Wnt/β-catenin-activated rosette-forming carcinoma of the lung: a case report of a possible pulmonary counterpart of a recently recognized cutaneous entity.

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.