Pulmonary Diffuse Large B-cell Lymphoma Research Articles

Prognostic factors and predictive models for primary pulmonary diffuse large B-cell lymphoma: a population-based analysis

ABSTRACT Background Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. Methods We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. Results A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. Conclusion This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making.

Primary Pulmonary Diffuse Large B-Cell Lymphoma - a Rare Case Report

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive hematological malignancy, and a common histological form of non-Hodgkin's lymphoma. However, its extra-nodal presentation is seen in 30-40% of cases with involvement of gastrointestinal tract, skin, testes, adrenals and bone. ( Lugogo NL et al., 2006) A pulmonary manifestation is an extremely rare entity. We present an atypical case of DLBCL presenting as pleuritic chest pain with imaging consistent with bilateral pulmonary nodules suggestive of metastasis. Case description: A healthy 87 year old male former smoker with a history of type 2 diabetes mellitus, hypertension presented to the emergency department with pleuritic chest pain. There was no associated cough, shortness of breath, palpitations, nausea, dizziness or diaphoresis. No recent infections or B symptoms. He had a good appetite. He had prostate cancer 20 years ago and had a radical prostatectomy. Upon presentation, work up showed mild anemia (Hb 11.1 g/dL). Cardiac work up for chest pain was unremarkable. Chest X-Ray revealed mass like opacities in each lung with largest in left mid lung measuring up to 6 cm. CT chest with IV contrast revealed multiple lung nodules bilaterally with 2 largest in left upper lobe measuring 5.6 x 3.7 cm and 5.7 x 3.3 cm. Multiple other small nodules are present in both lung fields consistent with diffuse lung metastasis. No lymphadenopathy was noted. (Image 1) PET CT scan was significant for bilateral FDG avid lung lesions. No evidence of other FDG avid disease. CT guided biopsy of the left lung mass surprisingly revealed diffuse large B cell non-Hodgkin's lymphoma, non-germinal center type. (Image 1) Immuno-histochemistry showed atypical lymphocytes positively stained with CD20, BCL6, BCL2, PAX5 and MUM1. C-myc had 50% positivity. Ki67 had 90% proliferative index. FISH analysis was negative for MYC, BCL2 and BCL6; hence there was no double hit lymphoma detected. According to Lunago classification, patient had advanced stage disease with IPI (prognosis index) of 2. His ECOG PS score was 0. He was initiated on R-Pola-CHP. Given his age, Cyclophosphamide and Adriamycin doses were reduced as done with R-mini CHOP. Vincristine was avoided given neurotoxicity. Discussion: Primary pulmonary B-cell lymphomas (PP-BCLs) represent less than 3-4% of all extra-nodal NHL. They primarily affect the lung without evidence of extrapulmonary disease at the time of diagnosis. PP-DLBCL accounts for only 10% cases of PP-BCLs. ( Sanguedolce et al., 2021) Most cases have atypical presentation. Likewise, in our patient, he manifested with atypical chest pain without any B symptoms. Radiographic imaging can show variable findings of consolidation, single/multiple nodules, reticular interstitial infiltrate or bilateral ground glass opacities. In view of the insidious onset and lack of specificity in clinical symptoms, primary pulmonary lymphomas are frequently misdiagnosed as refractory pneumonia, lung abscess, asthma, primary lung cancer, or lung metastasis. ( Liu et al., 2020) Patients with DLBCL are typically treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). However, with this regimen, only 60% of patients are cured and the rest might relapse. In the POLARIX phase 3 trial, polatuzumab vedotin (a monoclonal antibody to CD79b ubiquitously expressed on B cells) combined with R-CHP significantly improved 2 year progression-free survival compared to the routine R-CHOP therapy in previously untreated DLBCL patients. ( Tilly et al., 2022) Given our patient's advanced stage disease, he was initiated on the Pola-R-CHP regimen. Doses of cyclophosphamide and doxorubicin were reduced as per the R-mini CHOP dose-reduced regimen for a physically fit elderly individual. Patient continues on therapy at the time of this abstract. In conclusion, primary pulmonary DLBCL is a rare entity with only a few case reports in literature. It should be considered in patients presenting with large pulmonary masses, mimicking metastatic disease.

INCIDENTAL PRIMARY PULMONARY DIFFUSE LARGE B-CELL LYMPHOMA

INCIDENTAL PRIMARY PULMONARY DIFFUSE LARGE B-CELL LYMPHOMA

Primary Pulmonary EBV-positive Diffuse Large B-cell Lymphoma in a Patient with Primary Myelofibrosis on a JAK Inhibitor

Primary Pulmonary EBV-positive Diffuse Large B-cell Lymphoma in a Patient with Primary Myelofibrosis on a JAK Inhibitor

Primary pulmonary diffuse large B-cell lymphoma in a young female patient.

