Lung cancer associated with cystic airspaces: Current concept,pathogenesis,imaging features,pathological basis,and management

Abstract

This narrative review summarizes the current concept, CT imaging features, pathologic basis, and the correlation between imaging and pathology in lung cancer associated with cystic airspaces (LCCAs). Lung cancer associated with cystic airspaces is a distinct subtype of lung cancer with unique imaging and pathological features. Lung cancer screening can identify patients with cystic lesions on imaging, but distinguishing benign from malignant lesions remains challenging. The pathologic types of LCCAs vary, and early diagnosis and accurate identification are of great clinical value for patient management and improved prognosis. Clinicians should pay more attention to LCCAs to promote early diagnosis, improve the timing of interventions, and achieve better survival benefits for patients.

Keywords

lung cancer CT imaging pathology diagnosis treatment

1. Introduction

Lung cancer is one of the malignant tumors with the highest morbidity and mortality rates worldwide.¹ The latest data show that the incidence of lung cancer is gradually increasing, and the mortality rate of lung cancer has exceeded that of breast cancer, making lung cancer the leading cause of death from tumor-related diseases.^2,3 Lung cancer is a significant problem affecting public health, imposing a heavy burden on the government healthcare system and the socio-economy. In the past decade or so, with the development and widespread use of low-dose CT, many extensive cohort studies have determined that low-dose CT screening can increase the diagnosis and treatment of lung cancer in its early stages, thereby reducing lung cancer mortality rates.^4–6 However, the differential diagnosis of early-stage lung cancer has been a major concern and difficulty for clinicians.

The early-stage lung cancer appears as lung nodules on CT imaging. Lung nodules were categorized into small solid nodules (<8 mm), large solid nodules (≥8 mm), and sub-solid nodules, and sub-solid nodules were categorized into ground-glass nodules and mixed ground-glass nodules (both ground-glass and solid components)⁷(Figure 1). The diagnosis of subsolid nodules is essential. Subsolid nodules are difficult to diagnose and are complex nodules that may be manifestations of inflammation, infection, or fibrosis but can also be precursors of adenocarcinoma (atypical adenomatous hyperplasia, AAH) or adenocarcinoma in situ (AIS), which are difficult to manage and diagnose. It is difficult to assess morphologically on imaging because the outline of a non-solid nodule tends to be irregular, or the margins are not well defined, making measurements rather inaccurate and difficult to repeat.⁸ Fortunately, the development of this subsolid nodule is a slow, inert process and is less likely to metastasize, with a better prognosis after pneumonectomy treatment.^9,10 In recent years, a special type of subsolid nodule, the lung nodule presenting as a cystic lesion (Figure 1), has gradually gained the attention of clinicians. And the reports of lung cancer associated with cystic airspaces (LCCAs) have gradually increased. This narrative review focuses on the clinical and imaging characteristics, pathological basis, diagnostic approaches, and management of lung cancer associated with cystic airspaces (LCCAs). We do not aim to provide detailed treatment protocols but rather to summarize current knowledge to assist clinicians and radiologists in recognizing and managing this unique entity. This narrative review was prepared following the guidance of the Scale for the Assessment of Narrative Review Articles (SANRA).¹¹

Figure 1.

(a) On chest radiographs, solid opacity refers to an exudate or other product of disease that replaces alveolar air, rendering the lung solid. There is a homogeneous hyperdense nodular shadow in the right lower lung. (b) Ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. There is a mixed ground glass nodule in the right upper lung. (c) LCCAs appears as cystic lesions on imaging, with or without solid or ground-glass lesions. There is a thin-walled cystic airspace lesion in the left lower lung.

2. Methods

This review was conducted as a narrative review based on a comprehensive literature search. We searched PubMed, Web of Science, and CNKI databases for articles published up to March 2025 using the following keywords: “lung cancer associated with cystic airspaces”, “cystic lung cancer”, “thin-walled cystic lung cancer”, “lung cancer and pulmonary cyst”, and “cavitary lung adenocarcinoma”. We included original articles, case series, and review articles that reported imaging, pathological, or clinical features of LCCAs. Studies without full text or non-English articles without available translations were excluded. Reference lists of included articles were also screened for additional relevant studies. Descriptive statistics (frequencies and proportions) were used to summarize the epidemiological characteristics of LCCAs across included studies. No inferential statistical tests were performed.

