Abstract Background Hepatoid adenocarcinoma of the lung (HAL) is an exceptionally rare and aggressive histologic variant of pulmonary adenocarcinoma characterized by morphologic and immunophenotypic resemblance to hepatocellular carcinoma. It accounts for fewer than 1% of primary lung malignancies and predominantly affects older male smokers. HAL typically presents at an advanced stage with mediastinal lymphadenopathy, endobronchial lesions, or distant metastasis. Due to overlapping morphology with metastatic hepatocellular carcinoma and other hepatoid tumors of gastrointestinal origin, diagnosis requires a high index of suspicion. Immunohistochemical staining plays a pivotal role, with hepatocyte-specific antigen (HepPar-1), AFP, and cytokeratin positivity supporting the diagnosis in the absence of a hepatic primary. Case Presentation A 79-year-old male with a history of bladder cancer, hypertension, and heavy smoking presented with one week of generalized weakness, poor oral intake, and 35-40 lb unintentional weight loss over two months. He denied hemoptysis, fever, or chest pain. CT chest revealed a 3.4 cm left infrahilar mass with bulky mediastinal lymphadenopathy causing left mainstem bronchial occlusion and left lower lobe collapse. Bronchoscopy showed bilateral mainstem tumors with distorted left lower lobe airways. Endobronchial ultrasound-guided transbronchial needle aspiration and bronchial biopsies were performed.Histopathologic examination revealed a poorly differentiated non-small cell carcinoma with hepatoid features. Immunohistochemistry demonstrated positivity for AE1/AE3, hepatocyte-specific antigen, and focal CK20, while negative for p40, Napsin-A, TTF-1, CDX2, CK7, and PAX8—findings consistent with hepatoid adenocarcinoma of the lung. No hepatic or gastrointestinal primary was identified. The patient was staged as at least stage III disease with mediastinal and bilateral airway involvement. Given his frailty and extensive disease, he was not a surgical candidate. Weekly carboplatin and paclitaxel were initiated with radiation-sensitizing intent, and genomic sequencing was ordered for potential checkpoint inhibitor therapy. Treatment was later paused due to functional decline and failure to thrive. Supportive care with bronchodilators and nutritional optimization was provided. Multidisciplinary discussion guided individualized management in the absence of established guidelines. Discussion and Conclusion HAL is a rare and diagnostically challenging entity that mimics metastatic hepatocellular carcinoma. Recognition depends on histopathologic evaluation and immunoprofiling to confirm pulmonary origin. This case highlights HAL’s aggressive local behavior, rapid progression, and limited therapeutic options. Early tissue diagnosis, interdisciplinary coordination, and integration of molecular and immunotherapeutic strategies remain essential to improving outcomes in this rare and lethal variant of lung adenocarcinoma. This abstract is funded by: none
Biscuitwala et al. (Fri,) studied this question.