Wnt/β-catenin-activated rosette-forming carcinoma (WARFC) is a recently proposed cutaneous tumor entity characterized by rosette formation, CDX2 expression, RB1 loss, and Wnt/β-catenin pathway activation. Extracutaneous counterparts of WARFC have not been documented to date. We report a distinctive case of lung carcinoma closely resembling WARFC. An 80-year-old man with a smoking history presented with a rapidly enlarging lung nodule. The resected tumor consisted of a rosette-forming large cell carcinoma with a trabecular pattern and lacking neuroendocrine marker expression, combined with squamous cell carcinoma. The rosette-forming component showed aberrant nuclear β-catenin expression, diffuse CDX2 expression, and RB1 loss. Targeted sequencing identified a pathogenic APC splice-site mutation. This case likely represents the pulmonary counterpart of cutaneous WARFC. Pulmonary WARFC should be considered in the differential diagnosis of large cell lung carcinoma with neuroendocrine morphology.
Tsuji et al. (2026) studied this question.