Even if the patient is young or female, a primary pulmonary diffuse large B‐cell lymphoma could be considered as a differential diagnosis of multifocal consolidation in the lung.

Primary pulmonary diffuse large B-cell lymphoma with multiple ground-glass nodules as the primary manifestation

Introduction:Primary pulmonary lymphoma (PPL) is a rare extranodal lymphoma. Only 5% to 20% of patients suffering from PPL have diffuse large β-cell lymphoma (DLBCL), and their chest computed tomography (CT) findings show single- or double-lung patchy or flocculated shadows, isolated or multifocal nodules, or masses. In this research paper, we report an older woman having multiple ground-glass nodules, who was eventually diagnosed with primary pulmonary diffuse large β-cell lymphoma (PPDLBCL).Patient concerns:A 69-year-old woman suffering from cough was admitted to the Second Hospital of Jilin University.Diagnoses:A chest CT scan showed multiple ground-glass nodules. She had received 2 weeks of antibiotic treatment, but the multiple ground-glass nodules were still present. Lung biopsy was performed by tracheoscopy, which showed non-Hodgkin diffuse large β-cell lymphoma.Interventions:The patient received R-CHOP-21 chemotherapy.Outcomes:The multiple ground-glass nodules were absorbed.Conclusion:The current study shows that spotting multiple ground-glass nodules in the lungs is a clear indication of the presence of PPDLBCL. It is important to spread awareness of PPDLBCL, which needs timely diagnosis and management.

AN UNUSUAL CASE OF PULMONARY CAVITARY LESIONS IN AN IMMUNOSUPPRESSED PATIENT

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The differential diagnosis of pulmonary cavitary lesions is broad. They can be categorized in to infectious and non-infectious diseases, including neoplasms. Among malignancies, squamous cell carcinoma is a common cause of lung cavitation (1). Herein, we report a rare case of primary pulmonary diffuse large B-cell lymphoma (DLBCL) in a patient with rheumatoid arthritis that presented with multiple cavitary lesions and hypercalcemia. CASE PRESENTATION: 83-year-old male presented with hemoptysis, dyspnea, confusion, and constipation for several weeks. His past medical history was significant for tobacco abuse and interstitial lung disease from rheumatoid arthritis (RA) treated with methotrexate. CT chest showed bilateral cavitary lung lesions, left-pneumothorax and pneumomediastinum, needing chest-tube placement. Pulmonary function test showed a mild restrictive defect with a severe reduction in diffusion capacity. Labs showed hypercalcemia of 13.7 mg/dl, suppressed parathyroid hormone (PTH), elevated PTH-related peptide (PTHrp), and 1-25(OH) 2 Vitamin-D level. Quantiferon gold, sputum acid-fast bacilli and cultures were negative. Blood cultures (1/4 bottles) grew Actinomyces viscosus that was treated with 6-weeks of piperacillin-tazobactam. Bronchoscopy with lavage was unrevealing; however, due to a suspicion for malignancy with elevated PTHrp level, a CT-guided biopsy of left lower lobe lung mass was performed that confirmed a diagnosis of DLBCL, non-germinal center B-cell type. DISCUSSION: Pulmonary lymphoma is very rare and presents with nonspecific pulmonary symptoms (2). The pathogenesis of primary pulmonary DLBCL remains elusive. Patients with autoimmune disorders and recurrent bacterial infections are at a higher risk for developing DLBCL. Chest imaging may show nodular lesions, consolidation or interstitial /mixed alveolar infiltrates (2). DLBCL presenting with multiple cavitary lesions, is rarely reported. In our patient hypercalcemia was mediated by elevation of both PTHrp and 1-25(OH)2 Vitamin-D, which is unusual. Most primary pulmonary lymphomas (PPL) are low-grade mucosa-associated lymphoid tissue (MALT)-type, compared to more aggressive pulmonary diffuse large B-cell lymphoma (DLBCL), which is very uncommon (3). Most likely, our patient's autoimmune disorder (RA) and chronic methotrexate use contributed in the development of his DLBCL. CONCLUSIONS: We report a rare case of primary pulmonary DLBCL that manifested with multiple cavitary lesions and hypercalcemia. DLBCL must be considered in the differential diagnosis of cavitary lung lesions particularly in immunosuppressed patients. Reference #1: Chaudhuri MR. Primary pulmonary cavitating carcinomas. Thorax. 1973;28:354-366 Reference #2: Fujita N, Ando M, Goto A, Sakata M, Ogata M, Usagawa Y, et al. Diffuse large B-Cell lymphoma arising from the lesion of chronic lobar atelectasis. Tohoku J Exp Med. 2020;250(2):129–35. Reference #3: Brown S, Horton J, Rosario D, Dorsey DA, Hetz S, King CS. High-grade primary pulmonary B cell lymphoma presenting as a Necrotic mass. Respir Care. 2011 Jun 1;56(6):871–3. DISCLOSURES: No relevant relationships by Haytham Adada, source=Web Response no disclosure on file for Mahmoud Amarna; No relevant relationships by Pavan Annamaraju, source=Web Response No relevant relationships by Camelia Chirculescu, source=Web Response No relevant relationships by Nino Nemsadze, source=Web Response No relevant relationships by Sana Yakoob, source=Web Response

