Pulmonary pleomorphic carcinoma with trophoblastic differentiation: diagnostic challenges in a rare sarcomatoid lung malignancy

Abstract Background Pulmonary pleomorphic carcinoma is an uncommon subtype of sarcomatoid non-small cell lung carcinoma characterized by marked morphologic heterogeneity. Accurate diagnosis can be challenging due to overlapping features with other poorly differentiated primary and metastatic malignancies. Trophoblastic differentiation within pulmonary pleomorphic carcinoma is rarely described and represents an unusual pattern that may further complicate histopathologic interpretation. This case highlights the diagnostic approach to a morphologically heterogeneous pulmonary tumor and emphasizes the role of adequate sampling and immunohistochemical evaluation. Case presentation A 62-year-old male chronic smoker presented with a two-month history of cough, intermittent fever, and progressive shortness of breath. Radiologic evaluation revealed a lobulated mass involving the right lower lobe of the lung. The patient underwent right lower lobectomy with mediastinal lymph node dissection. Gross examination showed a 6.0 cm infiltrative tan-white tumor. Histopathology demonstrated acinar adenocarcinoma admixed with markedly pleomorphic multinucleated giant tumor cells showing focal trophoblastic differentiation. Immunohistochemistry revealed diffuse CK7 expression, focal Napsin A positivity, weak TTF-1 expression, and focal β-hCG staining within the giant tumor cells. Clinical and radiologic assessment showed no evidence of an extrapulmonary primary malignancy. The patient is currently under follow-up and planned for adjuvant chemoradiotherapy. Conclusions Pulmonary pleomorphic carcinoma requires careful histopathologic evaluation, extensive tumor sampling, and exclusion of metastatic mimics for accurate diagnosis. Recognition of unusual differentiation patterns, including trophoblastic differentiation, may help avoid diagnostic misclassification and contributes to understanding the morphologic spectrum of this rare tumor.