Methotrexate-associated Lymphoproliferative Disorder with Diffuse Ground-Glass Opacities
Methotrexate-associated Lymphoproliferative Disorder with Diffuse Ground-Glass Opacities
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甲氨蝶呤相关的淋巴组织增生性疾病，伴有弥漫性毛玻璃样混浊
DOI：
10.1164/rccm.201806-1115im
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发表时间：
2019
影响因子：
24.7
通讯作者：
Suda Takafumi
中科院分区：
文献类型：
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作者：
Tsuchiya Kazuo;Suzuki Yuzo;Yasui Hideki;Hozumi Hironao;Karayama Masato;Furuhashi Kazuki;Enomoto Noriyuki;Fujisawa Tomoyuki;Nakamura Yutaro;Inui Naoki;Baba Satoshi;Suda Takafumi
在此，我们介绍了第一例与弥漫性磨玻璃样混浊相关的甲氨蝶呤相关淋巴组织增生性疾病（MTX 相关淋巴组织增生性疾病）。一名 53 岁女性被转诊至日本滨松大学医学院，她有 3 个月的发烧和疼痛性淋巴结病史。她的病史包括使用 MTX 治疗 8 年的类风湿性关节炎、干燥综合征以及使用左旋甲状腺素治疗 8 年的慢性甲状腺炎。她很瘦（体重指数，12.5 kg/m2）、低氧血症（通过脉搏血氧饱和度测量，室内空气中的氧饱和度为 91%）、呼吸急促（呼吸频率，30 次呼吸/分钟）和发烧（37.78°C）。体检发现口干、尺偏、胸部听诊双侧细湿啰音、肝脾肿大、腋窝、腹股沟淋巴结肿大。她没有已知的近期旅行史、接触史或患病接触史。实验室数据显示血清C反应蛋白（8.82 mg/dl）、乳酸脱氢酶（335 IU/L）、可溶性IL-2受体（6,281 U/ml；正常，220-530 U/ml）和IL-6（44.7 pg/ml；正常，4.0 pg/ml）升高。血清b-D-葡聚糖（6.0 pg/ml）、Krebs von den Lungen-6（444 U/ml）和表面活性蛋白-D（119 ng/ml）未升高（参见在线补充中的表E1）。计算机断层扫描显示弥漫性磨玻璃影和微弱的小叶中心结节状阴影（图 1A 和 1B），以及腋窝淋巴结肿大和肝脾肿大。患者的肺功能测试结果显示中度限制和中度弥散障碍。 BAL 液体分析显示细胞计数为 1.81 3 105/ml，细胞差异为 15% 巨噬细胞、66.2% 淋巴细胞、16.4% 中性粒细胞，CD4/CD8 比率为 0.35（正常为 0.9-1.9）。 BAL 液体培养中未检测到微生物（包括肺孢子虫 DNA PCR）。左腋窝淋巴结活检示非典型小淋巴细胞弥漫性增生、毛细血管增生及透明细胞，CD3、CD4、CD8、TIA-1阳性； CD20 和 PD-1 散在阳性； CD21 呈阴性。原位杂交显示，这些淋巴细胞对 Epstein-Barr 病毒编码的小 RNA 呈阳性（图 2A-2D）。经支气管活检标本中还发现了用 Epstein-Barr 病毒重新激活的 T 细胞积聚
Herein, we present the first case of methotrexate-associated lymphoproliferative disorder (MTX-associated lymphoproliferative disorder) associated with diffuse groundglass opacities. A 53-year-old woman was referred to Hamamatsu University School of Medicine, Japan, with a 3-month history of fever and painful lymphadenopathy. Her medical history was significant for rheumatoid arthritis treated with MTX for 8 years, SjogrenLs syndrome, and chronic thyroiditis treated with levothyroxine for 8 years. She was thin (body mass index, 12.5 kg/m2), hypoxemic (oxygen saturation as measured by pulse oximetry, 91% on room air), tachypneic (respiratory rate, 30 breaths/min), and febrile (37.78C). Physical examination revealed dry mouth, ulnar deviation, bilateral fine crackles on chest auscultation, hepatosplenomegaly, and axillary and inguinal lymph node swelling. She had no known history of recent travel, exposures, or sick contacts. Laboratory data revealed elevated serum C-reactive protein (8.82 mg/dl), lactate dehydrogenase (335 IU/L), soluble IL-2 receptor (6,281 U/ml; normal, 220-530 U/ml), and IL-6 (44.7 pg/ml; normal, 4.0 pg/ml). Serum b-D-glucan (, 6.0 pg/ml), Krebs von den Lungen-6 (444 U/ml), and surfactant protein-D (119 ng/ml) were not elevated (see Table E1 in the online supplement). Computed tomography revealed diffuse groundglass opacities and faint centrilobular nodular shadow (Figures 1A and 1B), together with axillary lymphadenopathy and hepatosplenomegaly. The patientLs pulmonary function test results demonstrated moderate restriction with moderate diffusion impairment. BAL fluid analysis revealed cell count of 1.81 3 105/ml, with cell differential of 15% macrophages, 66.2%, lymphocytes, 16.4% neutrophils, and a CD4/CD8 ratio of 0.35 (normal 0.9-1.9). No microorganisms (including Pneumocystis DNA PCR) were detected on BAL fluid culture. Left axillary lymph node biopsy revealed diffuse proliferation of atypical small lymphocytes, capillary hyperplasia, and clear cells, positive for CD3, CD4, CD8, and TIA-1; scattered positive for CD20 and PD-1; and negative for CD21. On in situ hybridization, these lymphocytes were positive for Epstein-Barr virus-encoded small RNA (Figures 2A-2D). Accumulations of T cells reactivated with Epstein-Barr virus were also found in transbronchial biopsy specimens