Cardiac myxoma with glandular component: case report

Cardiac myxoma has varying clinical presentation, uncertain histogenesis and debatable immunohis-tochemical profile. Glandular epithelial differentiation is a rare phenomenon, but glandular elements are known to be present in cardiac myxoma as an intrinsic component of the tumor. We present a case of cardiac myxoma having focal glandular differentiation, with special reference to the morphologic features and immunohistochemical profiles. CASE REPORT Clinical history A 54-year-old woman was started on anti-biotic therapy two months ago at another hospital for nonproductive cough and low fever. In June 2005, she was admitted to this hospital complaining of sudden palpitation, tic and numbness of back. Her pulse and blood pressure were normal at admission. On physical examination, there was no evidence of enlarged lymph node and edema in the lower extremities. No signs of tumor were detected in lung and mediastinum by chest X-ray. Echocardiogram demonstrated a 4.6 cm×2.4 cm echo-dense mass in left atrium, with severe mitral regurgitation II° and tricuspid regurgitation I°. Surgery was performed as the diagnosis of cardiac myxoma. At surgical resection, the myxoma appeared to have a narrow base, which was attached to the myocardium right upon the interatrial septum. The mass was removed, along with the pedicle. Pathologic findings The gross examination showed a loose lobulated tumor in left atrium measuring 7.5 cm×5 cm×1.5 cm with incomplete capsule. The fragile tumor was dark red, with a pedicle measuring 1.5 cm×1 cm. The incision was semitransparent and gelatinous with partially tan-red hemorrhagic region. Microscopic description: the myxoma surface lined by a single layer of squamous epithelium, partially stratified epithelium. The predominant component was that of a classical myxoma with stellate or spindle-shaped “myxoma cells” lying in a myxoid background, with oval nuclei and a moderate amount of eosinophilic cytoplasm. Short cords of myxoma cells were occasionally detected. Numerous capillaries scattered among the typical areas and the myxoma cells were evenly distributed with occasional perivascular aggregates. The myxoid background had additional focal hemorrhage fibrin insuccation with hemosiderin and blood cells such as erythrocytes, neutrophils and lymphocytes. The glandular component was located predominantly at the base of the myxoma (Figs. 1 and 2). There were irregular tubular glands lined by a single layer of cuboidal to tall columnar cells with the presence of goblet cells at places. The epithelial cells had basally oriented round nuclei with prominent nucleoli and eosinophilic cytoplasm and apical mucinous bubbles. There was no nuclear atypia, mitosis or necrosis.Fig. 1.: Microscopic appearance of the glandular component in cardiac myxoma. (HE, original magnification ×200)Fig. 2.: The gland lined by cuboidal to columnar cells in “myxoma cells” background. (HE, original magnification ×400)Immunohistochemical staining showed Vimentin positive in myxoma cells as well as vascular endothelial cell. Only the glandular structures showed diffuse positivity for cytokeratin (AE1/AE3)(Fig. 3), but not for CEA, CD68 or chromogranin A. Actin stained some muscle fibers and S-100 protein stained a few dendric cells.Fig. 3.: Immunohistochemical stain for cytokeratin showing diffuse positive in the epithelial cells. (Elivision, original magnification ×200)All of primary antibodies were bought from Fuzhou Maxim Corp., China. All myxoma cells in the background were negative for any of these stains. Additionally, the glandular epithelium showed strong positivity with PAS (red) and AB (blue) staining. DISCUSSION Myxoma is reported to occur in about 50% of primary cardiac tumor. Patients with myxoma tend to be younger and more likely in female, occasionally with a familial background. They can manifest with a variety of signs and symptoms, including palpitation, shortness of breath, syncope and heart murmurs. These symptoms, usually based on the location of the tumor, vary with its size, shape, and also with the length of the pedicle. In almost all the patients preoperative diagnosis of intracardiac myxoma was sufficiently established by echocardiogram. The morphologic characteristics in diagnosis of classical cardiac myxoma is the stellate or spindle-shaped “myxoma cells” lying in a myxiod background. Glandular differentiation is a rare feature, and constitutes approximately 3% or less of all cardiac myxomas.1 The glands were predominantly mucous-secreting and well-differentiated, which were frequently found at the base or the pedicle of the myxoma. Reactivity for cytokeratin was noted in the myxomas which showed glandular differentiation. The intracellular mucin was composed of both neutral (PAS positive) and acid mucin (AB positive). So the light microscopic appearance of the glandular epithelium, including the histochemical and immunohistochemical patterns, suggests the gastrointestinal or enteric nature of the epithelium. In Goldman's study,2 electronic microscopic observation of one cardiac myxoma demonstrated well-formed glands having basement membranes, junctional complexes, and apical secretory granules. These findings indicate the capacity for true epithelium differentiation of cardiac myxoma. Most authors now believe that cardiac myxoma is a neoplastic lesion derived from “embryonal rests”, and the presence of various mesenchymal cells, smoothmuscle cells, fibroblasts, myofibroblasts, and chondroid cells represents divergent differentiation. The presence of the epithelial element as glandular structure is an example of one spectrum of the multidirectional differentiation.3 Alternatively, cardiac myxoma was described as entrapped foregut rests or intracardiac endodermal heterotopia in some other literatures.4 Recognition of the glandular element in classical myxoma background is important as they can mimic metastasis from a adenocarcinoma.4,5 In clinical practice, it is essential to inquire the patient for the past history of adenocarcinoma elsewhere. Sometimes abdominal B-mode ultrasound is required to exclude metastasis. Atypical glands with frequent mitosis, including abnormal forms and areas of necrosis support the diagnosis of metastastic adenocarcinoma. Additionally, it lacks the presence of myxoma cells or lepidic cells in the background. In the present case, the patient has no carcinoma elsewhere. Multiple mucoid spaces lined by a single layer of well-formed glandular epithelial cells were scattered among the typical areas of myxoma. No nuclear atypia was observed. Cytoplasm of the glandular cells was immunoreactive for cytokeratin and negative for CEA. All these findings strongly suggested the diagnosis of cardiac myxoma. After surgery, the patient was generally asympt- omatic and leading a normal life. The effect on the prognosis by the occurrence of glandular differentiation has no statistical data because of its rare incidence, but recurrence or metastasis has been reported in literatures.6,7 In a word, long-term postoperative follow-up and serial echocardiography are advisable especially for young or familial patients.