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  Table of Contents  
Year : 2020  |  Volume : 57  |  Issue : 3  |  Page : 351-353

Diffuse Large B-Cell Lymphoma presenting as isolated pleural effusion with excellent response to R-PEPC regimen

1 Department of Medical Oncology, Dr. Bhim Rao Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission11-Mar-2019
Date of Decision31-May-2019
Date of Acceptance07-Jun-2019
Date of Web Publication22-Jun-2020

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, Dr. Bhim Rao Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_217_19

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How to cite this article:
Mittal A, Gogia A, Mallick S. Diffuse Large B-Cell Lymphoma presenting as isolated pleural effusion with excellent response to R-PEPC regimen. Indian J Cancer 2020;57:351-3

How to cite this URL:
Mittal A, Gogia A, Mallick S. Diffuse Large B-Cell Lymphoma presenting as isolated pleural effusion with excellent response to R-PEPC regimen. Indian J Cancer [serial online] 2020 [cited 2020 Sep 20];57:351-3. Available from:

Pleural involvement as part of systemic Non-Hodgkin's Lymphoma is seen in around 16% of cases,[1] however, isolated pleural effusion as a presentation of systemic Non-Hodgkin Lymphoma (NHL) is very rare. In an observational study, Shuman et al. reported 71 cases of NHL with pleural involvement but none had isolated pleural effusion.[2]

A 87-year-old man, known case of hypertension (requiring three antihypertensives telmisartan, amlodipine and metoprolol), hypothyroidism (on 100 microgram thyroxine daily) and coronary artery disease (post coronary artery bypass grafting five years back for triple vessel disease) presented to us with worsening shortness of breath and low grade fever for five months. On initial evaluation he was found to have a left sided pleural effusion [Figure 1]i. Pleural fluid analysis revealed a lymphocytic exudative effusion (total leucocyte count 300, 80% lymphocytes) with elevated adenosine deaminase (75 IU/L) and negative “Xpert Mycobacterium Tuberculosis (MTB) / Resistance to Rifampicin (RIF) test” and cultures. On strong clinical suspicion of tuberculosis, he was started on anti-tubercular therapy which he took for almost four months with no symptomatic improvement. A repeat pleural fluid analysis was then performed, flow cytometry and cytopathology of which showed large monoclonal atypical lymphoid cells positive for CD20, multiple myeloma 1 (MUM1) and B-cell chronic lymphocytic leukemia/lymphoma 6 (BCL6) and negative for CD5, CD23, Ebstein Barr Virus (EBV) and CD10 [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]h. A 18- fluorodeoxyglucose (FDG) PET-CT scan was done as part of staging workup which showed FDG avid (SUV max. 10.2) left sided pleural effusion with no other nodal involvement. His bone marrow examination did not show evidence of lymphoma involvement. He was negative for retroviral disease and pleural fluid serology for Human Herpes Virus -8 (HHV-8) was negative. A diagnosis of diffuse large B-cell lymphoma (DLBCL) stage IV, International Prognostic Index 3/5 (isolated pleural effusion) was made. In view of advanced age and multiple comorbidities, he was started on rituximab plus oral metronomic therapy with procarbazine, etoposide, cyclophosphamide and prednisone (rituximab 375mg/m2/3 weekly, procarbazine 50mg alternate day, etoposide 50mg once a day, cyclophosphamide 50mg once a day and prednisolone 20mg once a day, R-PEPC regimen). He has received four cycles so far with significant clinical benefit and decrease in pleural effusion suggestive of an excellent partial response [Figure 1]j.
Figure 1: (a - h) Microphotograph shows atypical lymphoid cells in pleural effusion [a, Papanicolaou ×200], Cell block [b, H and E ×200]. The cells are immuno positive for CD20 [c], BCL6 [f] while negative for CD3 [d], CD30 [e], EBV LMP [g] and MUM1 [h]. (i and j) Baseline CXR showing left moderate pleural effusion [i] and excellent response after four cycles of R - PEPC chemotherapy [j]

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Predominantly two major types of primary pleural lymphomas have been described in literature; primary effusion lymphoma (PEL) in immunocompromised patients associated with HHV-8 infection (less commonly EBV) and pyothorax-associated lymphoma (PAL) arising from chronic pyothorax with universal EBV infection.[3],[4] PEL is exclusively reported in immunocompromised hosts and is usually CD20 negative.[5] In this patient, there was no evidence of immunodeficiency, HHV-8 was negative and CD20 was strongly positive thus effectively ruling out PEL. The relationship between chronic pyothorax and tuberculosis was first shown by Luchi et al. in 1987.[6] It is important to keep in mind this possibility especially in a tuberculosis endemic country like India where differentiating between these two entities can be extremely challenging. The above patient did not respond to anti-tubercular therapy thus making PAL less likely. In view of above findings and strong CD20 positivity, DLBCL with pleural involvement was the likely diagnosis which has been further supported by excellent response to rituximab-based chemoimmunotherapy.

