Histogenesis of cardiac myxomas. An immunohistochemical study of 19 cases, including one with glandular structures, and review of the literature.

To elucidate the histogenesis of cardiac myxomas, the literature has been reviewed, including all previous immunohistochemical studies, and an extensive immunohistochemical study of 19 cardiac myxomas has been undertaken with antibodies to factor VIII, desmin, vimentin, myoglobin, cytokeratin (CAM 5.2 and AE1/AE3), and S100 protein. In all cases, vimentin stained endothelial as well as "myxoma" (stromal) cells. In contrast, factor VIII only stained endothelial cells. In 16 cases, desmin stained cells in the vascular structures; in 5 cases, desmin stained myxoma cells. In 6 cases, S100 protein stained the myxoma cells strongly. Myoglobin was absent in all cases. In 1 case, CAM 5.2 and AE1/AE3 stained glandular structures. The results indicate the following: that most cardiac myxomas are true neoplasms derived from "embryonal rests"; that the various mesenchymal cells found in cardiac myxomas (myxoma cells, endothelial cells, smooth-muscle cells, fibroblasts, myofibroblasts, and chondroid cells), express differentiation, not histogenesis; that, apparently, only the myxoma cells are neoplastic; and that the glandular structures infrequently found in cardiac myxomas originate from entrapped foregut rests.

Aggressive angiomyxoma of the pelvis and perineum. Report of a case with immunohistochemical and electron microscopic study.

A case of aggressive angiomyxoma (AAM) of the pelvis and perineum is reported, whose clinical and pathological findings are consistent with the literature. This is a clinicopathological entity recently described by Rosai and colleagues (1983) who stressed its locally infiltrative nature and its tendency to recur. Its differential diagnosis includes a series of benign and malignant soft tissue tumours.

Immunohistochemical staining for vimentin filaments and S-100 protein in myxoma of the jaws.

Two jaw myxomas have been analyzed by a panel of antibodies to characterize this tumour type. Vimentin, but not keratin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), neurofilament (NF), desmin and Factor VIII-related antigen (FVIII-AG), demonstrated positivity in the cytoplasm of the neoplastic cells. Moreover, an antibody against S-100 protein also showed a strong positive reaction in the cytoplasm of the tumour cells examined. Thus directly indicating a mesenchymal derivation for odontogenic myxoma, and is the first demonstration of S-100 protein within the cells of this tumour type.

Oral nerve sheath myxoma. Report of a case with findings of ultrastructural and immunohistochemical studies.

The first Asian case of oral nerve sheath myxoma is presented, along with the findings of light and electron microscopy, and immunohistochemistry. Ultrastructurally, intracytoplasmic microfilaments and convoluted basement membrane were identified in the tumor cells. Immunohistochemically, S-100 protein and neuron-specific enolase were positive in the tumor cells. These findings may indicate that the tumor is a lesion of Schwann-cell origin. The literature on oral nerve sheath myxoma is also reviewed and discussed.

Cardiac myxoma. A retrospective immunohistochemical study.

Seven cardiac myxomas were studied by immunoperoxidase and immunofluorescence in formalin fixed and paraffin embedded tissues. Specific antisera to factor VIII related antigens, vimentin, myosin of smooth muscle, actin, desmin, alpha-1-antitrypsin, muramidase, fibrin and prekeratin antigens were used. All myxoma cells reacted positively with antibodies to vimentin and showed no staining reaction with antibodies to alpha-1-antitrypsin, muramidase, myosin, or prekeratin. Factor VIII related antigen was found only in endothelial cells and not in myxoma cells proper. Fibrin was found in patchy areas within the stroma. Antisera to actin and desmin failed to react with formalin fixed tissue. Our results suggest that the main cellular component of cardiac myxoma is a primitive mesenchymal cell without immunohistochemical evidence of more specific differentiation.

Cardiac myxomas. An immunohistochemical study using endothelial, histiocytic, and smooth-muscle cell markers.

Previous immunohistochemical studies of cardiac myxomas are few in number, limited in scope and, in part, discrepant. We studied the immunoreactivity of five cardiac myxomas for factor VIII-related antigen, Ulex europaeus agglutinin I, smooth-muscle myosin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin. Positive staining was present in all five tumors with each cell marker used, but varied according to the area of tumor examined. The result of this study provides further evidence of the cellular heterogeneity in these tumors that probably originate by differentiation of multipotential mesenchymal cells.

Dermal nerve sheath myxoma: a study of three cases.

Three cases of dermal nerve sheath myxoma have been studied by light microscopy, histochemistry and immunohistochemistry. The pertinent literature has been reviewed. This lesion, which is a rare benign tumour of probable nerve sheath origin, arises most often in young adults and shows a predeliction for females. Histologically it has a characteristic appearance. Histochemically, the heteroglycan content of the mucoid matrix is more in keeping with a cartilaginous lesion. The histogenesis and differential diagnosis are discussed.

