Diffuse Infiltration of Lymphoma of the Myocardium Mimicking Clinical Hypertrophic Cardiomyopathy
A 51-year-old man with good health previously presented with a 1-month history of shortness of breath on exertion. Transthoracic echocardiography revealed marked biventricular hypertrophy, mild mitral regurgitation, and moderate tricuspid regurgitation, suggestive of hypertrophic cardiomyopathy (Figure 1A and 1B; Movie I and Movie II). In the parasternal short-axis view, thickening of the left atrial wall and para-aortic tissue were evident, which is unusual in typical hypertrophic cardiomyopathy, a disease that primarily affects the ventricular myocardium (Figure 1C and Movie III). Computerized tomographic arteriography revealed no coronary artery disease. His heart failure symptoms worsened, and atrial fibrillation developed. At the same time, maculopapular skin rash developed on the upper trunk and the head and neck region. Hypercalcemia with an adjusted serum calcium level greater than 4 mmol/L was recorded. Other blood chemistry and hematologic examinations were unremarkable. His conditions deteriorated rapidly and, despite maximal supportive measures, he died 1 week after hospitalization. Limited clinical postmortem examination revealed a well-built gentleman with a heart weighing 790 g (Figure 2A). The walls of all 4 chambers of the heart were diffusely thickened by tan-colored infiltrative growth. The left and right ventricular walls were 2.5 and 1.5 cm thick, respectively (Figure 2B). The cross-sectional area of the superior vena cava was significantly reduced, with nodules resulting from subendothelial infiltrate. The leaflets of valves were not involved. Mild atherosclerosis was seen in the coronary arteries and major vessels. About 50 mL of straw-colored pericardial effusion was also noted. The maculopapular skin rash was distributed over the head and neck region, extending down to the umbilicus. Hemorrhage is seen superficially at the skin lesions. Microscopic examination revealed that diffuse large B-cell lymphoma (DLBCL) had infiltrated the myocardium and replaced a substantial amount of the cardiac muscle bulk (Figure 2C). The atypical lymphoid cells were large- to medium-sized, with abundant basophilic cytoplasm and large, moderately pleomorphic nuclei (Figure 2D). Prominent, centrally located nucleoli were also noted. These atypical lymphoid cells were immunoreactive to CD20 and were negative to T-cell markers such as CD3, CD5, and CD10. Epstein-Barr virus–encoding small nuclear RNA was not detected. Frank myocardial infarction was not detected in the residual myocardium, although contractile band necrosis can be seen in individual cardiomyocytes (Figure 2D, arrows). Infiltration of atypical lymphocytes was also noted in the pericardium. In the skin, perifollicular and perivascular infiltrations of these lymphoma cells were also detected.
Cardiac involvement with lymphoma was the most significant clinical and pathological process in our patient. Our case fits into the broader clinical definition of primary cardiac lymphoma.1 The incidence of cardiac lymphoma in postmortem examination is low, with a reported range of 0.15% to 1%. Secondary cardiac infiltration from nodal lymphoma of the mediastinum appears to be more common in clinical practice.2 In the past, most cases were discovered in postmortem examination.3,4 Recently, case reports were dominated by antemortem diagnosis and chemotherapy.5 DLBCL accounts for 30% to 40% of all adult non-Hodgkin lymphomas. DLBCL is, however, the most common type of primary cardiac lymphoma. Eighty percent of the case reports and 60% of autopsy series revealed DLBCL.1
Most cases of cardiac lymphoma are solid, infiltrative nodule tumors in 1 or multiple chambers of the heart. The right heart is the most common site of cardiac lymphoma. Lymphomatous infiltration of the pericardium is also seen in a number of cases.1,3,5 However, the diffuse lymphoma infiltration of the myocardium in all 4 chambers in our patient is unusual. Massive infiltration of lymphoma cells in the myocardium results in irregular thickening of the walls of the heart, mimicking classic hypertrophic cardiomyopathy. Hypertrophy of the ventricular septum, without dilation of the heart chambers, results in the characteristic hemodynamic disturbances.6 Although only a limited autopsy was performed on our patient, we saw that the disease in our patient has spread beyond the heart and was disseminated at the final stage.
The clinical symptoms of primary cardiac lymphoma are nonspecific and are related to the location of the tumor bulk as well as the functional status of the heart. Clinical presentations are acute, including dyspnea, edema, arrhythmia, and pericardial effusion.1,4,5 In one autopsy series, cardiac symptoms were found to be more common in T-cell lymphomas. Silent infiltration is more frequent in B-cell lymphomas.4 The pathophysiology of such clinical differences in lineages of lymphomas is not fully understood.
The diagnosis of DLBCL was attained by postmortem examination in our patient, who presented with end-stage disease. Transesophageal echocardiography, computed tomography, and magnetic resonance imaging have shown characteristic features of cardiac lymphoma.1,7 Because of the variability of the morphology of the lymphomatous infiltrates, however, image findings may be nonspecific. Chemotherapy is indicated in these patients after a diagnosis with histological confirmation is established. Extra care needs to be exercised in the early stage of treatment to prevent overrapid tumor lysis, which may lead to rupture of the heart.
The online-only Data Supplement, which contains Movie I through Movie III, can be found at http://circ.ahajournals.org/cgi/ content/full/113/12/e662/DC1.
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Wynne J, Braunwald E. Cardiomyopathy and myocarditis. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Co; 2004.