Case 2 -

Cardiac Myxoma with Glandular Component Renu Virmani CV Path Gaithersburg, Maryland

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Clinical History The patient is a 33-year-old man employed as a roofer with a 20-pack-year history of tobacco use who presented with chest pain. He was admitted to the hospital at which time an acute myocardial infarction was ruled out. On physical exam a pericardial friction rub was noted and was subsequently found to have pericarditis with effusion. He was given Indomethacin, which resulted in marked improvement, but the chest pain returned. An echocardiogram showed a large left atrial mass with possible mitral valve involvement. Past medical history was significant for left leg and arm arterial thrombsis, a year prior to this admission. The patient underwent surgical removal of the left atrial mass, which measured 5.5 cm in diameter, gelatinous in appearance and was attached to the interatrial septum. Case 2 - Figure 1 - Low power view of cardiac myxoma with focal glandular elements Case 2 - Figure 2 - A higher magnification of the glandular component; the glands have irregular contours and are lined by cuboidal to columnar cells Case 2 - Figure 3 - An area of cardiac myxoma composed of myxoma cells found in a myxoid matrix Diagnosis: Left atrial mass: cardiac myxoma with glandular component Differential Diagnosis: Malignant tumors, sarcomas of the heart often occur in the left atrium and can have extensive myxoid areas. There are several examples of recurrent left atrial sarcomas that have erroneously diagnosed as myxomas. Adenocarcinoma because of presence of glandular structures in the myxoma have been diagnosed but typical features of the carcinoma are absent and there are characteristics features of myxoma present. (see below) Papillary fibroelastoma generally located on the valve and the papillary fronds are avascular, whereas capillary network is always present in myxoma. Mural thrombi are occasionally diagnosed as myxoma because the diagnostic features of myxoma are absent despite multiple sections. The distinction between an organizing thrombus and myxoma can be difficult. Discussion Primary cardiac tumors are very rare and the majority (90%) are benign. Seventy-five percent of benign cardiac neoplasms resected at surgery are cardiac myxomas. Cardiac myxoma with glandular structures is a rare variant of cardiac myxoma, representing 1-5% of cardiac myxomas. Despite its low incidence, awareness of this unusual entity is important because histologically it may be confused with metastatic adenocarcinoma, thus careful evaluation is required especially in patients with a known history of carcinoma elsewhere. Considering the long history of tobacco use in this patient, it was prudent to consider metastasis from a primary pulmonary tumor in the differential diagnosis especially as lung carcinoma is the most common metastatic malignancy to the heart. Other metastatic carcinomas known to involve the heart include breast, stomach, hepatocellular, and colonic carcinoma. Histologically, cardiac myxomas with glandular structures are characterized by the presence of glands lying within a myxoid background in association with typical cardiac myxoma cells. The glandular component may range from a single layer of cuboidal cells to tall columnar cells with or without the presence of goblet cells and luminal mucin. Morphologically, these glands resemble benign gastrointestinal epithelium, although reactive cytologic atypia has been described in some cases. Typical myxoma cells are stellate or ovoid, with eosinophilic cytoplasm and indistinct cell borders. The cells form rings, cords and syncytia, often forming multilayered rings around blood vessels. Nuclei typically display open chromatin and inconspicuous nucleoli. In summary, the tumor is characterized by two essential components: islands of benign glandular epithelium and the obligatory presence of typical myxoma cells in a myxoid background. The clinical presentation, location, and prognosis of cardiac myxoma with glandular elements is virtually identical to that of classical myxoma. Clinically, cardiac myxomas notoriously cause a wide variety of symptoms. This patient presented with chest pain and embolization, two fairly common modes of presentation. Other presentations include cardiac arrythmias, dyspnea, mitral stenosis and constitutional symptoms such as fever. Cardiac myxoma is most often located in the left atrium (80%) as a solitary lesion, an important feature when considering a metastatic tumor which tends to be diffuse and multifocal. The average age at presentation is 50 years, with a slight female predominance. The gross appearance of cardiac myxoma with glandular structures does not differ from a typical myxoma; it may vary from a gelatinous mass with frond-like excrescences that are likely to embolize, to a tumor with a smooth firm surface and rarely embolizes. Symptoms related to embolic phenomena include strokes, transient ischemic attacks, claudication of the extremities, renal insufficiency, myocardial infarction, and pulmonary emboli if the tumor is right sided. The presence of glandular