A Case of Pulmonary MALT Lymphoma Arising From

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A Case of Pulmonary MALT Lymphoma Arising From http://dx.doi.org/10.4046/trd.2012.73.2.115 Case Report ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2012;73:115-121 CopyrightⒸ2012. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. A Case of Pulmonary MALT Lymphoma Arising from Lymphocytic Interstitial Pneumonitis Ki Hoon Park, M.D.1, Soon Seog Kwon, M.D., Ph.D.1, Myung Hee Chung, M.D., Ph.D.2, Jeana Kim, M.D., Ph.D.3, Hee Jung Lee, M.D., Ph.D.3, Ji-Won Min, M.D.4, Yong Hyun Kim, M.D.1 Departments of 1Internal Medicine, 2Radiology, and 3Pathology, Bucheon St. Mary's Hospital, The Catholic University of Korea School of Medicine, Bucheon, 4Department of Internal Medicine, Catholic Medical Center, The Catholic University of Korea School of Medicine, Seoul, Korea Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare disease. This disorder is considered to be a model of antigen-driven lymphoma, which is driven either by autoantigens or by chronic inflammatory conditions. Low-grade B-cell MALT lymphoma may develop from a nonneoplastic pulmonary lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP). A recent estimate predicts that less than 5% of LIP patients acquire malignant, low-grade, B-cell lymphoma. In Korea, there has been no previous report of malignant low-grade, B-cell lymphoma, acquired from LIP. Here, we present the case of a patient with LIP that developed into pulmonary MALT lymphoma, six years after diagnosis. Key Words: Lymphoma; Lymphoproliferative Disorders; Lung Diseases, Interstitial; Lymphoid Tissue Introduction orders, or autoimmune diseases is thought to be the ini- tial event leading to the development of MALT lympho- There are various lymphoproliferative disorders which ma5,6. In rare cases, a nonneoplastic pulmonary lym- affect the lung parenchyme. Among these, primary pul- phoproliferative disorder (p-LPD), such as lymphocytic monary lymphomas (PPLs) represent only 3∼4% of ex- interstitial pneumonitis (LIP) can develop into malig- tranodal non-Hodgkin's lymphoma (NHL). Pathologically, nant, low-grade, B-cell lymphoma. A recent and real- Low grade B-cell NHL accounts for 58∼72% of cases istic estimate is closer to 5% of patients with LIP acquire of PPL1. Mucosa-associated lymphoid tissue-derived malignant, low-grade, B-cell lymphoma7,8. In Korea, (MALT) lymphoma is a low grade B-cell extranodal lym- there has been no previous report of pulmonary MALT phoma characterized by a proliferation of clonal margin- lymphoma acquired from LIP. We describe here, a rare al zone lymphocytes2,3 that arise from bronchial-associated case of pulmonary MALT lymphoma that arose from a lymphoid tissue4. Stimulation of bronchus-associated LIP. lymphoid tissue by antigens, smoking, inflammatory dis- Case Report Address for correspondence: Yong Hyun Kim, M.D. Division of Allergy and Pulmonology, Department of A 60-year-old woman was admitted to our hospital Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea School of Medicine, 327, with cough and dyspnea. At the time of admission, her Sosa-ro 327beon-gil, Wonmi-gu, Bucheon 414-717, Korea medical history included medically controlled essential Phone: 82-32-340-7039, Fax: 82-32-340-2669 E-mail: [email protected] hypertension, diabetes mellitus and old cerebral infarction. Received: Apr. 9, 2012 She was a smoker of 10 pack-years. Physical examina- Revised: Apr. 13, 2012 Accepted: Apr. 26, 2012 tion revealed that she had no skin lesions or neuro- CC It is identical to the Creative Commons Attribution Non-Commercial logical abnormalities. There was no lymphadenopathy License (http://creativecommons.org/licenses/by-nc/3.0/). in the cervical, axillary, or inguinal regions. On auscul- 115 KH Park et al: A case of pulmonary MALT lymphoma arising from LIP Figure 1. Initial radiographic findings. (A) Chest posterior- anterior shows multifocal peribronchial consolidations, involving both lungs. (B, C) There are diffuse bilateral ground-glass opacity with intralobular septal thicken- ings and condolidative le- sion on a chest computed tomography scan. (D) A chest X-ray after 8 months steroid treatment. tation of the chest, a coarse breathing sound with crack- thoracoscopic lung biopsy specimens from the left up- les in both lower lung fields was heard. Chest radio- per lobe revealed diffuse severe lymphoid cell infiltra- graphs and computed tomography (CT) scans showed tion with some plasma cells in the interstitium and al- diffuse bilateral ground-glass opacity with intralobular veolar walls (Figure 2A). Immunohistochemical exami- septal thickenings and consolidative lesions (Figure 1A nation revealed lymphoid cells evenly admixed with B ∼C). Laboratory investigations revealed a total leuko- lymphocytes and