Case Report: Unusual Combined Merkel, Squamous Cell Carcinoma in Situ

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Investigators report a rare case of combined Merkel cell and squamous cell carcinoma confined almost exclusively to the epidermis.
Investigators report a rare case of combined Merkel cell and squamous cell carcinoma confined almost exclusively to the epidermis.

Introduction

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor typically found in the dermis. Pathogenesis is imperfectly understood, but a majority of tumors are associated with the Merkel cell polyomavirus (MCPyV). Risk factors include immunosuppression, older age, and ultraviolet (UV) radiation. MCC is an aggressive cancer with a high rate of mortality, recurrence, lymphatic spread, and metastasis. We report a rare case of combined MCC and squamous cell carcinoma (SCC) confined almost exclusively to the epidermis. To the best of our knowledge, there have been 14 cases of intraepidermal MCC to date.1 Only 6 of these cases have presented as “combined” MCC in situ (MCCIS) and SCC in situ (SSCIS), with this being the seventh.1

Report of a Case

A 67-year-old woman with a history of skin and lung cancer, status post lung transplantation, came to the clinic for examination of a 6-mm pink pearly patch on her right shoulder. Shave biopsy was performed and revealed a pagetoid intraepidermal carcinoma with involvement of peripheral margins, concerning for MCC.

Immunohistochemistry was positive for neuron-specific enolase, synaptophysin, chromogranin, CAM 5.2, CK20, and neurofilament, all of which are characteristic of MCC. A minority of cells demonstrated dot-like paranuclear expression, which is highly specific for MCC. Additionally, there was increased squamous cell atypia at one edge of the biopsy, and on re-excision, concurrent SCCIS was confirmed. Sentinel lymph node biopsy was negative for metastatic carcinoma.

Discussion

The pathogenesis of MCC is likely an interplay of various factors, including both viral and UV-related contributions.2 Since the discovery of MCPyV in 2008, approximately 80% of MCC tumors have been thought to be driven by viral-induced oncogenesis.3 However, there is also support for a UV-related pathway, as MCC usually occurs in sun-exposed areas of the skin and can be associated with other UV-induced malignancies.

In addition to classifying MCC based on viral status, there is a subtype of MCC that occurs in association with other lesions, the majority being SCC.4 Additionally, the majority of reported MCCIS cases have also been associated with SCCIS.1 Three of these 6 “combined” cases were analyzed for viral status, and all 3 were MCPyV negative.1 This combined subtype tends to be genetically and molecularly different from “pure” MCC, with increased UV-induced mutations such as tp53 and RB1 and a viral negative status.4,5 This suggests that combined tumors are distinct pathogenic entities from those arising from viral-associated pathways, which have a UV-related pathogenesis.

One theory suggests that combined tumors are pathogenically similar to other UV-related cancers that initially undergo a wholly in-situ stage that is not seen in virus-related tumors.6 Although MCPyV status is unknown, our patient's case supports this theory because of her fair skin, history of skin cancer, combined tumor type, and epidermal presentation, suggesting that, in her case, MCC was associated with UV damage and is being seen in a predominantly in situ stage.

There should be high clinical suspicion for MCCIS, as it can be mistaken for other malignancies. Because of increasing prevalence, strong efforts need to be made to characterize pathogenesis and determine various subsets of MCC accurately. Once mechanisms of oncogenesis are more thoroughly understood, we will be better equipped to prevent and manage all types of MCC, regardless of the pathogenesis. If there are various clinically distinct pathways leading to oncogenesis, it could warrant different targets in treatment, which could potentially reduce recurrence and mortality.

This case was submitted by Fasiha Syed, BS1, German Treyger, DO2, Chelsea Duggan, DO2, Stephen Olsen, MD3, and Steven Grekin, DO2.

1Chicago College of Osteopathic Medicine, Chicago, IL.
2Department of Dermatology, Beaumont Hospital, Trenton, MI.
3Pinkus Dermatopathology Laboratory, Monroe, MI.

References

1. Jour G, Aung PP, Rozas-Muñoz E, Curry JL, Prieto V, Ivan D. Intraepidermal Merkel cell carcinoma: a case series of a rare entity with clinical follow up. J Cutan Pathol. 2017;44(8):684-691.

2. Coggshall K, Tello TL, North JP, Yu SS. Merkel cell carcinoma: an update and review: pathogenesis, diagnosis, and staging. J Am Acad Dermatol. 2018;78(3):433-442.

3. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096-1100.

4. Pulitzer MP, Brannon AR, Berger MF, et al. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma. Mod Pathol. 2015;28(8):1023-1032.

5. Busam KJ, Jungbluth AA, Rekthman N, et al. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol. 2009;33(9):1378-1385.

6. Tan BH, Busam KJ, Pulitzer MP. Combined intraepidermal neuroendocrine (Merkel cell) and squamous cell carcinoma in situ with CM2B4 negativity and p53 overexpression. J Cutan Pathol. 2012;39(6):626-630.

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