3. Overview of LCCAs

Lung cancer with cystic lesions is a rare imaging presentation. According to the criteria of the Fleischner Society, a cystic lesion can be defined as any attenuated border space, including gas or fluid, surrounded by a wall of epithelial or fibrous tissue, with a clear demarcation from normal lung tissue.¹² Cystic lesions vary in thickness but are usually thin-walled. Because of the lack of objective indicators to accurately describe and quantify this cystic lesion, the cystic lesion is a descriptive adjective and does not imply etiology. There is a lack of specificity in the imaging features of cystic lesions; for example, cystic lesions can result from pulmonary bullae, interstitial lung disease, bronchiectasis, or atypical lung infections etc. (Figure 2). Womack and Graham first reported cystic lung disease associated with lung cancer in 1941,¹³ and since then, many cases have been reported in a variety of ways, including “Lung cancer with thin-walled cystic manifestations”,¹⁴ “solitary thin-walled cystic lung cancer”,¹⁵ “Lung cancer due to long-term lung cysts”¹⁶ and “bronchopulmonary carcinoma with herpetic lung disease”.¹⁷ In this paper, LCCAs are defined as lung cancer diagnosed pathologically with cystic lesions on imaging, with or without solid or ground-glass lesions.

Figure 2.

Presenting as a cystic benign lesion. (a): There is a thin-walled cystic lesion with uneven wall thickness in the right upper lung and the pathologic diagnosis is pulmonary aspergillosis. (b): There is a thick-walled cystic lesion in the right lower lung, intimately connected to the pleura, with blood vessels passing through the lesion. The pathological diagnosis is pulmonary aspergillosis (c): There is a multicystic luminal lesion is visible in the right upper lung, with visible separation of the cystic lumens, surrounded by blood vessels and a ground-glass opacity, and the pathological diagnosis is pulmonary cysts. All images are from the authors’ institutional database, and patient identifiers have been removed.

4. Epidemiology of LCCAs

The reported incidence of LCCAs ranged from 0.4% to 16.1% (Table 1). The patients in the reports were histologically confirmed as having lung malignancies, and all reports were retrospective studies. The mean age of cystic lung cancer was 58-70 years in reports, with a total number of cases greater than 10. The results of gender distribution and smoking history varied from study to study; Shen,¹⁸ Xue,¹⁵ Jung,¹⁹ and Mascalchi et al.²⁰ had a much larger proportion of males than females in their study. In contrast, Fintelmann²¹ and Zelin Ma²² had more female than male patients in their studies, and Zhu²³ and Farooqi²⁴ had a balanced gender distribution of patients in their studies. Overall, it seems that there are more male patients with LCCAs and a large number of female patients. This result should be related to the limited number of cases and the fact that there is a correlation factor with the population. Most of the cases had a history of smoking (past or present). Farooqi²⁴ and Fintelmann et al. ²³ suggested that LCCAs are associated with emphysema, which also reflects an association with smoking status. However, Wang²⁵ and Yang’s ^14,20 study, 65.5% (57/87) and 53.8% (57/106) of the patients never had a smoking history. This result may be related to ethnicity, as there were fewer East Asian female patients with a history of smoking. The larger study mainly involved surgical patients, so most of the patients’ tumor stages were in the early and intermediate stages. With early interventional therapy, patients can have a better prognosis. Most LCCAs patients are adenocarcinomas, and some other histologic types have been reported, such as large cell carcinoma, carcinoid tumor, lymphoma, sarcomatoid carcinoma, and so on.^{14,21,22,24,26,27} The most common type of cystic lung cancer is adenocarcinoma.

Table 1.

Summary of epidemiologic characteristics of cystic lung cancer.

