Merkel Cell Carcinoma

Article initiated by:

Derek Huang, MD, Rona Z Silkiss, MD FACS

All authors and contributors:

Derek Huang, MD, Jill Wells, MD, Michael T Yen, MD, Rona Z Silkiss, MD FACS, Cat Nguyen Burkat, MD FACS

Assigned editor:

Rona Z Silkiss, MD FACS, Adam de la Garza, MD

Review:

Assigned status Up to Date

 by Rona Z Silkiss, MD FACS on July 4, 2023.

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Merkel Cell Carcinoma

DiseasesDB

31386

MeSH

D015266

Disease Entity

Merkel cell carcinoma of the eyelid is a rare, highly malignant neuroendocrine tumor. These tumors originate from sensory Merkel cells, first discovered by Friedrich Merkel in 1875 and found to be associated with light touch and the discrimination of shapes and textures. When these cells undergo malignant transformation, Merkel cell carcinomas can arise. Merkel cell carcinomas have a predilection for the head and neck area -representing 50% of cases. Relevant to ophthalmology is that 5-10% of all cases occur on the eyelid. The annual incidence is 0.23 cases per 100,000 persons.

Risk Factors

• Age > 50
• Female gender
• Caucasian ethnicity
• History of sun exposure
• Immunocompromised states
• Polyomavirus (80% of MCC are positive for polyomavirus)
• Use of chronic TNF-alpha inhibitors such as Adalimumab or Golimumab

General Pathology

Lesions tend to have large subepidermal nests of cells with scant cytoplasm. They have large nuclei that are round to oval in shape with finely dispersed chromatin, a vesicular appearance and numerous mitotic figures. Because it can be confused with sebaceous carcinoma, additional immunohistochemistry and electron microscopy can be of great value. Merkel cell carcinoma express cytokeratin polypeptides 8, 18, and 19, which are characteristic of epithelia. It also exhibits a distinct marker profile with dot like co-expression of pancytokeratin with cytokeratin 20. It stains positively for neuron specific enolase and negatively for S-100 protein. Electron microscopy demonstrates dense-core cytoplasmic granules.

Primary prevention

Modifiable risk factors include decreasing the amount of sun exposure one receives and wearing sun protection. 

Diagnosis

When Merkel cell carcinoma is suspected, ensuring the correct diagnosis as well as delineating the extent of disease promptly is paramount.

Physical examination

A complete physical exam should be performed including comprehensive ophthalmic exam to assess the extent of the disease. Palpation of the preauricular and cervical lymph nodes is important to assess for possible lymphatic spread. If there is any evidence of lymphadenopathy or the disease appears to be diffusely involving the eyelid, additional imaging is required to evaluate for systemic spread of the disease.

Signs and Symptoms

Merkel cell carcinomas tend to involve the upper eyelid. They commonly present as a painless nodule with a “violaceous”, purple-red hue with occasional ulceration. There may be sparing or partial loss of the eyelashes. As well as transformation of the overlying skin to a hard, smooth surfaced texture that can be red with telangiectasia. There is rapid growth (usually within 6 months) and early lymph node metastasis.

Diagnostic procedures

An excisional or full thickness incisional biopsy should be performed of the suspected lesion followed by careful histopathologic analysis.

Laboratory test

After the biopsy is performed, samples can be sent for detection of polyomavirus which can help aid in the diagnosis.

Differential diagnosis

The differential diagnosis includes chalazion, sebaceous carcinoma, squamous cell carcinoma, and basal cell carcinoma.

Management

Management consists of wide surgical excision with suggested margins of 2.5-3 cm and pathologic nodal staging. Mohs surgery or frozen sections are used for histopathologic confirmation of disease free margins of 5mm around the eyelids. Sentinel lymph node biopsy may also allow for detecting metastases that spread through the lymphatic system and aid in staging. Adjuvant chemotherapy and combination treatments have been reported to be successful in limited cases for palliative purposes or in those with inoperable disease. The role of adjuvant radiotherapy remains controversial as there is inconclusive evidence for improvement in disease specific mortality. The use of combined radiotherapy and programmed death-1 inhibitor pembrolizumab, a novel biologic for treatment is promising.

Prognosis

The estimated mortality rate for all patients with Merkel cell carcinoma is 25-35%. A review of 255 MCC patients found a 97% 5 year survival rate in pathologically node negative patients. 5 year survival dropped to 52% with pathologically positive nodes. Some factors associated with a worse prognosis include male gender which portended a survival rate of 58% compared to 80% in one study. Histologic characteristics that may have a poorer prognosis include the size of the tumor cell, invasion of subcutaneous fat, heavy lymphocytic infiltrate and a high number of mitotic figures.

References

3. Allen PJ, Bowne WB, Jaques DP, Brennan MF et al. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005;23;2300-9
4. Barrett RV, Meyer DR. Eyelid and periocular cutaneous Merkel cell carcinoma (aka. neuroendocrine or trabecular carcinoma). Int Ophthalmol Clin. 2009 Fall; 49(4):63-75. doi: 10.1097/IIO.0b013e3181b7f1d5. Review. PubMed PMID: 20348858.
5. Colombo F, Holbach LM, Jünemann AG, Schlötzer-Schrehardt U, Naumann GO. Merkel cell carcinoma: clinicopathologic correlation, management, and follow-up in five patients. Ophthal Plast Reconstr Surg. 2000 Nov; 16(6):453-8. PubMed PMID: 11106191.
6. 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
7. Furuno K, Wakakura M, Shimizu K, Iwabuchi K, Kameya T. Immunohistochemical studies of Merkel cell carcinoma of the eyelid. Jpn J Ophthalmol. 1992; 36(3):348-55. PubMed PMID: 1281512.
8. Herbert HM, Sun MT, Selva D, Fernando B, Saleh GM, Beaconsfield M, Collin R, Uddin J, Meligonis G, Leatherbarrow B, Ataullah S, Irion L, McLean CJ, Huilgol SC, Davis G, Sullivan TJ. Merkel cell carcinoma of the eyelid: management and prognosis. JAMA Ophthalmol. 2014 Feb; 132(2):197-204. doi: 10.1001/jamaophthalmol.2013.6077. PubMed PMID: 24287584.
9. Pathai S, Barlow R, Williams G, Olver J. Mohs' micrographic surgery for Merkel cell carcinomas of the eyelid. Orbit. 2005 Dec; 24(4):273-5. PubMed PMID: 16354638.
10. Peters GB 3rd, Meyer DR, Shields JA, Custer PL, Rubin PA, Wojno TH, Bersani TA, Tanenbaum M. Management and prognosis of Merkel cell carcinoma of the eyelid. Ophthalmology. 2001 Sep; 108(9):1575-9. PubMed PMID: 11535453.
11. Hanafi H, Verdijk RM, Paridaens D, Eyelid Merkel cell carcinoma in a patient treated with golimumab, Orbit. 2018 Feb;37(1):21-25. doi: 10.1080/01676830.2017.1353118. Epub 2017 Aug 25.