An Aggressive Neoplasm with Mixed Epithelial and Sarcoma-like Features, of Uncertain Primary Origin, Presenting as an Upper Lip Mass: A Case Report.

Carcinosarcoma is a rare and aggressive malignancy characterized by both epithelial and mesenchymal components. It most commonly arises in the uterus, lung, or gastrointestinal tract, whereas occurrence in the oral cavity is exceptionally rare. Here, we report a rare case of an aggressive neoplasm with mixed epithelial and sarcoma-like features that initially presented as a benign-appearing upper lip lesion. A 47-year-old male first presented in March 2025 with a painless upper lip mass that had persisted for two months. The lesion appeared clinically benign, and an excisional biopsy was performed. However, during surgery, intraoperative frozen section analysis revealed features highly suspicious for malignancy. Following surgery, systemic imaging demonstrated multiple hypermetabolic lesions in the lung, colon, liver, pancreas, adrenal glands, and lymph nodes. Biopsies from the lip, colon, and lung revealed a high-grade malignant tumor with variable epithelioid and sarcomatoid features across sampled sites. Immunohistochemistry showed co-expression of cytokeratin and vimentin, supporting mixed epithelial and sarcoma-like features. As no primary tumor was identified despite extensive work-up, the available findings favored an aggressive malignant neoplasm of uncertain primary origin with mixed epithelial and sarcoma-like features, although the final histologic sub-classification remained uncertain due to incomplete original pathology information. The patient subsequently received palliative systemic chemotherapy with an alectinib-based targeted regimen starting in April 2025, but showed progressive disease on follow-up, even with additional second-line gemcitabine/cisplatin and third-line pembrolizumab therapy. The patient ultimately succumbed in September 2025. This case highlights that even relatively subtle-appearing lesions require a high index of suspicion for malignancy, emphasizing the importance of early biopsy and comprehensive systemic evaluation. Carcinosarcoma, though rare, should be considered in the differential diagnosis of aggressive tumors arising in atypical locations.