Severe mitral regurgitation in chronic adult T-cell leukemia/lymphoma with granulomatous valvular inflammation

Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a mature peripheral T-cell neoplasm caused by human T-cell leukemia virus type I (HTLV-1) infection. Besides the oncogenic property, HTLV-1 causes HTLV-1-associated myelopathy/tropical spastic paraparesis and certain inflammatory diseases via a complex host immune response to latent virus infection. Cardiac involvement of ATLL is rare, with the majority of cases being disclosed in postmortem autopsy in patients with advanced subtypes. We herein report the case of a 64-year-old female patient with indolent chronic ATLL with severe mitral regurgitation. Although the condition of ATLL was stable, dyspnea on exertion gradually progressed over the course of three years and echocardiography revealed marked thickening of the mitral valve. Finally, the patient experienced hemodynamic collapse with atrial fibrillation and underwent surgical valve replacement. The removed mitral valve was grossly edematous and swollen. A histological examination revealed a granulomatous reaction mimicking the active phase of rheumatic valvulitis, with the infiltration of ATLL cells that were immunohistochemically positive for CD3, CD4, FoxP3, HLA-DRα, and CCR4. The postoperative course was uneventful, with the exception that Sjögren's syndrome was noted. The history of rheumatic fever was unclear, and such unique valvular pathology was presumably related to autoimmune mechanisms associated with HTLV-1 infection.

Learning objective: We report a case of chronic adult T-cell leukemia/lymphoma (ATLL) with isolated valvular infiltration with a unique histology of granulomatous reaction. Human T-cell leukemia virus type I infection may accelerate autoimmune reactions and cardiac inflammation, irrespective of indolent clinical subtype. Among ATLL cases, possible progression of valvular insufficiency and heart failure in patients with cardiac symptoms should be carefully evaluated.

Keywords: Adult T-cell leukemia/lymphoma; Chronic subtype; Granulomatous valvulitis; Mitral regurgitation; Rheumatic heart disease.

Fig. 1

Mitral regurgitation and aortic regurgitation on transthoracic echocardiography (apical four-chamber view and parasternal long-axis view). (A) Irregular thickening of mitral valve (arrow) and dilated left atrium (LA). (B) Color flow imaging demonstrating severe mitral regurgitant jet into the LA. (C) Mitral valve and aortic valve on parasternal long-axis view. (D) Color flow imaging demonstrating moderate aortic regurgitation. LV, left ventricle; RA, right atrium; RV, right ventricle; Ao, aorta. Left ventricular end-diastolic and end-systolic diameter was 53/35 mm with preserved ejection fraction (60 %), and the thickness of interventricular septum and left ventricular posterior wall was 10/9 mm, respectively.

Fig. 2

Histology of the mitral valve. (A) Gross appearance (atrial view). Three segments of anterior mitral leaflet (AML: A1-A3) and posterior mitral leaflet (PML) are indicated. (B) Low-power view of AML shows diffuse infiltration of lymphoid cells. (C) High-power view of AML. Small granulomatous lesion with multinuclear giant cells (dotted circle). (D) High-power view of AML. Mixed infiltration of lymphoid cells, histiocytes, and a small number of polymorphonuclear leukocytes are seen. (B-D) Hematoxylin and eosin staining. Immunohistochemical staining for CD3 (E) and CCR4 (F) in the same part as panel D.

Fig. 3

Histology of the aortic valve. (A) Gross appearance (aortic side view). Left and right coronary cusps (LCC, RCC) and noncoronary cusp (NCC) are indicated. (B) Low-power view of LCC shows severe calcification. (C) Medium-power view of LCC shows scattered small granulomatous lesions (dotted circles). (D) High-power view of NCC shows a small granulomatous lesion (dotted circle) and multinuclear giant cell (arrow). (E) Medium-power view of RCC shows diffuse infiltration of lymphoid cells. (B-E) Hematoxylin and eosin staining. (F) Immunohistochemical staining for CD3 in RCC.