Clin Oncol Cancer Res (2011) 8: 47-50 DOI 10.1007/s11805-011-0559-7
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Primary Pleural Extranodal Non-Hodgkin’s Lymphoma Presenting As Pleural Thickening—A Case Report
Pradipta Guha 1 Debasis Sarkar 2 Arindam Ray 2 Indranil Thakur 2 Sekhar Mukherjee 2 Sanjoy Kumar Chatterjee 2
1 RMO Cum Clinical Tutor, Department of General Medicine, Calcutta National Medical College, Kolkata 700014, West Bengal, India. 2 Department of General Medicine, Medical College, Kolkata 700073, West Bengal, India.
ABSTRACT Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. This paper reports on a 27 year old man with no history of HIV infection or pyothorax who presented with progressive dyspnea and heaviness of chest. Chest radiography revealed complete opacification of the left hemithorax, and contrast enhanced computed tomography showed large left pleural effusion and homogeneous, extensive thickening of the parietal pleura. CT guided biopsy of thickened pleura is suggestive of non-Hodgkin’s lymphoma-T cell lymphoblastic variety. Physicians should be aware of this rare location of primary pleural lymphoma manifested by thickening of the pleura. KEY WORDS: non-Hodgkin’s lymphoma, T cell, lymphoblastic type, lymphoma, extranodal NK-T-cell. Copyright © 2011 by Tianjin Medical University Cancer Institute & Hospital and Springer
Correspondence to: Pradipta Guha E-mail:
[email protected] Tel: 091-33-25412415 Fax: 091-33-22198727
Received November 8, 2010; accepted January 20, 2011. E-mail:
[email protected] Tel (Fax): 86-22-2352 2919
Introduction Primary pleural lymphoma is extremely rare[1]. There are two types of primary pleural lymphoma in the literature: primary effusion lymphoma (PEL) in patients with human immunodeficiency virus (HIV1) infection and pyothorax-associated lymphoma (PAL) [2]. Pleural effusion in the absence of an identifiable tumor mass is the main radiological finding in PEL, whereas PAL manifests commonly as a homogeneous or infrequently an inhomogeneous soft tissue mass with or without surrounding bone destruction[3]. Apart from these, an extremely rare type of primary pleural lymphoma, particularly seen in immunocompetent patients with no prior history of pyothorax, has been mentioned in a few case studies. Pleural effusion associated with a pleural mass[4], consolidation[4], or inhomogeneous pleural thickening[5] are the normal radiological findings in this group of patients. Although pleural effusion is a common manifestation of both secondary and primary pleural lymphoma, extensive homogeneous thickening of the pleura has not been described previously as a chief clinical manifestation of any type of primary pleural lymphoma. This paper reports on a case of primary pleural lymphoma not associated with HIV infection or pyothorax having large pleural effusion and extensive thickening of the pleura.
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Case Report A 27-year-old male patient from East Midnapore (India) complained of gradually progressive respiratory distress, chest pain and heaviness of the chest for the past 2 months along with low grade intermittent fever for the same duration. After consultation with a local doctor the fever subsided but chest pain and respiratory distress increased in severity. Chest X-Ray (CXR) at that time revealed minimal left-sided pleural effusion. On clinical grounds Anti-Tubercular Drugs (ATD) were commenced. After continuation for 2 months of empirical ATDs his complaints did not regress. A repeat CXR surprisingly revealed increased pleural effusion in the same side (Fig.1). He attended another higher Institution where his pleural fluid aspiration was performed and the report showed blood mixed fluid with fibrin coagulum, cell count-11500/cmm (L-70N30E-0, RBC-fair), sugar 6 mg/dL and protein 3.1 g/dL. Adenosine Deaminase (ADA) level was monitored, which