MGA is a tumor that originates in mucus-secreting cells in the bronchi or trachea and typically develops in the central area of the lung. Mucinous adenomas that are located peripherally (i.e., away from the center of the lung) are extremely rare (Table 1). The first report of a case of bronchial adenoma that originated from the mucous glands was published by Ramsey and Reimann in 1953 and shed light on the unique nature of MGA(1). Fourteen years later, in 1967, Kroe and Pitcock not only confirmed the existence of MGA but also coined its name and accurately depicted its characteristic features(2). Researchers have since discovered that GNAS mutations play a significant role in the development of MGA (3). However, only a limited number of diagnostic molecules are currently associated with MGA. Discovering more pathological features and genetic information for this type of tumor will help doctors take timely and effective treatment measures, avoid worsening of the condition, and improve the success rate of treatment. This information also helps deepen the understanding of diseases and promotes research and treatment progress for related diseases.
Table 1
Clinical data and outcomes in cases of mucous gland adenoma reported in the literature
| Case | Age | Initial symptoms | Location | Treatment | Outcome | Recurrence | References |
| 1 | 32 | —— | Peripheral | lobectomy | alive | no | (17) |
| 2 | 70 | cough、expectoration | Peripheral | wedge resection | alive | no | (7) |
| 3 | 57 | Short of breath | center | endoscopic resection | alive | no | (22) |
| 4 | 80 | —— | center | lobectomy | alive | no | (20) |
| 5 | 65 | chills、fever | center | continuous anastomosis | alive | no | (21) |
| 6 | 59 | cough | center | lobectomy | alive | no | (24) |
| 7 | 28 | chills、fever、chest pain | center | lobectomy | alive | no | (25) |
| 8 | 32 | hemoptysis、cough、fever | center | lobectomy | alive | no | (18) |
| 9 | 52 | cough、asthma | center | lobectomy | alive | no | (5) |
| 10 | 54 | cough | center | lobectomy | alive | no | (4) |
Clinically, MGA cause a range of respiratory symptoms, particularly hemoptysis, cough, dyspnea, and recurrent pneumonia (4). However, our patient had none of these typical symptoms except for occasional chest pain. Obstructive tracheobronchial tumors, such as pulmonary mucinous adenomas, tend to grow expansively and are most commonly found in the short bronchi and the trachea. Owing to their polypoid growth pattern, these tumors often obstruct the airway lumen, leading to symptoms that resemble those of chronic obstructive pulmonary disease (5). Therefore, it usually takes longer to make a correct diagnosis. The clinical presentation of pulmonary mucinous adenoma often resembles asthma or other chronic lung disease, causing patients to be misdiagnosed for a long period of time (6). There has even been a report of a patient with a pulmonary mucinous adenoma arising in the left lobe of the lung that was misdiagnosed as tuberculosis for up to 2 years (7). The lesion was located peripherally in our patient, which may explain why she had no obvious symptoms.
A thorough investigation of the lungs, including CT, bronchoscopy, and fluordeoxyglucose-positron emission tomography, is important for the diagnosis of MGA. Chest CT may be helpful for identifying centrally located MGA by revealing a well-defined mass that either has an air meniscus sign or is adjacent to the bronchi, indicating its location within the airway (8). However, Komatsu et al. reported a case in which chest CT showed a cavity in a peripheral mucinous adenoma. This variant finding highlights the difficulty in diagnosing peripherally located MGA using CT alone (9). Moreover, bronchoscopic findings do not provide enough information to distinguish MGA from other bronchial lesions, whether neoplastic or non-neoplastic. Therefore, the key to making a correct diagnosis is pathologic examination of the tumor after resection (10). Macroscopically, MGA usually appears as a round mass with a smooth appearance, but in some cases presents as a solid tumor with a multilobulated morphology outside the bronchial lumen (11).
In our case, invasive adenocarcinoma could not be completely excluded owing to alveolar invasion by the tumor, although it lacked cellular atypia and karyokinesis, and because this tumor rarely occurs in the lung periphery, tending to involve the lung parenchyma rather than the lung center, making diagnosis on frozen section difficult. We demonstrated microscopically that the stroma of the neoplastic cells in this case showed features of fibrosis; however, the stroma of mucinous adenomas can also appear hyalinized (11) or fibromyxoid (12). At the same time, there was atypical local hyperplasia in the lesion, indicating various histological changes in the intercellular stroma.
