Merkel Cell Carcinoma (MCC)

  • MCC is a rare neuroendocrine malignancy of the skin:
    • Predominately affecting older white individuals:
      • It commonly arises in sun-exposed areas such as the head, neck, and extremities
  • The incidence of MCC is very low when compared to other cutaneous malignancies:
    • With an estimated 1,500 cases diagnosed annually within the United States.
  • In 1875, Friedrich Sigmund Merkel:
    • Described large, pale cells in the basal layer of the epidermis:
      • Forming synapse-like contacts with enlarged nerve terminals (mechanoreceptors)
  • In 1972, Toker described a trabecular carcinoma of the skin:
    • Thought to have derived from sweat glands
      • These cells, now known as Merkel cells, resemble cells of the diffuse neuroendocrine system or the amine precursor uptake decarboxylation system
  • The clinical and pathologic diagnosis of MCC can be challenging, especially when it presents as a nodal metastasis:
    • Because as a small round blue cell it can be difficult to differentiate from other undifferentiated small-cell neoplasms of different primary origin such as the lung
  • The diagnosis of MCC of a primary lesion by using hematoxylin and eosin staining:
    • Should be further confirmed by immunohistochemistry (IHC) staining
  • CK20 is a sensitive marker for MCC:
    • It is positive in 89% to 100% of cases
  • TTF-1 is expressed in 83% to 100% of small-cell lung cancer:
    • But is negative for MCC
  • Other IHC markers such as chromogranin A, synaptophysin, neurofilament protein, CD56, and neuron-specific enolase may be used in addition to CK20 and TTF-1 to exclude other diagnoses
  • When patients present with clinically positive nodal disease in the absence of a history of an identifiable primary tumor, and the tumor fulfills the diagnostic pathologic criteria:
    • It is known as MCC of unknown primary origin (MCCUP):
      • The incidence of MCCUP presenting in the nodal basins has been described in case reports in the literature as ranging from 2% to 19% of all cases of MCC
      • The exact origin of MCCUP is unknown, but several theories have been postulated, including:
        • Incorrect or misdiagnosis of a previously excised cutaneous tumor
        • Spontaneous regression of a primary MCC lesion
        • Immunosuppression:
          • Transplant recipients
          • Lymphoproliferative disorders
          • Human immunodeficiency virus [HIV] infection
        • MCC arising from a mucosal origin
        • The small double-stranded DNA polyomavirus (Merkel cell polyomavirus)
  • The treatment of MCC:
    • Is stage-dependent
  • A multidisciplinary panel:
    • Is recommended to assure appropriate treatment of this rare and challenging disease
  • Surgery:
    • Is the primary treatment modality for MCC
    • For patients with a cutaneous lesion in the absence of clinical lymphadenopathy:
      • The recommendation is for wide excision with a 1 to 2 cm margin and SLN biopsy
  • Adjuvant radiation therapy to the primary tumor site is generally recommended:
    • Unless the primary tumor is small (less than 1cm)
    • Widely excised
    • And without other risk factors such as:
      • Lymphovascular invasion
      • Immunosuppression
  • If SLN biopsy is negative for metastasis:
    • Adjuvant radiation therapy to the regional nodes is generally avoided
  • Regional lymph node dissection is recommended when nodal micrometastasis is identified by SLN biopsy:
    • Generally without adjuvant nodal irradiation (although nodal radiation therapy may be considered in high-risk cases)
  • For patients who present with clinical lymphadenopathy:
    • The recommendation is for confirmation with fine-needle aspiration or core-needle biopsy
  • Imaging studies, including computer tomography, magnetic resonance imaging, or positron-emission tomography, are performed to rule out visceral involvement followed by nodal dissection and / or radiation therapy
  • In the presence of distant metastasis:
    • Multidisciplinary tumor board evaluation is recommended with best supportive care or any combination of chemotherapy, radiation and / or surgery.
  • The 5-year survival for clinically node-negative patients with localized disease is 75%
  • Patients with lymph node metastases and distant metastases fairing worse, with 59% and 25% 5-year survival rates, respectively
  • Recurrences are most likely to occur within two years of diagnosis of the primary tumor
  • The outcome of patients with MCCUP is perhaps slightly better than stage III MCC patients with known primary tumors based on retrospective data
  • References:
    • Allen P, Bowne W, Jaques D, et al. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23(10):2300-2309.
    • Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096-1100.
    • Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58:375-381.
    • Merkel cell carcinoma, Chapter 30. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2009: 315-323.
    • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Merkel Cell Carcinoma. Available at http://www.nccn.org.
    • Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105:107-110.

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