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Sentinel lymph node biopsy (SLNB) is performed for some thin melanomas in the presence of concerning histopathological features. There are no defined standards for how sentinel nodes should be processed to detect microscopic metastases. We compared our method of serially sectioning nodes at 2–3 mm intervals and performing one hematoxylin and eosin (H&E) slide versus multiple H&E levels and utilizing immunohistochemistry (IHC). This was a retrospective review of a prospectively collected database identified patients with thin melanomas treated with wide local excision and SLNB between 1995 and 2010. Two patients had positive nodes. Out of 95 patients with negative SLNBs, 48 (49 nodes) patients were evaluable. Additional sections of each SLNB tissue block were stained with H&E (×2), Melan-A (×2) and HMB45 (×2), and reviewed by two pathologists. Additional histopathological sections showed that 1/49 (2.0%) nodes originally called negative had evidence of metastasis, which was evident both on additional H&E levels and by IHC; 3/49 (6.1%) nodes had benign nodal rests. All other nodes (45/49, 91.8%) were negative by H&E and IHC for metastatic disease. This study supports previous work suggesting the value of IHC in detecting micrometastases in melanoma sentinel nodes. Especially for thin melanomas where metastases are uncommon, but where detection of the metastasis upstages considerably from stage IA to IIIA, evaluation of nodes may be enhanced by combining breadloafing at 2–3 mm intervals with multiple H&E sections and IHC analysis.