No.	Author	Time	Number of cases	Incidence	Sexes		Age/average age	Smoking history		Tumor staging				Pathological type
No.	Author	Time	Number of cases	Incidence	Male	Female	Age/average age	Yes	No	I	II	III	IV	Adenocarcinoma	Squamous carcinoma	Else
1	Shen¹⁸	2021	123	123/10835 (1.16%)	82	41	61							117	6
2	Xue¹⁵	2012	18		12	6	58.17	2	16					18
3	Keita²⁸	2017	1		1		75		1				1	1
4	Guo¹⁴	2013	15	15/3268 (0.4%)	12	3	58.3	5	10	9	2	3	1	11	2	2
5	Fintelmann²¹	2017	30	30/2954 (1%)	12	18	66.2	29	1	18	5	2	5	24	4	2
6	Zhu²³	2023	252	252/2093 (12%)	128	124	58							252
7	Annemiek²⁹	2019	13	2.3%	8	5		12	1	4	2	3	4	11	2
8	Jung¹⁹	2020	60		44	16	61.8	37	23					60
9	P Hurley¹⁶	1985	2			2	35.5		2					2
10	Farooqi²⁴	2012	26	26/706 (3.6%)	13	13	63.5			21	5			23	1	2
11	Ehsan Haide³⁰	2019	11		2	9	63.28	11						9	2
12	Mascalchi²⁰	2015	24		17	7	70	18	6	12	3	4	5	17	7
13	Wang²⁵	2021	87	87/541 (16.1)	33	54	57.5	30	57					87
14	Zelin Ma²²	2022	384		236	148	58.2	48	336					237	115	5
15	Yukio Watanabe³¹	2015	143	6.2%	97	46	63	95	48					143
16	Kunihiro³²	2016	60	60/426 (14%)	38	22	69.2	43	17	49	8	2	1	47	13
17	Yang²⁶	2019	106		69	37	58.8	49	57	67	12	11	16	81	7	5
18	Chen³³	2019	227		108	119	59	17	210					227
19	Deng³⁴	2018	45		32	13		14	31					43	2
20	Jie Zhang²⁷	2019	65		44	21		25	40					60	4	1
21	Pan³⁵	2020	35		23	12	61.4

Table 1 Summary of epidemiologic characteristics of lung cancer associated with cystic airspaces (LCCAs) in included studies. Data are presented as numbers of patients unless otherwise specified. Incidence rates were calculated based on the total number of patients with surgically resected lung cancer in each study when available. Empty cells indicate data not reported in the original study.

5. Pathogenesis of LCCAs

The current possible formation mechanisms of LCCAs include: (i) check valve mechanism, the cancer cells spread and diffuse along the alveolar and bronchial walls and interstitium, narrowing the bronchial wall. At this time, the bronchial tube forms a flap, causing the gas inside the tumor to keep increasing and the cavity to keep enlarging. Part of the cavity ruptures and fuses to form a larger cavity, and tumor cells grow along the cavity wall to form wall nodules or cystic walls of uneven thickness.^21,36 (ii) Liquefaction and necrosis occur within the solid lesion, and the destruction of the alveoli by ischemic necrosis and excess mucus, which is expelled through the bronchioles, forms a cavity.³⁷ The solid lesion has liquefaction and necrosis inside. However, necrotic tumor cells are not seen in the microscopic presentation of some cystic lung carcinomas, and this mechanism is considered to occur less frequently.³⁸ (iii) Tumors occur in the original thin-walled cavity lesions, such as pulmonary alveoli, pulmonary cysts, emphysema, etc. There is a lot of literature confirming that emphysema and pulmonary alveoli are the risk factors for lung cancer.³⁹ Pulmonary alveoli consist of cystic air sacs and conductive thin bronchioles, and the limited airflow within the air sacs can lead to microbial deposition on the walls of the sacs. Repeated infection and inflammation exacerbate the deposition of carcinogens on the sac walls, and carcinogens can lead to disruption of the alveolar septa and the formation of larger sac cavities.⁴⁰ Most researchers recognize the check valve mechanism.^23,35,41

6. Correlation of CT imaging features with pathology

6.1. CT imaging features

LCCAs are diverse on CT, but the main features include malignant features of uneven cyst wall thickness, septation, wall nodules, and irregular margins, which help to distinguish them from benign cystic cavities on CT images²⁶(Figure 3). Jiangshan AI et al.⁴² compared the imaging features of benign and malignant lesions presenting as cystic. They concluded that benign cystic lesions tend to have a uniform cyst wall thickness of <2 mm and are usually not associated with malignant signs such as burr signs or lobulation. However, there are also benign lesions with a cyst wall thickness of >5 mm, such as lung infections. Kim et al.⁴³ analyzed CT images of 24 patients with pulmonary tuberculosis presenting as cystic, and some of them also had malignant signs such as inhomogeneous thickening of the cyst wall, nodules, and burrs in the cyst wall. This finding makes it difficult to assess the pathologic nature of cystic lesions based on imaging morphology alone.

