POU4F3 Plus Keratin AE1/AE3 or Pan-keratin: An Optimal Sentinel Lymph Node Protocol for Merkel Cell Carcinoma

There is currently no standardized sentinel lymph node (SLN) immunohistochemistry (IHC) protocol for detecting Merkel cell carcinoma (MCC) metastases. A cost-effective, high-sensitivity panel could improve diagnostic accuracy and resource utilization. We evaluated 226 SLNs from 81 MCC patients using a panel of POU4F3, keratin 20, and keratin AE1/AE3 or pan-keratin. Metastasis was defined as positive staining for any of the tested IHC markers. Patients' age ranged from 49 to 92 years (median, 73.5 years), with a male:female ratio of 1.8:1. Primary tumor sites were extremities (48.1%), head/neck (34.6%), and trunk (17.3%). SLN locations included cervical (29.6%), axillary (27%), femoral (20.8%), inguinal (9.7%), facial (7.1%), pelvic (3.1%), and epitrochlear (2.7%) sites. Metastases were identified in 102 of 226 SLNs (45%). Single-marker sensitivities were POU4F3 (96%, 98/102), keratin 20 (67%, 68/102), and keratin AE1/AE3 or pan-keratin (64%, 70/102). The most sensitive combinations were POU4F3 with keratin AE1/AE3 or pan-keratin (100% sensitivity) or POU4F3 with keratin 20 (98% sensitivity). Keratin 20 with keratin AE1/AE3 or pan-keratin was the least sensitive (74%). In 6 patients (7.4%), POU4F3 detected single metastatic cells in SLNs that were previously diagnosed at time of clinical diagnosis as negative by keratin 20 and keratin AE1/AE3 or pan-keratin panel. POU4F3 is the most sensitive individual IHC marker for detecting MCC SLN metastases. The optimal cost-effective panel is POU4F3 with keratin AE1/AE3 or pan-keratin, which achieves 100% sensitivity while reducing reliance on less effective stains. Adoption of this focused IHC panel may serve to standardize SLN evaluation for MCC and improve diagnostic accuracy and efficiency.