Summary Overexpression of transforming growth factor-4 isoforms (TGF-f1, -P2, -,B3) has been previously reported in human melanoma cell lines and tumours. The aim of the present study was to evaluate the plasma levels of TGF-f isoforms in melanoma patients. Significantly elevated levels of TGF-,1l (4.2 x the controls, P= 0.0094) and of TGF-,2 (1.5 x the controls, P= 0.012) but not of TGF-13 were measured in patients with disseminated but not locoregional melanoma. These results indicate systemic circulation of potentially immunosuppressive peptides of the TGF-P family in end-stage melanoma patients.

Reverse transcriptase polymerase chain reaction for the detection of tyrosinase-mRNA-positive cells in peripheral blood of melanoma patients, as a possible marker of hematogenous dissemination, has demonstrated varying detection rates. This study examined the sensitivity and reproducibility of the technique using a protocol of multiple polymerase chain reaction to determine circulating melanocytic cells. For each of the 123 melanoma patients included in this study, four nested polymerase chain reactions were performed from two blood specimens requiring both polymerase chain reactions from at least one blood sample to be positive to consider a patient as positive. Thus, a definitive result was obtained in 98% of the cases, whereas only 1.6% lacked conclusive findings. Thus, we found a correlation between the tyrosinase detection rate and the clinical stage. Circulating tyrosinase-mRNA-positive cells were detected in 13% of patients with primary tumor, 17% with regional skin/lymph node metastasis, and 44% with distant metastasis. Positivity also correlated with known melanoma progression markers such as gender, tumor thickness, and histologic type. Positive results were obtained more frequently in (i) men compared with women, (ii) patients with thick primary melanomas (> 4 mm: 38%) compared with those with thinner tumors (1.1-4 mm, 22%; < or = 1 mm, 5%), and (iii) patients with nonclassifiable (38%), nodular (34%), and occult primary melanomas (30%) compared with those with acrolentiginous (17%), superficial spreading (9%), or lentigo maligna melanoma (0%). These findings suggest that detection of tyrosinase-mRNA-positive cells in peripheral blood is not an adequate marker for identifying melanoma patients with distant metastasis. Reverse transcriptase polymerase chain positivity in early melanoma stages, however, as corresponding to other prognostic parameters, may indicate increased risk for the development of hematogenous metastasis and may be of value as a progression marker.

High variability of the clinical appearance of malignant melanoma (MM) and its metastases render the differential diagnosis of solid amelanotic tumours difficult. We report a 71-year-old woman with several unusual cutaneous tumours of cerebriform morphology, suggesting skin metastases from occult internal cancer. Histopathological findings and thorough investigations, however, revealed a late-stage metastatic MM. We discuss the differential diagnosis of skin metastases of various origin and underline the difficulties for early detection of MM.

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