T lymphocytes, which were immunor- cyte count of 7,200 cells/mm3, comprising 40.8% of eactive for CD79a (Figure 2B) and CD3 (Figure 2C), neutrophils, 49.7% lymphocytes, 7.2% monocytes, 1% respectively. These findings were consistent with the di- basophils, and 1.3% eosinophils. The level of C-reactive agnosis of LIP with follicular bronchiolitis components. protein was slightly elevated to 2.39 mg/dL. The serum Our patient was treated with prednisone 1 mg/kg per lactate dehydrogenase level had increased to 543 U/L day with gradual tapering for 8 months. She showed (normal, 110∼230 U/L). Arterial blood gas analysis in progressive clinical and radiographic improvement room air showed a PaO2 of 56.5 mm Hg, PaCO2 39.3 (Figure 1D). mm Hg, SaO2 90.5% and pH 7.41. Autoantibody tests Five years later, at the age of 65 years, our patient were negative. Cellular analysis of the bronchoalveolar started re-experiencing dyspnea and cough symptoms. lavage fluid (BALF) revealed a composition of 25% lym- A chest CT scan revealed diffuse bilateral ground-glass phocytes, 3% eosinophils, 0% neutrophil, and 72% opacity with fine reticulation, traction bronchiectasis macrophages. Histological examination of video-associated and consolidative lesions (Figure 3A, B). Pulmonary 116 Tuberculosis and Respiratory Diseases Vol. 73. No. 2, Aug. 2012 Figure 2. Initial histopathological findings. (A) Video-asso- ciated thoracoscopic lung biopsy specimens from the left upper lobe revealed diffuse severe lymphoid cell infiltration with some plasma cells in the interstitium and alveolar walls (H&E stain, ×40). (B) Immunohistochemical exami- nation revealed that the lymphoid cells were evenly ad- mixed with B lymphocytes and T lymphocytes, which were immunoreactive for CD79a and (C) CD3 (B, ×400; C, ×400). function tests revealed a reduced vital capacity (VC) of phoid cells (Figure 5A). Immunohistochemical examina- 73% predicted value, a reduced total lung capacity tion revealed that the lymphoid cells were diffusely pos- (TLC) of 69% predicted value and a reduced diffusion itive for CD79a and B-cell markers (Figure 5B), but neg- lung capacity for carbon monoxide of 49% predicted ative for Bcl6 (Figure 5C), CD10 and MUM-1 (Figure value. Cellular analysis of the BALF revealed a composi- 5D). These findings were consistent with the diagnosis tion of 80% lymphocytes, 2% eosinophils, 5% neu- of pulmonary MALT lymphoma. Our patient was treated trophil, 13% macrophages and a CD4/CD8 ratio of with 3 cycles of cyclophosphamide, hydroxydaunor- 0.959. Our patient was again treated with 60 mg of pre- ubicin (doxorubicin), Oncovin (vincristine), and predni- dnisone per day, which was gradually tapered for 6 sone. Her chest radiographs (Figure 4C, D) and symp- months. This led to improvement of VC (92% of pre- toms showed improvement. Chemotherapy was continued. dicted value), TLC (100% of predicted) and radiographic findings (Figure 3C, D). Discussion Eighteen months later, our patient suffered a relapse of dyspnea. A chest CT scan revealed diffuse peribron- Major nonneoplastic p-LPD, which includes lesions of chial thickening, extensive consolidative lesions and the intrapulmonary lymph nodes, consists of follicular nodular lesions in both lung fields (Figure 4A, B). bronchitis/bronchiolitis, lymphocytic interstitial pneu- Histological examination of percutaneous lung needle monia, and nodular lymphoid hyperplasia. Such disease biopsy specimens revealed marked infiltration of lym- entities are inflammatory and reactive lesions that are 117 KH Park et al: A case of pulmonary MALT lymphoma arising from LIP Figure 3. Radiographic find- ings of second episode. (A, B) Initial chest computed tomography (CT) scan re- vealed diffuse bilateral gro- und-glass opacity with fine reticulation, traction bronchi- ectasis and consolidative le- sion. (C, D) A chest CT scan after 6 months of ste- roid treatment. often difficult to diagnose, since it is difficult to differ- infiltrates that diffusely expand alveolar septa. The in- entiate them from each other and from other neoplastic filtrate is composed of lymphocytes admixed with varia- entities. Therefore, these disorders should be dis- ble numbers of histiocytes and plasma cells. Reactive tinguished by clinical, radiographic, and histologic lymphoid follicles are more prominent and consistent in features. Radiologic findings of nodular lymphoid hy- nodular lymphoid hyperplasia. In follicular bronchioli- perplasia consist of well-demarcated nodules or masses. tis, numerous lymphoid follicles with associated reactive On the other hand, the CT features of LIP consist of germinal centers are present around the bronchi and a bilateral area of poorly defined centrilobular nodules, bronchioles10. Interstitial lymphocytes
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