Pulmonary Mucosa-associated Lymphoid Tissue (MALT) Lymphoma with Multiple Thin-walled Pulmonary Cysts: A Case Report and Review of the Literature

Transcription

1 CASE REPORT Pulmonary Mucosa-associated Lymphoid Tissue (MALT) Lymphoma with Multiple Thin-walled Pulmonary Cysts: A Case Report and Review of the Literature Shingo Noguchi 1, Kazuhiro Yatera 1, Takashi Kido 1, Takaaki Ogoshi 2, Shuya Nagata 1, Chinatsu Nishida 1,KeiYamasaki 1, Toshinori Kawanami 1, Yukiko Kawanami 1, Hiroshi Ishimoto 1 and Hiroshi Mukae 1 Abstract We herein report a rare case of pulmonary mucosa-associated lymphoid tissue (p-malt) lymphoma with multiple cystic lesions. A previously healthy 58-year-old Japanese woman visited our hospital for an evaluation of abnormal chest computed tomography (CT) findings. Chest CT revealed multiple cystic lesions in both lungs, and she was diagnosed as having p-malt lymphoma based on the pathological findings. The patient had no underlying autoimmune diseases. She has not received any chemotherapy and has been stable for two years. This case suggests that, although rare, the possibility of p-malt lymphoma should be considered in patients with multiple cystic lung diseases. Key words: mucosa-associated lymphoid tissue (MALT) lymphoma, multiple cysts, MALT1 gene rearrangement (Intern Med 52: , 2013) () Introduction Primary pulmonary mucosa-associated lymphoid tissue (p- MALT) lymphoma is a low-grade B cell lymphoma that was first described in 1983 by Isaacson and Wright (1). P-MALT lymphoma accounts for only % of malignant lung tumors and less than 1.0% of all malignant lymphomas. However, it constitutes approximately 90% of all primary pulmonary lymphomas (2). The symptoms of p-malt lymphoma include coughing, mild dyspnea, chest pain and occasionally hemoptysis; however, all symptoms are nonspecific, and nearly half of patients are asymptomatic. Therefore, it is difficult to diagnose the disease based only symptoms (3). P-MALT lymphoma presents with various findings on chest computed tomography (CT), ranging from typical single or multiple nodules or areas of consolidation to rare findings, such as pulmonary cysts (4, 5). CT findings of multiple thin-walled cysts are often observed in patients with lymphocytic interstitial pneumonia (LIP) or follicular bronchiolitis (FB) and are useful in distinguishing p-malt lymphoma (6). We herein report a rare case of p-malt lymphoma with multiple cystic lesions and present a review of the literature. Case Report A 58-year-old Japanese woman initially visited a local hospital for an evaluation of an abnormal chest X-ray film in December No abnormal findings were observed on the chest X-rays findings at that time; however, chest CT revealed multiple cystic lesions in both lungs. Therefore, the patient was referred to our hospital in February She had been healthy with no sicca symptoms, such as dry eyes or dry mouth. She had not undergone a chest X-ray for 10 Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan and Department of Respiratory Medicine, Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan Received for publication February 17, 2013; Accepted for publication June 2, 2013 Correspondence to Dr. Kazuhiro Yatera, yatera@med.uoeh-u.ac.jp 2325

