Abstract:

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.

Key words: Adenocarcinoma with enteroblastic differentiation, Immunohistochemistry, Genetic testing, Clinicopathologic features