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To the editor, Pleural effusion, the most common manifestation of pleural disorders, is an abnormal accumulation of fluid in the pleural cavity. In a developing country such as China, infections, particularly tuberculosis, are the predominant cause of pleural effusion [1]. Other causes, such as inflammation and malignancy, are also common. In this report, we describe a 65-year-old woman with massive bilateral pleural effusion and a left pulmonary nodule. The results of fine needle aspiration of the pulmonary nodule suggested fungal infection, likely caused by Cryptococcus. After the regular treatment of fluconazole for 4 months, the left pulmonary nodule disappeared, but bilateral pleural effusion persisted (Fig. 1). The results of phenotypic lymphocyte screening by flow cytometry of both blood and bilateral pleural effusion supported the diagnosis of primary pulmonary monoclonal B-cell lymphocyte proliferative disease. We further discuss the current understanding of this disease, including the possible pathogenesis. In February 2017, a 65-year-old Chinese woman with no significant past medical history presented with apparent nocturnal dyspnea accompanied by a dry cough. Radiological findings revealed massive bilateral pleural effusion and a left lower pulmonary nodule. Complete positron emission tomography-computed tomography was performed (2nd May 2017) at the Second Affiliated Hospital of Xiangya, Central South University, showing that the inferior lobe of the left lung had a nodular shadow with a size of 15 × 13 mm and an obscured edge. An abnormal increase in radioactive uptake was observed. Other parts of the body showed no obviously abnormal increase in [18F]-2-fluoro-2-deoxy-D-glucose metabolism. Histological examination of the left pulmonary nodule with alkaline phosphate and periodic acid-Schiff staining indicated consolidation, proliferation of interstitial fibers, a large number of multinucleated cells, absence of necrosis, infiltration of lymphocytes and individual spores. Acid-fast staining produced negative results. These findings confirmed the diagnosis of fungal infection, with a tendency towards Cryptococcus as the cause. Immunohistochemical analysis showed CK7 (+), TTF-1 (+), CD68 (+), CD3 (+), IgG (+), CD20 (+), Ki67 (3%+), IgG4 (−), P40 (−), and CD34 (−). The patient was administered fluconazole regularly for 4months, and a repeated CT scan indicated the absence of pulmonary nodule; however, the pleural effusion persisted. Therefore, the patient was empirically treated with antituberculosis therapy, but it failed to provide an effect. Pleural effusion was proven to be exudate, and the interferon gamma release assay, Cryptococcus neoformans antigen test, galactomannan test, fungus G test and tumor marker assays were negative. No carcinoma cells were detected by exfoliative cytological examination of pleural effusion. Pleural biopsy showed no evidence of either neoplasms, tuberculosis or fungal infections. To elucidate the definitive cause of pleural effusion, the patient was transferred to West China Hospital, Sichuan University, and laboratory investigation indicated no evidence of tuberculosis or immunodeficiency. The patient underwent bilateral thoracentesis; intriguingly, the chyle test of bilateral pleural effusion was positive, but the triglyceride-to-cholesterol ratio was < 1, which was a result of recurrent pleural effusion for a long time and not true chylothorax. The pleural effusion was a yellow, limpid liquid with the following counts: total protein, 49.8 g/L; karyocytes, 700 × 10^6/L; erythrocytes, 400 × 10^6/L; mononuclear cells, 81%; multinucleated cells, 19%. Contrast-enhanced high-resolution computed tomography * Correspondence: zhouhy@scu.edu.cn Qin Du and Lili Fan contributed equally to this work. Department of Neurology, West China Hospital, Sichuan University, Guo Xuexiang #37, Chengdu 610041, China Full list of author information is available at the end of the article

Pleural effusion as an initial manifestation in a patient with primary pulmonary monoclonal B-cell lymphocyte proliferative disease