Beyond Sinonasal Undifferentiated Carcinoma: Molecular Reclassification of a SMARCB1-Deficient Sinonasal Carcinoma With Pulmonary Metastasis

A 56-year-old man presented with a nine-month history of progressive left-sided nasal obstruction, epistaxis, facial and palatal pain, and proptosis.Imaging demonstrated a large destructive left sinonasal mass extending into the left maxillary sinus and orbit.An endoscopic biopsy revealed a poorly differentiated epithelial malignancy, initially classified as a sinonasal undifferentiated carcinoma (SNUC).Immunohistochemistry demonstrated strong cytokeratin expression and complete loss of integrase interactor 1 (INI1) nuclear expression in tumor cells, with retained staining in non-neoplastic elements.The patient underwent a left subtotal maxillectomy with hard palate resection.The tumor measured at least 8 cm, involved the pterygoid muscle, and extended to the medial and superior resection margins.Following surgery, he received platinum-based chemotherapy and radiotherapy.Approximately two years later, he presented with progressive exertional dyspnea.Imaging revealed a large left pleural effusion and bilateral soft-tissue-attenuation pulmonary nodules.Pleural fluid evaluation was nondiagnostic for malignancy because of limited cellularity; however, a computed tomography-guided core biopsy of a right pulmonary nodule revealed metastatic carcinoma morphologically concordant with the sinonasal primary, with strong cytokeratin expression and persistent loss of INI1.The patient subsequently received six cycles of pembrolizumab combined with cyclophosphamide, doxorubicin, and vincristine.Comprehensive molecular profiling of archived primary tumor tissue later identified a pathogenic SMARCB1 copy-number deletion, establishing the diagnosis of SMARCB1-deficient sinonasal carcinoma.At the last documented follow-up, fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) demonstrated persistent metabolically active thoracic metastatic disease without interval progression or new sites of disease.This case illustrates how integration of morphology, immunohistochemistry, metastatic-site comparison, and molecular testing can refine the classification of a poorly differentiated sinonasal carcinoma initially diagnosed as SNUC.