The pathogenesis of primary pleural lymphoma is based on chronic inflammation which leads to the uncontrolled proliferation of B-cell lymphocytes, and can eventually result in the occurrence of pleural lymphoma.[7] Majority of patients with primary pleural lymphomas are symptomatic with cough, chest pain and shortness of breath. Due to non-specific nature of symptoms, high index of suspicion is necessary when a differential of primary pleural lymphoma is kept. The imaging findings can be varied in primary pleural lymphoma with only effusion, pleural thickening or pleural nodules.[8] None of these findings are specific and diagnosis depends on histopathological confirmation via needle aspiration/thoracoscopic pleural biopsy. Our patient had pleural effusion only without any nodules/thickening which is consistent with previous literature. Histopathologically, DLBCL is the most common subtype of NHL involving the pleural cavity. In a clinicopathological study of lymphomas involving the pleural cavity from MD Anderson cancer center, 17 of 29 cases (58.6%) were DLBCL with follicular lymphoma, the second most common histology.[9] Rare cases of involvement by Hodgkin lymphoma, post-transplant lymphoproliferative disorder, primary mediastinal B-cell lymphoma and EBV positive PAL were also reported. Presence of pleural effusion in isolation or as a part of systemic involvement portends a poor prognosis in DLBCL. In a study of 41 patients from China, presence of pleural effusion correlated with higher IPI scores, higher stage and inferior survival.[10] In another study in patients with double expressor or c-myc rearranged lymphoma, presence of pleural effusion had a significant negative prognostic impact on survival.[11]

Optimal management of patients with primary pleural lymphoma is a matter of debate. Standard treatment of advanced DLBCL in the current era is based on chemoimmunotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) with overall survival of around 40% at 5 years. However, in view of advanced age and multiple comorbidities in our patient, it was decided to treat him with oral therapy PEP-C regimen (prednisolone, etoposide, procarbazine and cyclophosphamide) with rituximab. In a study by Coleman et al., patients with relapsed refractory DLBCL treated with PEP-C achieved an objective response in around 70% of the cases with a complete response rate of 36%.[12] Our patient has shown good partial response after four cycles of treatment and is currently doing well.

In conclusion, isolated pleural involvement in DLBCL is a rare and underdiagnosed entity and should be suspected in patients with non-resolving pleural effusions. Immunohistochemistry for CD20 can be helpful in differentiating primary pleural lymphoma from DLBCL with secondary pleural involvement especially in immunocompetent hosts and has treatment implications. The importance of keeping a high index of suspicion for this diagnosis is further enhanced in tuberculosis endemic countries like India where such patients may be treated with empirical anti-tubercular therapy.

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There are no conflicts of interest.

  References Top

Das DK, Gupta SK, Ayyagari S, Bambery PK, Datta BN, Datta U. Pleural effusions in non-Hodgkin's lymphoma: A cytomorphologic, cytochemical and immunologic study. Acta Cytol 1987;31:119-24.  Back to cited text no. 1
Shuman LS, Libshitz HI. Solid pleural manifestationsof lymphoma. AJR Am J Roentgenol 1984;142:269-73.  Back to cited text no. 2
Alexandrakis MG, Passam FH, Kyriakou DS, Bouros D. Pleural effusions in hematologic malignancies. Chest 2004;125:1546-55.  Back to cited text no. 3
Aozasa K. Pyothorax-associated lymphoma. J Clin Exp Hematop 2006;46:5-10.  Back to cited text no. 4
Usuda D, Arahata M, Takeshima K, Sangen R, Takamura A, Kawai Y, et al. A case of diffuse large B-cell lymphoma mimicking primary effusion lymphoma-like lymphoma. Case Rep Oncol 2017;10:1013-22.  Back to cited text no. 5
Iuchi K, Aozasa K, Yamamoto S, Mori T, Tajima K, Minato K, et al. Non-Hodgkin's lymphoma of the pleural cavity developing from long-standing pyothorax. Summary of clinical and pathological findings in thirty-seven cases. J Clin Oncol 1989;19:249-57.  Back to cited text no. 6
Krol EM, Ogrodnik A, Sieber S, Chronakos J, Mahfoozi AP. Unusual case of isolated pleural B-cell lymphoma. Conn Med 2015;79:347-9.  Back to cited text no. 7
Malatskey A, Fields S, Libson E. CT appearance of primary pleural lymphoma. Comput Med Imaging Graph 1989;13:165-7.  Back to cited text no. 8
Vega F, Padula A, Valbuena JR, Stancu M, Jones D, Medeiros LJ. Lymphomas involving the pleura: A clinicopathologic study of 34 cases diagnosed by pleural biopsy. Arch Pathol Lab Med 2006;130:1497-502.  Back to cited text no. 9
Chen YP, Huang HY, Lin KP, Medeiros LJ, Chen TY, Chang KC. Malignant effusions correlate with poorer prognosis in patients with diffuse large B-cell Lymphoma. Am J Clin Pathol 2015;143:707-15.  Back to cited text no. 10
Nitta H, Gotoh A, Tanaka M, Ochiai T, Ota Y, Komatsu N. The presence of pleural effusion at diagnosis predicts poor outcomes in diffuse large B-cell lymphoma patients with MYC-rearrangement or double protein expression. Blood 2017;130(Suppl 1):4165.  Back to cited text no. 11
Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, et al. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: Low-dose metronomic, multidrug therapy. Cancer 2008;112:2228-32.  Back to cited text no. 12


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