2 Table 1. Laboratory Findings on Admission Hematology WBC 4,800 / L Neut 57.0 % Lymp 36.3 % Eos 1.5 % RBC / L Hb 13.2 g/dl Plt / L Pulmonary function test FVC L VC 2.74 L FEV L %FEV % FEV 1 /FVC 65.2 % %DLco 86 % Biochemistry TP 8.8 Alb 4.5 AST 17 ALT 15 T-bil 0.9 LDH 170 -GTP 18 Glu 88 BUN 15 Cre 0.76 Na 141 K 4.1 g/dl g/dl meq/l meq/l Serology CRP RF ANA(speckled) Anti SS-A Anti SS-B IgG IgG4 IgA IgM KL-6 sil-2r MPO-ANCA PR3-ANCA 0.02 meq/l U/dL IU/mL 3 IU/mL 2, U/dL 372 U/mL U/mL <10 <10 V L/sec V L/sec years. She was a never-smoker, had no drinking history or inhalation history of any toxic materials and had never taken any drugs. She was an office worker with a history of normal parturition. She did not have any relevant family history or allergic diseases. The patient s height was cm and her body weight was 64.0 kg on admission. Her vital sign were as follows: body temperature, 36.8 ; heart rate, 72 beats/min; blood pressure, 116/61 mmhg. Her oxygen saturation was 97% on room air and her respiratory sounds were clear on auscultation. The laboratory findings obtained on admission (Table 1) included a complete blood count and biochemistry. An elevation of the serum rheumatoid factor and antinuclear and anti-ss-a antibody levels was observed, while the serum anti-ss-b antibody level was normal. A pulmonary function test showed mild obstructive impairment; however, the vital capacity and diffusing capacity were normal. Both the Schirmer and Rose-Bengal tests were negative. The chest X-rays obtained on admission (Fig. 1A) did not show any obvious abnormal findings. Chest CT performed on admission (Fig. 1B-E) revealed diffuse multiple thinwalled cysts and small ill-defined nodules (black arrows) in the bilateral lungs. Fluorodeoxyglucose-positron emission tomography did not demonstrate a high uptake level of the standard uptake value. Flexible bronchoscopy disclosed no abnormal findings in the trachea or bronchi, and bronchoalveolar lavage fluid (BALF) was obtained from the right B 5. The total cell count was slightly increased in number ( /ml; macrophages: 81.0%, lymphocytes: 19.0%, eosinophils: 0.0%, CD4/CD8: 0.9). The increased lymphocytes were morphologically normal. The histopathology of the specimens obtained with a transbronchial lung biopsy (TBLB) showed no specific findings. Therefore, lung biopsy specimens of the right S 2 and S 8 were obtained via video-assisted thoracoscopic surgery (VATS). The histopathology of the specimens (Fig. 2) revealed infiltration of small- and middlesized lymphocytes, follicular colonization and the presence of lymphoepithelial lesions with a large amount of proliferation of lymphocytes around the bronchovascular bundles and bronchioles. The lymphocytes were immunohistochemically positive for CD20 and CD138 and negative for CD3 and exhibited a monoclonal expression of λ-chain. These findings were consistent with a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma translocation gene 1 (MALT1) gene rearrangement was negative in both the BALF cells and tissue specimens obtained via VATS. There was a lack of evidence of extrapulmonary involvement for three months after diagnosis, and the patient was diagnosed with primary p-malt lymphoma. She has not received any chemotherapy, and her clinical symptoms and radiologic findings have been stable for two years. Discussion In the present case, we initially suspected the possibility of LIP and/or FB based on the CT findings observed at the time of admission. In cases of multiple thin-walled cysts, a diagnosis of p-malt lymphoma should be considered not only in patients with autoimmune diseases, including Sjögren s syndrome, but also in patients with no prior medical history. P-MALT lymphoma presents with various findings on chest CT. (5) showed that the chest CT findings of p-malt lymphoma consist of single nodular or consolidative patterns (33%), multiple nodules or areas of consolidation (43%), bronchiectasis and bronchiolitis (14%) and diffuse interstitial lung disease (10%). In addition, Ahmed et 2326

3 Intern Med 52: , 2013 Figure 1. Chest radiography and computed tomography (CT) images obtained on admission. Chest radiography performed on admission (A) showing no obvious abnormal findings. Lung windows of chest CT performed on admission (B-E) demonstrating diffuse multiple thin-walled cysts and small ill-defined nodules (black arrows) exhibiting a perilymphatic pattern in the bilateral lung fields. Figure 2. Histopathological and immunohistochemical findings of the specimen obtained from the right S8. A and B (magnified view): Hematoxylin and Eosin staining showing infiltration of smalland middle-sized lymphocytes around the bronchovascular bundles and bronchioles, follicular colonization and lymphoepithelial lesions. C and D: An immunohistochemical analysis demonstrating that the lymphocytes were positive for CD20 (C) and the lymphoepithelial lesions were positive for CAM5.2 (D). al. (4) reported CT findings of solitary or multiple nodules (55%), masses and/or airspace consolidation (18%), patchy airspace and/or interstitial infiltrates (23%), peribronchial thickening (9%), hilar or mediastinal lymphadenopathy (5%) and pleural effusion (9%). In these reports, the authors dem- onstrated that single or multiple nodules or areas of consolidation are the major patterns observed in patients with pmalt lymphoma. We found only eight cases of p-malt lymphoma with cystic lesions on chest CT, as summarized in Table 2 (5, 7-11). On the other hand, the major CT find- 2327

