INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy, representing the most common histologic subtype of non Hodgkin's Lymphomas (NHLs) (1). Forty percent of patients with DLBCL present with extranodal disease involving skin, gastrointestinal tract, testis, bone, liver, adrenals and nasal cavity. The pulmonary presentation of DLBCL is a rare entity and represents a minority of cases of NHL. Most patients present with solitary pulmonary nodules or pleural based nodules with mediastinal adenopathy. We describe a case of DLBCL presenting as large coalescing pulmonary nodules.
CASE PRESENTATION: A 67-year-old female presented with slowly progressive shortness of breath and fatigue. She denied having fever, chills, joint pain/swelling or rash. Chest radiography showed multiple pulmonary nodules and consolidation without pleural effusions. Chest CT scan revealed large bilateral non-calcified pulmonary nodules without cavitation or necrosis, and areas of consolidation (figure 1A, B). A fine needle aspiration of the left upper lobe nodule revealed focal necrotizing granulomatous inflammation. The sedimentation rate and lactate dehydrogenase levels were elevated. Blood chemistry and hematological analysis were normal except for mild anemia. Bronchoscopy revealed narrowing of the posterior and apical subsegmental bronchi of the left upper lobe. Transbronchial biopsies revealed bronchial tissue with atypical lymphomatoid infiltrate and necrotizing granulomatous inflammation. Special stains for fungi and mycobacteria were negative as was culture of bronchoalveolar lavage fluid. Our leading diagnoses were lymphomatoid granulomatosis (LG) and lymphoma. The patient developed rapidly progressive respiratory failure requiring mechanical ventilation. A chest radiograph revealed worsening nodular infiltrates and focal areas of consolidation. A video-assisted thoracoscopic (VATS) wedge resection of the left lower lobe nodule was performed. Microscopic examination revealed pulmonary tissue with vasocentric proliferation of atypical smaller lymphocytes with focal necrosis (figure 2A). Immunohistochemical staining showed a lymphoid proliferation of predominately B-cell origin with CD20 positivity (figure 2B). The smaller lymphocytes had positive staining for CD3, CD43, CD15 and CD45. Stains for Ebstein Barr virus (EBV), bacteria, mycobacteria and fungi were all negative. PCR examination detected a prominent B cell clonal peak. EBV encoded RNA in situ hybridzation was negative indicating no presence of EBV. Chemotherapy with R-CHOP (rituximab, vincristine, doxorubicin, cyclophosphamide and prednisone) was initiated with subsequent improvement in the patient's respiratory failure.
DISCUSSIONS: DLBCL is the most common histologic type of non-Hodgkins lymphoma; pulmonary manifestations are rare. The distinction of DLBCL from lymphomatoid granulomatosis is often difficult yet essential. Lymphomatoid granulomatosis is a T-cell rich, B-cell lymphoma, almost invariably driven by EBV. The intesity of the B-cell infiltration and the absence of EBV infection precluded its diagnosis in this case. LG is currently thought to be a form of indolent malignant lymphoma. The presentation is varied and includes pulmonary and extra-pulmonary manifestations (2). There have been reports of spontaneous resolution of disease. No guidelines exist for treatment and patients are commonly treated with corticosteroids and cyclophosphamide. DLBCL can present as an intravascular form with atypical B-cell predominant lymphocytic proliferation noted primarily in the small vessels of various organs including the lungs. DLBCL is treated with multi-agent chemotherapy and carries a good prognosis in the low to intermediate risk groups.
CONCLUSION: In summary, diffuse large B-cell lymphoma can present as multiple pulmonary nodules. Differentiating DLBCL from lymphomatoid granulomatosis is critical as these diseases require different modes of treatment and have varying prognosis. Pathologic examination of biopsies is critical in making the diagnosis and should be pursued whenever possible.
DISCLOSURE: Njira Lugogo, None.