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

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.

To further proceed with the diagnosis, phenotypic lymphocyte screening by flow cytometry of both blood and bilateral pleural effusion was performed, and all of the results showed monoclonal B-cell lymphocyte proliferation (Figs. 2, 3 and 4). Based on the above findings showing no extrapulmonary involvement, primary pulmonary monoclonal B-cell lymphocyte proliferative disease was ultimately diagnosed. Due to a lack of medical support, the patient refused further treatment.

Primary pulmonary monoclonal B-cell lymphocyte proliferative disease with atypical clinical manifestation is usually a malignant hyperplastic disease of the hematological system. Herein, we describe a patient who presented with pleural effusion, according to pathological findings and treatment results, and the pulmonary nodule was confirmed to have Cryptococcus infection. Cryptococcus is more common in patients with immunodeficiency; thus, we sought to determine whether a fundamental disease such as immune deficiency was present. Because of refusal to undergo thoracoscopy, the patient underwent bilateral pleural biopsy and multiple thoracentesis. Ultimately, we established a diagnosis of primary pulmonary monoclonal B-cell lymphocyte proliferative disease based on pathology. Although this case lacked direct histopathological evidence, comprehensive examinations excluded tuberculosis and the recurrence of fungal infection. Furthermore, phenotypic lymphocyte screening by flow cytometry of blood and bilateral pleural effusion indicated monoclonal B-cell lymphocyte proliferation. Extrapulmonary diseases were also excluded; therefore, we concluded that primary pulmonary lymphoma (PPL) was likely. PPL is an extremely rare form of lymphoma with an incidence of 0.4% [2]; for the sake of making a diagnosis of PPL, extrapulmonary diseases must be ruled out [3]. Approximately half of PPL cases have no symptoms or lack specific respiratory manifestations, such as cough, dyspnea, chest pain and so on [4]. Due to its nonspecific presentation, the diagnosis of PPL is exceptionally challenging and usually leads to misdiagnosis or delayed diagnosis [5]. Radiographic appearances include patchy opacity, mediastinal masses, solitary or multiple nodules, and pleural effusion, either unilateral or bilateral. Serum protein electrophoresis anomalies are observed in 33% of patients with PPL [3]. To the best of our knowledge, clinical manifestations of PPL have various forms, but pleural effusion as the initial manifestation is extremely rare. Considering the patient’s manifestations, including recurrent pleural effusion, as well as the respiratory findings and other examinations of the various systems, malignancy remained highly suspicious in the differential diagnosis. According to a series of examinations, ultimately the diagnosis of PPL was highly suspected, but it was not confirmed by the histopathological evidence, perhaps because the patient’s plasma cells did not secrete and express some special proteins, or the patient’s condition was in the early stage of PPL and unable to show the typical clinical manifestations. Therefore, we failed to determine where the monoclonal B lymphocytes originated from. During the 10 months of follow-up, the patient’s bilateral pleural effusion volume grew slowly, which demonstrated that her underlying disease has not been eradicated. We speculate that the cause is a relatively low-grade lymphoma. The patient’s condition is currently under observation and requires long-term follow-up.

Primary pulmonary monoclonal B-cell lymphocyte proliferative disease is an uncommon disease with varied atypical manifestations where pleural effusion is even rare, especially as the initial clinical manifestation. For our patient with agnogenic Cryptococcus infection, investigating the unexplained pleural effusion for other underlying causes resulted in a delayed diagnosis. There are many reasons for pleural effusion, and despite the common causes of pleural effusion such as tuberculosis, lung carcinoma and other solid tumors, nonsolid tumors such as primary pulmonary B lymphocyte monoclonal proliferative disease should also be considered.