S5816 Epithelial Meets Mesenchymal: Exploring a Case of Advanced Sarcomatoid Carcinoma

Introduction: Sarcomatoid carcinoma is a rare, aggressive malignancy combining epithelial and sarcoma-like spindle cell features. It may arise in the lung, liver, kidney, or soft tissues and is associated with rapid progression and poor prognosis, with median survival typically less than a year. The pathogenesis involves epithelial-to-mesenchymal transition (EMT), enhancing invasiveness. Diagnosis relies on immunohistochemistry (IHC), using markers like cytokeratins and vimentin, though overlap with GATA3 and D2-40 complicates differentiation from mesothelioma. Imaging, including computed tomography (CT) and PET/CT, aids in staging. Molecular diagnostics help detect actionable mutations, but treatment remains difficult, with limited responses to chemotherapy, immunotherapy, and targeted therapies. Case Description/Methods: A 62-year-old man with diabetes, coronary artery disease, and recent shoulder surgery presented with right upper quadrant pain, fever, and 18 kg weight loss over a year. He was an ex-smoker with a family history of breast cancer. Labs showed leukocytosis, elevated CRP, and thrombocytosis. Imaging revealed hepatic and pulmonary lesions with mediastinal lymphadenopathy. Initially treated for sepsis, his partial improvement prompted further workup. A 13.6 × 11.0 cm liver mass was biopsied, revealing a poorly differentiated neoplasm with spindle and epithelioid morphology. Histology showed intersecting fascicles, necrosis, pleomorphism, and atypical mitoses. IHC showed positivity for GATA3, vimentin, focal CK AE1/AE3, and D2-40; negative markers excluded melanoma, GIST, and hepatocellular carcinoma. PET/CT revealed widespread metastases in lungs, peritoneum, bones, and lymph nodes. Diagnosis: metastatic sarcomatoid carcinoma. Tumor board discussion was initiated. Discussion: Sarcomatoid carcinoma presents diagnostic and treatment challenges due to its resemblance to mesothelioma, melanoma, and GIST. Broad IHC panels aid differentiation, but ambiguity often remains. Literature highlights aggressive behavior in similar cases: pulmonary sarcomatoid carcinoma with poor outcomes despite surgery; jejunal tumors with delayed diagnosis; and gallbladder cases with early metastasis. These underscore the importance of early recognition, comprehensive molecular testing, and multidisciplinary care. Continued research into molecular targets and therapies remains vital to improving outcomes in this rare cancer.