Jpn J Radiol (2010) 28:62–65 DOI 10.1007/s11604-009-0377-5
CASE REPORT
Primary pleural lymphoma: plaque-like thickening of the pleura Anastasia Oikonomou · Alexandra Giatromanolaki Dimitrios Margaritis · Marios Froudarakis Panos Prassopoulos
Received: July 20, 2009 / Accepted: September 2, 2009 © Japan Radiological Society 2010
Abstract Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. We report a 63-year-old-man with no history of HIV infection or pyothorax who presented with progressive dyspnea and nonproductive cough. Chest radiography revealed complete opacification of the left hemithorax, and contrastenhanced computed tomography showed large left pleural effusion and thin, homogeneous, plaque-like thickening of the parietal pleura. Thoracoscopic pleural biopsy was consistent with grade 1 extranodal follicular lymphoma of the pleura. The authors suggest that physicians should be aware of this rare location of primary pleural lymphoma manifested by plaque-like thickening of the pleura but not accompanied by mediastinal lymphadenopathy. Key words Primary lymphoma · Pleura · CT
A. Oikonomou (*) · P. Prassopoulos Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece Tel. +30-25510-76803; Fax +30-25510-30473 e-mail:
[email protected] A. Giatromanolaki Department of Pathology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece D. Margaritis Department of Hematology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece M. Froudarakis Department of Pneumonology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
Introduction Primary pleural lymphomas are rare. Two types of primary pleural lymphoma have been described in the literature: primary effusion lymphoma (PEL) in patients with human immunodeficiency virus (HIV) infection1 and pyothorax-associated lymphoma (PAL).2 The radiological findings in PEL consist of pleural effusion in the absence of an identifiable tumor mass, whereas PAL presents as a homogeneous or inhomogeneous nonenhancing soft tissue mass with or without adjacent bone destruction.3 In addition, an extremely rare type of primary pleural lymphoma, seen in immunocompetent patients with no history of pyothorax, has been described in a few case studies in the literature. The radiological findings consisted of pleural effusion associated with a pleural “mass,”4–6 “consolidation,”4 or “inhomogeneous pleural thickening.”5 Although pleural effusion is a common manifestation of both secondary and primary pleural lymphoma, “plaque-like thickening (i.e., homogeneous mild thickening) of the pleura” has not been described previously as a manifestation of any type of primary pleural lymphoma. We report a case of primary pleural lymphoma not associated with HIV infection or pyothorax that presented on computed tomography (CT) with a large pleural effusion and plaque-like thickening of the pleura.
Case report A 63-year-old man presented with a 1-month history of progressive dyspnea and nonproductive cough without chest pain, hemoptysis, fever, chills, night sweats, or weight loss. The patient was an ex-smoker with no occu-
Jpn J Radiol (2010) 28:62–65
Fig. 1. Nonenhanced computed tomography (CT) of the chest reveals a large left pleural effusion associated with passive atelectasis (arrows) of the left lung
Fig. 2. Contrast-enhanced CT of the chest detects mild homogeneous, plaque-like thickening of the left posteromedial parietal pleura (arrowheads). Atelectatic lung shows vivid enhancement (arrow)
pational history. On clinical examination, there was no evidence of peripheral lymphadenopathy or hepatosplenomegaly. Laboratory findings were normal. Chest radiography showed complete opacification of the left hemithorax with right-sided shift of the mediastinum. Pleural fluid analysis showed transudative effusion. Investigation of the pleural fluid for Mycobacterium tuberculosis and cytology for malignancy were negative. CT of the chest revealed a large left pleural effusion occupying almost half of the left hemithorax. Passive atelectasis of the left lower lobe and lingula were also seen (Fig. 1). Following intravenous contrast medium administration, a homogeneous, mild, plaque-like thickening of the parietal pleura (3–4 mm) was demonstrated, extending mainly to the posteromedial aspect of the parietal pleura of the left lower lobe (Fig. 2). Mild homoge-
63
Fig. 3. Contrast-enhanced CT of the chest also depicts mild homogeneous thickening of the mediastinal parietal pleura adjacent to the left upper lobe (arrowheads)
