By Gary M. White, MD
Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin associated in 80% of cases with the Merkel cell polyomavirus (MCP).
A solitary, red-purple or violaceous, shiny, dome-shaped nodule or plaque on the face, head or neck of an elderly person is characteristic. Approximately 94% of patients are white with an average age at presentation of 72 years. The diagnosis is often not entertained before the pathology is back as the red, nodular growth may be mistaken for a benign cyst, BCC, SCC or amelanotic melanoma.
Heath et al [JAAD 2008;63;751] have coined the mnemonic “AEIOU: for Asymptomatic, or lacking tenderness, Expanding rapidly, Immune suppression, Older than 50 years, and Ultraviolet exposed skin. In their series, 89% had 3 or more “AEIOU” features.
Paraneoplastic syndromes may be associated with neuroendocrine cancers and MCC is no exception [JAAD 2016;75;541]. Reported abnormalities include:
The risk of nodal involvement for MCC is high. It varies from study to study. One showed as follows (JAAD April 2014):
|Size Tumor (median size)||Risk Nodal Involvement|
|6 cm or larger||36%|
5-year relative survival:
|Number of nodes||5-year relative survival|
Workup and treatment is usually done by a specialist experienced with MCC. Workup may include history and physical with complete skin exam and special attention to lymph node and liver/spleen palpation, and various advanced imaging modalities (e.g., PET/CT) to assess for metastatic disease.
Consensus recommendations for MCC are evolving as new information becomes available. The following is meant to be an overview only.
Radiation therapy to the draining basin is commonly done, especially for large tumors, positive SLN, or gross nodal disease.
The value of radiation therapy to the primary site is debated. One important point here is that nodal basin recurrence is much higher than local recurrence. If the SLN is negative, there is no clinical lymphadenopathy, and the tumor is small, e.g., < 2 cm, radiation therapy to the surgical site may not be necessary as the local recurrence rate is very low [JAMA Derm 2016;152;1001].
In one study of MCC of the head and neck with gross nodal disease at presentation, there were no regional recurrences in 22 patients treated with radiation therapy to the gross nodal disease without neck dissection [Head Neck. 2015 Feb 2.].
Single fraction radiation therapy (SFRT) has recently been shown to be much more effective in treating distant MCC metastases. Researchers used 8-Gy SFRT. Complete response was seen in 81% of tumors in low-risk patients and 52% of tumors in high-risk patients (immunosuppressed and/or had prior chemotherapy). No tumor that completely responded ever recurred [Skin and Allergy News June 2014--Dr. Paul Nghiem].
Addition of chemotherapy has not yet shown benefit in locoregional control.
Mean time to recurrence in one study of MCC was 9 months.
There are several experimental approaches to trying to detect recurrence of MCC via measuring circulating oncoproteins or tumor cells. As of this writing, they are not standard of care. The question of course arises, what do you do therapeutically if you see the test indicates a potential recurrence?
AMERK, for example, is an assay to detect antibodies to oncoprotein and has been shown useful in detecting recurrence of Merkel cell. It is only useful in the 52% of patients who at the outset have these antibodies at the presentation of Merkel cell. (Patients do not go on to develop it if initially negative.) The level drops off on the order of 90% after successful treatment and rises, e.g., 10 times, when the tumor recurs [Cancer Res 2010;70;8388].
Immune checkpoint inhibitors have recently shown good results for metastatic MCC. Avelumab (10 mg/kg administered as an IV infusion every 2 weeks) is now FDA approvewd and can provide rapid and durable responses in chemotherapy-resistant MCC. In a study of 88 patients with chemotherapy-refractory MCC 33% of patients experienced complete or partial shrinkage of their tumors. The response lasted for more than 6 months in 86% of responding patients and more than 12 months in 45% of responding patients [published online September 1, 2016, in Lancet Oncology].