Rapid improvement of massive bloody pleural effusion after splenectomy for splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare malignant lymphoma involving marginal zone B cells, accounting for only 1% of non-Hodgkin lymphomas. No previous reports have documented SMZL accompanied by massive bloody pleural effusion. Herein, the case of a patient with SMZL that was only diagnosed after splenectomy and thoracoscopic pleural biopsy is presented. SMZL in this patient was accompanied by massive bloody pleural effusion. The characteristics of the patient’s pleural effusion changed from bloody to transudative after splenectomy, and rapid improvement was observed. It was considered that the splenectomy was valid for treatment of unidentified pleural effusion with enlarged spleen.

Splenic marginal zone lymphoma (SMZL) is a malignant lymphoma involving marginal zone B cells. This low-grade non-Hodgkin lymphoma (NHL) was first reported by Schmid et al in 1992.1 SMZL is a rare disease accounting for 1% of NHLs.2 Since SMZL is a low-grade lymphoma that progresses slowly,3 no previous reports have documented SMZL accompanied by marked bloody pleural effusion. We encountered a patient in whom SMZL was accompanied by massive bloody pleural effusion. Surprisingly, the characteristics of pleural effusion changed after splenectomy from bloody to transudative, and the effusion disappeared. CASE PRESENTATION A 46-year-old woman first visited her family doctor with heart palpitations and dyspnoea. She had noticed bloating of the abdomen for 2 months prior to the visit, and chest radiography revealed massive pleural effusion of the left thorax (fig 1). Tuberculous pleurisy was initially suspected, but pleural effusion revealed no definitive findings for malignancy or tuberculosis. She was referred to our hospital for further investigation. The patient had received hormone therapy for the treatment of endometriosis starting 10 years earlier and lasting 3 years. She had never smoked and did not drink alcohol. On physical examination, she did not look particularly ill, because she didn’t have a high fever, severe desaturation or body weight loss. No superficial lymph nodes were palpable. The abdomen was slightly bloated. The spleen was non-tender and palpable, 10 finger-widths below the left costal arch, but the liver was not palpable. Routine blood testing yielded no findings of note other than mild anaemia (haemoglobin (Hb), 10.6 g/dl) and hyperuricaemia (uric acid, 10.0 g/dl). White blood cell count (WBC) was 5200/mm3. Pleurocentesis showed bloody pleural effusion and positive Rivalta reaction. No malignant cells were identified on microscopy, with negative results for acid-fast bacilli and other microorganisms. Pleural biopsy only indicated lymphocytic pleuritis. As much as 1 litre of bloody fluid was drained every day and the patient’s condition was considered serious. Further serological examination revealed: soluble interleukin receptor (sIL2R), 3090 U/ml (normal, 124–466 U/ml); vitamin B12, 12 000 pg/ml (normal, 233–914 pg/ml); and β2 macroglobulin, 2.8 mg/litre (normal, 0.9–1.9 mg/litre). Given these unusually high laboratory values, lymphocytic malignancy was highly suspected. INVESTIGATIONS Chest radiography on admission (fig 1) showed massive left pleural effusion that displaced the mediastinum, but no abnormalities were evident in the lung field. Contrast-enhanced CT of the chest revealed massive pleural effusion in the left thorax, and mediastinal lymphadenopathy was identified (fig 2). Abdominal CT showed marked enlargement of the spleen with partially uneven intensities, and a 1 cm enlarged periaortic lymph node (fig 3). Gallium scintigraphy confirmed abnormal accumulation within the enlarged spleen, but no significant accumulation in the thoracic cavity. The above-mentioned laboratory findings and various imaging modalities were highly indicative of malignant lymphoma originating from the spleen. To confirm this diagnosis, surgical investigation was performed. A splenectomy and thoracoscopic pleural biopsy were performed at the same time. The spleen was enlarged past the median line to the size of a child’s head, and displayed fibrous adhesion to the diaphragm. The spleen was also firmly adherent to the left hepatic lobe. The splenic hilar, splenic artery and periaortic lymph nodes were enlarged. Pathological analysis of the excised spleen revealed an enlarged marginal zone around the splenic white pulp. The marginal zone was shaped like a corona surrounding the splenic white pulp. Proliferating cells were CD20 positive and CD79a positive (B cell markers), but CD3 negative (T cell marker) (fig 4). Similar findings were found in splenic hilar lymph nodes excised at the same time. Based on these findings, the patient was diagnosed as having SMZL (stage IV, International Prognostic Index (IPI) 2). The patient was placed back in the right lateral position and thoracoscopy was performed. No clear sign of neoplasm was apparent. Microscopic examination of this biopsied specimen revealed invasion by small lymphocytes expressing T cell surface markers. Lesions suggesting malignancy were not found microscopically. After splenectomy, pleural effusion improved dramatically and turned pale yellowish in colour, transparent and transudatory. Since marked retention dissipated, the thoracic cavity drainage tube was removed on postoperative day 6. No further retention of pleural fluid was observed. DIFFERENTIAL DIAGNOSIS Hairy cell leukaemia. B cell chronic lymphocytic leukaemia. Mantle cell lymphoma. TREATMENT The patient received chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)). OUTCOME AND FOLLOW-UP Chemotherapy was effective; the patient has survived for 18 months with complete remission.

