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Merkel-cell carcinoma

Merkel-cell carcinoma (MCC) is a rare and aggressive skin cancer, affecting approximately three people per million. Also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, and trabecular carcinoma of the skin, MCC development involves factors such as Merkel cell polyomavirus (MCV), weakened immune systems, and ultraviolet radiation exposure. Commonly arising on the head, neck, extremities, perianal region, and eyelid, MCC is more prevalent in individuals over sixty years old, Caucasians, and males, and is rare in children.

Small spot on the left arm is Merkel cell cancer.
Small spot on the left arm is Merkel cell cancer.

Signs and Symptoms

Merkel cell carcinoma. Gross pathology specimen.
Merkel cell carcinoma. Gross pathology specimen.

MCC usually presents as a firm nodule or mass, flesh-coloured, red, or blue, varying in size from 0.5 cm to over 5 cm and potentially enlarging rapidly. Tumours can be painless, tender or itchy, and may present as papules or plaques. MCC frequently occurs in sun-exposed areas like the head, neck, and extremities. The acronym AEIOU (Asymptomatic, Expanding rapidly, Immune suppression, Older than 50 years, and Ultraviolet-exposed site on a person with fair skin) summarises key attributes of MCC. Ninety percent of MCC cases have three or more of these features. MCC is often mistaken for other cancers or benign cysts and tends to invade locally, infiltrating underlying subcutaneous fat, fascia, and muscle, and metastasizing early, most often to regional lymph nodes, liver, lung, brain, and bone.


Micrograph of a Merkel cell carcinoma. H&E stain.
Micrograph of a Merkel cell carcinoma. H&E stain.
Merkel cell carcinoma (arrow) infiltrating skin tissue, stained brown for Merkel cell polyomavirus large T protein
Merkel cell carcinoma (arrow) infiltrating skin tissue, stained brown for Merkel cell polyomavirus large T protein

While initially named for its histologic similarity to Merkel cells, the precise cellular origin of MCC is debated. Merkel cells, involved in pressure sensation in the epidermis, are unlikely progenitors. Evidence suggests MCC may originate from precursor cells such as fibroblasts or epithelial cells in hair follicles. Factors involved in MCC pathogenesis include MCV infection, UV radiation, and immune suppression. MCV, a small double-stranded DNA virus, is integrated into the host genome in about 80% of MCC tumours, though most MCV infections remain asymptomatic. UV radiation is implicated in 20% of MCC cases, which tend to have high mutational burdens with UV damage signatures. Immunosuppression also increases MCC incidence and impacts prognosis.


Photomicrographs of a typical Merkel cell carcinoma at various magnifications.
Photomicrographs of a typical Merkel cell carcinoma at various magnifications.

Diagnosis begins with clinical examination and requires biopsy tissue for histopathologic features. MCC shows basaloid tumour nests with neuroendocrine features. Immunohistochemistry (IHC) is often needed to differentiate MCC from similar tumours. Markers like synaptophysin, chromogranin A, PAX5, and cytokeratin 20 help in diagnosis. Sentinel lymph node biopsy and imaging (e.g., PET or CT scan) are recommended for staging and determining treatment.


Preventing excessive UV exposure is very important in reducing MCC risk. Recommendations include limiting sun exposure between 10 am and 4 pm, seeking shade, wearing sun-protective clothing, using sunscreen, and avoiding tanning beds.



Surgical resection, often a wide excision or Mohs surgery, is typically performed prior to other treatments. Sentinel lymph node biopsy is often conducted simultaneously.


Radiation therapy is a primary treatment modality, sometimes used alone, achieving outcomes comparable to surgery followed by radiation.


Traditional chemotherapy is reserved for late-stage cases due to significant adverse effects and limited long-term benefits. No FDA-approved standard chemotherapy regimens exist.

Drug Therapy

Immunotherapies targeting the PD1-PDL1 checkpoint pathway, such as avelumab and pembrolizumab, have shown benefits in advanced or chemotherapy-resistant MCC, with clinical response rates between 50 and 65%.


Prognosis varies significantly by stage at diagnosis, with five-year survival rates ranging from 80% for stage IA to 20% for stage IV. Factors influencing prognosis include MCV viral status, histological features, and immune status. The antibody titer to MCV oncoprotein serves as a treatment response biomarker in some patients.


MCC is most common in Caucasians aged 60-80, with a higher incidence in males. It is a rare skin cancer, with increasing incidence, particularly in regions with high sun exposure, such as Australia. Other primary cancers and immunosuppression increase MCC risk.

Self-assessment MCQs (single best answer)

What is the estimated incidence rate of Merkel-cell carcinoma (MCC)?

Which virus is associated with the development of MCC?

What is the most common age group affected by MCC?

Which of the following is NOT a common site for MCC occurrence?

What does the acronym AEIOU stand for in the context of MCC?

What is the primary method for diagnosing MCC?

Which immunohistochemical marker is NOT typically used in diagnosing MCC?

Which treatment modality is often reserved for late-stage MCC due to its adverse effects?

What is the approximate five-year survival rate for stage IV MCC?

Which factor is NOT associated with an increased risk of MCC?


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