Cleveland Clinic Abu Dhabi Abu Dhabi, Abu Dhabi, United Arab Emirates
Zahrah Alhomedi, MD, Fatma Mahmoud, MD, Amanullah Khan, MD, Ahmad Alduaij, MD Cleveland Clinic Abu Dhabi, Abu Dhabi, Abu Dhabi, United Arab Emirates 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 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.
Figure: Figure 1. Coronal and cross-sectional images of the right lobe hepatic complex mass
Figure: Figure 2. The histologic sections of the liver cores biopsy showing: Almost entire involvement by spindled cells with pleomorphic nuclei and occasional bizarre forms. Foci of necrosis with a brisk mitotic activity, including atypical forms also identified. Epithelioid formation of neoplastic cells are seen with rounded to oval nuclei with eosinophilic to amphophilic cytoplasm. (A&B) Immunohistochemical stains performed at the National Reference Laboratory/ Cleveland Clinic Abu Dhabi show neoplastic cells expressing Vimentin and focally with CKAE1/3 and D2-40 and negative for S100, SOX-10, MDM2, TTF-1, PAX 8, Calretinin, Napsin-A, Hepar1, Arginase, MOC31, p40 CD117, Desmin, DOG-1, CD34, PSA, CDX2 and Myogenin. (C&D). The overall immunomorphologic features are non-specific but suggest the differential diagnosis of sarcomatoid carcinoma and sarcomatoid mesothelioma. Hematoxylin and eosin (H&E) staining in A&B and Vimentin in C and CKAE1/3 in D. Original magnification x100 (A), x200 (B), x100 (C&D).
Disclosures: Zahrah Alhomedi indicated no relevant financial relationships. Fatma Mahmoud indicated no relevant financial relationships. Amanullah Khan indicated no relevant financial relationships. Ahmad Alduaij indicated no relevant financial relationships.
Zahrah Alhomedi, MD, Fatma Mahmoud, MD, Amanullah Khan, MD, Ahmad Alduaij, MD. P6006 - Epithelial Meets Mesenchymal: Exploring a Case of Advanced Sarcomatoid Carcinoma, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