Fig. 4. Thoracoscopic view of the patient’s parietal pleura shows multiple confluent islets of inflammatory thickening (arrows)
neous thickening of the mediastinal parietal pleura adjacent to the left upper lobe was also depicted (Fig. 3). There were no associated pleural nodules or masses, no evidence of involvement of the visceral pleura, and no enlarged lymph nodes in the mediastinum. Lung parenchyma appeared normal without nodules or consolidation. CT of the abdomen and pelvis did not disclose any abnormalities. Bronchoscopy found left lower lobe bronchus compression. Subsequently, medial thoracoscopy was performed and revealed multiple islets of inflammatory thickening involving about half of the parietal pleura (Fig. 4). Pleural biopsies showed diffuse, partially nodular infiltration by neoplastic B-lymphoid cells (Fig. 5a) that were positive for CD20 (Fig. 5b) and CD79a antigens. These cells were weakly positive for the CD10 marker and negative for CD5 and cyclin D1. The mouse
64
Jpn J Radiol (2010) 28:62–65
a
b Fig. 5. a Primary follicular lymphoma of the pleura (H&E, ×200). b Primary follicular lymphoma of the pleura. (IHC stain for CD20, ×200)
monoclonal antibody CS.1-4 (M0897) was used to detect the latent membrane protein (LMP) of Epstein-Barr virus (EBV), and staining was negative. The diagnosis was grade 1 extranodal follicular lymphoma of the pleura. Bone marrow biopsy followed and the findings were normal. The patient was started on six cycles of R-CHOP chemotherapy (monoclonal antibody rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone). He was found to be in clinical remission at the 6-month follow-up.
Discussion Primary pleural lymphomas are extremely rare. comprising only 2.4% of chest wall tumors. Two types of primary pleural lymphoma have been described in the literature: (1) primary effusion lymphoma (PEL) in patients with HIV1 and (2) the pyothorax-associated lymphoma (PAL), seen in patients with a history of chronic pyothorax (2.2% of cases) or as a result of chronic pleural
inflammation due to previous artificial pneumothorax to treat tuberculosis.2,5 PEL has been reported to be strongly associated with human herpesvirus-8 (HHV-8) infection and occasionally with EBV infection,1,4 and PAL has been reported to be strongly associated with EBV infection.2,4 Both types are diffuse, large, B-cell lymphomas. The radiological findings have been described for both types of primary lymphoma: PEL is seen with pleural effusion in the absence of an identifiable tumor mass, whereas PAL presents as a homogeneous or inhomogeneous nonenhancing soft tissue mass, with or without adjacent bone destruction.3 In addition, an extremely rare type of primary pleural lymphoma seen in immunocompetent patients with no history of pyothorax or HIV infection—and not associated with HHV8 or EBV infection—has been described in few case studies in the literature. The histology in these few cases was extranodal marginal zone lymphoma.4–6 The radiological findings of these rare non-PAL/PEL primary lymphomas have been briefly reported as being pleural effusion associated with a pleural “mass,”4–6 “consolidation,”4 or “inhomogeneous pleural thickening.”5 The reported case was a primary pleural extranodal follicular lymphoma (FL) that presented on CT with a mild unilateral homogeneous (plaque-like) thickening of the posteromedial and mediastinal parietal pleura associated with a large pleural effusion. Although involvement of the pleura with FL has been described in disseminated disease,7 primary FL of the pleura has not been described before according to the authors’ knowledge. FL represents about one-fourth of the total cases of non-Hodgkin’s lymphoma (NHL) and is the second most prevalent subtype of NHL in Western countries.8 FL is characterized by an indolent course, with a relatively long survival, but with a continuous pattern of relapses resulting in a currently incurable disease. Although most patients with FL have disseminated nodal involvement at presentation, primary extranodal involvement is not uncommon.8 Large studies evaluating all lymphoma subtypes occurring in specific extranodal locations, suggest that primary extranodal FL comprises 1 to 38% of all primary lymphomas occurring at specific sites, comprising 13% female genital tract, 17% testes, and 38% duodenal lymphomas.8 Although pleural effusion is a common manifestation of both secondary and primary pleural lymphoma, “plaque-like thickening of the pleura” has not been described previously as a manifestation of any type of primary pleural lymphoma. The parietal thickening in our case was continuous and so minimal (3–4 mm) that it was hardly evident on the noncontrast images, although it was clearly disclosed after intravenous contrast medium administration, highlighting the role of contrast
