Etiology
- The Merkel cell is a nondendritic, nonkeratinocytic, clear epithelial cell usually located in or near the basal layer of the epidermis and associated with nerve terminations.
- The Merkel cell is believed to be a mechanoreceptor that mediates the sense of touch.
- There is increasing evidence that the Merkel cell polyomavirus (MCPyV) has a role in the development of Merkel cell carcinoma (MCC), making MCPyV the first polyomavirus to be clearly associated with human cancer (Borchert, J Virol 2014).
- Merkel cell polyomavirus (MCPyV), is integrated in about 90% of Merkel cell carcinomas and seems to interfere with tumor suppressor pathways (Borchert, J Virol 2014).
- The cell of origin in MCC might be the Pro/Pre B cell rather than the Merkel cell (Zur Hausen, Cancer Res 2013).
Epidemiology
- About 1200 cases of Merkel cell carcinoma have been reported in the literature.
- Incidence is estimated to be about 0.45 cases per 100,000 population
- 50% occur in the head and neck region, 40% in the extremities, and 10% in the buttocks/trunk
- 5–10% of Merkel cell carcinoma occurs in the eyelid.
- There is no gender predilection with MCC.
History
- Rapidly expanding mass
- Symptoms usually less than 6 months
- Often confused with benign inflammation such as chalazion
Clinical features
- Purple-red swelling of the skin
- Mass effect
- AEIOU mnemonic: Asymptomatic, Expanding rapidly, Immune suppression, Older than 50, Ultra-violet exposed site on a person with fair skin (Heath, J Am Acad Dermatol 2008)
Figure 1. Merkel cell carcinoma. Image courtesy Raymond Cho, MD.
Figure 2. Merkel cell carcinoma. Image courtesy Gregory J. Griepentrog, MD.
Figure 3. Merkel cell carcinoma. Image courtesy Michael J. Hawes, MD.
Figure 4. Merkel cell carcinoma. Image courtesy Mark. J. Lucarelli, MD.
Figure 5. Merkel cell carcinoma. Image courtesy Navdeep Nijhawan, MD.
Figure 6. Merkel cell carcinoma. Image courtesy Rona Z. Silkiss, MD, FACS.
Histopathology
- Small cell carcinoma composed of granular cells with scant cytoplasm, large oval nuclei, prominent nucleoli, salt and pepper dense chromatin, and many mitoses
- Immunohistochemistry positive for low molecular weight cytokeratin markers (cytokeratin 20), neuroendocrine markers (neuron-specific enolase, chromogranin, synaptophysin), and neurofilament protein
- Negative for S-100 protein and human melanoma markers (helps differentiate it from amelanotic melanoma), vimentin, leucocyte common antigen, HMB-45, TTF-1, and high molecular weight cytokeratins
- The presence of more than 50% of Ki67+ (a marker for replication) cells is a negative prognostic indicator.
- High expression of Bcl-2 and MIB-1 also indicate a bad prognosis (Missotten, Ophthalmology 2008).
Figure 7. Merkel cell carcinoma gross appearance. Image courtesy Rona Z. Silkiss, MD, FACS.
Clinical Staging
- In a retrospective case series of 21 primary eyelid Merkel cell carcinomas from 5 tertiary care centers in the United Kingdom and Australia staged according to the American Joint Committee on Cancer, 7th Edition (Herbert, JAMA Ophthalmol 2014).
- There were 12 T2 lesions, tumor size 2–5 cm.
- There were 7 T3 lesions, tumor size > 5 cm.
- Distant metastases were detected in 19% and 2 patients died of metastatic disease.
- In 18 primary eyelid Merkel cell carcinomas (Sniegowski, OPRS 2014).
- Four patients (22%) had lymph node metastasis at presentation, the strongest predictor of reduced disease free survival and risk of distant metastases.
- Two patients died of metastatic disease.
- Patients who had T2 (eyelid carcinoma T category) or more extensive tumors had significantly worse disease free survival than patients with less than T2 tumors.