4 Table 2. Reported Cases of MALT Lymphoma with Cystic Lesions Author Underlying Age/Sex disease Main CT findings as described in original manuscripts Treatment Outcome Ito et al. Parambil et al. Miao et al. Zhang et al. Watanabe et al. 41 / M 63 / F 49 / F 40 / F 49 / F SLE cysts patchy areas of consolidation and nodules as well as two cysts diffuse interstitial disease with cystic lesions multiple nodules or areas of consolidation with cystic lesions multiple nodules or areas of consolidation with cystic lesions patchy ground-glass attenuation, cystic lesions multiple bilateral cystic lesions multiple cystic lesions, ground-glass opacity and small nodules chemotherapy chemotherapy stable stable improved : Sjögren s syndrome, SLE: Systemic lupus erythematosus ings of LIP are characterized by the presence of groundglass attenuation, poorly defined centrilobular nodules, subpleural small nodules, thickening of the bronchovascular bundles, interlobular septal thickening and the presence of cystic airspace (12, 13). The typical CT findings of FB are characterized by centrilobular or peribronchial nodules measuring 3-12 mm in diameter (14). Therefore, we also suspected that the pulmonary findings in this case could possibly be due to LIP and/or FB based on the presence of multiple pulmonary cysts, ground-glass attenuation and small nodules. Collectively, CT findings of multiple thinwalled cysts are common in patients with LIP and/or FB and rare in those with p-malt lymphoma (6). It has been reported that chronic inflammation and autoimmune disorders, such as Sjögren s syndrome and rheumatoid arthritis, are risk factors for MALT lymphoma (15). As shown in Table 2, four of the eight cases of p-malt lymphoma with cystic lesions were complicated by autoimmune disorders, and three of the four patients had Sjögren s syndrome. These reports suggest that Sjögren s syndrome should be considered as an underlying disease in patients with p-malt lymphoma with multiple cystic lesions. In the present case, elevation of the levels of serum RF and antinuclear and anti-ss-a antibodies was noted; however, no subjective symptoms, including decreased levels of saliva or lacrimal gland secretion, were observed. Therefore, the present case did not fulfill the diagnostic criteria for Sjögren s syndrome (16). P-MALT lymphoma is difficult to diagnose using small tissue samples obtained via TBLB or CT scan-guided lung biopsies, particularly in patients with atypical CT findings. Therefore, many patients are diagnosed based on the results of surgical biopsies (4, 5). We previously reported that detecting MALT1 gene rearrangement in BALF cells is useful for diagnosing p-malt lymphoma (17, 18). In this case, there were no MALT1 gene rearrangement-positive cells in the BALF or lung tissue samples obtained using VATS. Okabe et al. reported that positivity for MALT1 gene rearrangement in patients with MALT lymphoma is pathologically more typical (19). There are no reports showing a relationship between CT findings and MALT1 gene rearrangement; however, all of our previously reported MALT1 gene rearrangement-positive cases involved the typical CT findings of p-malt lymphoma (18). Accordingly, patients who are negative for MALT1 gene rearrangement may present with atypical CT findings, although more cases should be accumulated to confirm this speculation. In conclusion, we herein reported a case of p-malt lymphoma with multiple thin-walled cysts. This case suggests that, although rare, the possibility of p-malt lymphoma should therefore be considered in patients presenting with multiple cystic lung diseases. The authors state that they have no Conflict of Interest (COI). References 1. Isaacson P, Wright DH. Malignant lymphoma of mucosaassociated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 52: , Fiche M, Caprons F, Berger F, et al. Primary pulmonary non- Hodgkin s lymphomas. Histopathology 26: , Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. EurRespirJ20: , Ahmed S, Kussick SJ, Siddiqui AK, et al. Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease. Eur J Cancer 40: , Bae YA, Lee KS, Han J, et al. Marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: imaging findings in 21 patients. Chest 133: , Honda O, Johkoh T, Ichikado K, et al. Differential diagnosis of lymphocytic interstitial pneumonia and malignant lymphoma on high-resolution CT. AJR Am J Roentgenol 173: 71-74, Ito I, Nagai S, Kitaichi M, et al. Pulmonary manifestations of primary Sjögren s syndrome: a clinical, radiologic, and pathologic study. Am J Respir Crit Care Med 171: , Miao LY, Cai HR. Cystic changes in mucosa-associated lymphoid tissue lymphoma of lung: a case report. Chin Med J (Engl) 122: , Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjögren syndrome. Chest 130: , Watanabe Y, Koyama S, Miwa C, et al. Pulmonary mucosaassociated lymphoid tissue (MALT) lymphoma in Sjögren s syn- 2328

5 drome showing only the LIP pattern radiologically. Intern Med 51: , Zhang WD, Guan YB, Li CX, Huang XB, Zhang FJ. Pulmonary mucosa-associated lymphoid tissue lymphoma: computed tomography and 18 F fluorodeoxyglucose-positron emission tomography/ computed tomography imaging findings and follow-up. J Comput Assist Tomogr 35: , Hare SS, Souza CA, Bain G, et al. The radiological spectrum of pulmonary lymphoproliferative disease. Br J Radiol 85: , Johkoh T, Müller NL, Pickford HA, et al. Lymphocytic interstitial pneumonia: thin-section CT findings in 22 patients. Radiology 212: , Seaman DM, Meyer CA, Gilman MD, McCormack FX. Diffuse cystic lung disease at high-resolution CT. AJR Am J Roentgenol 196: , Kurtin PJ, Myers JL, Adlakha H, et al. Pathologic and clinical features of primary pulmonary extranodal marginal zone B-cell lymphoma of MALT type. Am J Surg Pathol 25: , Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjögren s syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum 36: , Kido T, Yatera K, Mukae H. Response. Chest 142: , Kido T, Yatera K, Noguchi S, et al. Detection of MALT1 gene rearrangements in BAL fluid cells for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma. Chest 141: , Okabe M, Inagaki H, Ohshima K, et al. API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Am J Pathol 162: , The Japanese Society of Internal Medicine