Histopathologic Features for Overall Survival in Merkel Cell Carcinoma: A Case Series with Intact Mismatch Repair Protein Expression

Abstract

Objective: In a study of Merkel cell carcinoma (MCC), a fusion transcript between MLH1 and SPATA4 was identified. This fusion has the potential to generate the inactive or dominant-negative form of the protein. Therefore, we aimed to investigate whether mismatch repair protein deficiency occurr in MCC cases or not, in addition to the overall survival association with histopathologic features.

Material and method: A retrospective review of 15 patients diagnosed with a biopsy-proven Merkel Cell Carcinoma between 2012 and 2019 was performed. Mismatch repair (MMR) protein expressions were evaluated by immunohistochemistry.

Results: The median follow-up time was 36 months (mean 41, range 2-103 months). Six (40%) patients died during follow-up. The overall survival (OS) at 1 year, 2 years, 3 years, and 5 years were 87%, 80%, 62%, and 53%, respectively. The patients diagnosed at < 60 years had an improved OS compared to those ≥60 years of age (p=0.016). Patients in clinical stage I had better OS than patients in clinical stage IV (p=0.011). Cases with pathological tumor stage (pT) 1 had better OS than pT3 and pT4 (p=0.045). Adjuvant radiotherapy or adjuvant radiotherapy+chemotherapy treatment improved OS compared to adjuvant chemotherapy (p=0.003). MMR protein nuclear expression was intact in 12 cases available for immunohistochemical study.

Conclusion: To the best of our knowledge, this is the second study that preferentially investigated the mismatch repair protein status of Merkel Cell Carcinoma. No mismatch repair protein deficiency of MCC cases was identified in the current study.

Figure 1

A) In this case, The tumor presented as a fast-growing 10 cm nodule with multifocally ulcerated, violaceous-colored overlying skin located at the right thigh. B) The cut surface revealed a tumor with a firm, tan brown-colored, multinodular growth pattern in the dermis and subcutis in the formalin-fixed excisional specimen.

Figure 2

In this example (A,B), subepidermal edema and dermal lymphatic invasion were evident. Uniform basophilic tumor cells formed nests and diffuse sheets surrounding the adnexal structures. Dissection of collagen and some crushing artifacts accompanied tumor cells (C). Paranuclear dot-like cytokeratin 20 stainings (D). MLH1 (E) and PMS2 (F) nuclear stainings were intact with internal controls. (Hematoxylin and Eosin stain, magnifications 40X [A, B], 200X [C], immunohistochemical stainings, magnifications 200X [CK20], 100X [MLH1, PMS2]).

Figure 3

Kaplan-Meier overall survival curves for Merkel cell carcinoma patients compared for variables by age (B), clinical-stage (C), pathological tumor stage (pT) (D), adjuvant treatment (E), tumor thickness (F).