What is Merkel cell carcinoma?

Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor with high mortality rates exceeding those of melanoma, characterized by rapid growth and high metastatic potential, with 5-year survival rates ranging from 30-64%. 1, 2

Definition and Epidemiology

• Rare skin cancer accounting for less than 1% of all cutaneous malignancies
• Primarily affects older white individuals (≥65 years of age)
• More common in males than females
• Occurs predominantly on sun-exposed areas (81% of cases), with head and neck being common locations (29-48% of cases) 2

Etiology and Risk Factors

• Two main pathogenic pathways:
  • Merkel cell polyomavirus (MCPyV) infection - detected in 43-100% of tumors 1
  • Ultraviolet radiation exposure - especially important in virus-negative cases 3
• Additional risk factors:
  • Advanced age (>90% of patients are over 50 years)
  • Immunosuppression (organ transplant recipients, HIV infection, lymphoproliferative malignancies) 1
  • Fair skin

Clinical Presentation

• Rapidly growing, asymptomatic cutaneous or subcutaneous nodule
• Typically presents as a red, firm, non-tender lesion
• Lacks distinguishing clinical characteristics, making diagnosis challenging 1
• AEIOU features often present:
  • Asymptomatic
  • Expanding rapidly
  • Immunosuppression
  • Older than 50 years
  • UV-exposed site

Diagnosis

• Complete examination of skin and regional lymph nodes followed by biopsy 1

• Histopathologic diagnosis:

  • Small, round, blue cell tumor with neuroendocrine features
  • Immunohistochemistry crucial for confirmation:
    • Cytokeratin 20 (CK20) - positive in 89-100% of MCC cases
    • Thyroid transcription factor-1 (TTF-1) - negative in MCC (helps distinguish from small cell lung cancer) 1
    • Additional markers: chromogranin A, synaptophysin, neurofilament protein

• Imaging studies as clinically indicated to evaluate for metastatic disease 1

Staging and Prognosis

• Staging according to AJCC/UICC 8th edition

• Poor prognostic indicators:

  • Larger tumor size
  • Lymphovascular invasion
  • Immunosuppression
  • Regional or distant metastases

• High recurrence rates:

  • Local recurrence: 25-30% of cases
  • Regional disease: 52-59% of cases
  • Distant metastatic disease: 34-36% of cases 1, 2

Treatment

• Localized disease:

  • Surgical excision with postoperative margin assessment
  • Sentinel lymph node biopsy recommended for all patients without clinically detectable lymph nodes
  • Adjuvant radiation therapy often recommended 2, 4

• Regional disease:

  • Complete lymph node dissection with or without postoperative radiation therapy
  • Adjuvant radiation therapy alone may be considered for micrometastatic nodal involvement 4

• Advanced/metastatic disease:

  • Immunotherapy with anti-PD-(L)1 antibodies (avelumab, pembrolizumab) as first-line systemic treatment
  • Chemotherapy for patients who fail to respond to or are intolerant of immunotherapy 4

Monitoring and Follow-up

• Close surveillance is essential due to high recurrence rates
• More intensive monitoring for immunosuppressed patients
• Regular skin examinations and imaging studies as clinically indicated

Pitfalls and Caveats

• MCC is often misdiagnosed initially due to its innocuous appearance
• Delay in diagnosis can lead to advanced disease at presentation
• Differentiation from small cell lung cancer is crucial and requires appropriate immunohistochemistry
• Despite aggressive treatment, recurrence rates remain high
• Immunosuppressed patients have worse outcomes and require closer monitoring

MCC requires prompt diagnosis and aggressive management due to its high mortality rate. Early detection and multidisciplinary care involving dermatology, surgical oncology, radiation oncology, and medical oncology are essential to improve outcomes.