What is the origin of the Merkel cell and Merkel cell carcinoma (MCC)?

Answer

The origin of Merkel cells is unclear, as they share both epidermal and neuroendocrine features. Research suggests that they may be derived from pluripotential stem cells of the dermis or, as an alternative, from neural crest cells. Cytologic and immunohistochemical data support both contentions.

Merkel cells display paranuclear staining for cytokeratins, which are also found in other neuroendocrine tumors. Osmiophilic granules contain neuropeptide, such as neuron-specific enolase, chromogranins, and synaptophysin. Evidence suggests that Merkel cells communicate with nerve terminals by means of a glutamatergic pathway, implying that they may have a neuroendocrine origin.

The general assumption is that MCC originates from Merkel cells, though this does not appear to be entirely correct. For example, MCC develops almost exclusively in the dermis, whereas the overwhelming majority of Merkel cells are found in the epidermis, a site rarely involved with MCC. Some suggest that the cells of origin may be immature pluripotential stem cells found in the dermis. These stem cells share phenotypic similarities with Merkel cells, though they do not appear to communicate with nerve terminals. It is postulated that these cells may acquire neuroendocrine features during malignant transformation.

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Media Gallery

Large, violaceous nodule of a Merkel cell carcinoma on the antecubital fossa (photo courtesy of Dr Jonathan Cook).
Histologic appearance of nodular Merkel cell carcinoma. This dermal nodule has a cohesive, expansile growth of basophilic cells.
Note the small, round, basophilic cells arranged in sheets, rests, or trabeculae in this Merkel cell carcinoma. The cells possess hyperchromatic nuclei, minimal cytoplasm, and frequent mitotic and apoptotic figures (hematoxylin-eosin stain).
Electron photomicrograph of a Merkel cell carcinoma shows a dense core granule (arrow).

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Author

Arjun S Joshi, MD Assistant Professor of Surgery, Division of Otolaryngology–Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Arjun S Joshi, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Medical Association, American Thyroid Association

Disclosure: Nothing to disclose.

Coauthor(s)

Neil S Nayak George Washington University School of Medicine and Health Sciences

Disclosure: Nothing to disclose.

John Boone, MD Consulting Staff, Department of Otolaryngology, Naval Hospital Oak Harbor

John Boone, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nader Sadeghi, MD, FRCSC Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, McGill University Faculty of Medicine; Chief Otolaryngologist, MUHC; Director, McGill Head and Neck Cancer Program, Royal Victoria Hospital, Canada

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, American Thyroid Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;The Physicians Edge;Sync-n-Scale;mCharts<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; .

Additional Contributors

Mark K Wax, MD Professor and Program Director, Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University; Service Chief, Department of Surgery, Section of Otolaryngology, Veterans Affairs Medical Center

Mark K Wax, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Head and Neck Society, Canadian Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American College of Surgeons, American Rhinologic Society, American Society for Laser Medicine and Surgery, North American Skull Base Society, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

What is the origin of the Merkel cell and Merkel cell carcinoma (MCC)?

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