Circulating benign nevus cells detected by ISET technique: warning for melanoma molecular diagnosis.

Abstract Background: The notion that only malignant melanoma cells circulate and diffuse is shared by oncologists and pathologists. Isolation by size of epithelial tumor cells (ISET) allows the identification of circulating tumor cells by filtration according to size. Observations: During a study of identification of circulating melanoma cells using ISET, blood samples from a 69-year-old man with an atypical melanocytic lesion on his back were evaluated. Binucleated and multinucleated cells that fulfilled the criteria for circulating tumor cells were found. The morphological features were similar to those of the excised skin tissue specimen, and the patient was subsequently diagnosed as having a congenital melanocytic nevus. BRAF (V600E)-mutated DNA was detected in both plasma and formalin-fixed tissue specimens, and the blood samples demonstrated an increase in tyrosinase messenger RNA levels. Conclusion: The finding that benign nevus cells may circulate in blood brings into question the value of tyrosinase or other melanocytic markers as a molecular surrogate for circulating melanoma cells.