came out to be much more than the normal level (515.7 U/ L; normal < 40 U). A small subcutaneous nodule was noticed over the left subclavicular area a few days later and a fine needle aspiration cytology (FNAC) was performed from that site accordingly which showed intermediate and large sized lymphoid cells; coarse chromatin & scanty cytoplasm”-suggest “lymphoproliferative disorder” (Fig.2). Thereafter he was referred to the research institution for further management. General examination did not reveal any abnormalities apart from mild pallor complexion. There was no significant lymphadenopathy. Systemic examination showed massive left pleural effusion, a very small pareital nodule in the left infraclavicular region which was not tender, not fixed to the overlying skin but was fixed to the underlying structures. No abdominal organomegaly was documented. Concomitantly, the other relevant investigations were performed along with pleural fluid aspiration study. Complete hemogram values were within normal limits, Serum LDH was 1546 U/L (N- < 410 U/L) and serum uric acid was 12.3 mg/dL (N- < 7 mg/dL for male). HIV and EBV serologies were negative. It was thought the disease was a hematological malignancy. Keeping in mind, results of the bone marrow aspiration study were surprisingly within normal limits. As the pleural fluid was deeply hemorrhagic, an immunophenotyping (IPT) study was done from pleural fluid which revealed CD2, CD5 and CD38 positivity. A CT scan of the thorax suggested pleural thickening and collection with collapsed left lung and mediastinal shift to the right (Fig.3) raising the probability of pleural malignancy without any involvement of the mediastinal group of lymph nodes. The CT scan of abdomen and pelvis was also unable to detect any lymph node involvement. CT guided trucut biopsy from thickened pleura revealed a linear strip of tissue
showing sheets of atypical lymphoid cells compatible with NHL (Fig.4). In the immunohistochemistry study, the tumor cells expressed positivity of CD3, CD10, CD99 and Tdt (focally expressed) and were immune negative for CD20 & CD34, suggesting the diagnosis was NHL of T cell lymphoblastic type. Afterwards, bone marrow trephine biopsy was undertaken. However, the result was astonishingly within normal limits. Afterwards, a hematologist was consulted to formulate the treatment protocol in this atypical form of disease. As NHL T cell lymphocytic variety behaves like acute leukaemia, it was proposed to treat this patient with BFM-90 regime. In the induction phase I, he was treated with oral prednisone at a dose of 60 mg/m2/day on days 1-28, intravenous Vincristine at a dose of 1.5 mg/m2 (max 2 mg) on days 8, 15, 22 and 29, intravenous Daunorubicin at a dose of 30 mg/m2 on days 8, 15, 22 and 29, intravenous L-Asparaginase at a dose of 10,000 IU/m 2 on days 12, 15, 18, 21, 24, 27, 30 and 33and intrathecal Methotrexate of 12 mg on days 1, 15 and 29. In the induction phase II, he received intravenous Cyclophosphamide at a dose of 1000 mg/ m2 on days 36 and 64, andintravenous Cytarabine at a dose of 75 mg/m2/day on days 38-41, 45-48, 52-55 and 59-62 along with oral 6-marcaptopurine at a dose of 60 mg/m2/day on days 36-64. In the consolidation phase, he was treated orally with 6–marcaptopurine at a dose of 25 mg/m2/day on days 1-56 and 24 h intravenous infusion of Methotrexate at a rate of 5 mg/m2 on days 8, 22, 36 and 50 along with intrathecal Methotrexate of 12 MG on days 8, 22, 36 and 50. After the induction phase of therapy, pleural effusion subsided, but the pleural thickening persisted (Fig.5). Splenic enlargement subsided to some extent along with complete resolution of the subclavicular nodule. Although he tolerated the induction phase well, he subsequently developed sepsis secondary to pancytopenia in the late consolidation phase and eventually died despite all possible medical supportive therapy.
