Both tumor depth and diameter are predictive of sentinel lymph node status and survival in Merkel cell carcinoma

Abstract

Background: The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC).

Methods: An institutional review board-approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively.

Results: Three hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2-12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3-45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P = .007 and P = .017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P = .007, P = .003, and P = .025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P = .018).

Conclusion: For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically.

Keywords: Merkel cell carcinoma; sentinel lymph node; survival; tumor depth; tumor diameter.

Figure 1

(A) Tumor depth versus the risk of a positive SLN in Merkel cell carcinoma. The estimated probability of having a positive SLN for a tumor 1 mm in depth was 23% (95% CI, 13%–38%), and the estimated probability of having a positive SLN for a tumor 8 mm in depth was 45% (95% CI, 36%–56%). (B) Tumor diameter versus the risk of a positive SLN in Merkel cell carcinoma. The estimated probability of having a positive SLN for a tumor 1 cm in diameter was 32% (95% CI, 23%–43%), and the estimated probability of having a positive SLN for a tumor 4 cm in diameter was 59% (95% CI, 42%–74%). CI indicates confidence interval; LN, lymph node; SLN, sentinel lymph node.

Figure 2

(A) Incidence of recurrence stratified by nodal disease categories. There was no significant difference across the nodal disease categories (P =.39). Patients with Merkel cell carcinoma of unknown primary had the fewest recurrences. Patients who did not have an SLN biopsy performed had the highest incidence of recurrence. (B) Incidence of recurrence in SLN-negative and SLN-positive patients. SLN indicates sentinel lymph node.

Figure 3

Overall survival and mortality stratified by nodal disease categories. (A) Overall survival stratified by the 5 nodal disease categories. There was a statistically significant difference (P =.007) in overall survival between the groups. The best overall survival was seen in patients with a negative SLN. (B) Overall survival for SLN-negative and SLN-positive patients. The median survival was 85 months for the SLN-negative patients (not shown in plot) and 59.5 months for the SLN-positive patients (P =.065). (C) Mortality from Merkel cell carcinoma stratified by the 5 nodal categories. Patients with a negative SLN had the best disease-specific survival. The worst disease-specific survival was observed in patients with clinically evident regional nodal disease at presentation. (D) Mortality from Merkel cell carcinoma in SLN-negative and SLN-positive patients (P =.059). SLN indicates sentinel lymph node.