Simultaneous occurrence of invasive pulmonary aspergillosis and diffuse large B-cell lymphoma: case report and literature review

BackgroundPatients with lymphoma are at risk for developing pulmonary opportunistic infections due to immunocompromise. However, clinical reports of concurrent lymphoma and opportunistic infection at presentation are rare and often confined to single cases. A delayed diagnosis of either opportunistic infection or lymphoma usually occurs in this complex situation. Here, we report such a case and analyse 18 similar cases searched in the PubMed database to deepen clinicians’ understanding.Case presentationA 48-year-old man presented with a 3-month history of fever, cough and emaciation. High-resolution computed tomography revealed bilateral cavitating lesions of different sizes. Aspergillus fumigatus complex was identified from a bronchoalveolar lavage fluid culture. However, antifungal treatment combined with multiple rounds of antibacterial therapy was unsuccessful, and the patient’s lung lesions continued to deteriorate. Multiple puncture biopsies finally confirmed the coexistence of diffuse large B-cell lymphoma. Despite the initiation of combination chemotherapy, the patient died of progressive respiratory failure.ConclusionsSynchronous pulmonary lymphoma and simultaneous opportunistic infection is rare and usually lacks specific clinical and imaging manifestations. Lymphoma should be considered as part of the differential diagnosis of patients with an opportunistic infection when treatment fails or other symptoms are present that could be considered “atypical” for the condition. Tissue biopsy is the gold standard, and multiple biopsies are essential for making the final diagnosis and should be performed upon early suspicion.

Pulmonary Intravascular Large B-cell Lymphoma in a Patient Administered Methotrexate for Rheumatoid Arthritis.

A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.

A Case of Primary Pulmonary Diffuse Large B-Cell Lymphoma Diagnosed by Transbronchial Biopsy

A Case of Primary Pulmonary Diffuse Large B-Cell Lymphoma Diagnosed by Transbronchial Biopsy

Primary pulmonary diffuse large B-cell lymphoma diagnosed by transbronchial biopsy: report of one case

Primary pulmonary diffuse large B-cell lymphoma diagnosed by transbronchial biopsy: report of one case

A rare case of primary pulmonary diffuse large B cell lymphoma with CD5 positive expression

Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet been well-defined. Further description is important for the diagnosis and treatment of PPDLBCL. Herein, we reported a case of a patient who suffered from bilateral chest pain and dyspnea. Computed tomography (CT) of chest demonstrated bilateral lung mass, consolidations and reverse halo sign, while consolidations and reverse halo sign are uncommon according to previous reports. Tissue samples were taken by CT guided needle biopsy. The histological samples showed PPDLBCL. This case was special in view of positive expression of CD5. After the case was treated by cyclophosphamide pirarubicin vindesine dexamethasone (CHOP) chemotherapy for six courses, her clinical symptoms were partially alleviated, while CT showed progression disease. This case report highlights different imaging features and characteristics of molecular biology, and reviews study progress of PPDLBCL.

Diagnosis and management of a patient with primary pulmonary diffuse large B-cell lymphoma: A case report and review of the literature.