This patient displayed SMZL accompanied by massive bloody pleural effusion in which the characteristics of pleural effusion changed after splenectomy. SMZL is a malignant lymphoma originating from the spleen and involving marginal zone B cells. This low-grade NHL was first reported by Schmid et al in 1992 and accounts for about 1% of NHLs. In this low-grade lymphoma disease progression is slow, and SMZL has not been recognised as an independent disease concept for some time.1,2 A PubMed search using “splenic marginal zone lymphoma”, “pleural effusion” and “effusion” as key words did not yield any cases of SMZL presenting with marked pleural effusion. Diagnosis is thus often difficult, and SMZL is frequently diagnosed only after splenectomy.4 In the present patient, SMZL could not be confirmed by non-invasive tests and was only confirmed after splenectomy. Malignant lymphoma is relatively often accompanied by intrathoracic lesions, and autopsy studies have documented pleural lesions in 20% to 33%, and pleural retention in about 16% to 20% of NHLs.5–8 Pleural effusion may accompany malignant lymphoma because of: (1) pleural invasion of tumour cells, (2) lymph node occlusion due to tumour cell invasion, (3) chylous pleural effusion due to thoracic duct occlusion and (4) production of vascular endothelial growth factor (VEGF) by tumour cells.8 When pleural effusion is reactive, most lymphocytes are small mature polyclonal T lymphocytes.8 In the present patient, pathological examination of the pleura indicated reactive pleuritis. This agreed with the results of flow cytometry in which CD5+ T cells were dominant and unusual cell populations were absent. The presence of bloody fluid is usually indicative of pleural involvement, but in this case there was no involvement. Starting 1 day after splenectomy massive bloody pleural effusion decreased below 100 ml/day and the characteristics of pleural effusion after splenectomy improved dramatically and changed from bloody to transudatory. Thus, with regard to the most possible mechanisms of pleural fluid retention, direct compression of the posterior lymphatics and vessels by the enlarged spleen was considered, given the rapid disappearance of pleural effusion after splenectomy. Regarding other possible mechanisms, studies have documented that extranodal marginal zone B cell lymphoma accompanies autoimmune diseases such as Hashimoto disease, and that in gastric marginal zone lymphoma Helicobacter pylori-induced B cell proliferation involves T cells and cytokines, possibly as autoimmune mechanisms.9,10 Similarly, studies have shown that SMZL can accompany autoimmune diseases and that splenectomy improves platelet-associated IgG (PAIgG)-related idiopathic thrombocytopenic purpura (ITP).11,12 In the present patient, VEGF levels were not high in bloody effusion, but could have been high in pleural effusion. Thoracoscopy showed bloody pleural effusion with marked coagula, but pleural effusion quickly became leaky after surgery and the volume of effusion was dramatically reduced. Direct or indirect invasion of lymphoma or thoracic duct closure was thus less likely and, as in the above-mentioned reports, bloody pleural effusion could have involved some autologous humoral factors. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with initial presentation in the pleura was reported13 and if the level of lymphocytes is abnormally high in the thoracic cavity, tuberculous pleuritis is likely. We considered that the splenectomy was valid for treatment of unidentified pleural effusion with enlarged spleen. LEARNING POINTS No previous reports have documented splenic marginal zone lymphoma (SMZL) accompanied by marked bloody pleural effusion. We considered that splenectomy was valid for treatment of unidentified pleural effusion with enlarged spleen. Regarding the most possible mechanisms of pleural fluid retention, direct compression of the posterior lymphatics and vessels by the enlarged spleen. Acknowledgments The authors are deeply indebted to Dr Yusuke Oji from the Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine and Naoki Ueda from the Department of Pathology (C3), Osaka University Graduate School of Medicine for help with the diagnosis of this patient. Footnotes Competing interests: none. Patient consent: Patient/guardian consent was obtained for publication.

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