Vasoactive intestinal polypeptide in cardiac myxoma.

A case of left atrial myxoma is reported in which tumor tissue was found to contain high levels of vasoactive intestinal polypeptide. This finding further supports the concept that myxomas are true neoplasms and may explain some of the poorly understood clinical manifestations of this tumor.

Glycosaminoglycans in myxoma of the jaw: a biochemical study.

Myxoma of the jaw is classified as an odontogenic tumor although final proof for an odontogenic origin is lacking. In the present study glycosaminoglycans (GAG's) in the extracellular matrix of a jaw myxoma were analyzed and compared with known data on GAG's in dental tissues. It was noted that the GAG's formed approximately 1% of the total tumor weight and 17% of the dry weight. Hyaluronic acid formed 72.4% of the GAG-fraction. Neither this high GAG-content nor the high fraction of hyaluronic acid are found in dental tissues and it is concluded that the myxoma matrix differs from the matrix in dental pulp and periodontal ligament.

Heterogeneous expression of factor VIII/von Willebrand factor by cardiac myxoma cells.

The expression of factor VIII/von Willebrand factor (FVIII/vWF), a marker for endothelial differentiation, was examined immunohistochemically in normal cardiac tissue and seven cardiac myxomas. In normal tissue, FVIII/vWF was detected in the surface endocardial cells and the vascular endothelial cells. In tumors, the isolated myxoma cells and the small groups and cords of myxoma cells did not express FVIII/vWF. Some of the surface cells contained FVIII/v/WF, but most did not. The predominant sites of FVIII/vWF localization were the multilayered, concentric vascular structures. In most of these, FVIII/vWF was present only in the inner layer of cells immediately surrounding the vascular lumens. In some, however, intense staining was present in both the inner and outer cell layers. In general, the FVIII/vWF-positive cells had the appearance of endothelial cells. These observations correlate with the recognized histologic, histochemical, and ultrastructural heterogeneity of cardiac myxoma cells, and conform to the current view that such cellular heterogeneity arises via the divergent differentiation of multipotential mesenchymal cells.

[Endocardial myxoma. Current aspects of its histopathogenesis]. / Endokardmyxome. Neue Aspekte zur Histopathogenese.

Primary tumours of the heart are rare. Among these the myxoma is not only the most common but also the most fascinating neoplasm, because some proponents have argued in favour of a thrombotic rather than a true neoplastic origin. The most compelling arguments against the theory of a thrombotic origin are based on ultrastructural characteristics. Using light-microscopy and immunohistochemistry, the authors attempt to clarify the histogenesis of this peculiar tumour which does not arise from any tissue normally occurring in the heart. It is assumed that the stem cell of the cardiac myxoma is a multipotential mesenchymal cell able to differentiate into fibroblasts, smooth muscle cells and endothelial cells. The most striking feature of the myxoma is excessive production of gelatinous matrix. This abundance of mucoid ground substance is typically observed in embryonic tissue. It is suggested that cardiac myxoma derives from multipotential embryonic remnants of the subendocardium.

Ultrastructure and mechanical properties of chordae tendineae from a myxomatous tricuspid valve.

The ultrastructure and mechanical properties of chordae from a surgically removed myxomatous tricuspid valve were examined. Transmission and scanning electron microscopy showed the internal structure of the abnormal chordae to consist of a loose and relatively sparse network of disorganized collagen fibrils, with no well defined collagen bundles present. The abnormal tissue was found to be more extensible than normal and it ruptured at a stress that was only about 6% of the breaking stress for normal chordae. Chordal rupture, a common complication in this disorder, can be attributed to this decrease in chordal strength. At high strains, a decreased elastic modulus was also observed, which may be attributed to tissue changes and an alteration in collagen fibril structure and/or composition.

[The so-called cardiac myxoma. Histological, electron microscopical, immunofluorescence, and biochemical investigations in 3 cases (author's transl)]. / Das sog. Endokardmyxom. Histologische, elektronenmikroskopische, immunfluoreszenz- und biochemische Untersuchungen an drei Fällen.

