Merkel Cell Carcinoma
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Direct answer
Merkel cell carcinoma is an aggressive neuroendocrine carcinoma of the skin, usually presenting as a painless, rapidly growing, firm red or violaceous nodule on sun-exposed skin of elderly people. Most cases carry Merkel cell polyomavirus, and the tumour cells are CK20 positive in a perinuclear dot-like pattern. Wide local excision with sentinel lymph node assessment and adjuvant radiotherapy form the core of treatment, while immunotherapy is used for advanced disease.
What you must remember
- Cell of origin: the Merkel cell, a neuroendocrine cell of the basal epidermis; histology shows small, blue, round cells with scant cytoplasm and high mitotic activity.
- Viral link: Merkel cell polyomavirus is detected in most cases, while virus-negative tumours carry a high burden of ultraviolet-induced mutations.
- Immunohistochemistry: CK20 shows a characteristic perinuclear dot-like pattern; neurofilament, chromogranin and synaptophysin are positive, and TTF-1 is negative.
- Risk groups: elderly, fair-skinned people and immunosuppressed patients, including those with HIV infection or on transplant immunosuppression.
- Sites: the head and neck, especially the face, is the commonest site, followed by the extremities and trunk; the nodule is often painless.
- Spread: early lymphatic spread to regional nodes is common, so sentinel lymph node biopsy is part of staging.
- Management: wide local excision with appropriate margins, adjuvant radiotherapy to the primary site and draining nodes, and avelumab or pembrolizumab for metastatic disease.
From a painless nodule to a staged diagnosis
A rapidly enlarging, painless nodule in an older person on sun-exposed skin should prompt early biopsy. The steps below follow the usual path from suspicion to treatment planning.
- Biopsy the lesion: a deep punch or excisional biopsy gives enough tissue for architecture and immunohistochemistry.
- Confirm with CK20: dot-like perinuclear positivity with TTF-1 negativity supports the diagnosis and separates it from small cell carcinoma of the lung.
- Test for the virus: detection of Merkel cell polyomavirus by PCR or immunostaining supports the diagnosis, and its absence points to a UV-driven tumour.
- Examine the nodal basin: palpate the regional nodes and examine them by ultrasound when they are abnormal.
- Stage the nodes: sentinel lymph node biopsy is offered in clinically node-negative patients, because nodal status guides further treatment.
- Image for distant disease: CT or PET-CT is used to look for metastasis in staged or advanced disease.
- Plan treatment: wide local excision with margins is standard, followed by adjuvant radiotherapy; immune checkpoint inhibitors are used for advanced or recurrent disease.
Where the exam tries to catch you
Merkel cell carcinoma is confused with several small blue round cell tumours and with metastases to the skin.
- Trap: calling it lymphoma because the cells are small and blue. Correct: Merkel cell carcinoma is cytokeratin positive with CK20 dot positivity, whereas lymphomas stain for leukocyte common antigen.
- Trap: choosing a lung primary for a skin nodule with small cells. Correct: a CK20-positive, TTF-1-negative tumour in skin is Merkel cell carcinoma, while a lung metastasis is typically TTF-1 positive.
- Trap: accepting a superficial shave specimen as adequate. Correct: a deeper punch or excisional biopsy is needed to show the dermal architecture and to perform the right stains.
Frequently asked questions
Which immunohistochemical marker is characteristic of Merkel cell carcinoma?
CK20 is the characteristic marker, showing a perinuclear dot-like staining pattern in Merkel cell carcinoma. Neurofilament and chromogranin are also positive, and a CK20-positive, TTF-1-negative profile helps separate it from metastatic small cell carcinoma of the lung.
What is the link between Merkel cell carcinoma and a virus?
Merkel cell polyomavirus is detected in most cases of Merkel cell carcinoma, where its DNA is integrated into the tumour genome. Virus-negative tumours instead carry a high burden of ultraviolet-induced mutations, which is why sun exposure is linked to both forms.
Which treatment is used for advanced Merkel cell carcinoma?
Immune checkpoint inhibitors such as avelumab or pembrolizumab are used for metastatic Merkel cell carcinoma. Surgery and radiotherapy remain the mainstay for localised disease, while chemotherapy is reserved for patients who cannot receive or do not respond to immunotherapy.
Why is sentinel lymph node biopsy performed in Merkel cell carcinoma?
Merkel cell carcinoma spreads early to regional lymph nodes, and nodal status strongly influences the need for further treatment. Sentinel lymph node biopsy is therefore performed in clinically node-negative patients to stage the disease accurately.
Which site is most often affected by Merkel cell carcinoma?
The head and neck, particularly the face, is the commonest site, followed by the extremities and trunk. Sun-exposed skin and immunosuppression both increase the risk of developing this neuroendocrine skin tumour.