The potential usefulness of sputum cytology in the conclusive diagnosis of methotrexate-associated lymphoproliferative disorders: A case report

Background: Methotrexate has been used as an anchor drug for the treatment of rheumatoid arthritis and is considered to be a cause of methotrexate-associated lymphoproliferative disorder. Spontaneous regression can occur after withdrawal of methotrexate and may be associated with Epstein–Barr virus positivity and non-diffuse large B cell lymphoma histological type. Methotrexate-associated lymphoproliferative disorders are often diagnosed pathologically by lung biopsy. To the best of our knowledge, there have been no studies on the cytological diagnosis of methotrexate-associated lymphoproliferative disorder using sputum smears. Case: A 70-year-old man, who was diagnosed with rheumatoid arthritis 13 years previously and who had been treated with methotrexate, presented shortness of breath and productive cough. Methotrexate-associated lymphoproliferative disorder was suspected as the sputum cytology showed many atypical lymphoid cells with hyperchromatic enlarged nuclei, foamy cytoplasm and distinct nucleoli. Chest computed tomography revealed multiple nodular shadows with interstitial pneumonia in the bilateral lower lung field. A lung biopsy specimen contained atypical lymphoid cells that were immunohistochemically positive for CD20 and MUM-1, and weakly positive for bcl-6, but negative for CD3 and CD10. There were no Epstein–Barr virus-infectious lymphoid cells by ISH-EBER. He was finally diagnosed with methotrexate-associated lymphoproliferative disorder (non-germinal center B-cell-like diffuse large B cell lymphoma histological type). Most of the nodules disappeared spontaneously following the withdrawal of methotrexate. Discussion and conclusion: A cytologically conclusive diagnosis of methotrexate-associated lymphoproliferative disorder may be reached using sputum smears and clinical information.