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Vanishing Cardiac Tumor: Cardiac Involvement in Methotrexate-Associated Lymphoproliferative Disorders.

November 2019 1 Naohiro Kishiue, MD Toshiyuki Yano, MD, PhD Masayuki Koyama, MD, PhD Ryo Nishikawa, MD Nobutaka Nagano, MD Hidemichi Kouzu, MD, PhD Nobuaki Kokubu, MD, PhD Ryota Kawamura, MD Atsuko Muranaka, MD, PhD Shohei Kikuchi, MD, PhD Akihito Tsuchida, MD, PhD Tetsuji Miura, MD, PhD An 83-year-old woman with general fatigue, dyspnea on exertion, and weight loss were referred to our hospital. Her rheumatoid arthritis was diagnosed 10 years ago, and she had received medical therapy including methotrexate (MTX) at a dose of 6 mg/wk for 9 years. She experienced complete atrioventricular block and received pacemaker implantation 4 months before admission to our institute. Transthoracic echocardiography revealed severely calcified tricuspid aortic valves with a maximum speed of aortic flow of 4.5 m/s, average pressure gradient of 43.5 mm Hg, and aortic valve area calculated by a continuity equation was 0.53 cm2/m2 of the body surface area. A heterogeneous mass adhering to the right atrial and ventricular wall was found by echocardiography (Movie I in the Data Supplement). T1-weighted images obtained by cardiac magnetic resonance imaging showed a well-demarcated mass with isointensity to the myocardium, extending into the pericardial space, together with pericardial effusion (Figure 1A, Movie II in the Data Supplement). In contrast-enhanced computed tomography images, the mass had heterogeneous hypodense areas and appeared to invade in the interatrial and interventricular septum (Figure 1B). Masses with similar computed tomography characteristics were also found in the left adrenal gland and the anterior mediastinum (Figure 1C and 1D). Blood examinations revealed a marked elevation in serum sIL-2R (soluble interleukin-2 receptor level; 4263 U/ mL, normal range: 145–519) and a low lymphocyte count (550/μL). Histological analyses of a surgically resected anterior mediastinum mass revealed increased proliferation of atypical lymphocytes with nuclear enlargement, and the majority of the atypical lymphocytes expressed pan B cell antigens (CD20 and CD79a), indicating a histological diagnosis of diffuse large B-cell lymphoma (Figure 1E and 1F). In addition, results of in situ hybridization showed that most of atypical lymphocytes were Epstein-Barr virus (EBV) small RNAs-positive (Figure 1G). Based on the results of the examination and her medical history, we suspected MTX-associated lymphoproliferative disorders (MTX-LPD) and discontinued MTX administration. At 4 months after MTX withdrawal, the masses including the cardiac tumor were spontaneously regressed, and pericardial effusion were disappeared together with a marked reduction in sIL-2R level (700 U/mL, Figure 2, Movies III and IV in the Data Supplement) and recovery of reduced lymphocyte count. Collectively, a diagnosis of MTX-LPD was made. She was then scheduled to receive transcatheter aortic valve replacement. Although cardiac lymphoma is an extremely rare manifestation of lymphomas, accounting for only 0.03% of all lymphomas, it is the second-most frequent malignant cardia tumor. The cardiac involvement of lymphomas, occasionally leading to arrhythmic events, including atrioventricular block, cardiac tamponade, and heart failure is associated with worse prognosis and higher treatment-related mortality than that of extracardiac lymphomas. © 2019 American Heart Association, Inc. CARDIOVASCULAR IMAGES