Accuracy of pathologic techniques for the diagnosis of metastatic melanoma in sentinel lymph nodes

Background: Sentinel lymph node (SLN) biopsy can accurately predict the presence of metastatic melanoma (MM) and has been used to identify patients with occult metastases. We present an analysis of the sensitivity and specificity of standard pathological techniques including intraoperative frozen section, permanent section, and immunohistochemistry in diagnosing MM within the SLN. Methods: Sixty-nine consecutive patients with primary malignant melanoma thickness of >1.0 mm or thinner lesions invading the reticular dermis (Clark level IV) who underwent SLN biopsy were reviewed. Lymph nodes were examined intraoperatively by frozen section (FS), permanent section (H and E), and by immunohistochemistry (IH) for S-100 protein and HMB45. Results: MM was found in 14 of 69 cases (20%). Permanent section H and E was performed in all cases, FS in 64 cases, and IH in 65 cases. FS analysis diagnosed MM in 4 of 14 cases (29%). was suspicious in 2 of 14 (14%), and falsely negative (FN) in 8 of 14 (57%) ultimately found to be positive with further workup. Within the FN group, MM was identified on review of the original FS slides in 3 of 8 cases (38%). Furthermore, within the FN group, the remaining 5 cases were identified as positive for MM by either permanent and/or deeper H and E sections and IH. IH alone with permanent H and E sections would have diagnosed MM in only 8 of 10 cases (80%) that were FS negative or suspicious. In no cases was MM identified by IH alone with the permanent and deeper H and E sections being negative. It is noteworthy that no false-positive cases were identified. Conclusions: Intraoperative FS has low sensitivity in identifying MM within the SLN. IH alone does not increase the diagnostic yield. A combination of permanent H and E sections with deeper levels and S-100 and HMB45 IH dramatically increases the overall diagnostic sensitivity of SLN biopsy. Definitive diagnosis should await permanent H and E sections and IH staining.