Merkel Cell Carcinoma

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Neuroendocrine, lymphotropic, radiosensitive, immunogenic, aggressive malignant tumor
Linhagem
  • Not truly derived from normal Merkel cells
    • Meckel cells are mechanoreceptos found in the basal layer of epidermis (face, palms and soles) and hair follicles
  • Merkel Cell Carcinoma originate from dermal stem cells, epidermal progenitors, or fibroblasts that undergo transformation into a neuroendocrine phenotype
    • “Merkel Cell Carcinoma derives from a pluripotent stem cell that has acquired the ability to differentiate into a malignant neuroendocrine phenotype” (Saurat)
 
AEIOU rule
  • Asymptomatic
  • Expanding rapidly
  • Immunosupression
  • Older than 65 years old
  • UV exposed sites
 
Etiologia
  • Virus: Merkel cell polyomavirus (MCPyV) (80%)
  • UV-induced mutations (20%)
  • Imunosupressão aumenta o risco 24x
    • LLC aumenta 30-50x o risco
  • Advanced age
 
Apresentação clínica
  • Rapidly growing purple/red nodule or plaque in sun exposure areas
 
Histology
  • small cell neuroendocrine appearence
  • small blue cels
  • Imunohistoquímica
    • Marcação neuroendócrina (ex. CD56, sinaptofisina e cromogranina A)
    • Marcadores específicos do Merkel (outros neuroendócrinos não)
      • CK20 (with characteristic perinuclear staining)
    • Marcadores negativos no Merkel, positivos noutros neuroendócrinos
      • TTF-1 → small cell lung cancer
      • CK7 → small cell lung cancer
  • Pode marcar poliomavírus
  • pode ter diferenciação divergente, isto é, ter uma parte do tumor diferencia-se noutro tumor - CEC, triquilemocarcinoma, etc. O Merkel que tem diferenciação divergente não marca poliomavírus, ao contrário do Merkel puro
 
Estadiamento
  • AJCC8 TNM staging
 
Prognosis
  • 5year OS 45% in stage cI to 13,5% in stage IV
 
High risk features
  • Size ≥2cm
  • Chronic immunosuppression
  • Head/neck primary site
  • Positive lymph node
  • Lymphovascular invasion
 
Pre opterative staging procedure
  • US of regional nodes
  • Whole body imaging: TC CTAP or PET
  • No brain imaging needed
 
Management of primary
  • Primary tumor
    • Surgical therapy with 1cm safety margin followed by RT on the tumor bed
      • Margem >1 vs. <1cm não afeta a sobrevivência se associada a RT adjuvante
    • Adjuvant RT should be preformed within 8 weeks
      • Tumor is highly sensitive to radiation. Dose ~50Gy in 2Gy per fraction
    • Sentinel lymph node biopsy should be done
      • If SLNB negative → no RT on lymph node
      • If positive SLNB (microscopic nodal disease): adjuvant RT alone (50-55 Gy) or eventualy combined with CLND
      • If macroscopic nodal disease: therapeutic CLND should be performed
        • Adjuvant treatment should be discussed in multidisciplinary team (nivolumab)
 
Management of locally advanced or metastatic disease:
  • immunocompetent patients with locally advanced or metastatic MCC shall receive anti PD1 based immunotherpy as first line treatment
    • Pembrolizumab (anti-PD-1)
    • Nivolumab (anti-PD-1)
    • Avelumab (anti-PD-L1)
      • Case “Lokale Tumorkontroolle eines metastasierten Mekel-Zell-Karzinoma” - 90 year old female with locally advanced merkel cell carcinoma
  • Chemotherapy can be used when patients fail to responde, are intolerant or contraindicated. Include in clinical trial
  • Palliative RT may be considered when surgery is not feasible
Follow up guidelines
notion image
  • High risk of recurrence (25-50%)
  • Higher risk in first 3 years
  • Even more aggressive than melanoma, so aggressive follow up