Three cardiac Myxomas were studied by light-, immuno-fluorescence and electron microscopy. Acid mucopolysaccharides of the tumour were isolated chromatographically. The surfaces of the "myxomas" were papillary in two cases and smooth in one. The smooth surfaced tumour recurred six months after primary resection; histological specimens were more cellular than those of the papillary tumors and showed nuclear polymorphism and mitoses. The cells of two papillary tumours were identified as endocardial by electron microscopy, however, the cells of the smooth surfaced tumour were typical myofibroblasts. In both types of "myxomas" the cells were rich on cytoplasmic filament that contained acto-myosin. Biochemical investigation failed to reveal any difference between the acid mucopolysaccharide pattern of the two tumour types; isolated mucopolysaccharides being typical for embryonal mesenchymal tissue. The authors agree with Albertini (1963), that "cardiac myxoma" is a misnomer for two different typical endocardial tumours: a true endothelioma and a "special fibroma" (myofibroma or myofibrosarcoma).

Myxoma of the heart: clinical and experimental observations.

During the past 12 years, 13 patients with atrial (10 left and 3 right) myxoma have been treated. The tumors of the left atrium produced signs and symptoms of mitral valve obstruction and/or subacute bacterial endocarditis and those of the right atrium manifestations of tricuspid valve disease or of pulmonary embolus or hypertension. The diagnosis was established by angiocardiography in 8 patients, at surgery performed for suspected mitral stenosis in 3 patients, and at autopsy in 2 patients. Resection of the atrial myxoma alone in 5 patients or with atrial septum where the atrial myxoma was attached in 4 or with the whole right atrial wall where the atrial myxoma was attached in one patient was performed and all are doing well without evidence of recurrence. Studies of experimentally produced 1.5-3 cm in diameter left atrial thrombus in 30 dogs divided into 5 groups and followed cineangiocardiographically and sacrificed from 14 days to 6 months indicated that the implanted thrombus is absorbed over a 3 to 6 month period. These experimental and human left atrial thrombi were found to be histologically and histochemically different from human atrial myxomas. The electron microscopic studies performed on some of the resected atrial myxomas suggested that the atrial myxoma cells are active cells of endotheilial origin. These observations suggest that atrial myxoma is a primary tumor of the heart which can mimic other clinical entities, and the results of its surgical treatment are gratifying and long lasting.

Histochemical characteristics of muco-substances in three soft-tissue tumours.

The mucosubstances present in myxoid liposarcomas, malignant fibrous histiocytomas and intramuscular myxomas were investigated. The results suggest that such investigations are unlikely to provide a useful diagnostic aid in these three lesions.

Histochemical characterization of mucosubstances in bone and soft tissue-tumors.

The present investigation endeavors to characterize the mucosubstance content of 170 myxoid and chondromatous tumors and chordomas by histochemical methods. The results obtained using the critical electrolyte concentration (CEC) method as introduced by Scott and co-workers23,24 were compared with those obtained by staining with alcian blue and toluidine blue at different pH's with and without pretreatment with bovine testicular hyaluronidase. Tissues known biochemically to contain different heteroglycans were used as controls: synovial fluid and cock's comb (hyaluronic acid) stained with alcian blue up to a MgCl2 concentration of 0.1 M; fetal cartilage (chondroitin 4- and 6-sulphate) pulposus with notochordal remnants (keratan sulphate) up 10 1.0 M. The staining reaction of intramuscular myxoma and myxoid liposarcoma corresponded to that of synovial fluid and cock's comb (containing hyaluronic acid). Benign chondromatous tumors (osteochondroma, enchondroma, extraskeletal chondroma, chondromatosis in bursae, synovia, and tendon) as well as well-differentiated chondrosarcomas had a similar staining reaction to that of adult cartilage (containing keratan sulphate). However, the intensity of the reaction was lower in these tumors than in the adult cartilage, indicating that the keratan sulphate content of the tumors is lower. Most of the moderately well-differentiated chondrosarcomas, the poorly differentiated chondrosarcomas, and pulmonary metastases of chondrosarcoma, as well as mesenchymal chondrosarcoma and extra-skeletal chondrosarcoma possessed the same staining properties as fetal cartilage, known to contain chondroitin 4- and 6-sulphate but not keratan sulphate. A few of the moderately well-differentiated chondrosarcomas stained up to a MgCl2 concentration of 1.0 M. Three cases of poorly differentiated chondrosarcomas stained with alcian blue up to 0.35-0.45 M in the lowest differentiated areas, indicating the presence of sulphated heteroglycans, as chondroitin 4- and 6-sulphate. Most chordomas possessed the same staining properties as fetal cartilage; however, a few chordomas stained in the same way as notochordal remnants of nucleus pulposus (containing keratan sulphate), which are thought to be the origin of these tumors. The results of staining of the tumors in the present series with the Scott technique corresponds well with toluidine blue and alcian blue at different pH's with and without pretreatment of the sections with testicular hyaluronidase. Since bone and soft tissue tumors may contain varying mucosubstances depending on the tissue of origin and on differentiation, histochemical investigation of the heteroglycan content of these tumors may be a valuable diagnostic aid.