Increased nuclear volume in metastasizing "thick" melanomas.

Tumor invasion is the most reliable prognostic factor for primary stage I melanoma. "Thick" melanomas, with a Breslow thickness of more than 4 mm, tend to have a poor prognosis. Exceptions occur: some patients have no further recurrence of tumor. In an attempt to determine prognostic markers for "thick" clinical stage I melanomas, we investigated the volume-weighted mean nuclear volume of primary melanomas with tumor invasions > or = 4.0 mm in 32 patients. Seventeen of these patients developed melanoma metastases within a follow-up period of 60 mo; 15 patients who did not developed metastases and were comparable with regard to clinical and histological criteria were selected as a comparison group. Volume-weighted mean nuclear volume (Vv) is determined by a technique that permits an unbiased, efficient, shape- and orientation-independent, 3-dimensional estimation of nuclear size in tissues. This technique has been employed successfully in the prognostic assessment of stage I and II melanomas and was recently proven to be a sensitive marker for thin, high-risk melanomas. In our patients, Vv was determined by computer-assisted image analysis on Feulgen-stained sections by stereologic estimation of the Vv. The mean Vv (+/-SD) of primary melanomas with subsequent metastatic course was 794.99 +/- 209.18 micron3 (range: 409.48-1161.9 micron3), whereas primary melanoma lesions without subsequent metastases exhibited a mean Vv 640.54 +/- 205.07 micron3 (range: 206.7-927.48 micron3). This difference was found to be statistically significant (p = 0.0439). "Thick" melanomas with subsequent metastases thus exhibited a significantly higher Vv than did melanomas that did not metastasize.