Figure 3.

Common images of LCCAs: (a) There is a thick-walled cystic nodule in the left upper lung, which is close to the pleura, and the burr sign is visible around it. (b) There is a thin-walled cystic airspace in the right upper lung, and the vascular course is visible around it. (c) There is a cystic airspace nodule in the left lower lung that looks like a foam net. (d) There is a cystic airspace with irregular morphology in the left upper lung, and nodules are visible in the wall. All images are from the authors’ institutional database, and patient identifiers have been removed.

Previous studies of LCCAs have focused on the changes in imaging morphology and classification. Danielle’s study⁴⁴ showed that the precursors of LCCAs can be solid, partially solid, or in a ground-glass form. Jung’s study ²⁸ also confirms that cystic lesions are a dynamic process and may be transiently present during lung cancer development. Jung et al.¹⁹ closely followed the CT imaging data of patients and divided the development of cystic lung cancer into four stages: ① a cystic airspace component appeared in the ground-glass lesion ② the area of the cystic airspace gradually enlarged, while the surrounding ground-glass component thinned or remained unchanged ③ the cystic airspace wall gradually derived a solid component from the ground-glass portion of the cystic airspace ④ the solid portion gradually encircled the cystic airspace. The cystic wall thickness continued to increase, and the space within the cystic airspace continued to be filled. However, this model is only based on the pathologic type of lung adenocarcinoma. LCCAs is also partly squamous, and the evolution of cystic squamous lung cancer has not been confirmed by research.

The first morphological classification of LCCAs was proposed by Mascalchi et al.²⁰ proposed four subtypes: (1) cystic lesions with exophytic wall nodules, (2) cystic lesions with endophytic wall nodules, (3) cystic lesions with thickened cystic walls, (4) mixed cystic and soft tissue lesions. Later, Fintelmann’s²¹ classification criteria were improved by adding subsystems to it. In 2019, Shen⁴¹ developed a more concise classification system: ① thin-walled, mean wall thickness <2 mm ② thick-walled, mean wall thickness ≥2 mm ③ wall-nodular, nodules on the wall of the capsule (endophytic or ectophytic) ④ mixed, solid or non-solid tissues are mixed in polycystic lesions. This classification is also accepted by most researchers. Many researchers would like to design the classification to try to create a new method to assess the staging of cystic lung cancer and correlate it with pathology and prognosis, but this approach is difficult. This is because the interpretation results are influenced by the transient nature of the imaging findings and the subjectivity of the interpreting physician. Some cystic lesions have more than one feature simultaneously, such as when the lesion contains both nodular and multicystic findings, and staging depends on the subjective judgment of the interpreting physician.

6.2. Pathology of cystic lung cancer

Most LCCAs are adenocarcinomas, especially subtypes of lung adenocarcinoma. In or around the walls of cystic spaces, pathologic examination reveals the proliferation of tumor cells.^21,29 Jung ‘s study,¹⁹ based on the proposed stages of development of cystic lung cancer imaging, also explored the pathologic component content at each stage. In the second stage, the epithelial tissue component was 59.5%, and the papillary component was about 18.7%; in the fourth stage, the thickness of the cyst wall gradually increased, as did the percentages of micropapillary and solid components (18.6% and 15%). In comparison, the epithelial tissue component was only 11.8%, which suggests that the wall of cystic lung carcinoma is associated with pathologic invasiveness. Zhu et al. ¹⁹ also demonstrated that multicystic structures with irregular cystic lumens and the size and attenuation of the tumor diameter were predictors of the pathological aggressiveness of cystic lung adenocarcinoma. The authors suggested that possibly cystic lesions were a manifestation of lung adenocarcinoma progressing to the infiltrative stage or a manifestation of more poorly differentiated lung adenocarcinomas, which is in line with the findings reported by wang et al.,²⁵ who reported findings consistent with their suggestion that cystic airspace is an independent predictor of invasiveness.

