindle cell nevus (PSCN) was surmised to be a type of pigmented Spitz nevus. In order to distinguish pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma, 5 PSCN cases and 12 PSN cases were analyzed by the fine-needle aspiration fluorescence method, touch fluorescence method and measurement of the 5-S-CD level in the lesion. With the touch fluorescence method, fluorescent tumor cells were detected in one case of PSN. With the fine-needle aspiration fluorescence method, fluorescent tumor cells were detected in one PSCN case and 2 PSN cases. In comparison with fluorescent melanoma cells, the detected fluorescent tumor cells were smaller in size and number and resembled melanocytes. The 5-S-CD level in the lesion was 50 ng/mg or less in all cases, whereas the level in melanoma is known to be a high 100 ng/mg or more. In the final analysis, measurement of the 5-S-CD level in the lesion was concluded to have the greatest utility for differential diagnosis of pigmented spindle cell nevus and pigmented Spitz nevus from early melanoma.

Topics: Adolescent; Adult; Biomarkers, Tumor; Child; Child, Preschool; Cysteinyldopa; Diagnosis, Differential; Female; Histocytochemistry; Humans; Melanoma; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms

The appearance of 5-[(L)-S-cysteinyl]dopa, a major product in pheomelanogenesis was examined in affected and nonaffected skins from 20 patients with clinical signs of dysplastic melanocytic nevi. Analysis by high performance liquid chromatography and electrochemical detection showed that 20 of the 35 lesions had a pathological formation of 5-[(L)-S-cysteinyl]dopa (0.04-28.86 ng/micrograms acid soluble protein). 5-[(L)-S-cysteinyl]dopa was not detected in any of the normal uninvolved skin samples analyzed.

Topics: Biopsy; Chromatography, High Pressure Liquid; Cysteinyldopa; Dihydroxyphenylalanine; Humans; Melanocytes; Nevus, Pigmented; Precancerous Conditions; Skin

Histochemical findings of primary and metastatic amelanotic melanomas were shown by the formaldehyde-induced fluorescence method (Falck and Hillarp). All or some of the amelanotic melanoma cells were discovered to emit green specific fluorescence. Results of the determination of 5-S-cysteinyldopa and DOPA in amelanotic melanoma tissues indicated that the specific fluorescence emitted by these cells is primarily due to the presence of 5-S-cysteinyldopa. The values of 5-S-cysteinyldopa in these tissues were lower than those in melanotic melanoma, but were approximately the same as those in pigmented nevus. When unpigmented tumors were histopathologically revealed to be malignant, amelanotic melanoma could be definitely diagnosed by the fluorescence method of Falck and Hillarp and the biochemical analysis of 5-S-cysteinyldopa in the tissues.

Topics: Adult; Aged; Carcinoma, Basal Cell; Cysteinyldopa; Dihydroxyphenylalanine; Humans; Male; Melanoma; Microscopy, Fluorescence; Nevus, Pigmented; Skin Neoplasms

In an attempt to improve the diagnosis of melanotic tumors, we have compared the diagnosis obtained by histological examination of 216 skin tumors and their metastases with that obtained by using a conjunction of four techniques: tissue culture, cytoenzymology, in situ electron microscopy and 5-S-cysteinyldopa (5-S-CD) assay. In 46 cases the final diagnosis as determined by one or more of these tests differed from the initial histological diagnosis, but was confirmed by repeat histological examination. We conclude that this method presents a valuable new approach to the differential diagnosis of human malignant melanoma.

Topics: Adolescent; Adult; Aged; Ascitic Fluid; Culture Techniques; Cysteinyldopa; Diagnosis, Differential; Female; Histocytochemistry; Humans; Lymphatic Metastasis; Male; Melanoma; Methods; Microscopy, Electron; Middle Aged; Nevus, Pigmented; Pleural Effusion; Skin Neoplasms

Previous studies have demonstrated a specific cytoplasmic fluorescence in human melanocytes, as well as in pigmented nevi and in malignant melanomas, when the formaldehyde histofluorescence method for visualization of certain catechol and indole derivatives was used. In malignant melanoma two fluorogenic substances, dopa and cysteinyldopa, were found previously. In human melanocytes and benign nevi cells the fluorogenic catechols have so far not been characterized, since chemical analyses are difficult to perform on skin, due to the small amounts of catechols present. However, using split thickness skin quantitative determinations are possible by sensitive fluorometric methods. The chemical analyses of cysteinyldopa showed that in human adult skin most or all was located in the superficial layers. The only specific fluorescence in the thin skin was found in dendritic melanocytes. The findings leave little doubt that cysteinyldopa is stored in melanocytes although the possibility of a concomitant occurrence of other thioethers is not excluded. Nevi and giant nevi were also similarly studied and we found considerable amounts of cysteinyldopa in the nevi. It seems as if the cysteinyldopa is stored in the fluorescent nevi cells. There was no consistent difference in the content of the catechol derivatives between intradermal and compound nevi.

Topics: Adolescent; Child; Child, Preschool; Cysteinyldopa; Dihydroxyphenylalanine; Female; Humans; Male; Melanocytes; Nevus; Nevus, Pigmented; Skin Neoplasms