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CK20 (cytokeratin 20) in Merkel cell carcinoma

CK20; cytokeratin 20; CAM5.2 (related low-molecular-weight cytokeratin); paranuclear dot pattern

CK20 (cytokeratin 20) is the key IHC marker in the diagnosis of Merkel cell carcinoma (MCC). Approximately 90% of MCCs show characteristic paranuclear dot-like staining of CK20 — a pattern not seen in the principal differential of metastatic small-cell lung carcinoma (TTF-1+, CK20-) or other small-round-blue-cell tumours. The CK20 paranuclear dot is the single most useful IHC finding in MCC diagnosis and is reported as part of the standard MCC pathology dataset (RCPath). Complementary markers — chromogranin A, synaptophysin, CD56 for neuroendocrine differentiation; TTF-1 for distinguishing from small-cell lung carcinoma; CAM5.2 (a low-molecular-weight cytokeratin) often shows the same dot pattern.

CurrentLast reviewed 22 May 2026
Clinical image of CK20 in Merkel cell carcinoma
CK20 in Merkel cell carcinoma. Image sourced from DermNet New Zealand. Used under CC BY-NC-ND 4.0. No endorsement implied.

CK20 paranuclear dot pattern

  • Characteristic punctate / paranuclear dot of CK20 staining in the cytoplasm immediately adjacent to the nucleus.
  • Reflects the perinuclear cytokeratin filament cap of MCC cells.
  • ~ 90% sensitivity for MCC; high specificity vs other small-round-blue-cell tumours.
  • CAM5.2 (cytokeratins 8 and 18) often shows the same paranuclear dot pattern and can be used in conjunction.
  • Dual paranuclear-dot positivity for CK20 and CAM5.2 strongly supports MCC.

Differential diagnosis

  • Metastatic small-cell lung carcinoma (SCLC) — TTF-1 positive, CK20 negative; histologically similar to MCC. CK20 / TTF-1 distinction is critical because management diverges entirely.
  • Other neuroendocrine tumours — pancreatic NETs, intestinal NETs, parathyroid carcinoma; clinical context and additional IHC required.
  • Lymphoma — particularly cutaneous B-cell lymphoma — CD20 / CD79a / CD3 panel separates; CK20 negative.
  • Ewing sarcoma / PNET — CD99, EWSR1 rearrangement.
  • Melanoma — S100 / SOX10 / Melan-A / HMB-45 positive; CK20 negative.
  • Cutaneous metastasis from breast / colorectal / lung — distinct keratin profiles (CK7+/CK20+ for some, CK7-/CK20+ for colorectal, TTF-1+ for lung).

Standard MCC IHC workup

  • Confirming MCC:
    • CK20 (paranuclear dot — characteristic).
    • CAM5.2 (paranuclear dot — confirmatory).
    • Chromogranin A — neuroendocrine differentiation.
    • Synaptophysin — neuroendocrine differentiation.
    • CD56 — neuroendocrine.
    • Merkel cell polyomavirus (MCPyV) large-T-antigen IHC — positive in ~ 78% of UK MCCs (clone CM2B4).
  • Excluding mimics:
    • TTF-1 — usually negative (positive in SCLC; some MCCs are weakly TTF-1+ — interpret with morphology).
    • LCA / CD45 — negative (positive in lymphoma).
    • S100 / SOX10 — negative (positive in melanoma).
    • p63 / EMA — for squamous / epithelial origin.
  • RCPath MCC dataset requires CK20, TTF-1 and neuroendocrine markers minimum.

MCPyV-positive vs MCPyV-negative MCC

  • UK MCCs split roughly 78% MCPyV-positive / 22% MCPyV-negative.
  • MCPyV-positive MCC — typically arises in chronically sun-damaged skin; integrated viral large-T antigen drives oncogenesis; lower mutational burden.
  • MCPyV-negative MCC — much higher UV mutational signature; higher tumour mutational burden; often more aggressive.
  • Both express CK20 paranuclear dot; MCPyV status does not affect IHC diagnostic approach.
  • MCPyV IHC (CM2B4) — supportive of MCC but negative result does not exclude (22% truly MCPyV-negative MCC).
  • Checkpoint inhibitors such as avelumab and anti-PD-1 / PD-L1 therapy are active irrespective of MCPyV status; MCPyV-negative tumours have higher TMB, but comparative response differences by viral status remain mixed.

References

  1. Bobos M et al. Immunohistochemical distinction between Merkel cell carcinoma and small cell carcinoma of the lung. Am J Dermatopathol; 2006.
  2. Feng H et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science; 2008.
  3. Royal College of Pathologists. Dataset for histopathological reporting of primary cutaneous Merkel cell carcinoma and regional lymph nodes. G126. London: RCPath; February 2019.

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