6.3. Correlation of imaging and pathology

The characteristics of cystic lesions observed on CT are helpful in assessing the pathologic aggressiveness of the tumor. Increasing thickness of the cystic space wall on CT may correlate with tumor aggressiveness, suggesting that the tumor may have invaded the surrounding tissue. Watanabe et al.^18,45 analyzed the pathological features of different groups of LCCAs with wall thicknesses of 4 mm as a cutoff. The histological results showed statistically significant differences between the thick-walled group and the thin-walled group in terms of solid tumor components, vascular infiltration, lymphoid infiltrative necrosis, obstructive pneumonitis, intraluminal abscess formation, and fine bronchial obstruction. Moreover, cystic walled nodules or mass pits on CT correspond to substantial tumor components on pathology and can be used to assess the degree of tumor differentiation and prognosis. Shen et al. identified 123 patients with LCCA and correlated the imaging features and pathologic aggressiveness of these patients, and found that different types of LCCA differed in the degree of pathologic differentiation and that certain imaging features (e.g., cystic wall components, intracapsular surface irregularities) were independent risk factors for the moderately/poorly differentiated subtype. LCCAs with wall nodule type have the highest degree of malignancy. Ground-glass shadows on CT may be associated with non-substantial portions of the tumor, and ground-glass shadows have been shown to reflect an early or pre-invasive tumor state in previous studies.^46,47 This may represent the possibility that ground-glass lesions may be a marker of a better prognosis for cystic lung cancer, but no studies have been done to prove this.

7. Diagnosis of LCCAs

Diagnosis of LCCAs is difficult, and obtaining tissue for pathologic analysis is the gold standard for diagnosis. Most of the studies included in this article were surgical patients with postoperative pathologically confirmed lung cancer.

¹⁸F-fluoro-2-deoxyD-glucose (¹⁸F-FDG) PET/CT is an advanced medical imaging technology that combines the metabolic imaging of PET with the anatomical imaging of CT to provide more comprehensive functional and structural information in vivo.⁴⁸ ¹⁸F-FDG PET/CT plays a complementary role in the evaluation of LCCAs, particularly when malignancy is suspected despite inconclusive CT findings. Malignant cystic lesions typically show increased FDG uptake in the solid components or thickened walls. However, the diagnostic performance of PET/CT in LCCAs is limited by the low metabolic activity of thin-walled or ground-glass components. In a study by Mascalchi et al.,²⁰ only a subset of LCCAs demonstrated avid FDG uptake, and false-negative results were not uncommon in lesions with minimal solid components. The sensitivity of PET/CT for thin-walled cystic lung cancer has been reported to be lower than that for solid nodules, with a false-negative rate ranging from 30% to 50% in some series.³⁴ Therefore, a negative PET/CT finding does not reliably exclude malignancy in cystic lesions, and histopathological confirmation remains essential. A recent review by Kumbasar et al.⁴⁹ further emphasized the importance of integrating PET/CT findings with morphological features to avoid delayed diagnosis.

CT-guided percutaneous lung aspiration biopsy is a well-established method for the cytologic or histologic diagnosis of lung lesions, with high diagnostic accuracy even for ground-glass nodules.^50,51 However, cystic lesions pose specific challenges. Theoretically, the cystic cavity may be vascularized and communicate with the airway, raising concerns about an increased risk of hemoptysis and pneumothorax.⁵² Nevertheless, several studies have demonstrated that CT-guided biopsy of cavitary pulmonary lesions can achieve high diagnostic accuracy with acceptable complication rates. Kiranantawat et al. ⁴⁷ reported a diagnostic accuracy of 91.4% for cavitary lesions, with a pneumothorax rate of 27.1% and a chest tube placement rate of 8.6%. Similarly, Shin et al. ⁵³ and Zhuang et al.⁵⁴ confirmed the safety and efficacy of this approach in thin-walled and cavitary lesions. Therefore, while theoretical risks exist, CT-guided biopsy remains a feasible and effective diagnostic tool for selected LCCAs when performed by experienced operators.