differentiation does not generally alter the long-term prognosis, as most behave as typical cardiac myxomas. The majority of patients with cardiac myxoma are cured with surgical excision, although there is a 2% recurrence rate. Rare isolated cases of malignant glandular cardiac myxomas with systemic metastases have been reported, although the malignant behavior of these tumors may possibly be explained by local recurrence or embolic phenomena. According to a recent publication, only 27 cases of cardiac myxoma with glandular elements have been reported. Two patterns of glandular distribution have been recognized; glands may be scattered in a loose myxoid matrix or glands maybe be centrally located in islands of myxoma cells. The glandular structures are always associated with characteristic areas of myxoma, but the extent of the glandular elements may vary. Some cases show only focal glandular differentiation, and in others the glandular elements dominate the histologic picture. Many reports describe the location of the glandular component in the basal aspect of the tumor. Histology is the most reliable method for differentiating malignant metastatic tumor from cardiac myxoma with glandular elements. Histologic characteristics favoring a diagnosis of cardiac myxoma with glandular elements include: the absence of atypia in the glandular epithelium, lack of mitotic figures, the absence of tumoral extension and the findings of typical myxomatous areas with myxoma cells. In this case the histology shows the characteristic features of cardiac myxoma but also has glandular elements. The sections show cords and ring-like clusters of myxoma cells surrounding vascular structures in a proteoglycan-rich myxoid matrix. There is focal glandular differentiation in the midst of these typical myxoma cells. Areas of hemorrhage and hemosiderin deposition are also present, findings typically associated with cardiac myxoma. Subendocardial arterial thickening is present at the site of attachment to the atrial wall. Immunohistochemical staining applicable to the myxoma elements is strongly positive for calretinin, weakly positive for CD15, and negative for CEA. Calretinin is reported to be present in 73-100% of myxoma cells. Calretinin staining performed in our case was strongly positive. CEA staining was positive only in the glandular part of the myxoma. Myxoma cells were negative for Factor VIII but endothelial cells were positive. Immunohistochemical analyses performed on glandular elements of the myxomas commonly express cytokeratin, EMA, and carcinembryonic antigen (CEA). One study demonstrated co-expression of cytokeratins 7 and 20, a profile similar to foregut derivatives. In addition, the glandular epithelium is often mucicarminophilic and periodic acid-Schifff (PAS) positive, diastase resistant. In general, immunohistochemistry does not allow one to differentiate a cardiac myxoma with glandular component from the more ominous diagnosis of metastatic adenocarcinoma. As mentioned above, the diagnosis is most reliably based on recognizing the benign morphology of the glandular component within an otherwise typical cardiac myxoma. The histogenesis of the glandular elements in cardiac myxomas is uncertain. Two theories have been proposed to explain the origin of these glands. The glands have been interpreted as arising from entrapped embryonal gastrointestinal rests in the tumor or may be derived from progressive differentiation of pluripotential myxoma cells. In our case, the glands were seen within clusters of typical myxoma cells supporting the theory that the glands represent a progression from myxoma cells to glandular elements. However, in cases where the glands are located away from the myxoma cell clusters, entrapment of foregut rests seems more likely. References Virmani R, Burke A, Farb A, Atkinson JB (eds). Tumors and tumor-like lesions of the heart and great vessels. In: Cardiovascular Pathology. pp 424-464. Philadelphia: WB Saunders, 2001. Pucci A, Bartolini G, Tessitore E, Carney AJ, Papotti M. Cytokeratin profile and neuroendocrine cells in the glandular component of cardiac myxoma. Virchow Arch. 443: 618-24; 2003. Virmani R, Burke A, Farb A (eds). Benign cardiac tumors. In: Atlas of Cardiovascular Pathology. pp 81-92. Philadelphia: WB Saunders, 1996. Lindner V, Edah-Tally S, Chafke N, Onody T, Eisenmann B, Walter P. Cardiac myxoma with glandular component: case report and review of the literature. Path Res and Pract. 195: 267-272; 1999. Chopra P, Ray R, Singh MK, Venugopal P. Cardiac myxoma with glandular elements: a histologic, histochemical, and immunohistochemical evaluation. Indian Heart J. 55: 182-184; 2003. Eckhardt BP, Dommann-Scherrer C, Stuckmann Gerd, Zollikofer CL, Wentz K. Giant cardiac myxoma with malignant transformed glandular structures. Eur. Radiol. 13: 2099-2102; 2003. Acebo E, Val-Bernal JF, Gomez-Roman JJ. Thrombomodulin, calretinin, and c-kit (CD117) expression in cardiac myxoma. Histol Histopathol. 16: 1031-1036; 2001. Terracino L, Mhawech P, Suess K, D'Armiento M, Lehmann F, Jundt G, Moch H, Sauter G, Mihatsch M. Calretinin as a marker for cardiac myxoma. Am J Clin Path. 114: 754-759; 2000.