Sentinel lymph nodes in malignant melanoma: extended histopathologic evaluation improves diagnostic precision.

The optimal technique for sentinel lymph node (SN) assessment in patients with melanoma is controversial. Molecular analysis (reverse transcriptase-polymerase chain reaction) detects significantly greater numbers of SNs with suspected micrometastases (up to 71%) than does routine histopathology (approximately 20%). The authors sought to identify possible reasons for this discrepancy and to determine whether using an extended histopathologic protocol could improve diagnostic precision. Two hundred thirty-one SNs from 100 consecutive patients with cutaneous melanomas that measured 1-4 mm in thickness were bisected, and half of the lymph node was examined according to an extensive histopathologic protocol involving serial sectioning and immunohistochemical analysis of 3 melanocyte-associated markers (S-100, HMB-45, and Melan-A). Lymph node melanocytic lesions were frequent, with micrometastases and benign nevus inclusions (BNI) found in SNs in 28% and 28% of patients, respectively (4 SNs contained both). Melan-A was the most sensitive immunohistochemical marker and was positive in all BNI-positive SNs and 97% of micrometastasis-positive SNs. Although HMB-45 showed differential labeling in micrometastases compared with BNI (82% vs. 16%), immunohistochemistry could not distinguish between those lesions. Micrometastases were already identified on the first central level in 49% of positive SNs, whereas only 23% of SNs with BNI were diagnosed on the first level. Extensive serial sectioning with immunohistochemical analysis substantially increased the histopathologic detection of micrometastases and BNI in melanoma SNs to a level approaching the level reported for molecular techniques. The large number of BNIs represents an important potential source of imprecision (false positivity) in SN assays based on nonmorphologic methods.