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 <.01, 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 =.01). 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.

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – update 2018

“…At the time of initial diagnosis, up to 20 % of patients present with clinically manifest lymphogenic metastases and thus have a poor prognosis . In addition, almost one‐third of the patients have lymphogenic, clinically inapparent micrometastases . It is therefore imperative that patients be worked up for locoregional spread at the time of initial diagnosis, either by lymph node ultrasound of the draining lymph node basins and/or cross‐sectional imaging.…”

Prognostic factors and immunobiologic insights into Merkel cell carcinoma

“…Fields et al reported that MCC size and LVI were correlated with SLN status, whereas Schwartz et al showed that MCC thickness, mitotic rate, and histologic growth pattern significantly predicted SLN status in a multivariate analysis. Smith et al also report that MCC size and thickness significantly predict SLN status in a univariate analysis, and their results provide more evidence that these factors are prognostic markers for SLN status. Interestingly, 1 study looked at the Veterans Affairs national health care database and reported that MCC patients with tumors ≤ 1 cm in size may not benefit from nodal staging .…”

“…Instead, Smith et al evaluated the prognostic significance of tumor thickness in MCC. Although MCC size has been correlated with survival, the prognostic value of tumor thickness remains undefined.…”

“…Another focus of the study by Smith et al is an evaluation of the prognostic significance of the extent of nodal involvement at presentation. The most consistently reported prognostic factor for MCC is the presence of clinically evident macroscopic nodal disease .…”

“…In contrast, Fields et al reported no significant difference in recurrence rates or survival between SLN‐positive and SLN‐negative patients. Smith et al also evaluated the prognostic significance of SLN status in MCC patients and failed to show a significant difference in recurrence risk, OS, or DSS based on SLN status, although there were trends toward lower recurrence risk ( P = .095), improved OS ( P = .065), and improved DSS ( P = .059) in SLN‐negative patients versus SLN‐positive patients. It is possible that with a larger study, a significant difference in outcomes based on SLN status may be found.…”