Mesothelial/monocytic incidental cardiac excrescence mimicking cardiac tumor

Introduction

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare condition that was first described by Rosai and colleagues ¹ in 1979 as intracardiac histiocytic hemangioma. The term MICE was coined by Veinot and colleagues ² in 1994. The exact etiology in not known. The size of these lesions varies from few millimeters to 3.5  cm. The most common location is the left atrial endocardium. ³ Microscopically, mesothelial cells and macrophages are seen in a fibrin meshwork without an intervening vascular network. Regardless of histogenesis, these lesions are of clinical interest because they may be mistaken for malignancies.

Case report

A 32-year-old woman presented with progressive dyspnea on exertion (New York Heart Association class III) of 3 years’ duration. Clinical examination revealed the absence of pallor, jaundice, cyanosis, clubbing, subcutaneous nodules, and lymphadenopathy, and her vital parameters were within normal limits. Echocardiography showed thickening of the anterior mitral leaflet with doming. The aortic valve was thickened with restricted opening, and there was severe tricuspid regurgitation; the tricuspid valve showed similar thickening. The left atrium, right atrium and ventricle were enlarged. A diagnosis of rheumatic heart disease with severe aortic, mitral and tricuspid stenosis, and moderate aortic regurgitation was made. Triple-valve replacement was performed. Intraoperatively, a small cardiac excrescence was found over the aortic valve, which was excised and sent for histopathological examination. Grossly, the specimen was composed of a single hemorrhagic soft tissue fragment measuring 0.6 × 0.3 × 0.3 cm. Sections of paraffin-embedded tissue showed diffuse proliferation of histiocytes, occasional mesothelial cell islands, and scattered inflammatory cells. The mesothelial strips were composed of cuboidal to low columnar cells with eosinophilic cytoplasm and dark-staining nuclei, arranged in gland-like structures. No vascular network was seen in the lesion (Figure 1a). Immunohistochemically, the histiocytes showed diffuse cytoplasmic positivity for CD68 (Figure 1b) and were negative for pancytokeratin and calretinin. The mesothelial cells showed positivity for cytokeratin (Figure 1c) and calretinin (Figure 1d), and were negative for CD68.

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Figure 1.

(a) Photomicrograph showing diffuse proliferation of histiocytes with occasional mesothelial islands and scattered inflammatory cells. Hematoxylin and eosin stain, original magnification × 200. Immunohistochemistry showing (b) histiocytes positive for CD68 (original magnification × 200), and mesothelial cells positive for (c) cytokeratin (original magnification × 200) and (d) calretinin (original magnification × 200), and negative for CD68.

Discussion

MICE is an uncommon reactive proliferation of histiocytes and mesothelial cells, which was first proved to be of monocyte and mesothelial origin by Luthringer and colleagues. ⁴ Later, Veinot and colleagues ² suggested that the lesion is probably a reactive process related to previous cardiac catheterization. It is usually detected incidentally during cardiac surgery, and more frequently found attached to the left mitral and aortic valve surfaces. Other sites include the right atrium, ascending aorta, right atrial appendage, left atrioventricular groove, left atrium, pericardial sac, and right ventricle. A review of 40 cases by Hu and colleagues ⁵ showed an equal distribution between males and females, with an age range of 5 to 80 years and mean age of 60 years. Lesions similar to MICE, termed nodular histiocytic mesothelial hyperplasia, have also been described in extracardiac locations including hernial sacs, ⁶ pleural and abdominal cavities.

There are 2 hypotheses to explain the presence of mesothelial cells in the intravascular space. Reactive theory describes the possible role of mechanical irritation, inflammation, or neoplasm as a trigger, as well as a previous cardiac intervention that allowed mesothelial cells entry into the cardiac chambers. These foreign bodies inside the vascular space lead to mechanical irritation, resulting in histiocytic proliferation. ⁴ The association of tuberculosis supports the role of inflammation.Two cases of malignancy (squamous cell and adenocarcinoma) have been described in association with MICE, and a possible mechanism of cardiac MICE was suggested to be due to the prothrombogenic activity of invasive carcinoma.^7,8 This prothrombogenic activity might have some role in the histogenesis of MICE, later reported to be associated with antiphospholipid syndrome. The other hypothesis is an artifactual origin proposed by Courtice and colleagues ⁹ who found tissue fragments with similar histomorphology in extracorporeal bypass pump filters and mediastinal drains, and suggested that MICE was an amalgam of mesothelial strips, tissue, and debris artifactually compacted in the operating field. Most reports have accepted the artifactual hypothesis as a convincing explanation for MICE. Our case probably belongs to this category because no prior catheterization was performed.

However, some cases without a history of prior cardiac instrumentation or any surgical manipulation have also been reported. Therefore, the pathogenesis of cardiac MICE should be reevaluated and redefined in further studies. ¹⁰ Suárez-Vilela and colleagues ¹¹ suggested the possible role of adhesion molecules in the formation of MICE. They found CD34 positivity, so this aberrant expression may lead to adhesion of mesothelial cells to histiocyte/monocyte elements by the L-selectin ligand.Kuwana and colleagues ¹² suggested that mesothelial cells may originate from monocyte-derived multipotential cells which are capable of differentiating into other cell lineages. This might be an explanation for the presence of intravascular mesothelial cells. Apart from monocytes and mesothelial cells, the presence of erythrocytes, leucocytes, and calcification, as well as foreign bodies such talc and cotton have also been also described. ¹³

Although these lesions are most commonly asymptomatic and incidental findings, they may sometimes cause intractable arrhythmia, pulmonary embolism, and cardiopulmonary failure. The most common differential diagnosis is metastatic adenocarcinoma, particularly a clear cell or mesothelial tumor. ⁸ As MICE, carcinoma, and mesotheliomas are pancytokeratin-positive, a panel of immunohistochemical markers including cytokeratin 5/6, Wilms’ tumor gene product, and calretinin is required for precise diagnosis. Immunostaining with CD31 is helpful to differentiate MICE from vascular lesions such as histiocytoid hemangioma and epithelioid hemangioendothelioma.^2,13,14 Although MICE is very rarely encountered, it is important to recognize this entity because it mimics metastatic malignancies.