In this case, immunohistochemical analysis revealed only a small number of cells with TTF-1 positivity, which was weak. TTF-1 is a crucial protein molecule that is involved in the development of a fully functional lung (13). In healthy lung tissue, TTF-1 is typically expressed exclusively in type I and II pneumocytes (the cells responsible for gas exchange) as well as in the small bronchiolar epithelium (the lining of the small airways) (13, 14). Another interesting finding in this case was that the epithelium overlying the tumor showed clear expression of the TTF-1 antigen (15). We stained for CK7, CK20, and CK5/6 and found a positive CK7 response and negative CK20 and CK5/6 responses.
Most researchers have found that this tumor cell lacks cell specificity and mitotic figures (5, 11, 16). However, microscopically, we observed that cells in focal lesions showed mild heteromorphism with occasional nuclear mitosis. Smooth muscle myosin heavy chain was positive in myoepithelial cells around the gland, suggesting that the tumor may have originated from myoepithelial cells. To the best of our knowledge, the Ki67 index was negative in MGA cases reported to date (7, 11, 17, 18); however, in our case, the Ki67 index was 0–60%, indicating that some of the tumor cells were atypical and proliferating rapidly, reminding us to keep in mind the malignant proliferation potential of this tumor.
Zaleski et al. observed five different growth patterns in mucinous adenomas, including pure mucinous, combined cystic and acinar, combined cystic—microcystic—papillocystic, pure cystic, and mucoepidermoid-like (19). The main pathologic features of the tumor in our case were lack of a capsule, few vesicular cavities, and numerous microacini and glands (tubules) with prominent infiltration of plasma cells and lymphocytes, basically corresponding to the growth pattern of coexisting cystic and acinar features. The tumor in our case showed foci of lymphoid follicle formation, which has not been reported as a pathologic finding for most pulmonary mucinous adenomas. However, Zhang et al. also observed formation of lymphoid follicles in their series (11). Formation of lymphatic follicles once again suggests that the tumor may progress to malignancy.
In addition to distinguishing MGA, it is important to differentiate between mucinous adenocarcinoma and mucoepidermoid carcinoma. Mucinous adenocarcinoma is characterized by an infiltration and growth pattern, and the cells exhibit mitotic figures and necrosis. This type of carcinoma typically consists of glandular structures with abundant production of mucin. In contrast, mucoepidermoid carcinoma can be distinguished from MGA by the presence of squamous cells. In mucoepidermoid carcinoma, a combination of mucin-producing cells, intermediate cells, and squamous cells can be observed. This differentiation is crucial for accurate diagnosis and planning of appropriate treatment.
Centrally located tumors are found in the central part of the lungs and near the larger airways. When these tumors need to be surgically removed, the primary approach is to perform airway resection. This technique aims to remove the tumor while preserving as much of the lung parenchyma as possible. The lung parenchyma includes functional tissues that are responsible for gas exchange. However, in some cases, the tumor may have grown or spread into the lung parenchyma itself. In this situation, additional measures may be necessary. Owing to the inability to completely rule out the possibility of low-grade adenocarcinoma, some surgeons choose lobectomy(17, 20). Some surgeons have performed wedge resection and achieved good results (7) and others have opted for tracheal anastomosis surgery to remove a tumor while preserving the lung parenchyma (21). Endoscopic treatment may be preferable when a patient also has chronic obstructive pulmonary disease and the tumor is polypoid and attached to the bronchial wall (22). Considering the rarity of this disease, we recommend that patients be followed up long-term after surgery, especially when the tumor has invaded the lung parenchyma.
Currently, there are few studies on abnormal gene expression in MGA. Some researchers have found that NKX3.1 gene expression is significantly elevated in patients with MGA (23), and others have identified mutations in the GNAS gene (R201C) in these patients (20). Discovery of additional MGA-related gene mutations will facilitate a better understanding of their impact on development and treatment of disease, providing more possibilities for personalized medicine and precise treatment.
In summary, this article discusses the laboratory findings of adenoma in the lung mucosa in a patient with MGA, which differed from those in earlier reports, and reviews the relevant literature. We hope that this report will serve as a reference for clinicians and assist them in diagnosing this tumor.