Primary Pulmonary Epithelioid Inflammatory Myofibroblastic Sarcoma With SQSTM1 :: ALK Fusion

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and aggressive variant of inflammatory myofibroblastic tumor (IMT) characterized by epithelioid morphology, atypical features, ALK rearrangements, and early metastatic potential. Primary pulmonary EIMS is exceptionally uncommon, and diagnosis on cytologic specimens can be challenging. A 58-year-old woman presented with cough and shortness of breath and was found to have a right lung mass. Transbronchial needle aspiration revealed scattered spindle cells in a lymphoplasmacytic background on the smears. Cell block sections demonstrated mainly spindle to few epithelioid cells with focal necrosis. Immunohistochemistry showed diffuse ALK positivity with focal SMA and desmin expression. The lesion was diagnosed as a spindle cell neoplasm concerning for an IMT with possible malignant transformation. Subsequent lobectomy revealed epithelioid morphology, marked atypia, increased mitotic activity, and extensive necrosis, establishing the diagnosis of EIMS. Molecular testing identified an SQSTM1::ALK fusion and a TERT promoter mutation. The patient developed metastatic disease and showed a limited response to ALK inhibitor therapy. This case highlights the diagnostic challenges of EIMS on cytology and underscores the importance of integrating cytomorphology, immunohistochemistry, and molecular testing for accurate diagnosis and management. It also expands the molecular spectrum of EIMS by demonstrating a rare SQSTM1::ALK fusion in a primary pulmonary tumor.