Metastasizing basal cell carcinoma: A clinicopathologic and immunohistochemical study of 22 cases

J Cutan Pathol. 2021 Mar;48(3):374-383. doi: 10.1111/cup.13888. Epub 2020 Nov 5.

Abstract

Basal cell carcinomas metastasize rarely, and there have been limited studies of potential drivers for this metastasis. Epithelial-mesenchymal transition (EMT) may play a role, although this has not been investigated in detail. We reviewed clinicopathologic features of 22 patients with metastasizing basal cell carcinoma (MBCC). Immunohistochemical markers of EMT, including CD44, E-cadherin, claudin, smooth muscle actin, beta-catenin, Twist1, and Oct 3/4, were evaluated on 10 MBCC (primary and metastases) and 18 non-metastasizing BCC. Primary sites included the head and neck, trunk, and extremity, while metastatic sites included lymph nodes, lung, bone, and soft tissue. Of 19 cases with follow-up, the range of follow-up after diagnosis of metastasis was 5 to 248 months (median: 50 months). Two cases were of unknown primary, nine metastases were diagnosed concurrently with primary tumors, and remaining cases showed a median latency between diagnosis of primary and metastatic tumors of 27.5 months (range: 3-81 months). Median survival was 66 months. Compared to non-metastasizing BCC, MBCC demonstrated reduced CD44 expression (primary [P = .0036], metastatic [P = .011]) and increased Twist1 expression (primary, P = .0017). MBCC shows variably aggressive behavior, and reduced CD44 and increased Twist1 expression may indicate significant EMT in metastasizing tumors and signify a metastatic phenotype.

Keywords: CD44; Twist1; basal cell carcinoma; immunohistochemistry; metastasizing; metastatic.

MeSH terms

  • Actins / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins / metabolism
  • Carcinoma, Basal Cell / diagnosis
  • Carcinoma, Basal Cell / metabolism*
  • Carcinoma, Basal Cell / secondary*
  • Case-Control Studies
  • Claudins / metabolism
  • Epithelial-Mesenchymal Transition / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Immunohistochemistry / methods*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Nuclear Proteins / metabolism*
  • Octamer Transcription Factor-3 / metabolism
  • Skin Neoplasms / pathology*
  • Survival Analysis
  • Twist-Related Protein 1 / metabolism*
  • Young Adult
  • beta Catenin / metabolism

Substances

  • Actins
  • CD44 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Claudins
  • Hyaluronan Receptors
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • beta Catenin