Inflammatory Myofibroblastic Tumor of the Right Ventricle Causing Tricuspid Valve Regurgitation

Abstract

Cardiac inflammatory myofibroblastic tumor is a rare lesion consisting of inflammatory cells and myofibroblastic spindle cells. We describe a case of inflammatory myofibroblastic tumor that involved the right ventricle, thereby causing tricuspid valve regurgitation in an 18-year-old man who presented with a fever of unknown origin and of 1 month's duration. With the patient on cardiopulmonary bypass, we excised the lesion and replaced the tricuspid valve without serious intraoperative or postoperative sequelae. The patient had a favorable outcome.

Inflammatory myofibroblastic tumor (IMT), an entity known by various terms, rarely involves the cardiac chambers. However, it is potentially fatal when it does. Since the 1st description of cardiac inflammatory pseudotumor in 1975,¹ there have been only a few additional reports in the medical literature, mostly of occurrence in children and young adults. Its precise biologic nature and clinical characteristics are still uncertain. Currently, IMT is considered to be a low-grade neoplasm that comprises spindle cells and mononuclear inflammatory cells.^2–5 Surgical resection of the tumor remains the definitive treatment and has a satisfactory outcome. We describe a case in which IMT of the right ventricle mechanically distorted the tricuspid valve in a previously healthy 18-year-old man and resulted in moderate valvular regurgitation.

Case Report

In March 2008, an 18-year-old man from the southern area of the country was referred by an infectious-disease clinic to our heart center for evaluation of a heart mass detected during echocardiography. The patient suffered from growth retardation and from fever of 1 month's duration, accompanied by chills, sweating, malaise, and anemia. He was first evaluated at another center, where he had tested negative for brucellosis, salmonellosis, and malaria and had shown no response to antibiotic regimens. We reevaluated him for fever of unknown origin.

The patient had tachycardia but was normotensive, and his oral temperature was 39 °C. The laboratory data showed a white blood cell count of 13,800/mm³ with a normal differential count. The hemoglobin level was 9.1 mg/dL, the C-reactive protein level was elevated at 21 mg/L, and the erythrocyte sedimentation rate was 120 mm/hr. All routine blood cultures were negative. Transthoracic and transesophageal echocardiography showed a fixed right ventricular mass (with dimensions of 2.5 × 2.5 × 3.5 mm), attached to the right ventricular free wall (Fig. 1). Moderate tricuspid regurgitation, with pulmonary artery pressure of 25 mmHg, was also revealed. We observed no involvement of the pericardium or the left ventricle. Computed tomographic angiography showed a 30-mm round mass that originated from the free wall of the right ventricle and bulged into the right ventricular outflow tract (Fig. 2). The left ventricle, superior vena cava, and inferior vena cava appeared to be normal.

Fig. 1 Transthoracic echocardiography reveals a large nonhomogeneous mass (34 × 25 mm) on the right ventricular free wall (arrow), bulging into the right ventricular cavity.

Fig. 2 Computed tomographic angiography shows a round mass (30 mm in diameter) in the free wall of the right ventricle (arrow), bulging into the right ventricular outflow tract.

Under cardiopulmonary bypass, the patient underwent cardiac surgery for resection of the tumor. In the operating room, we excised a solid mass measuring 3.5 × 2.5 cm, which was firmly adherent to the right ventricular septum and to the base of the papillary muscle and chordae tendineae. At the same time, we replaced the native tricuspid valve with a 27-mm St. Jude bileaflet valve (St. Jude Medical, Inc.; Minneapolis, Minn). The tumor specimen was sent for histopathologic examination. The day after tumor removal, the patient's fever abated. His postoperative course was uncomplicated, and he was discharged on the 8th postoperative day. However, 1 week later, he developed severe pericardial effusion; the effusate was uneventfully drained. At 8 months' follow-up, he was taking no medications and remained asymptomatic.

Macroscopic examination showed a lobular mass measuring 3.5 × 2.2 × 1.5 cm, with a creamy color and a broad base. A cut section was creamy white, with a hard consistency (Fig. 3). Histologic examination revealed spindle- and ovoid-shaped cells arranged in fascicular and storiform growth patterns, with plump vesicular nuclei. A prominent inflammatory infiltrate was present, as was marked hyperchromatism. Mitotic activity was low, and there was no evidence of atypical mitosis. Inflammatory cells consisted mainly of lymphocytes, histiocytes, and plasma cells, together with a few eosinophils and neutrophils. In other areas, sclerotic fibrous tissue, focal myxoid stroma, and fibrinous material were present (Fig. 4). Upon immunohistochemical staining, a large number of spindle cells expressed MSA (muscle-specific actin), and inflammatory cells expressed CD68 (Fig. 5). There was no positive staining for desmins, S100 protein, anaplastic lymphoma kinase (ALK), or thrombomodulin—except at the base of the mass, where some nets of mature myocytes with striation expressed desmins and S100 protein due to papillary muscle involvement. In light of this macroscopic and microscopic evidence, we diagnosed inflammatory myofibroblastic tumor.

Fig. 3 Macroscopic view of the inflammatory myofibroblastic tumor.

Fig. 4 The inflammatory myofibroblastic tumor is composed of bland spindle-shaped cells and bands of sclerotic tissue. A) Hematoxylin and eosin stain (orig. ×40); B) hematoxylin and eosin stain (orig. ×10).

Fig. 5 A) Immunostaining revealed muscle-specific actin in spindle cells (peroxidase–antiperoxidase method, orig. ×10); B) immunostaining revealed CD68 positivity in inflammatory cells (peroxidase–antiperoxidase method, orig. ×40).

Discussion

Inflammatory pseudotumor is an uncommon tumor-like reactive lesion that typically presents as an intrapulmonary mass in children and young adults. It occurs most commonly in the lungs and gastrointestinal tract.⁶ These inflammatory fibrosclerosing lesions have rarely been reported in the cardiac tissues. Clinically, patients with IMT tend to have varying degrees of fever, growth impairment, iron-deficiency anemia, thrombocytosis, and hypergammaglobulinemia. Past IMTs of the heart have involved various sites; the atria are the most common.^2–5 Ours is one of the extremely rare cases reported to involve the right ventricle, causing tricuspid regurgitation.

The pathogenesis of inflammatory pseudotumor remains unclear, and the clinical outcome remains unpredictable. Currently, the pathogenesis of IMT is thought to be an abnormal and exaggerated immunologic response by proliferated spindle cells and primary myofibroblasts to injury, inflammation, and infection. In cytogenetic analysis, one third to one half of IMT patients present with a genetic translocation on chromosome 2p23, the ALK receptor gene that is often fused with tropomyosin genes.^6–9 The rate of ALK positivity in cardiac IMT is unknown.² However, the specificity of ALK expression in IMT cases may help in differential diagnosis, which explains our application of that immunostain in this case. No histologic or clinical indicators can predict reliably the course of IMT.¹⁰ Although surgical resection seems to be the treatment of choice, there is as yet no consensus on the optimal approach to cardiac IMTs found at surgical exploration. This lack of consensus can be attributed to the rarity of these lesions and to the scant knowledge of their pathogenesis and course. However, the involvement of crucial sites such as a cardiac valve and the coronary arteries can be catastrophic.

Cardiac IMTs are usually benign lesions with a favorable prognosis. Thorough investigation is paramount in identifying this rare condition. Whenever feasible, surgical resection should be the mainstay of treatment. Patients with cardiac IMT should be informed that these lesions carry a small but definite possibility of aggressive behavior.