Can SOX-10 or KBA.62 Replace S100 Protein in Immunohistochemical Evaluation of Sentinel Lymph Nodes for Metastatic Melanoma?

Microscopic evaluation of sentinel lymph nodes for metastatic melanoma relies, in part, on the use of immunohistochemical analysis to identify minute metastatic deposits that may be overlooked on routine microscopy. At present S100 protein is widely used in this role, in large part for its superior sensitivity; however, interpretation is hampered by the presence of benign S100 protein-positive cellular elements present in every lymph node, leading to reduced specificity and consequent difficulties in interpretation. In recent years, multiple melanocytic markers have emerged that promise superior sensitivity and specificity, including KBA.62 and SOX-10. SOX-10 shows a nuclear pattern of staining. In normal tissue it is expressed in Schwann cells, melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. KBA.62 is also specific except for staining of endothelial cells and shows a membranous staining pattern. This study was undertaken to determine whether KBA.62 or SOX-10 could equal (or surpass) the sensitivity of S100 protein while offering superior specificity in the immunohistochemical evaluation of sentinel lymph nodes for metastatic melanoma. In this study we performed immunohistochemical stains for S100 protein, Sox-10, and KBA.62 on 50 lymph nodes with proven metastatic melanoma. SOX-10 detected all cases of metastatic melanoma (50 of 50 cases; 100%) compared with S100 protein (48 of 50 cases; 96%) and KBA.62 (37 of 50 cases; 74%). There was no "background" staining of normal cellular elements with SOX-10 or KBA.62. In contrast, S100 protein was expressed in scattered dendritic interdigitating reticulum cells in the paracortex of lymph nodes, showing cytoplasmic and nuclear positivity, sometimes posing significant difficulty in differentiating benign reticulum cells from single cell metastatic melanoma. Our findings suggest that SOX-10 may be superior to S100 protein for identifying metastatic melanoma in a lymph node. KBA.62 was less sensitive than either marker, although more specific than S100 protein.