Primary pulmonary lymphoma (PPL) is an extranodal lymphoma involving the bronchi and/or lung parenchyma, and there is no history of extrapulmonary lymphoma at initial diagnosis or the subsequent 3 months (1). PPL is a rare neoplasm, accounting for 0.4% of all lymphomas, 0.5% of the primary pulmonary malignancies, and 3.6% of extranodal lymphomas. Mucosal-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone B-cell lymphoma, can arise from any mucosal site and is the most common type of PPL, accounting for 70% to 90% (2). Among them, the lung is the most commonly involved organ, especially the bronchus. Some pulmonary MALT lymphoma patients may have respiratory symptoms such as cough, chest pain, mild dyspnea, and hemoptysis (3). However, these symptoms are non-specific and approximately half of the patients are asymptomatic. Pulmonary MALT lymphoma remains a clinical diagnostic challenge, and currently, definitive diagnosis still relies on histological confirmation.

In recent years, with the improvement of image anatomical resolution, shortening of scanning time, and application of multi-planar reconstruction technology, computed tomography (CT) has become a powerful tool in the evaluation of pulmonary lesions and has been widely used (4). The CT manifestations of pulmonary MALT lymphoma are diversiform (5). On imaging, there are four main types of pulmonary MALT lymphoma: consolidation pattern, nodular mass pattern, ground-glass pattern, and diffuse interstitial pattern (6). Among them, consolidation is the most common pattern manifested as polygon-based parenchymal consolidation involving the lobes/segments of the lung (7). Lung cancer is the main cause of cancer incidence rate and mortality worldwide, and lung adenocarcinoma (LADC) is the most common histological type of lung cancer. Due to the overlap of clinical symptoms and radiological features, the consolidation pattern of MALT lymphoma (C-MALT) can be misdiagnosed as pneumonic-type lung adenocarcinoma (P-LADC) (8). Usually, MALT is indolent and progresses more slowly than LADC, patients with MALT lymphomas have a better prognosis than LADC. For most C-MALT, the mainstay of treatment is chemotherapy and immunotherapy (9, 10); however surgery is the first choice of treatment for P-LADC (11). Therefore, timely and accurate differential diagnosis of P-LADC from C-MALT is crucial for the formulation of appropriate treatment to improve the prognosis of patients.

Although several studies had been conducted to develop characteristic clinical, pathological, and imaging perspectives of pulmonary MALT lymphoma, and imaging perspectives (12), few reports have focused on its differential diagnosis from lung adenocarcinoma. Thus, the aim of the study was to evaluate whether C-MALT can be distinguished from P-LADC on the basis of clinical characteristics and CT imaging manifestations. We hope to increase clinical understanding of C-MALT through this study, improve treatment effectiveness, and reduce the risk of misdiagnosis of this disease.

The retrospective study protocol was approved by the ethics committee of the Affiliated Hospital of Nanjing University of Chinese Medicine, and the patient informed consent was waived because of the retrospective, observational, and anonymous nature of this research.

The treatment of C-MALT and P-LADC is different, misdiagnosis of C-MALT as P-LADC may lead to overtreatment, and misdiagnosis of P-LADC as C-MALT may lead to delayed surgical treatment (13, 14). Therefore, it is crucial to distinguish between C-MALT and P-LADC before the treatment. In clinical practice, clinical and radiological features are considered valuable tools for distinguishing them (15). Although several researchers have given attention to assessing the clinical, pathological, and imaging characteristics of C-MALT, few reports have focused on its differential diagnosis from P-LADC, and non-invasive distinguishing C-MALT from P-LADC in clinical practice is a challenge. Therefore, in the present study, we compared the clinical characteristics and CT imaging features of 31 patients with C-MALT and 58 patients with P-LADC, and established a logistic regression model to distinguish them. The results demonstrated that age, bronchiectasis within the consolidation, lymph node enlargement, and pleural effusion showed great potential in distinguishing C-MALT from P-LADC.

C-MALT patients mostly appear at about the age of 60, but young patients have also been reported (16), while P-LADC patients are mostly elderly and relatively older (17). In the study, we found the average age of patients of C-MALT was younger than that of P-LADC, which was consistent with previous studies. Some scholars indicated that nearly half of MALT lymphoma patients are asymptomatic, while some with clinical symptoms may present with respiratory symptoms such as cough, chest pain, mild dyspnea, and hemoptysis, similar to lung adenocarcinoma (18, 19). Consistent with previous studies, we found no significant difference in clinical symptoms between C-MALT and P-LADC patients(20). Furthermore, no significant difference was observed in gender and elevation of white blood cell count between the two groups.

