Is a “Merkel” Just Like a Melanoma? The Pathologic Analysis of Merkel Cell Carcinoma Specimens

Abstract

I remember being presented my first pathology report for a patient with Merkel cell carcinoma (MCC). What caught my attention the most was the absolute lack of detail in the report, which was generated from a leading academic medical center. Were treatment decisions really being made on such rudimentary variables, such as tumor diameter? At the time, however, a busy clinic and the multiple obligations of a surgical fellow pushed the thoughts to the back of my head. Yet that experience was brought back to the forefront of my mind once again only a few days later when our internal review of that Merkel cell cancer specimen was completed. I was now staring at a pathology report with a wealth of descriptive information similar to what a standard melanoma pathology report would include: tumor thickness, ulceration, mitotic count, etc. Now I was thoroughly engaged because I was completely confused––what was the important primary tumor data that a clinician should use to make subsequent treatment recommendations in this rare cutaneous malignancy? Do the same variables that are associated with outcomes in melanoma apply a priori to MCC? The idea seems logical enough, given that they are both ‘‘skin cancers.’’ However, there also are many differences (cell of origin, growth pattern, proliferative index/growth rate, etc.) that might make using the melanoma prognostic factors to risk stratify MCC, such as placing the proverbial ‘‘square peg in a round hole’’; it is entirely possible that the most significant similarity between melanoma and MCC is that they both start with ‘‘m.’’ In melanoma, the American Joint Committee on Cancer (AJCC) stage classification and determination of the prognostic significance of tumor thickness, mitotic rate, and ulceration is based on an exhaustive analysis of more than 30,000 patients with stage1–3 melanoma with excellent clinical, pathologic, and follow-up data. In contrast, the AJCC staging system in MCC is based on a populationbased analysis (utilizing data from the National Cancer Database [NCDB]) of 5,823 patients. However, unlike the melanoma dataset, the NCDB data is quite limited. For example, detailed pathology data and long-term follow-up are missing. Also, cause of death is not recorded, and thus it is not possible to determine associations between clinical and pathologic variables and death from MCC. In rare diseases like MCC, where large, prospective, randomized, clinical trials will almost certainly never occur, detailed reports of natural history provide excellent insight into the disease and form the best foundation to guide treatment recommendations. Our 2010 report on 412 patients represents the largest single-institution experience in MCC. Although this analysis provides a comprehensive analysis (similar to the AJCC melanoma database) of the natural history of MCC at a tertiary referral center, it is still limited by the rarity of the disease and the biases of any single-institution study. For example, as a stand-alone cancer center, we did not have a large number of immunosuppressed solid organ transplant patients with MCC in our data set, which differs from many other single-institution series of MCC. Despite these limitations, strong attention to detail in data collection and excellent follow-up in some single-institution series represent the best strategy to study patients with rare diseases, such as MCC. For example, we clearly Editorial regarding ‘‘Increasing tumor thickness is associated with more frequent recurrence and poorer survival in Merkel cell carcinoma patients,’’ by Lim & Thompson, et al. (Manuscript ID ASO-2011-12-2319.R1).