目的：探讨原发性肺腺癌伴肠母细胞分化(lung adenocarcinoma with enteroblastic differentiation, LAED)的临床病理特征及鉴别诊断要点。方法：回顾性分析2018年至2022年搜集的2例LAED患者的临床及影像学资料、病理形态学、免疫表型特征及基因检测结果等,并复习相关文献。结果：2例患者均为中老年男性，且长期吸烟，血清甲胎蛋白（alpha-fetoprotein，AFP）水平分别为>20 000 ng/mL、914.17 ng/mL；病灶分别位于右肺上叶及左肺下叶，最大径为12.5 cm及4.0 cm。患者的手术切除标本可见，肿瘤切面呈灰白、灰红，为实性，质软，局部易碎。镜下见大部分肿瘤组织呈实性，少部分呈腺管状、乳头状或呈囊腺样生长；肿瘤细胞学的细胞质透亮，富含糖原。免疫组化检测可见，肿瘤组织同时具有胚胎性分化和肠型分化的表型，不表达肝细胞分化标志。分子检测显示，EGFR、ALK/ROS1、RET、KRAS，BRAF、NTRK及MET均未见突变，HER-2未见扩增，EBER阴性。2例患者均诊断为LAED，因形态学及免疫表型有交叉，且均可有AFP水平升高，易被误诊为肺肝样腺癌及其他具有透明胞质的低分化腺癌。1例患者放弃治疗，于诊断2个月后去世；另1例患者接受根治性肺叶切除，术后行辅助化疗及免疫、靶向治疗，治疗后AFP水平降至正常，随访40个月时，患者因发生肿瘤骨、脑转移去世。结论：LAED目前国际上尚未见报道，其诊断及鉴别诊断主要依赖特征性的组织结构及细胞形态，并结合免疫组化标志物及血清AFP水平。本报道拓宽了产AFP的原发肺腺癌的疾病谱，LAED总体上临床进展快，患者预后差。

Objective To investigate the clinicopathologic features and differential diagnosis of primary lung adenocarcinoma with enteroblastic differentiation ( LAED ). Methods The clinical and imaging data, pathological morphology, immunophenotypic characteristics, and genetic testing results of two patients with LAED collected from 2018 to 2022 were retrospectively analyzed, and relevant literature was reviewed. Results Both patients were middle-aged males and long-term smokers. Their serum alpha-fetoprotein (AFP) levels were >20 000 ng/mL and 914.17 ng/mL, respectively. The lesions were located in the right upper lobe and left lower lobe, with a maximum diameter of 12.5 cm and 4.0 cm, respectively. The surgical resection specimens of the patients showed that the tumor sections were grayish white and grayish red, solid, soft, and locally friable. Microscopically, most of the tumor tissues were solid, and a small part was glandular, papillary, or cystic glandular. The cytoplasm of the tumor cells was clear and rich in glycogen. Immunohistochemical tests showed that the tumor tissues had both embryonic differentiation and intestinal differentiation phenotypes, and did not express hepatocyte differentiation markers. Molecular tests showed no mutations in EGFR, ALK/ROS1, RET, KRAS, BRAF, NTRK, and MET, no amplification of HER-2, and EBER was negative. Both patients were diagnosed with LAED. Because of the overlap in morphology and immunophenotype with hepatoid adenocarcinoma and other poorly differentiated adenocarcinomas with clear cytoplasm, and the elevated AFP levels in both cases, LAED was easy to be misdiagnosed. One patient gave up treatment and died 2 months later. The other patient received radical lobectomy and adjuvant chemotherapy, immune and targeted therapy after surgery. After treatment, the AFP level dropped to normal, and the patient died of bone and brain metastasis at 40 months of follow-up. Conclusions LAED is a rare tumor that has not been extensively reported either domestically or internationally. The diagnosis and differential diagnosis of LAED mainly rely on characteristic histology and cell morphology in combination with immunohistochemistry and serum AFP levels. This report broadens the disease spectrum of primary lung adenocarcinoma producing AFP. In general, LAED has a rapid clinical progression and a poor prognosis.