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Table of Contents
CASE REPORT
Year : 2021  |  Volume : 8  |  Issue : 4  |  Page : 148-151

Pleural effusion as the initial presentation of synchronous small lymphocytic lymphoma and non-small cell lung cancer


1 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
2 Department of Pathology, National Taiwan University Cancer Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
3 Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Date of Submission27-May-2021
Date of Decision23-Jul-2021
Date of Acceptance27-Jul-2021
Date of Web Publication3-Dec-2021

Correspondence Address:
Dr. Chao- Hung Wei
Department of Oncology, National Taiwan University Hospital, No. 7, Zhongshan South Road., Zhongzheng., Taipei 100
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCRP.JCRP_20_21

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  Abstract 


We report a case of a 64-year-old woman who presented with chronic cough for 2 months. A chest X-ray showed new-onset left pleural effusion, and chest computed tomography confirmed left pleural effusion in addition to small ground-glass nodules in both lungs. Analysis of the pleural effusion including culture and cytology did not show specific findings at a local hospital. Due to suspected lung cancer with malignant pleural effusion, thoracoscopic surgery was performed. Histopathological and immunohistochemical examinations revealed Stage I lung adenocarcinoma and concurrent primary pulmonary small lymphocytic lymphoma (SLL). This is a very rare case of primary pulmonary SLL and a concurrent lung adenocarcinoma.

Keywords: Non-small cell lung cancer, primary pulmonary lymphoma, small lymphocytic lymphoma


How to cite this article:
Wei CH, Chang YL, Hou HA. Pleural effusion as the initial presentation of synchronous small lymphocytic lymphoma and non-small cell lung cancer. J Cancer Res Pract 2021;8:148-51

How to cite this URL:
Wei CH, Chang YL, Hou HA. Pleural effusion as the initial presentation of synchronous small lymphocytic lymphoma and non-small cell lung cancer. J Cancer Res Pract [serial online] 2021 [cited 2022 Aug 10];8:148-51. Available from: https://www.ejcrp.org/text.asp?2021/8/4/148/331650




  Introduction Top


Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a neoplasm characterized by clonal proliferation and accumulation of mature, typically CD5-positive B90-cells within the blood, bone marrow, lymph nodes, and spleen. SLL and CLL are the same disease entity; the term SLL is reserved for cases with a circulating CLL cell count <5000/μL and documented extramedullary involvement such as lymph nodes, spleen, or other tissues. Primary pulmonary SLL is rarely encountered. Here, we present a rare case of primary pulmonary SLL with the initial presentation of left pleural effusion.


  Case Report Top


A 64-year-old female presented to a local hospital due to an intermittent productive cough for 2 months. Otherwise, there were no associated respiratory tract symptoms, weight loss, or night sweats. She was a never-smoker, and there was no history of human immunodeficiency virus infection or pyothorax. Repeated low-dose computed tomography (CT) scan at previous health check-ups showed nonspecific small ground-glass nodules in bilateral lungs without interval change. Due to the persistent cough, a chest plain film, and chest CT were repeated, which revealed new left pleural effusion [Figure 1]. She received left pleurocentesis three times. The results of pleural effusion analysis were compatible with a transudate, and both culture and cytology results were negative.
Figure 1: 2-[fluorine-18]-fluoro-2-deoxy-D-glucose-positron emission tomography showed some patchy mild hot areas at left posterior and left lower pleura (SUVmax=3.13) (arrow) (a). Chest computed tomography revealed left pleural effusion in addition to bilateral small lung ground-glass nodules (arrow) (b)

