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Merkel cell carcinoma
Background
Overview
Definition
MCC is a rare but highly aggressive neuroendocrine carcinoma of the skin, often associated with advanced age and immunosuppression.
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Pathophysiology
The pathophysiology of MCC is linked to two distinct etiologies. One involves the clonal integration of Merkel cell polyomavirus DNA into the tumor genome, which leads to persistent expression of viral T antigens. The other etiology is related to UV damage, which results in highly mutated genomes and causes a nonviral form of MCC.
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Epidemiology
The incidence of MCC in the US is estimated at 0.35 per 100,000 person-years.
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Risk factors
Risk factors for MCC include advanced age, immunosuppression (leukemia, lymphoma, HIV infection), UV exposure, history of skin cancer, White race, chronic inflammatory disorders (rheumatoid arthritis), and chronic arsenic exposure.
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Disease course
Clinically, MCC typically presents as a rapidly growing, solitary, cutaneous or subcutaneous nodule, most frequently in sun-exposed areas, particularly the head and neck and less frequently in the extremities and buttocks. The nodules are often asymptomatic, red, purple, or skin-colored.
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Prognosis and risk of recurrence
The prognosis of MCC is generally poor due to its aggressive nature.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of Merkel cell carcinoma are prepared by our editorial team based on guidelines from the European Reference Network on Rare Adult Solid Cancers (EURACAN/ESMO 2024), the German Society of Dermatology (DDG 2023), the U.S. Preventive Services Task Force (USPSTF 2023,2018), and the European Association of Dermato-Oncology (EADO/EDF/EORTC 2022).
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Screening and diagnosis
Classification and risk stratification
Staging: as per DDG 2023 guidelines, use the current AJCC TNM classification for postoperative staging.
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TNM classification for Merkel cell carcinoma
Tumor classification
Tx: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: In situ tumor
T1: Tumor ≤ 2 cm in greatest dimension
T2: Tumor > 2 cm but ≤ 5 cm in greatest dimension
T3: Tumor > 5 cm in maximum dimension
T4: Tumor invading bone, muscle, fascia, or cartilage
Lymph node classification
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastases
N2: In transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis
N3: In transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis
Metastasis classification
M0: No distant metastasis
M1: Distant metastasis present
Stage cannot be fully assessed
Diagnostic investigations
Clinical assessment
As per ESMO/EURACAN 2024 guidelines:
Obtain a clinical assessment with a physical examination, including locoregional lymph nodes, and assessment of comorbid conditions and patient life expectancy.
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Consider performing dermatoscopy to enhance differential diagnostic accuracy, especially in patients with multiple skin lesions.
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Imaging for staging
Diagnostic procedures
Biopsy and histopathology: as per ESMO/EURACAN 2024 guidelines, obtain H&E staining with the dedicated immunopanel for histopathological confirmation.
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Sentinel lymph node biopsy
Medical management
General principles: as per ESMO/EURACAN 2024 guidelines, arrange a multidisciplinary team meeting comprising experts with significant MCC experience to make decisions about treatment, preferably with participation in clinical trials.
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Management of locoregional disease (surgical resection)
Management of locoregional disease (lymph node dissection)
Management of locoregional disease (adjuvant radiotherapy)
Management of locoregional disease (adjuvant chemotherapy)
Management of locoregional disease (definitive radiotherapy)
Management of locoregional disease (definitive systemic therapy)
Management of locoregional disease (management of recurrence)
Management of metastatic disease (general principles)
Management of metastatic disease (immunotherapy)
Management of metastatic disease (management of metastases)
Management of metastatic disease (palliative care)
Specific circumstances
Follow-up and surveillance
Follow-up: as per ESMO/EURACAN 2024 guidelines, obtain follow-up examinations in radically treated patients every 3-6 months for the first 3 years, and then every 6 months up to year 5. Perform a general physical examination, including a complete skin check-up, every 12 months lifelong after 5 years of observation.
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