Merkel Cell Carcinoma
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.
- 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
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.
Modifiable risk factors include decreasing the amount of sun exposure one receives and wearing sun protection.
When Merkel cell carcinoma is suspected, ensuring the correct diagnosis as well as delineating the extent of disease promptly is paramount.
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.
An excisional or full thickness incisional biopsy should be performed of the suspected lesion followed by careful histopathologic analysis.
After the biopsy is performed, samples can be sent for detection of polyomavirus which can help aid in the diagnosis.
The differential diagnosis includes chalazion, sebaceous carcinoma, squamous cell carcinoma, and basal cell carcinoma.
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.
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.
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