Primary pulmonary lymphoma (PPL) is an uncommon type of non-Hodgkin’s lymphoma. The majority of PPLs are of low-grade, mucosa-associated lymphoid tissue type. Primary pulmonary diffuse large B-cell lymphoma (DLBCL) is extremely rare, and prompt diagnosis may be challenging since its clinical symptoms and signs are nonspecific. Although the clinical features, diagnostic procedures, optimal management and prognostic factors of this disease have not yet been well defined, open thoracotomy and chest computed tomography (CT)-guided percutaneous biopsy are the preferred methods used in previous studies. In the present case report, the diagnosis and management of a patient with primary pulmonary DLBCL is reported. A 68-year-old patient was admitted to hospital in May 2013, with complaints of shortness of breath and intermittent wheezing and a cough associated with the production of small amounts of phlegm. Following admission, chest CT scans revealed a mass in the right middle lobe with ground-glass opacities at the lesion margins, as well as air bronchograms in the areas of consolidation. Bronchoscopy was performed and revealed an endobronchial lesion and partial stenosis in the distal end of the middle segment bronchus. Transbronchial needle aspiration (TBNA) of the right hilar lymph node, as well as endobronchial biopsy, was performed. The patient was diagnosed with primary pulmonary DLBCL by subsequent histopathological and immunohistochemical analysis of biopsy specimens collected via TBNA. Following the final diagnosis, standard treatment with CHOP chemotherapy resulted in significant clinical and radiological response and the patient remained in remission 8 months later. These results indicate that TBNA may be an effective method for the diagnosis of primary pulmonary DLBCL.

A Case Of Primary Pulmonary Diffuse Large B-Cell Lymphoma Initially Suspected Of Lung Abscess

A Case Of Primary Pulmonary Diffuse Large B-Cell Lymphoma Initially Suspected Of Lung Abscess

Cavitary pulmonary involvement of diffuse large B-cell lymphoma transformed from extra nodal marginal zone B-cell lymphoma MALT type

We describe a case of pulmonary diffuse large B-cell lymphoma (DLBCL), which was thought to arise from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 68-year-old woman presented with a 2-month history of cough and bloody sputum. The chest X-ray and computed tomography revealed a mass with cavitation in the right lower lobe. Transbronchial biopsy specimens revealed a granulomatous infiltration without malignant cells. However, diagnosis of MALT lymphoma was established from gastric biopsy specimen. Subsequently, a right lower lobectomy was performed because of hemoptysis. Examination of the resected specimen revealed a diffuse large B-cell lymphoma, which was considered to have transformed from MALT lymphoma, because both lung and stomach lesions had the chromosomal translocation t(11;18)(q21;q21) in common. In addition, there were no nodules, masses, alveolar or interstitial infiltrates in the lung fields, which are usually observed in the case of marginal zone B-cell lymphoma of bronchial mucosa-associated lymphoid tissue. These findings indicate that involvement of DLBCL have to be considered in patients with MALT lymphoma and cavitary lesion of the lung.

Primary pulmonary diffuse large B‐cell lymphoma

Primary pulmonary diffuse large B‐cell lymphoma

HIV-1 and 2009 H1N1 Influenza A in Adults

HIV-1 and 2009 H1N1 Influenza A in Adults

A Case of Diffuse Large B-cell Lymphoma of the Lung Demonstrating Diffuse Ground-glass Shadows

We report a case of 77-year-old woman suffering from breathlessness on exertion and dry cough. Chest computed tomography (CT) showed diffuse ground-glass shadows. A video-assisted thoracoscopic lung biopsy resulted in the diagnosis of diffuse large B-cell lymphoma (DLBCL). Gene rearrangement analysis using polymerase chain reaction (PCR) technique was performed on the cells in bronchoalveolar lavage (BAL) fluid, and showed the clonality of the immunoglobulin heavy chain (IgH) gene, supporting the diagnosis. DLBCL should be considered in the differential diagnosis of diffuse ground-glass shadows in the chest CT, and gene rearrangement analysis may have an impact on the diagnosis of pulmonary DLBCL.

P16/INK4a gene methylation is a frequent finding in pulmonary MALT lymphomas at diagnosis

p16/INK4a gene alterations have been associated with tumor progression in lymphoid malignancies. However, their significance in mucosa-associated lymphoid tissue (MALT) lymphoma is unclear. We investigated p16 gene methylation and mutation in a large series of untreated cases of pulmonary MALT lymphoma and diffuse large B-cell lymphoma (DLBL), and correlated p16 gene alterations with a MALT lymphoma-specific API2–MALT1 fusion and the clinicopathologic features of MALT lymphoma. The API2–MALT1 fusion was detected by multiplex reverse transcription polymerase chain reaction in 25/60 (42%) cases of MALT lymphoma, but none of 11 DLBLs. Methylation-sensitive single-strand conformation analysis showed that p16 gene methylation was frequently detected in 36/60 (60%) cases of MALT lymphoma. The gene was similarly methylated in DLBL cases (6/11, 55%). A p16 gene mutation was found in one (p16 gene-methylation) of 44 MALT lymphomas and in none of six diffuse large B-cell lymphomas. Statistical analysis showed that the p16 gene methylation status did not correlate with API2–MALT1 fusion or any of the clinicopathologic factors including serum LDH, clinical stage, and increased large cells. These findings suggest that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis that might be maintained through the progression of the tumor.