Jpn J Radiol (2010) 28:62–65
medium administration in the investigation of pleural effusions. “Pleural thickening” (diffuse or plaque-like) has been described as a quite common radiological manifestation of secondary solid involvement of the pleura— with or without pleural effusion—in both Hodgkin’s lymphoma and non-Hodgkin’s lymphoma7,9,10; but according to the authors’ knowledge, it has not been described so far in primary pleural lymphoma. The radiological differential diagnosis of both homogeneous and inhomogeneous pleural thickening would include metastatic adenocarcinoma, mesothelioma, and as has already been mentioned secondary involvement with lymphoma. CT apart from depicting the subtle abnormality of the pleura was used to help the pneumonologist find the most appropriate site for thoracoscopic biopsy from the pleura of the left lung base. Various mechanisms have been implicated for the development of primary pleural lymphoma including chronic stimulation of B cells by longstanding chronic pleural disease, such as in tuberculous pleuritis, autoimmune diseases, and EBV infection. In our case, there was no history of previous pyothorax or autoimmune disease, and EBV infection was not detected.6 The possible etiology of malignant pleural effusion in patients with lymphoma include either intrinsic tumor infiltration of the pleura, tumor obstruction of the lymphatics draining the pleura, or mediastinal lymphadenopathy with obstruction of the thoracic duct.10 The most possible scenario in our case is that the pleural effusion was generated by the pleural lymphoma itself despite the negative cytology results regarding malignancy. The latter could be explained by the scarceness of malignant cells in the pleural specimens, so that even experienced cytologists were unable to render a definitive diagnosis. However, tumor obstruction of the lymphatics draining the pleura might also coexist in the present case. CT-guided biopsy was avoided in this case because the thickening was minimal, and obtaining adequate tissue might not be feasible. Thoracoscopy, either medical or surgical, is the method of choice in undiagnosed pleural effusion, and medical thoracoscopy was performed in our case. The CT manifestation of continuous mild, homogeneous pleural thickening corresponded
65
to the thoracoscopic manifestation of contiguous multiple islets of inflammatory thickening involving about half of the parietal pleura. Conclusion Primary pleural lymphoma not associated with pyothorax or HIV infection may manifest on contrast-enhanced CT with extremely mild plaque-like pleural thickening associated with pleural effusion. Physicians should be aware of this rare location of primary pleural lymphoma manifested by plaque-like thickening of the pleura, not accompanied by mediastinal lymphadenopathy. References 1. Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcomaassociated herpes virus. Blood 1996;88:645–56. 2. Aozasa K. Pyothorax associated lymphoma. J Clin Exp Hematopathol 2006;46:5–10. 3. Brun V, Revel MP, Danel C, Fournier LS, Souilamas R, Frija G. Case report. Pyothorax-associated lymphoma: diagnosis at percutaneous core biopsy with CT guidance. AJR Am J Roentgenol 2003;180:969–71. 4. Mitchell A, Meunier C, Ouellette D, Colby T. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with initial presentation in the pleura. Chest 2006;129: 791–4. 5. Ahmad H, Pawade J, Falk S, Morgan JA, Balacumaraswami L. Primary pleural lymphomas. Thorax 2003;58:908–9. 6. Hirai S, Hamanaka Y, Mitsui N, Morifuji K, Sutoh M. Primary malignant lymphoma arising in the pleura without preceding long-standing pyothorax. Ann Thorac Cardiovasc Surg 2004;10:297–300. 7. Vega F, Padula A, Valbuena JR, Stancu M, Jones D, Medeiros LJ. Lymphomas involving the pleura: a clinicopathologc study of 34 cases diagnosed by pleural biopsy. Arch Pathol Lab Med 2006;130:1497–502. 8. Tan D, Horning SJ. Follicular lymphoma: clinical features and treatment. Hematol Oncol Clin North Am 2008;22: 863–82. 9. Shuman LS, Libshitz HI. Solid pleural manifestations of lymphoma. AJR Am J Roentgenol 1984;142:269–73. 10. Aquino SL, Chen MY, Kuo WT, Chiles C. The CT appearance of pleural and extrapleural disease in lymphoma. Clin Radiol 1999;54:647–50.
