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

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.