SMARCA4/BRG1-deficient non-small cell lung cancer: clinical, imaging, pathological features, and follow-up results of 23 patients

Abstract

Background: SMARCA4/BRG1-deficient non-small cell lung cancer (S/B-d NSCLC) is a rare subtype of non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical, imaging, serum tumor marker, and pathological features of S/B-d NSCLC, particularly computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan features.

Methods: Our analysis included 23 patients with pathologically confirmed S/B-d NSCLC from January 2021 to December 2023. A retrospective analysis of clinical, serum tumor markers, imaging [including CT, FDG PET/CT, magnetic resonance imaging (MRI)], pathological features, treatment protocols, and follow-up results was performed. Independent samples t-tests were used to assess statistical differences in short diameters and maximum standardized uptake value (SUV_max) between groups.

Results: S/B-d NSCLC occurs predominantly in male patients with a history of smoking and a mean age of 62.78 years (39-77 years). S/B-d NSCLC was found incidentally during physical examination in 56.52% of patients. The CT scan features were as follows: predominantly tumors (72.73%), peripheral in the lungs (77.27%), round or roundish morphology (81.28%), pleural or vascular invasion (95.46%), and moderately to severely enhanced (59.09%). The FDG PET/CT showed FDG-avid with mean SUV_max of 14.78±9.57. Lung cancer-related serum tumor markers had high positivity rates for carcinoembryonic antigen (CEA) (66.67%), recombinant cytokeratin fragment antigen 21-1 (CYFRA21-1) (61.91%), and carbohydrate antigen 125 (CA125) (57.14%). Pathological features are often characterized by grading (poor differentiation, 100%), tumor spread through the air space (STAS, 85.71%), and vascular invasion (85.71%). Immunohistochemistry showed that SMARCA4 (BRG1) was absent, and P40, P63, ALK-Ventana ALK (D5F3), and p-TRK were often negative. Genetic tests showed that the positivity rate of TP53 (76.92%) and KEAP1 (53.85%) was high. Despite diverse treatment options being available, high rates of progression during treatment and poor prognosis were observed. Among CT features (N=22), the short diameter of CT-diagnosed metastatic lymph nodes (LNs) was larger than that of non-metastatic LNs, and the difference was statistically significant (P=0.02). Among the FDG PET/CT features (N=12), SUV_max was larger in tumor group than lesion group, SUV_max was larger in M1 group than M0 group, and the difference was statistically significant in both groups (P=0.001 and P=0.04).

Conclusions: S/B-d NSCLC has distinct features in epidemiology, serum tumor markers, imaging, and pathology. In particular, FDG-avid is evident in the FDG PET/CT scan. The size of the lesion and the degree of FDG avidity provide information about the degree of malignancy and the high probability of distant metastasis in S/B-d NSCLC. FDG PET/CT is recommended when S/B-d NSCLC is suspected based on CT features, especially for large lesions. The FDG PET/CT scan can help with accurate staging and individual treatment planning.

Keywords: SMARCA4/BRG1-deficient non-small cell lung cancer (S/B-d NSCLC); computed tomography (CT); lung cancer; positron emission tomography-computed tomography (PET/CT).

Figure 1

Summary of treatment programs of 23 S/B-d NSCLC patients. S/B-d NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer.

Figure 2

Summary of clinical evaluation of 23 S/B-d NSCLC patients. PD, progressive disease; PR, partial response; CR, complete response; SD, stable disease; S/B-d NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer.

Figure 3

Summary of survival of 23 S/B-d NSCLC patients. S/B-d NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer.

Figure 4

A 69-year-old female patient with no history of smoking. She was admitted to the hospital with the chief complaint of left-sided chest pain. Chest MRI showed a tumor in the LLL (A-E), with a size of 4.1 cm × 3.0 cm and with inhomogeneous enhancement in the enhancement scan (E-G). Serum tumor markers associated with lung cancer: CEA was 22.72 ng/mL; ProGRP was 30.93 pg/mL; CYFRA21-1 was 4.90 ng/mL; CA125 was 30.60 U/mL; NSE was 9.36 ng/mL; and SCC was 0.79 ng/mL. Puncture biopsy confirmed by pathology: S/B-NSCLC (H,I). Pathological features: poorly differentiated (H, H&E staining, 200× field of view). Immunohistochemical staining features: BRG-1 (−, I, 200× field of view). Treatment regimen: surgery + chemotherapy. Effectiveness assessment: CR. Follow-up: 155 days survival time. MRI, magnetic resonance imaging; LLL, left lower lobe; CEA, carcinoembryonic antigen; ProGRP, pro-gastrin-releasing peptide; CYFRA21-1, recombinant cytokeratin fragment antigen 21-1; CA125, carbohydrate antigen 125, NSE, neuron-specific enolase; SCC, squamous cell carcinoma antigen; S/B-NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer; H&E, hematoxylin and eosin; CR, complete response.

