Bronchus-Associated Lymphoid Tissue is a lymphoid aggregate located in the submucosal area of the bronchioles and plays a central role in the mucosal immunity of the airways, by inducing the accumulation of secretory immunoglobulin A (IgA)-producing cells. Long-lasting antigen stimuli promote the hyperplasia of BALT, which may develop into pulmonary mucosa-associated lymphoma (12
). Chronic inflammatory diseases could evoke oligo- or monoclonal cell proliferation in the mucosal lymphoid tissue, resulting in the development of lymphoma (14
). Our patients included 1 patient with rheumatoid arthritis and 2 patients with allergic rhinitis.
It is rare for an endobronchial lesion to be the primary presentation of lymphoma. Most cases of endobronchial lymphoma occur along with systemic diseases, more often in Hodgkin's lymphoma than non-Hodgkin's lymphoma (15
). Primary marginal zone B-cell lymphoma of BALT in the central airway is extremely rare. Endobronchial lymphoma is classified into two patterns according to the pattern of involvement (6
). Pattern 1 demonstrates diffuse submucosal infiltrates that originate from hematogenous or lymphangitic spread, in the presence of systemic lymphoma. Pattern 2 demonstrates airway involvement of a localized mass, due to the direct spread of lymphoma from the adjacent lymph nodes, or a lymphoma that arise de novo from BALT. Localized primary endobronchial lymphoma that is confined to the tracheobronchial tree without dissemination which may be classified as the Pattern 2 is extremely rare. All of our patients only presented with endobronchial lesions in the central airway, without mediastinal, hilar lymphadenopathy, or pulmonary parenchymal involvement of BALT. Moreover, none of our patients presented with systemic involvement according to the whole-body lymphoma work-up and 18
F-FDG-PET/CT, suggesting de novo lymphoma in the central airway.
In the four patients in this series, the main CT features included a mural, polypoid, ovoid endobronchial mass of the trachea or lobar bronchus with postobstructive air trapping, atelectasis, or pneumonia. There are a few reports on endobronchial BALT lymphoma in the lobar bronchus with lobar atelectasis and left main bronchus with unilateral hyperlucent left lung, but most of these are the case report findings of a single patient (6
In the three patients in this series, the main CT features included multiple, tiny, nodules or diffuse wall thickening along the trachea and main stem bronchi. There is one case report in the literature that describes diffuse narrowing of the tracheobronchial tree with endobronchial nodularities of extranodal marginal zone lymphoma, occurring along the trachea and central airway (20
). However, to the best of our knowledge, BALT lymphoma manifesting as diffuse wall thickening in the central airway on CT has not been reported. As such, our novel observation of the primary endobronchial marginal zone B-cell lymphoma of BALT was that it can manifest in not only the small airways and lung parenchyma, but also in the larger such as the trachea and major bronchi. On bronchoscopy, there was a well-circumscribed nodule with a smooth margin which mimicked the submucosal lesion in each patient. This finding correlates well with the CT findings.
Based on the results of the study, the primary endobronchial marginal zone B-cell lymphoma of BALT can be classified into 3 patterns: solitary intraluminal nodule, several tiny nodular protrusion, and diffuse wall thickening. That is, primary endobronchial marginal zone B-cell lymphoma of BALT needs to be differentiated from other variable large-airway diseases, including neoplastic and nonneoplastic lesions, and the differential diagnosis of each patient is required, depending on the radiologic patterns of the endobronchial BALT lymphoma. Nevertheless, it is not easy to differentiate endobronchial BALT lymphoma from other airway diseases. As such, the use of the radiologic-bronchoscopic correlation with histological confirmation and 18F-FDG-PET/CT are necessary to confirm the diagnosis and to exclude any other origins of the primary lymphoma and systemic involvement.
According to several studies by Beal et al. (9
) and Bae et al. (10
), marginal zone B-cell lymphoma shows identifiable and demonstrable, but not avid, FDG uptake with mSUVs ranging in 2.6-26 (mean mSUV: 6.8) and mSUVs in the range of 2.2-6.3 (mean mSUV: 4.2 ± 1.48), respectively. In our series, the maximum FDG uptake on 18
F-FDG-PET/CT was 3.3 (range: 2.3-5.7), similar to those mentioned in the earlier studies (9
). It is expected that the indolent growth and metabolic stability of these lesions cause the relatively low level of FPG uptake.
Treating BALT lymphoma is controversial, ranging from only observation to surgical resection alone, or in combination with chemotherapy or radiotherapy (18
). However, BALT lymphomas tend to remain localized until late in the natural course. The histological progression from a low-grade BALT lymphoma to a high-grade lymphoma is rare (< 10%), and they show good prognosis and a favorable long-term survival with a complete response rate of 79% and a partial response rate of 21%. Moreover, the research of Solomonov et al. noted that primary endobronchial lymphomas show favorable response to treatment with complete remission (median follow-up period: 19-28 months) (5
). In our series, the follow-up radiographs were available for all patients (follow-up period: 1-48 months), and none of the 5 patients who had undergone 2-chemotherapy, 2-radiotherapy, or 1-cryotherapy showed any evidence of recurrent mass or further disease progression after treatment. Furthermore, 3 of the patients demonstrated complete remission within a few months after radiotherapy or chemotherapy. Remission of both the endobronchial mass and the nodules was clearly noted on the follow-up CT scans as well as on the follow-up bronchoscopic examination in all three patients. Up to this time, these results also support the favorable outcome of primary endobronchial marginal zone B-cell lymphoma of BALT. A favorable outcome is believed to be related to the endobronchial location, which may be associated with the signs of airway obstruction typically seen, when there is a large airway-obstructing lesion, such as cough, sputum, hemoptysis, dyspnea, and wheezing (6
According to Erbaycu et al. (19
) endobronchial BALT lymphomas can affect both genders equally. There are other previous case reports which have shown female predominancy (18
). All patients were female in our series.
This study has a few limitations. This study was retrospective and only enrolled a small number of patients. Therefore, we could not evaluate the specific findings for differentiating between primary endobronchial marginal zone B-cell lymphoma of BALT and other endobronchial tumor. However, to the best of our knowledge, our series of 6 patients is the largest study to show the potential variety of radiologic patterns of primary endobronchial marginal zone B-cell lymphoma of BALT. We expect that a more varied radiologic manifestation may be found by examining larger groups of patients. In addition, we did not determine the exact natural course of primary endobronchial marginal zone B-cell lymphoma of BALT, because the follow-up interval was relatively short. Further studies using data with longer follow-up intervals need to be used to define accurate prognosis and determine if optical management is necessary.
In conclusion, primary endobronchial marginal zone B-cell lymphoma of BALT can manifest in three distinct patterns in the tracheobronchial tree on CT scan, but the solitary intraluminal nodule is the primary pattern. It can be considered as the differential diagnosis of endobronchial lesions in the clinical setting, if there is no widely disseminated disease or lung parenchymal involvement, homogeneous and mild FDG uptake on PET scan in the middle-aged women.