8. Molecular features of LCCAs

Emerging evidence suggests that LCCAs may harbor distinct molecular profiles. Fintelmann et al.²¹ reported that among 30 patients with LCCAs, 60% had EGFR mutations, with a predominance of exon 19 deletions and L858R point mutations, similar to non-cystic lung adenocarcinomas. However, other studies have shown that LCCAs exhibit a higher frequency of KRAS mutations in Western populations, potentially reflecting differences in smoking history and ethnicity.⁵⁵ Whether the presence of cystic airspaces correlates with specific molecular subtypes remains unclear. Some authors have suggested that the cystic morphology may reflect a pattern of lepidic growth rather than a distinct molecular entity.²⁹ Further studies integrating genomic profiling with imaging phenotyping are needed to clarify the molecular underpinnings of LCCAs and to explore potential therapeutic implications.

9. Prognosis and management of LCCAs

Chen et al.³³ considered cystic lesions to be an independent influence on the prognosis of early-stage lung adenocarcinoma, with cystic lung adenocarcinomas having a poorer prognosis compared to non-cystic lung adenocarcinomas, especially those with cystic cavities of >5 mm or multiple cavities. A study by Watanabe et al.³¹ also demonstrated that patients with cystic adenocarcinomas had a significantly shorter survival time, with a 5-year survival rate of 67.7% and a median survival time of 61.2 months. The 5-year survival rate for patients without cavity formation was 80.8%. Multifactorial analysis showed that cavity formation was an independent prognostic factor for adenocarcinoma. Meanwhile, Chen et al. ⁵¹ also found that the postoperative recurrence rate of cystic lung cancer was higher than that of non-cystic lung cancer. Watanabe believed that the developmental process of cystic lung cancer was accompanied by thickening of the wall.⁴⁵ The results showed that the incidence of postoperative recurrence was greater in the thick-walled group of lung cancers (wall thickness >4 mm)) than in the thin-walled group of lung cancers (wall thickness ≤4 mm), and this result was statistically different. In recent years, many researchers have devoted themselves to studying the prognosis of LCCAs based on their morphologic stage. Shen et al.¹⁸ classified patients with LCCAs into four types based on imaging manifestations and matched the patients using the propensity matching score method. Their study showed that type III LCCAs with wall nodules had the worst prognosis. However, there was no statistically significant difference in recurrence-free survival between the cystic and non-cystic groups in their study, which may be related to confounding factors as well as sample size limitations. Ma’s study²² revealed different results, with 5-year OS rates of 100%, 49.4%, 74.6%, and 70.4% for type I, type II, type III, and type IV LCCAs, respectively, with type II cystic lung cancer having the worst prognosis. The number of LCCAs patients in the two studies was limited, and data from larger samples are still needed to confirm the conclusions in the future.

The 2017 Fleischner Society guidelines for CT impact incidentally detected pulmonary nodules define stratification based on smoking status and nodule size and number, with recommendations for follow-up observations related to pulmonary nodules at different risk levels.⁵⁶ For cystic lung nodules, there is no expert consensus guideline to guide follow-up because there are fewer studies. There is little information on staging progression during observation. Interestingly, the majority of patients involved in cystic lung cancer involve surgical patients, but information on postoperative lymph node involvement is not well collected.^22,31 This will determine whether patients with LCCAs should undergo lymph node dissection or whether patients should undergo postoperative adjuvant therapy. Frank et al. ⁵⁴ combined the Fleishner Society and previous studies to propose an observation protocol regarding cystic lesions. For the initial detection of a cystic airspace lesion, other pulmonary cystic lesions and infections should be ruled out first, and FDG-PET can be performed if necessary. In the presence of low FDG uptake, an observation period of greater than two years is recommended, with an initial interval of 3-6 months. For cystic lesions evolving from ground-glass lesions, chest CT can be reviewed annually if there is no change, while for cystic lesions presenting with a solid component, early intervention is needed, and surgical biopsy is the best way to confirm the diagnosis.