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She was referred to the National Taiwan University Hospital for further evaluation. The laboratory data showed hemoglobin 12.8 g/dL, white blood cell (WBC) 10,080/μL, platelet 198 K/μL, neutrophil 79.5%, lymphocyte 15.2%, monocyte 4.8%, albumin 4.3 g/dL, total bilirubin 0.6 mg/dL, alanine transaminase 6 U/L, BUN 12.7 mg/dL, creatinine 0.8 mg/dL, Na 139 mmol/L, K 4.8 mmol/L, Ca 2.39 mmol/L, and lactate dehydrogenase 144 U/L. With a tentative diagnosis of lung cancer with malignant pleural effusion, after three-dimensional CT-guided lung needle localization, uniportal video-assisted thoracoscopic surgery with wedge resection, lymph node dissection, and pleural biopsy was performed uneventfully. During the operation, one 0.5 cm × 0.5 cm, gray-white, elastic tumor over the left upper lobe, and another 1 cm × 1 cm, yellow-brown, elastic lesion over the left pleura were found. There were no pleural seeding nodules, pleural adhesion, or pleural retraction grossly. Resection of the tumors, pleural biopsy, and group 5/6 lymph node dissection were performed. The pathology of the left upper lobe tumor showed a well-differentiated adenocarcinoma, with thyroid transcription factor 1-positive tumor cells arranged in an acinar pattern [Figure 2]. The TNM T staging was pT1a. Microscopically, the pleural lesion revealed CD68 immunoreactive histiocyte aggregation and mesothelial cell proliferation, without evidence of malignancy. Interestingly, the parietal pleura and group 5/6 lymph nodes both showed SLL, characterized by a diffuse infiltrate of mostly small-sized lymphoid cells with round nuclei and admixed with scattered medium-sized prolymphocytes [Figure 3]. Immunohistochemical stains of the atypical lymphoid cells were positive for CD20, CD5, CD23, BCL-2, and HLA-DR and negative for CD3, CD10, and FMC7 [Figure 4]. The Ki-67 proliferative index was focally up to 50%. Repeated analysis of the left pleural effusion was compatible with an exudate by Light's criteria. Cytology revealed lymphocytosis with small and mature lymphocytes [Figure 5]. Flow cytometry showed mainly T cells, but about 12% of the lymphocytes were B-cells expressing CD19, partial CD5, dim CD20, CD22, partial CD23, and HLA-DR, but negative for FMC7 and mostly negative for surface light chain restriction [Figure 6]. These findings were compatible with SLL cells in the pleural fluid. After diagnosis, a complete staging workup was carried out. Whole-body positron emission tomography showed patchy 2-(fluorine-18)-fluoro-2-deoxy-D-glucose mild-avid lesions in the left pleura (SUVmax = 3.13) [Figure 1]. A bone marrow smear showed normocellular marrow and lymphocytosis with small lymphocytes, accounting for about 25% of all nucleated cells [Figure 7]. Bone marrow flow cytometry revealed clonal CD19 + B-cells, about 5.6% of the acquired WBCs, expressing CD5, sub CD20, sub CD23, CD200, and dim surface kappa light chain restriction but negative for CD10 [Figure 7]. Thus, a final diagnosis of primary pulmonary SLL arising from the pleura, Ann Arbor Stage IV, with bone marrow involvement and a concurrent lung adenocarcinoma, pT1aN0M0, Stage IA1 was made. Follow-up was suggested for her early-stage lung cancer. The amount of the left pleural effusion decreased significantly after one cycle of rituximab plus bendamustine and disappeared after three courses of immunochemotherapy.
Figure 2: Left upper lobe lung tumor wedge resection showed a well-differentiated adenocarcinoma

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Figure 3: Parietal pleura (a) and lymph node (b) biopsies demonstrated small lymphocytic lymphoma

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Figure 4: The lymph node was replaced by BCL-2 (a), CD5 (b), CD20 (c), and CD23 (d) immunoreactive lymphoma cells

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Figure 5: Pleural effusion cytology showed mainly small and mature lymphocytes

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Figure 6: Pleural effusion flow cytometry identified a clone of B lymphocytes expressing CD19 (a), partial CD5 (b), dim CD20 (c), partial CD23 (d), and most negative for surface light chain restriction (e)

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Figure 7: Bone marrow smear revealed lymphocytosis (a). The flow cytometry showed clonal CD19 positive B-cells (b), with the expression of dim surface kappa light chain restriction (c)

