Hepatoid adenocarcinoma of the lung with normal serum alpha-fetoprotein managed with thoracic radiotherapy followed by tislelizumab plus lenvatinib: a case report and systematic review

Background Hepatoid adenocarcinoma of the lung (HAL) is a rare pulmonary malignancy. This study presents a case of HAL with normal serum alpha-fetoprotein (AFP) and systematically reviews previously reported cases. Methods The clinicopathologic and molecular characteristics, treatment, and outcome of the index case were described. For the systematic review, PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched from January 2000 to 4 July 2026. Patient-level data were extracted from eligible reports. Methodological quality was assessed using the Joanna Briggs Institute checklists. Overall survival (OS) was evaluated using Kaplan–Meier analysis and Cox regression. Results The index patient was diagnosed with HAL, with normal serum AFP and no established actionable driver alterations identified. After thoracic radiotherapy followed by tislelizumab plus lenvatinib, the patient achieved a partial response and remained progression-free for nearly 10 months. The systematic review included 91 studies comprising 109 patients. The median age was 63 years. Men accounted for 91% of patients, and 86% of patients with available data had a smoking history. Stage III–IV disease was reported in 88/106 patients (83%). Serum AFP was elevated in 49/81 patients (60%), thyroid transcription factor 1 (TTF-1) was negative in 56/87 patients (64%), and genomic alterations were identified in 19/53 molecularly tested patients (36%). The median OS among 83 patients with available survival data was 14 months (95% CI, 9–19 months). Stage IV disease was associated with shorter OS in multivariable analysis (HR, 2.47; 95% CI, 1.18–5.19; P = 0.017). These findings should be interpreted in light of potential publication, selection, and reporting biases. Conclusion HAL was most frequently reported in older men with a history of smoking. Most patients had stage III–IV disease at diagnosis, and OS was generally short. Clinical stage was associated with OS, whereas the prognostic value of serum AFP remained uncertain. No standard treatment has been established. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261440722.