Quantitative assessment of fat cells in subcutaneous metastatic melanoma. Correlation with outcome.

The metastatic behavior of tumor cells largely depends on tumor-stroma interactions. In the present study, a particular morphological feature of tumor-stroma interaction was evaluated; hematoxylin-eosin-stained slides of 81 lesions of melanoma metastatic to the skin involving the subcutis were examined by automated image analysis for the presence of preexistent fat cells in the tumor. The area occupied by fat cells, expressed in micrometers squared per slide, was of prognostic significance; lesions with a fat cell area of < 41,000 microns 2 showed a 2-year survival rate of 42%, versus 10% in lesions with a fat cell area of > 41,000 microns 2 (log-rank test, z = 3.24; p < or = 0.01). The adverse effect of fat cell area on prognosis still was seen when age, sex, and site of metastatic spread were concomitantly taken into account in a Cox proportional-hazard model. These data indicate that melanoma deposits involving the subcutis with preservation of preexistent subcutaneous fat cells have high metastatic potential and a high risk for rapid internal dissemination.