To explore the clinicopathological and molecular characteristics, programmed cell death 1 ligand 1 (PD-L1) expression, and diagnosis and differential diagnosis of SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC).

The clinical morphological and immunohistochemical features of 8 cases of SMARCA4-dNSCLC diagnosed at Anqing Municipal Hospital from January 2017 to March 2023 were retrospectively analyzed, and the molecular genetic features of five cases were studied using next generation sequencing technique (NGS).

All of the 8 patients were male, aged from 48 to 73 years (mean 63 years). The tumors were located in unilateral lung and ranged from 2 to 7 cm in diameter. Microscopically, the tumor cells were epithelioid and rich in acidophilic or translucent cytoplasm, had vacuolar nuclei, obvious nucleoli, and easily visible mitotic figures, and were arranged in sheets, islands, or acini, with geoimagedata necrosis. Focal cancer cells were nonadherent and striated. Regarding immunophenotype, SMARCA4 protein (BRG1) was negative in 7/8 and partially positive in 1/8 cases. NGS was performed in 5 cases, of which one had both TP53 and ERBB2 mutations, one had TP53 mutation and NRAS micromutation, one had TP53 mutation alone, one had RET somatic missense mutation, and one had no gene mutation. PD-L1 protein expression was detected in 5 cases, of which one was negative for PD-L1, three had PD-L1 expression, and one had high expression. All patients underwent lobectomy. One case received preoperative adjuvant chemotherapy, and five cases received postoperative adjuvant therapy. Of the total seven patients who were followed from 1 month to 67 months, one had distant metastasis and the other six were alive without recurrence or metastasis.

SMARCA4-dNSCLC is a rare malignant tumor with unique clinicopathological features and special immunohistochemical phenotype, lacks common drug-targeting gene mutations, and has a high positive rate of PD-L1.