Discussion Primary pleural lymphomas are an extremely rare clinical entity comprising only 2.4% of chest wall tumors[1]. On the contrary, pleural involvement by systemic lymphoma is a relatively common finding. During the course of the disease, about 16% of patients with nonHodgkin’s lymphoma present pleural involvement, or subsequently develop it later[6]. The symptomatic patients, chiefly present dyspnea, cough, or chest pain depending upon the severity of the involvement [7]. Pleural involvement being the common accompaniment of lymphoma, manifesting pleural effusions have been considered a poor prognostic factor[8]. While primary effusion lymphoma (PEL) is seen in patients with HIV1 infection, pyothorax-associated lymphoma (PAL) is seen
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Fig.1. Chest X ray showing massive left-side pleural effusion with mediastinal shift to the right. Fig.2. FNAC from left anterior chest wall showed intermediate and large sized lymphoid cells. These cells had ”coarse chromatin & scanty cytoplasm-suggestive of Lymphoproliferative disorder”. Fig.3. CT scan of thorax was suggestive of pleural thickening and collection with collapsed left lung and mediastinal shift to the right. Fig.4. Trucut biopsy from thickened pleura revealed-sheets of atypical lymphoid cells-compatible with non Hodgkin’s lymphoma. Fig.5. After induction phase of therapy repeat CT scan of thorax showing regression of effusion but persistence of pleural thickening.
in patients with chronic pleural inflammation due to previous artificial pneumothorax to treat tuberculosis or in a patient with prior history of chronic pyothorax[2,5]. Although EBV infection is also occasionally related to PEL[4], it is reported to be strongly associated with PAL[2,4]. Pleural effusion in the absence of an identifiable tumor mass is the main radiological finding in PEL, whereas PAL manifests commonly as an homogeneous or infrequently as an inhomogeneous soft tissue mass with or without surrounding bone destruction [3]. In addition, an extremely rare type of primary pleural lymphoma seen in immunocompetent patients has been described in few case studies in the literature, with no history of pyothorax or HIV or HHV-8 or EBV infection. Extranodal marginal zone lymphoma was the histologic variety in these few cases[4,5]. The reported case study was a primary pleural T cell lymphoblastic lymphoma that was present with an extensive unilateral homogeneous thickening of the parietal pleura associated with a massive pleural effusion. Although both secondary and primary pleural lymphoma may be present with pleural effusion, extensive pleural thickening has not been described previously as a clinical feature of any kind of primary pleural lymphoma. In both Hodgkin’s and non-Hodgkin’s lymphomas, diffuse or plaque-like pleural thickening have been
described as quite a common radiological manifestation of secondary solid involvement of the pleura, with or without pleural effusion [9]. However, it has not been described so far in primary pleural lymphoma. There is a strong association between PEL and human herpesvirus-8 (HHV-8) infection[10]. According to some authors, various mechanisms have been discussed for the development of primary pleural lymphoma including chronic stimulation of B cells due to the chronic pleural disease, such as tuberculous pleuritis, EBV infection and autoimmune diseases. In this case study, there was no history of previous pyothorax or autoimmune diseases, and EBV infection was not detected during laboratory investigations. The possible mechanisms of development of pleural effusion in patients with lymphoma include either intrinsic tumor invasion of the pleura, obstruction of the lymphatics channels draining the pleura by tumor cells, or mediastinal lymphadenopathy with obstruction of the thoracic duct. Since this patient did not have features suggestive of involvement of mediastinal group of lymph nodes, the most possible scenario in this case study was that the pleural effusion was produced by the pleural lymphoma itself as the pleural fluid immunophenotyping report revealed CD 2, CD 5 and CD 38 positivity, suggestive of immature T lymphocytes in pleural fluid, but a PAP stain for malignant cell was
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negative. The latter finding could be explained by the scarceness of malignant cells in the pleural fluid specimens, so that even experienced cytologists were unable to declare a definitive diagnosis. However, for tumor obstruction of the lymphatics draining, the pleura might also coexist in the present case. Although this patient was treated as per advice of the hematologist, the final outcome in this case study was unsatisfactory, since the patient didn’t make it. Primary pleural lymphoma not associated with pyothorax or HIV infection may be present with extensive pleural thickening associated with pleural effusion, although it is a very rare clinical presentation. There is very few reported cases in the literature to date. This case study is the first to docu ment these complications in this rare form of disease. Physicians should be aware of this rare location of primary pleural lymphoma manifested by thickening of the pleura unilaterally without involving other reticulo-endothelial organs. Therefore, this case study is a rare one, both in the form of the unique variety of non-Hodgkin’s lymphoma and also in the form of presentation.
Conflict of interest statement No potential conflicts of interest were disclosed
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