Guidelines Summary

Below is a combined summary of updated clinical guidelines on Merkel cell carcinoma by the National Comprehensive Cancer Network (NCCN) (2018) and a European consensus‒based interdisciplinary group (European Dermatology Forum, European Association of Dermato-Oncology [EADO], and European Organisation of Research and Treatment of Cancer [EORTC] [2015]).^{[13, 52, 120]}

Cutaneous clinical features are not sufficient to make a diagnosis of Merkel cell carcinoma. Rather, histopathological (including immunohistochemical) evaluation of a skin biopsy specimen is mandatory to establish a pathologic diagnosis.

Whole-body positron-emission tomography with fluorodeoxyglucose (PET-FDG) scanning; CT with contrast of the neck, chest, abdomen, and pelvis; and/or brain MRI with contrast (in the United States) and ultrasound of the locoregional lymph nodes (in Europe) are helpful tools to evaluate for the presence of metastasis in the initial workup. Sentinel lymph node biopsy (SLNB) is recommended for patients without clinical evidence of regional lymph node involvement, and fine-needle aspiration or core needle biopsy is recommended for those with clinically palpable lymphadenopathy.

Surgical excision with 1- to 2-cm margins is the recommended management for primary tumors, potentially with adjuvant radiation therapy.

Radical lymphadenectomy is recommended for patients who have regional lymph node involvement, and adjuvant radiotherapy can be considered based on risk factors, especially in patients with multiple affected lymph nodes or extracapsular extension.

In the case of regional or distant metastases or recurrence, a multidisciplinary tumor board should be consulted to ascertain an appropriate management.

Checkpoint immunotherapies are the preferred systemic therapy for metastatic disease, preferably through enrollment in a clinical trial.

Multiple- or single-agent chemotherapy achieves high remission rates in unresectable, metastatic Merkel cell carcinoma; however, responses are usually short-lived.

Close clinical follow-up is critical, with complete skin and lymph node evaluation every 3-6 months for 3 years and every 6-12 months thereafter.

Medication

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Media Gallery

Large, violaceous nodule of Merkel cell carcinoma on the antecubital fossa. Courtesy of Dr. Jonathan Cook.
Histopathologic appearance of nodular Merkel cell carcinoma. Dermal nodule with a cohesive, expansive growth of basophilic cells.
High-power view demonstrates an open chromatin pattern and a high mitotic index.
Pseudorosette formation in Merkel cell carcinoma.
Merkel cell carcinoma with a focus of squamous differentiation.
Prominent in situ nested component of Merkel cell carcinoma, simulating malignant melanoma.
Electron micrograph of Merkel cell carcinoma showing a dense core granule (arrow).
Electron micrograph of Merkel cell carcinoma showing whorled bundles of intermediate filaments (arrow) near nucleus in Merkel cell carcinoma.
Dotlike paranuclear pattern of cytokeratin immunolocalization.
Recommended workup and protocols for biopsy-proven Merkel cell carcinoma.
Summary of Merkel cell carcinoma AJCC, 8th Edition, Staging. Courtesy of https://merkelcell.org/ with permission.

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Author

Meghana Agni, MD Resident in Anatomic and Clinical Pathology, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Meghana Agni, MD is a member of the following medical societies: American Association of Ophthalmic Oncologists and Pathologists, American Society of Dermatopathology, Chicago Pathology Society, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Coauthor(s)

Victor G Prieto, MD, PhD Ferenc and Phyllis Gyorkey Chair for Research and Education in Pathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Myriad (consultant regarding MyPath test in melanocytic lesions).

Christopher R Shea, MD Eugene J Van Scott Professor in Dermatology, Chief, Section of Dermatology, Department of Medicine, University of Chicago, The Pritzker School of Medicine

Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Arthur Purdy Stout Society, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society, International Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; Past President, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: QualDerm Partners; Novascan<br/>Have a 5% or greater equity interest in: QualDerm Partners - North Carolina.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Susan M Swetter, MD Director, Pigmented Lesion and Melanoma Program, Professor, Department of Dermatology, Stanford University Medical Center and Cancer Institute, Veterans Affairs Palo Alto Health Care System

Susan M Swetter, MD is a member of the following medical societies: American Academy of Dermatology, Women's Dermatologic Society, American Society of Clinical Oncology, Society for Melanoma Research, Eastern Cooperative Oncology Group, American Medical Association, Pacific Dermatologic Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.