Diffuse Large B-cell Lymphoma Presenting as Bronchial Mass

To the Editor: Primary mediastinal large B-cell lymphoma is a rare subtype of diffuse large B-cell lymphoma, constituting <0.5% to 1% of all primary pulmonary cancers.1 It rarely presents as an endobronchial mass, which can lead to airway obstruction and lobar atelectasis. It is thought to most commonly disseminate through direct, hematogenous, or lymphatic routes and frequently involves the main bronchi. Computed tomography (CT)–guided percutaneous biopsy or open thoracotomy have been considered the gold standard of diagnosis.1 However, the increasing availability of bronchoscopy modalities has proven effective in providing both an adequate biopsy sample for diagnosis as well as an opportunity for therapeutic interventions. Increased awareness of additional modalities such as airway ablation or stent placement is integral in the multidisciplinary management approach alongside chemotherapy and palliation for more advanced diseases. CASE PRESENTATION A 19-year-old female presented with fevers and dyspnea. CT chest with contrast demonstrated a right pleural effusion and a mediastinal mass effacing the superior vena cava, left innominate vein, and trachea (Fig. 1). There was also 90% stenosis of the bronchus intermedius due to tumor invasion. Thoracentesis showed an exudative sample with negative cytology. Rigid bronchoscopy was performed to allow tissue biopsy and safe recanalization of the airway. The obstructing mass was removed via cryoablation, and histologic analysis revealed diffuse large B-cell lymphoma (Fig. 2). Once the airway was cleared, the bronchus intermedius remained extrinsically compressed, requiring balloon dilation and stent placement (Aero 10×20) (Fig. 3). The left main bronchus also had extrinsic compression with 25% stenosis requiring balloon dilation.FIGURE 1: Computed tomography scan of the chest with contrast showing large mediastinal mass, extrinsic compression, and luminal involvement of the right lung airways.FIGURE 2: Bronchoscopic view of airways before intervention showing intraluminal tumor in proximal bronchus intermedius. Lobar branches to right middle and lower lobes were patent distally.FIGURE 3: Bronchoscopic view after tumor debulking showing stenosis due to extrinsic compression and subsequent stent placement.The patient received 6 cycles of R-EPOCH without significant complications. Subsequent positron emission tomography (PET) scans showed a significant decrease in mediastinal mass effect. Ultimately, the patient achieved a complete metabolic response. Repeat bronchoscopy for inspection revealed a patent bronchus intermedius with normal mucosa and no sign of the stent (Fig. 4). The patient does not recall coughing out the stent.FIGURE 4: Surveillance bronchoscopy after chemotherapy showing patent bronchus intermedius, normal appearing mucosa, and no sign of the stent.DISCUSSION Primary pulmonary lymphoma comprises ~0.5% to 1% of all primary pulmonary cancers.1 Furthermore, primary mediastinal Diffuse large B cell lymphoma (PMDLBCL) is estimated to make up 11% to 19% of all primary pulmonary lymphomas.2 Due to its rarity, PMDLBCL is difficult to differentiate from bronchus-associated lymphoid tissue lymphoma and primary pulmonary large B-cell lymphoma.3 Collectively, these tumors are separated into 2 classes: type 1, which is more common and spreads lymphatically or hematogenously into diffuse submucosal infiltrates, and type 2, which spreads directly from malignantly transformed lymphoid tissue.4 The patient’s neoplasm appears to be the latter type, with direct airway invasion, mass effect on mediastinal structures, and absence of distant metastases on PET CT. PMDLBCL originates from the thymus and most commonly presents in young women with constitutional symptoms, chest or back pain, lymphadenopathy, and sequelae of bronchial airway stenosis.5 PMDLBCL may also be seen in association with chronic inflammation, chronic methotrexate use, and immunosuppression in allograft solid organ transplantation.1,6 Typical biomarkers include CD 10, CD 20, Bcl-2, Bcl-6, and LCA.1–7 Our patient did not have the associated risk factors, and the tumor displayed CD 15, CD 20, CD 30, PAX5, Ki-67, and fascin biomarkers. Previous studies report that ~10% of PMDLBCL cases are diagnosed by bronchoscopy, and the majority still require CT-guided percutaneous biopsy or open thoracotomy.1 However, the shortfall of bronchoscopic biopsy has been the classic reliance on biopsy forceps, which yields limited samples with crush artifacts. Diagnosis of PMDLBCL can be performed by multiple modalities, such as forceps or needles, but cryoprobe ensures adequate tissue sampling to establish the diagnosis. Otherwise, a surgical biopsy would be warranted, burdening the patient with higher risk of complications and longer recovery duration. Pajares et al2 report a case of PMDLBCL that was diagnosed by cryoprobe after 2 failed attempts with forceps and theorize that tissue sampling by cryoprobe may be a higher yield due to the laminar cut from cryoprobe. Jiang et al6 also report a case of primary pulmonary Diffuse large B cell lymphoma (DLBCL) that required 2 bronchoscopies for diagnosis, initially via forceps and then via transbronchial need aspiration, before the successful diagnosis of PMDLBCL. As PMDLBCL commonly has a high burden of cell atypia, adequate sampling methods are crucial for diagnosis by histologic staining.2 The diagnosis in our patient was established by histologic analysis of the cryoablated endobronchial tumor that only required 1 bronchoscopy. This is a good example of how cryoablation is a safe and effective tool for ablating airway tumors and adequate tissue sampling. The stent could not be found on repeat bronchoscopy or postoperative imaging, including cross-sectional views, likely due to displacement following airway decompression subsequent to chemotherapy. The patient likely coughed up the stent, although she does not recollect this. Stent migration is a known risk and is especially prevalent in cases with very chemoresponsive tumors, such as lymphoma and small cell lung cancer.8 PMDLBCL has high rates of complete remission with a variety of chemotherapy regimens. Standard first-line therapy for all types of DLBCL includes rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone, which has shown a 60% success rate of sustained remission, although ~35% of patients will relapse.9 Second-line treatment may include cyclophosphamide, cytosine arabinoside, etoposide, dexamethasone, which has been documented to have rates as high as 71.5%.5 While rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone is the standard first-line therapy for all types of DLBCL, dose-adjusted R-EPOCH has been shown to have an overall survival rate of 97% in patients with primary mediastinal B-cell lymphoma.10 Our patient received dose-adjusted R-EPOCH and consolidative radiation therapy, with a complete metabolic response demonstrated on subsequent PET scan. CONCLUSIONS This case illustrates the utility of bronchoscopy for both diagnostic and therapeutic measures in patients with PMDLBCL. The availability of interventional pulmonology modalities such as cryobiopsy and airway stents, as well as trained operators, are important aspects in the multidisciplinary approach to treating thoracic malignancies. Prompt recognition and diagnosis are required for the early initiation of life-saving treatment.