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Cellular Classification of Merkel Cell Carcinoma

    Although the exact origin and function of the Merkel cell remains under investigation, it is thought to have features of both epithelial and neuroendocrine origin and arise in cells with touch-sensitivity function (mechanoreceptors).[1,2,3,4]

    Characteristic histopathologic features include dense core cytoplasmic neurosecretory granules on electron microscopy and cytokeratin-20 on immunohistochemistry (see Figure 4).[5]

    A panel of immunoreagents (see Figure 4) helps to distinguish Merkel cell carcinoma (MCC) from other similar-appearing tumors including neuroendocrine carcinoma of the lung (i.e., small cell carcinoma), lymphoma, peripheral primitive neuroectodermal tumor, metastatic carcinoid tumor, and small cell melanoma.[5]
    Figure 4. Merkel - Immunohistochemical differential diagnosis of Merkel-Cell Carcinoma (Typical Staining Pattern).

    Histologically, MCC has been classified into three distinct subtypes: [6,7,8,9]

    • Trabecular: classic pattern, large-cell type, high density or granules on ultrasound examination.
    • Intermediate: solid pattern (most common).
    • Small cell: diffuse, few high density granules on ultrasound examination (second most common).

    Mixtures of variants are common.[6,7,8] Although some small, retrospective case series have suggested correlations between certain histologic features and outcome, the evidence remains uncertain.[10,11,12]

    One group has suggested a list of 12 elements that should be described in pathology reports of resected primary lesions and nine elements to be described in pathology reports of sentinel lymph nodes. The prognostic significance of these elements has not been validated prospectively.[13]

    If the following data are recorded for every MCC patient, any patient can be staged with the existing or new staging system:

    • Size of primary tumor (maximum dimension pathologically or clinically in centimeters).
    • Presence/absence of primary tumor invasion into bone, muscle, fascia, or cartilage.
    • Presence/absence of nodal metastasis.
    • Method used to ascertain status of nodal involvement (clinical or pathological examination).
    • Presence/absence of distant metastasis.

    The College of American Pathologists has published a protocol for the examination of specimens from patients with MCC of the skin.[14]

    (Refer to the Stage Information section of this summary for more information.)

    The histologic variants of MCC are shown in Figure 5. [15]
    Figure 5. (A) Intermediate variant of MCC showing vesicular, basophilic nuclei with prominent nucleoli and multiple mitoses. (B) Small-cell variant, histologically indistinguishable from bronchial small-cell carcinoma. (C) Trabecular variant is rare and normally only seen as a small component of a mixed variant. Goessling W et al: Merkel Cell Carcinoma, J Clin Oncol, 20 (2), pp. 588–98. Reprinted with permission. © 2009 American Society of Clinical Oncology. All rights reserved.


    1. Nghiem P, McKee PH, Haynes HA: Merkel cell (cutaneous neuroendocrine) carcinoma. In: Sober AJ, Haluska FG, eds.: Skin Cancer. Hamilton, Ontario: BC Decker Inc., 2001, pp 127-141.
    2. Nghiem P, James N: Merkel cell carcinoma. In: Wolff K, Goldsmith LA, Katz SI, et al., eds.: Fitzpatrick's Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill , 2008, pp 1087-94.
    3. Eng TY, Boersma MG, Fuller CD, et al.: A comprehensive review of the treatment of Merkel cell carcinoma. Am J Clin Oncol 30 (6): 624-36, 2007.
    4. Medina-Franco H, Urist MM, Fiveash J, et al.: Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol 8 (3): 204-8, 2001.
    5. Busse PM, Clark JR, Muse VV, et al.: Case records of the Massachusetts General Hospital. Case 19-2008. A 63-year-old HIV-positive man with cutaneous Merkel-cell carcinoma. N Engl J Med 358 (25): 2717-23, 2008.
    6. Haag ML, Glass LF, Fenske NA: Merkel cell carcinoma. Diagnosis and treatment. Dermatol Surg 21 (8): 669-83, 1995.
    7. Ratner D, Nelson BR, Brown MD, et al.: Merkel cell carcinoma. J Am Acad Dermatol 29 (2 Pt 1): 143-56, 1993.
    8. Gould VE, Moll R, Moll I, et al.: Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest 52 (4): 334-53, 1985.
    9. Albores-Saavedra J, Batich K, Chable-Montero F, et al.: Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol 37 (1): 20-7, 2010.
    10. Alam M: Management of Merkel cell carcinoma: What we know. Arch Dermatol 142 (6): 771-4, 2006.
    11. Heath ML, Nghiem P: Merkel cell carcinoma: if no breslow, then what? J Surg Oncol 95 (8): 614-5, 2007.
    12. Andea AA, Coit DG, Amin B, et al.: Merkel cell carcinoma: histologic features and prognosis. Cancer 113 (9): 2549-58, 2008.
    13. Bichakjian CK, Lowe L, Lao CD, et al.: Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer 110 (1): 1-12, 2007.
    14. Rao P, Balzer BL, Lemos BD, et al.: Protocol for the examination of specimens from patients with merkel cell carcinoma of the skin. Arch Pathol Lab Med 134 (3): 341-4, 2010.
    15. Goessling W, McKee PH, Mayer RJ: Merkel cell carcinoma. J Clin Oncol 20 (2): 588-98, 2002.

      WebMD Public Information from the National Cancer Institute

      Last Updated: February 25, 2014
      This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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