The primary CT manifestation of C-MALT is large and lamellar consolidation involving lobe/segment, which is often misdiagnosed as P-LADC in clinical practice (21). In this study, we found that most C-MALT and P-LADC lesions were randomly distributed regardless of transverse and longitudinal distribution, with no obvious trend of central distribution, which was similar to the previous study (22). Although there was no significant difference was observed in air bronchogram signs between C-MALT and P-LADC groups, the pathological mechanisms were different. In C-MALT, tumors originate from the pulmonary interstitium and grow along or infiltrate the interstitial lung and bronchial submucosal epithelium, mainly destroying the pulmonary interstitium and bronchial wall is inviolable, therefore, residual bronchial shadows are often seen within the lesion (23). In the early stage of P-LADC, the tumor cells rarely obliterate the underlying pulmonary architecture, including the bronchi, resulting in the bronchial lumen staying smooth. As the tumor grows, due to the tumor invasion and desmoplastic reaction, the air bronchogram gradually disappears in P-LADC (24). The angiogram sign is a CT feature of pulmonary MALT lymphoma, but it is nonspecific as it is also observed in other diseases, such as lobar pneumonia, organizing pneumonia, pulmonary atelectasis, and lung adenocarcinoma, representing vascular wall destruction is absent (25, 26). Herein, there was no significant difference in angiogram signs between C-MALT and P-LADC groups. In accordance with previous studies, we also found there was no significant difference was observed between C-MALT and P-LADC in terms of lesion size, margin, CT attenuation value, calcification, and interlobular fissure bulging with p>0.05 (27).

Our results indicated that bronchiectasis within the consolidation was more frequently detected in the C-MALT group than P-LADC group (83.87% vs 20.69%, p<0.001). Hence, we supposed that bronchiectasis (especially cystic bronchiectasis) within the consolidation, as one of the relatively characteristic CT manifestations of C-MALT, helps to distinguish C-MALT from P-LADC (5). It is different from the permanent bronchial wall alterations observed in traditional bronchiectasis; there is no tumor necrosis or bronchial wall destruction in the dilated bronchus in C-MALT (28). The pathological basis of bronchial or bronchiolar dilation might result from the collapse and destruction of parenchyma adjacent to bronchus secondary to infiltration and proliferation of lymphoid tissue (22).

We found lymph node enlargement (75.86% vs 9.68%, p<0.001) and pleural effusion (43.10% vs 19.35%, p=0.025) were more frequently observed in the P-LADC group than C-MALT group. Consistent with other studies, a defining feature of MALT was the absence of significant mediastinal or hilar adenopathy. In the opinion of most researchers, MALT is essentially extranodal lymphomas according to the diagnostic criteria, rarely involving hilar and mediastinal lymph nodes (29). In addition, pleural invasion, as indicated by pleural effusion was less frequent in C-MALT than P-LADC.

In this study, we also constructed a logistic regression model using predictors with p<0.05 including age, bronchiectasis, lymph node enlargement, and pleural effusion, to distinguish C-MALT from P-LADC. Our data indicated that the model had good diagnostic efficacy with high AUC of 0.9555, 86.67% PPV, 91.53% NPV, specificity of 83.87%, sensitivity of 93.10%, and accuracy of 89.89%, suggesting that these features could assist in distinguishing C-MALT from P-LADC. Based on this result, we concluded that mastering these differential features was helpful for the accurate diagnosis of C-MALT, not only reducing the unnecessary surgical resection rate of C-MALT but also avoiding P-LADC delaying the optimal surgical timing (30).

There are several limitations that should be considered. First, this study was retrospective in nature, which might lead to selection bias. Second, given that the majority of consolidation pattern of lung cancer is found in adenocarcinomas, our studies were limited to adenocarcinomas, and other pathological types were not included. Further other pathological types of lung cancers should be investigated. Third, although the number of patients with C-MALT enrolled in the study was higher than in most previous studies, the number was still relatively small due to the rarity of C-MALT and our strict inclusion criteria. Therefore, prospective multicenter larger-cohort research may be needed to further confirm our results in future studies.

In conclusion, our findings demonstrated that C-MALT and P-LADC have differential clinical characteristics and CT features. An adequate understanding of these different characteristics can contribute to providing diagnostic clues for C-MALT and lead the clinician to make appropriate therapeutic strategies.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

The retrospective study protocol was approved by the ethics committee of the Affiliated Hospital of Nanjing University of Chinese Medicine. The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants’ legal guardians/next of kin because of the retrospective, observational, and anonymous nature of this research. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article because of the retrospective, observational, and anonymous nature of this research.

Design of experiment: ZD and ZW; acquire the clinical data: CD, PX, and WQ; image analysis: CD, WQ, and ZW; paper drafting: CD and WQ; data analysis: PX; paper correction: WQ. All authors contributed to the article and approved the submitted version.