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  Discussion Top


Primary pulmonary lymphoma, a rare subtype, is defined as clonal lymphoid proliferation affecting the lung in a patient without detectable extrapulmonary involvement.[1] While extranodal forms account for 24%–50% of all non-Hodgkin lymphoma (NHL), primary pulmonary lymphoma represents only 3%–4% of extranodal NHL, and only 0.5%–1% of primary pulmonary malignancies.[2] Primary lymphoid proliferations of the lung are most often of B-cell lineage and include three major entities: primary pulmonary marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), primary pulmonary diffuse large B-cell lymphoma (DLBCL), and lymphomatoid granulomatosis (LYG).[1] MALT lymphoma is the most common pulmonary lymphoma. It is slow-growing, most often asymptomatic, and revealed by chronic alveolar opacity on radiography. The outcome is generally favorable in most series, with a 5-year survival rate of >80% and a median survival time of over 10 years.[3] Primary pulmonary DLBCL is the second most common subtype, accounting for 5%–20% of all primary pulmonary B-cell lymphomas. It is generally found in elderly or immunocompromised patients.[4] Primary pulmonary LYG is an uncommon angiocentric and angiodestructive B-cell clonal lymphoproliferative disorder primarily affecting the lung. It is regarded to be a disease related to Epstein–Barr virus infection.[5] The disease may mimic pulmonary vasculitis and is often revealed by systemic signs.[6] Other subtypes of primary pulmonary lymphoma including SLL, follicular lymphoma, mantle cell lymphoma, and lymphoplasmacytic lymphoma are exceedingly rare.

A few case reports have described CLL with the presentation of lung involvement.[7],[8] Primary pulmonary SLL can present as single or multiple masses or as bilateral reticulonodular infiltrates. Histologically, SLL shows lymphangitic spread through the lung parenchyma. A rare bronchiolocentric pattern has also been reported.[9] In our case, the pleural effusion involved SLL. Pleural effusion can develop as a result of different mechanisms including pleural infiltration by a tumor, mediastinal lymphadenopathies with obstruction of the thoracic duct or tumor obstruction of the lymphatic drainage.[10] In our case, the flow cytometry analysis of pleural effusion showed that there was a group of clonal B-cell (12%) with aberrant surface markers expression, compatible with the involvement of SLL although most of the lymphocytes were T cells in this patient. It was relatively common to see these findings when there was an inflammation process related to the formation of the pleural fluid such as infection, malignancy, or autoimmune disease.[11] Clonality assessment is clinically relevant to make the definite diagnosis.[12] Thoracic surgery or thoracoscopic biopsy should be considered for the pleural effusion of unknown cause. Our case showed typical histopathological and immunohistochemical findings of SLL. Novel therapeutic strategies are being explored in numerous ongoing clinical trials. Whether treatments for primary pulmonary SLL are different from that of typical CLL/SLL is unknown due to limited cases reported before. Due to symptomatic pleural effusion, immunochemotherapy was initiated. What makes this case more special is the coexistence of parietal pleural SLL and non-small cell lung cancer. Previous studies have revealed that the risk of secondary lung cancer increased after treatment of lymphoma, probably related to chemotherapy and radiotherapy.[13] There are only rare case reports reporting concurrent lung cancer and pulmonary lymphoma.[14],[15] No underlying mechanism has been identified; however, the coexistence may influence the treatment modalities for each of the diseases. The relationship between lung cancer and parietal pleura SLL in our case is unknown. Next-generation sequencing of the two specimens may have helped to elucidate this question.


  Conclusion Top


We report a very rare case of concurrent primary pulmonary SLL and lung cancer, initially presenting as pleural effusion. Clinicians should always be careful about the possibility of the coexistence of different cancers, which needs a totally different treatment strategy.

Ethical approval

This study was approved by the IRB of National Taiwan University Hospital (IRB approval project number: 202104122W). The need for informed consent was waived by the IRB.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Mudie NY, Swerdlow AJ, Higgins CD, Smith P, Qiao Z, Hancock BW, et al. Risk of second malignancy after non-Hodgkin's lymphoma: A British cohort study. J Clin Oncol 2006;24:1568-74.  Back to cited text no. 13
    
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Pezzuto A, Piraino A, Mariotta S. Lung cancer and concurrent or sequential lymphoma: Two case reports with hypersensitivity to bevacizumab and a review of the literature. Oncol Lett 2015;9:604-8.  Back to cited text no. 14
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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