10. Discusssion

This narrative review provides a comprehensive overview of lung cancer associated with cystic airspaces (LCCAs), with an emphasis on imaging–pathology correlation, diagnostic challenges, and clinical management. In this section, we compare our findings with those of previous reviews, highlight the novelty of this work, discuss its limitations, and outline future research directions.

10.1. Comparison with previous reviews

Several previous reviews have addressed LCCAs, including those by Snoeckx et al.²⁹ and Detterbeck et al.,⁵⁷ which focused primarily on CT morphological classification and clinical management. While these works provided valuable frameworks, they did not systematically integrate pathological invasiveness with imaging phenotypes. In contrast, our review synthesizes recent evidence linking specific CT features—such as wall thickness, wall nodules, and ground-glass components—to pathological aggressiveness, as reported by Shen,¹⁸ Zhu,²³ and Watanabe.⁴⁵ This imaging–pathology correlation is a key contribution of our work, as it offers clinicians practical indicators for risk stratification.

10.2. Relevance and novelty

The increasing detection of LCCAs through low-dose CT screening underscores the need for practical guidance to distinguish benign from malignant cystic lesions. Current guidelines, such as those from the Fleischner Society,⁵⁶ provide recommendations for solid and subsolid nodules but do not specifically address cystic airspaces. Our review fills this gap by consolidating available evidence on LCCAs and proposing a diagnostic approach that integrates clinical, imaging, and pathological considerations. Additionally, we have summarized epidemiological characteristics across 21 studies, revealing a predominance of adenocarcinoma and a variable gender distribution that may reflect ethnic and methodological differences. This aggregated data serves as a useful reference for future studies.

10.3. Limitations

As a narrative review, this study has several limitations. First, the literature search was not systematic; although we covered major databases (PubMed, Web of Science, CNKI), we cannot guarantee that all relevant studies were included. Second, the heterogeneity in study designs, sample sizes, and reporting standards across the included articles precluded a formal quality assessment or meta-analysis. Third, most cited studies were retrospective and involved surgical cohorts, which may introduce selection bias and limit generalizability to non-surgical populations. Fourth, the imaging–pathology correlations, while supported by multiple studies, are based on observational data and require prospective validation.

10.4. Future directions

Several challenges remain in the field of LCCAs. The T staging of cystic lung cancer is particularly problematic, as tumor measurements typically include the entire lesion, with the central airspace often corresponding to tumor-free area, leading to inaccuracies in staging. There is also a need for objective and quantifiable imaging indices—similar to the percentage of solid component—to assess the aggressiveness of LCCAs and facilitate risk stratification in clinical practice. Furthermore, whether the pathogenesis of LCCAs differs across pathological subtypes (e.g., adenocarcinoma versus squamous cell carcinoma) requires further investigation. Finally, the threshold for safe follow-up remains undefined; prospective studies with larger cohorts and longer follow-up are needed to establish evidence-based guidelines for the management of LCCAs.

11. Conclusion

Lung cancer associated with cystic airspaces represents a diagnostically challenging subtype of lung cancer. Integration of CT imaging features with pathological characteristics is essential for risk stratification and early intervention. Increased awareness among clinicians and further prospective studies are needed to establish evidence-based management guidelines for this unique entity.

Footnotes

Acknowledgements

The authors thank the Department of Radiology at the First Affiliated Hospital of Nanchang University for providing imaging data.

ORCID iD

Longhua Sun

Author contributions

Xin Xu: Conceptualization, Writing – original draft, Visualization. Jidong Guo: Data curation, Formal analysis, Writing – review & editing. Rihua Hu: Data curation, Investigation, Writing – review & editing. Wenxin Yuan: Methodology, Validation, Writing – review & editing. Longhua Sun: Conceptualization, Supervision, Funding acquisition, Writing – review & editing. All authors read and approved the final manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the National Natural Science Foundation of China (grant number 82360474).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

No new data were generated or analyzed in this review. All data cited are from previously published studies as referenced in the manuscript.*

All images are from the authors’ institutional database, and patient identifiers have been removed.

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