Stereologic estimation of volume-weighted mean nuclear volume as a predictor of prognosis in "thin" malignant melanoma.

At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low-risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy.