Pulmonary lymphoma is rare, while the most common pathological type of PLL is MALT lymphoma or low-grade marginal zone B-cell lymphoma, and other types include DLBCL, follicular lymphoma, Burkitt lymphoma, T-cell lymphoma, and et al. For SPL, DLBCL accounts for around 36%, MALT for 23%, while HL for 15%. MALT lymphoma is believed to arise as a result of chronic inflammation of the marginal zone B cells of the “bronchial-associated lymphoid tissue”. It may associate with autoimmune disorders including Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto thyroiditis, chronic hepatitis, Helicobacter pylori infection or even smoke. Pulmonary DLBCL can be transformed from MALT, which is much more aggressive and tends to manifest with systemic symptoms B[6, 7].
The most common pathological diagnosis in our study is DLBCL, MALT and HL. Our study also showed high morbidity of chronic hepatitis B, chronic hepatitis C and Sjögren's syndrome in patients with pulmonary lymphoma, as 3 out of 4 Sjögren's syndrome patients were pathologically diagnosed as MALT.
Pulmonary lymphoma has specific radiographic patterns and endobronchial changes. Rose described two distinct patterns of lymphomatous involvement: Type 1 occurs in patients with clinically apparent systemic lymphoma, whose common symptom is pneumonitis. The airway involvement is diffuse submucosal nodules in airway, while other radiographic findings include parenchymal infiltrates, mediastinal lymphadenopathy. Some authors have suggested a preferential distribution at airway bifurcations. Type 2 consists of a solitary mass involving the central airways without evidence of systemic lymphoma, while the symptoms are airway obstruction, wheezing or cough. Other radiographic findings include atelectasis, lymph node enlargement in proximity.
Previous studies showed the most frequent patterns are consolidations (∼55%), nodules (∼55%) and masses (∼50%), and ∼85% of the patients have airways within the lesions. Micronodules (∼20%), ground-glass opacities (∼25%) and septal lines (∼10%) are less frequent. Hilar or mediastinal lymphadenopathy may be found in ∼15% of cases, which are usually < 1.5 cm and a mild pleural effusion in ∼10% of cases[1, 10, 11].
In our study, nearly half patients are type 1, that the major CT abnormality was consolidation accounts for 24.4%, and GGO accounts for 24.4%, may involve parenchymal and lymphomatous infiltrates. (1)As Fig. 1a,b showed, for consolidation lesions, endobronchial patterns under bronchoscopy are usually mucosae asperity or edema, occasionally focal solitary mass. The air bronchogram sign and angiogram sign are more characteristic manifestations of this disease. Its pathological basis is that the neoplasm originated from pulmonary interstitium, while the pulmonary blood vessels still remain. The neoplasm grows along the bronchial wall, so the original bronchial remains within the lymphoma. It was previously noted that MALT are associated with air bronchogram in nearly 50% of cases. While the hyperplasia of fibrous tissue can lead to traction bronchiectasis, that in consolidation lesions, bronchiectasis is another feature in pervious study. (2)For GGO lesions, endobronchial patterns under bronchoscopy are always normal(except only one case found focal solitary mass under bronchoscopy), as Fig. 1c,d showed, while TBLB can usually make the histological diagnosis. Another half patients are type 2, that the major CT abnormality was mass accounts for 43.9%, and nodule accounts for 7.3%. (3)For mass lesions, with or without cavitation, endobronchial patterns under bronchoscopy are diffuse airway submucosal nodules or thickening, frequently focal solitary mass, as Fig. 1e,f showed. It is considered that cavitary lesions suggest a higher grade lymphoma, while consolidation suggests a lower grade lymphoma with reserved bronchial tree. (4)For nodule lesions, endobronchial patterns under bronchoscopy are bronchiole stenosis, as Fig. 1g,h,i showed, frequently mucosae asperity or edema. We found bronchial obstruction and associated atelectasis, ultimately atelectasis is usually suggestive of concomitant endobronchial disease. It seems the frequency of nodule lesions is much lower than previous studies mentioned above, because nodules are always not accessible by bronchoscopy. However, there is tendency for these CT or endobronchial patterns to overlap, and patients may present with several simultaneously.
Since 2008 World Health Organization classification, subtype classification of lymphoma is necessary for an accurate diagnosis, to predict disease prognosis, and to guide the treatment. Our study excluded cases of suspected pathological diagnosis of lymphoma, but included 7 cases without subtype classification, that they needed following extrapulmonary biopsy. Previous studies suggested bronchoscopy may be of limited diagnostic value for pulmonary lymphoma diagnosis. For example, Ferraro et al. reported that bronchoscopy was performed in 39 patients with PPL but confirmed the diagnosis in only seven patients (18%). The sensitivity of bronchial and transbronchial biopsies in detecting MALT lymphoma have been reported to be 30 and 88%, respectively in different researches[1, 16].
However, for EBUS-TBNA, the diagnostic sensitivity seems better: the diagnostic sensitivity in lymphoma varied between 38% and 91% in the previous studies, according to diverse diagnostic criteria of the individual studies, proportion of new or prior lymphoma, prevalence of subtypes and implementing ancillary methods[17, 18]. For example, involved 65 cases with final diagnosis of lymphoma, Iqbal et al. indicated that the diagnostic sensitivity of EBUS-TBNA for patients with and without previously diagnosed lymphoma was 55% and 22%, respectively. Other researches studies the use of new techniques as transbronchial needle forceps or ROSE, indicating the benefit that the lymphoma diagnosis undertaken by an expert group working closely with lymphoma pathologists and a lymphoma MDT[19, 20]. Gonzalo et al. revealed the result of a meta-analysis, which involved fourteen studies with 425 patients. EBUS-TBNA reported an overall sensitivity of 66.2% and specificity of 99.3%. For a new diagnosis of lymphoma, thirteen studies including 243 participants reported sensitivity of 67.1% and specificity of 99.6%; for recurrence of lymphoma, eleven studies included 166 participants reported sensitivity of 77.8% and specificity of 99.5%. In the recurrence group, the use of ROSE, sample size and flow cytometry was found to increase the sensitivity of EBUS-TBNA, albeit a potential sources of heterogeneity.
Our study included definitive diagnosis of lymphoma under bronchoscopy, that only 7 patients underwent TBNA meanwhile, probably because of the low sensitivity of EBUS-TBNA without ROSE. From my point of view, the use of bronchoscopy to diagnose lymphoma is easy to perform and minimally invasive with low frequency of procedure-related complication. Approximately one-third of patients can be given a definitive diagnosis of lymphoma, with carefully patients selected according to CT features mentioned above(mass, GGO or consolidation), avoiding the need for further invasive procedures, such as CTguided transthoracic needle biopsy or thoracoscopy. Second, with high diagnostic accuracy in both benign and malignant diseases, bronchoscopy with or without EBUS-TBNA provides high differential diagnostic yield for lesions mimicking lymphoma such as lung cancer, infection and sarcoidosis. Third, either a definitive diagnosis or suspected lymphoma was provided currently for 85% of patients, which may be helpful for decisions with the management or further diagnostic procedures.