Figure 5

A 68-year-old male patient was found to have a tumor in the RUL during physical examination and had a history of heavy smoking for more than 40 years. The FDG PET/CT scan showed a tumor in the RUL (A), with a size of 4.6 cm × 3.7 cm (C), and an SUV_max of 25.4 (B). Chest CT enhancement showed marked enhancement. The serum tumor markers associated with lung cancer: CEA was 22.90 ng/mL; ProGRP was 34.20 pg/mL; CYFRA21-1 was 2.39 ng/mL; CA125 was 75.40 U/mL; NSE was 6.44 ng/mL; and SCC was 0.53 ng/mL. The clinical staging of the lung cancer by FDG PET/CT was cT4N2M0 (A-D). Puncture biopsy confirmed by pathology: S/B-NSCLC (E-J). Pathological features: poorly differentiated (E, H&E staining, 200× field of view). Immunohistochemical staining features: BRG-1 (−, F, 200× field of view), CK7 (3+, G, 200× field of view), KI67 (20–30%, H, 200× field of view), p40 (−, I, 200× field of view), TTF-1 (−, J, 200× field of view). The patient discontinued treatment after the diagnosis. He died after 83 days of follow-up. RUL, right upper lobe; FDG PET/CT, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography; SUV_max, maximum standardized uptake value; CT, computed tomography; CEA, carcinoembryonic antigen; ProGRP, pro-gastrin-releasing peptide; CYFRA21-1, recombinant cytokeratin fragment antigen 21-1; CA125, carbohydrate antigen 125; NSE, neuron-specific enolase; SCC, squamous cell carcinoma antigen; S/B-NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer; H&E, hematoxylin and eosin.

Figure 6

A 66-year-old male patient was admitted to the hospital with recurrent hemoptysis for 1 month and a history of heavy smoking for more than 40 years. The FDG PET/CT scan showed a nodule in the RLL (A,C,D,E), with a size of 2.6 cm × 2.2 cm (D), and SUV_max of 12.9 (C). Chest CT enhancement showed mild enhancement. The serum tumor markers associated with lung cancer: CEA was 3.98 ng/mL; ProGRP was 45.77 pg/mL; CYFRA21-1 was 4.25 ng/mL; CA125 was 20.70 U/mL; NSE was 15.89 ng/mL; and SCC was 1.74 ng/mL. Surgery confirmed that the patient had S/B-NSCLC, with postoperative staging: pT1N0M0 (B,F). Pathological features: poorly differentiated (B, H&E staining, 200× field of view). Immunohistochemical staining features: BRG-1 (−, F, 200× field of view). The patient was followed for 490 days without progression (CR). FDG PET/CT, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography; RLL, right lower lobe; SUV_max, standard uptake value; CT, computed tomography; CEA, carcinoembryonic antigen; ProGRP, pro-gastrin-releasing peptide; CYFRA21-1, recombinant cytokeratin fragment antigen 21-1; CA125, carbohydrate antigen 125; NSE, neuron-specific enolase; SCC, squamous cell carcinoma antigen; S/B-NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer; H&E, hematoxylin and eosin; CR, complete response.

Figure 7

A 67-year-old male patient was admitted to the hospital with the chief complaint of a left inguinal tumor. With a history of heavy smoking for more than 40 years, FDG PET/CT scan revealed a tumor in the RUL (A,C,D,E), with a size of 4.1 cm × 3.2 cm and an SUV_max of 28.7 (C). The tumor showed moderate enhancement on chest CT. Serum tumor markers associated with lung cancer: CEA was 14.84 ng/mL; ProGRP was 40.82 pg/mL; CYFRA21-1 was 5.22 ng/mL; CA125 was 986.50 U/mL; NSE was 10.24 ng/mL; and SCC was 1.01 ng/mL. The clinical staging of the tumor by FDG PET/CT was cT4N3M1 (A-D,F,G,H,J,K). Puncture biopsy confirmed by pathology: S/B-NSCLC (E,I,L,M). Pathological features: poor differentiated (E, H&E staining, 400× field of view). Immunohistochemical staining features: BRG-1 (−, I, 200× field of view), CD56 (−, L, 200× field of view), p40 (−, M, 200× field of view). Treatment regimen: chemotherapy + targeted + ICI. Effectiveness assessment: PD. He died after 131 days of follow-up. FDG PET/CT, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography; RUL, right upper lobe; SUV_max, maximum standardized uptake value; CT, computed tomography; CEA, carcinoembryonic antigen; ProGRP, pro-gastrin-releasing peptide; CYFRA21-1, recombinant cytokeratin fragment antigen 21-1; CA125, carbohydrate antigen 125; NSE, neuron-specific enolase; SCC, squamous cell carcinoma antigen; S/B-NSCLC, SMARCA4/BRG1-deficient non-small cell lung cancer; H&E, hematoxylin and eosin; ICI, immune checkpoint inhibitor; PD, progressive disease.