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.