The Index of Suspicion for Pulmonary Extranodal Marginal Zone Lymphoma of Mucosa Associated Lymphoid Tissue

Abstract Introduction: Pulmonary nodules are not uncommonly found in patients with Sjogren's disease. Although they frequently can be benign, nodules in the context of systemic autoimmune disease such as Sjogren's disease require broadened differentials including lymphoid intersitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia (NLH), amyloidosis and lung malignancy. Although lung carcinoma can occur, the most frequent malignant etiology is non-Hodgkin's lymphoma, including pulmonary extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). On the other hand, many of these differentials are benign; however, some such as NLH can progress to lymphoma while others such as nodular amyloidosis can be associated with MALT lymphoma. As pulmonary MALT lymphoma often presents with asymptomatic nodules or consolidations, the index of suspicion by pulmonologists is crucial for diagnosis. Description: A 66 year old female nonsmoker presented with incidentally found bilateral solid and subsolid pulmonary nodules, the largest being 1.3 centimeters in the left lower lobe, in the context of calcified lymph nodes and splenic and liver calcified granulomas. As she was asymptomatic, possible differentials included chronic granulomatous disease, inflammatory/autoimmune lesions and less likely multifocal pulmonary malignancy. Fungal serologies were negative. Antinuclear antibodies, SS-A, and SS-B serologies were strongly positive. Erythrocyte sedimentation rate and rheumatoid factor were also positive. Further diagnostic workup led to a diagnosis of Sjogren's disease. Repeat 3 month CT chest showed stability of the lymphadenopathy and pulmonary nodules. However, despite stability, our pre-test probability for neoplastic pulmonary nodules had increased due to her autoimmune diagnosis. PET-CT scan was completed, showing metabolically active nodules bilaterally with a SUV range of 2-3.5, with the largest nodule having the highest uptake. Transbronchial biopsy of the largest nodule was consistent with MALT lymphoma. Discussion: The diagnosis of Sjogren's disease led to more aggressive efforts towards diagnostic certainty including a PET-CT scan and ultimately transbronchial biopsy. It is postulated that autoimmune activity in the pulmonary lymphoid tissue is what gives rise to MALT lymphoma. In one retrospective study on pulmonary nodules in patients with Sjogren's disease, greater than 70% of biopsied nodules were malignant, of which half represented MALT lymphoma. MALT lymphoma is diagnosed at the stage of disseminated disease in one third of cases, frequently recurs and has potential for aggressive transformation. Therefore, in the case of multiple pulmonary nodules in patients with Sjogren's disease, the evidence of underlying autoimmunity should increase the index of suspicion for pulmonary malignancy, including MALT lymphoma.