Track

Clinical Studies

Abstract

Basal cell carcinoma (BCC) is the most common human cancer, accounting for 80% of all non-melanoma skin cancers. Although BCC rarely metastasizes, hematogenous spread to distant organs such as lungs and bones can occur, and often leads to diagnostic uncertainty and potential misclassification. Prior to the advent of next-generation sequencing (NGS), basaloid carcinoma in the lungs was generally regarded as a primary lung carcinoma. With the accumulation of NGS studies of lung tumors, we identified a distinct cohort of basaloid carcinomas (n = 15) that initially raised consideration for primary lung squamous cell carcinomas but which, through NGS, demonstrated features supporting origin from cutaneous BCC. The hallmark features indicative of cutaneous origin included a dominant ultraviolet (UV) mutational signature, high tumor mutation burden (TMB) and frequent mutations in PTCH1, TP53 and TERT.  We identified depth of invasion, tumor size, lymphovascular invasion and concurrent malignancies as high-risk features associated with metastasis in our cohort. Morphologically, the lung lesions closely resembled their corresponding cutaneous primaries; however, in isolation, they were indistinguishable from pulmonary basaloid squamous cell carcinomas. Notably, six patients received and benefited from vismodegib treatment following diagnosis of metastatic BCC, highlighting the importance of accurate diagnosis. Given the rarity and high potential for misdiagnosis, metastatic BCC should always be considered in the differential diagnosis of basaloid lung tumors, particularly in patients with a history of cutaneous malignancies and a never/light smoking history. Accurate diagnosis requires careful histopathologic evaluation, recognition of classic BCC features, but definitive diagnosis may require confirmatory NGS profiling.