Objectives Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort. Methods One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied. Results Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazards ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients. Conclusions This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging.

BACKGROUND Quantitation of circulating tumor cells (CTCs) has utility in managing breast, colon and prostate carcinomas. OBJECTIVE Determine whether a commercially available CTC assay provides prognostic information in MCC and/or insight into treatment responses. METHODS We analyzed CTCs in 52 specimens from 34 MCC patients. RESULTS The presence of CTCs correlated with extent of disease at blood draw (p=0.004). Among 15 patients with regional nodal disease, CTC-negative patients had 80% disease-specific survival at 2 years after the test, versus 29% for CTC-positive patients (p=0.015). Among the entire cohort, those without CTCs had 72% MCC-specific survival while CTC-positive patients had 25% survival (n=34, median follow-up 19 months, p=0.0003). 57% of MCC patients had a cytokeratin “dot” visible in ≥20% of CTCs, a feature that was absent among CTCs from other carcinomas (zero of 13 cases). LIMITATIONS CTC assay was performed at variable times after diagnosis and heterogeneity in extent of disease affects interpretability of the data. CONCLUSION CTC detection in MCC is feasible and appears to add prognostic information, particularly in patients with regional nodal disease. It may also assist clinical management in certain situations, including differentiating metastatic MCC cells from those of other carcinomas.