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. 2025 Aug 4;25(1):314.
doi: 10.1186/s12880-025-01851-6.

Exploring the relationships between CT and pathological characteristics and gene mutations in neoplastic ground glass nodules

Zi-Ya Zhao #  1 , Si-Zhu Liu #  1 , Xue-Ping Chen  2   3 , Yang-Li Zhang  2   3 , Bin-Jie Fu  1 , Wang-Jia Li  1 , Fa-Jin Lv  1 , Zhi-Gang Chu  4
Affiliations

Exploring the relationships between CT and pathological characteristics and gene mutations in neoplastic ground glass nodules

Zi-Ya Zhao et al. BMC Med Imaging. .

Abstract

Background: Neoplastic ground glass nodules (GGNs) are relatively indolent tumors, with slow progression in invasiveness and computed tomography (CT) features. This study aimed to explore the correlation between pathological and CT characteristics and gene mutations in neoplastic GGNs.

Methods: We retrospectively analyzed 1,348 neoplastic GGNs from January 2019 to November 2022, including 290 adenocarcinomas in situ (AIS), 448 microinvasive adenocarcinomas (MIA), and 610 invasive adenocarcinomas (IAC). The correlations between patients' characteristics, pathological subtypes and grades, CT features, changes in follow-up, and gene mutations were analyzed.

Results: Solid component (odds ratio [OR] = 1.493; P = 0.014), larger size (OR = 1.049; P = 0.006), ill-defined boundary (OR = 1.368; P = 0.027), and lobulation sign (OR = 1.824; P = 0.001) were revealed as independent CT predictors of gene mutation. From AIS to IAC, the epidermal growth factor receptor (EGFR) mutation rate significantly increased (P < 0.01), while the kirsten rat sarcoma viral oncogene (KRAS) and the anaplastic lymphoma kinase (ALK) mutation rates significantly decreased (P < 0.05). Among IACs, mutation rate was the highest in the intermediate-grade ones (P < 0.05). Gene mutations were more frequently detected in nodules showing changes during follow-up (76.3% vs. 61.1%, P = 0.02), especially in those with more than 2-year follow-up (77.1% vs. 43.7%, P = 0.023). However, the specific changes were not associated with gene mutations (P = 0.273).

Conclusions: Gene mutations in neoplastic GGNs were associated with CT features, pathological subtypes and grades, and changes observed during long-term follow-up.

Keywords: Adenocarcinoma; Computed tomography; Epidermal growth factor receptor; Gene mutation; Ground-glass opacity.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study conformed to the Declaration of Helsinki on Human Research Ethics standards and was approved by the institutional review board of the First affiliated hospital of Chongqing Medical University (NO. 2024-431-01). The requirement for informed consent was waived because of the retrospective nature of the study. Consent for publication: All the images and tables are consented to be published. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Distributions of driver oncogene mutations in GGNs
Fig. 2
Fig. 2
A patient with pathologically confirmed moderately differentiated invasive adenocarcinoma. A transverse thin-section non-enhanced CT image shows a smaller (12 mm) well-defined pGGN with vacuole located in the right upper lobe (a). Gene test shows it has no gene mutations. A patient with pathologically confirmed moderately differentiated invasive adenocarcinoma. A transverse thin-section non-enhanced CT image shows a larger (21 mm), lobulated, and ill-defined PSN located in the right upper lobe (b). Gene test shows it has G12A/13 C mutation of the KRAS gene. PSN: part-solid nodule, pGGN: pure ground glass nodule
Fig. 3
Fig. 3
A patient with pathologically confirmed invasive adenocarcinoma. A transverse thin-section non-enhanced CT image shows an ill-defined pGGN (5 mm) (arrow) located in the right upper lobe (a), it significantly increases in size (18 mm) and density after 54 months (b). Gene test shows it has the L858R mutation of EGFR gene. pGGN: pure ground glass nodule
Fig. 4
Fig. 4
A patient with pathologically confirmed invasive adenocarcinoma. A transverse thin-section non-enhanced CT image shows an ill-defined pGGN (7 mm) located in the right upper lobe (a), it significantly increases in size (12 mm) but has no significant change in density after 17 months (b). Gene test shows it has the L858R mutation of EGFR gene. A patient with pathologically confirmed invasive adenocarcinoma. A transverse thin-section non-enhanced CT image shows an oval pGGN (4 mm) (arrow) located in the right upper lobe (c), it significantly increases in size (15 mm) and density after 36 months (d). Gene test shows it has the G12D/S mutation of KRAS gene. pGGN: pure ground glass nodule
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