Extra-adrenal retroperitoneal paraganglioma in a dog.

An extra-adrenal retroperitoneal paraganglioma was observed in a 10.5-year-old male Boxer dog. Additionally, the dog had an aortic base tumor, multiple thyroid adenomas, multiple testicular interstitial cell tumors, bilateral nodular adrenal cortical hyperplasia, and parathyroid gland hyperplasia. The hypothesis that the retroperitoneal mass represents a primary extra-adrenal paraganglioma rather than metastatic mass from the aortic body tumor is considered. Either primary or metastatic extra-adrenal retroperitoneal paragangliomas are rarely reported in dogs.

Cardiac myxoma with glandular differentiation: an immunohistochemical and ultrastructural study.

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.

Cardiac neuroendocrine tumor with absence of sustentacular cells: immunohistochemical and ultrastructural findings.

A 68-year-old male presented with increased shortness of breath and intermittent chest pain. Cardiac catheterization along with echocardiogram imaging demonstrated 3-vessel coronary artery disease with severe left ventricular dysfunction and critical aortic stenosis. During coronary artery bypass surgery, a tumor was identified at the sulcus between the aorta and the right atrial appendage. This highly vascular tumor extended over the right coronary artery, prompting biopsy and further resection. Light microscopic evaluation showed packets of uniform round neoplastic cells without evidence of necrosis or increased mitotic figures. Immunohistochemical studies were positive for synaptophysin and weakly positive for chromogranin. Pankeratin, S-100, and GFAP stains were all negative. Ultrastructural examination of the neoplasm demonstrated numerous electron-dense secretory granules within the cytoplasm of the tumor cells. These secretory granules varied in size from 60 to 210 nm, with halos encircling many of them, suggesting the likelihood of epinephrine or norepinephrine granules. Within the specimen, abundant vascular spaces were identified, but no sustentactular cells were present. The patient agreed to undergo genetic testing, and a mutation in the succinate dehydrogenase complex subunit B (SDHB) was identified. This confirmed the molecular diagnosis of hereditary paraganglioma/pheochromocytoma syndrome. Now two years out from surgery, this patient continues to be asymptomatic in spite of the fact that his tumor was only partially resected.

A malignant and metastasizing feline cardiac ganglioneuroma.

In the current study, a case of a cardiac ganglioneuroma with systemic metastases in a cat is described. A 12-year-old male neutered Japanese domestic cat was brought to a veterinary hospital for dysorexia, coughing, vomiting, and diarrhea. Ultrasonography revealed a mass adjacent to the right atrium. The animal died of respiratory failure 1 month after the first visit to the hospital. At necropsy, an oval-shaped white mass 1.5 cm in diameter was observed within the right auricle. Diffusely, the right ventricle was infiltrated and thickened by the neoplastic lesion. Histologically, the mass was composed of 3 types of neoplastic cells: spindle cells, large polygonal cells, and small undifferentiated cells. Immunohistochemically, the neoplasia was positive for neuronal markers such as ßIII tubulin, S-100a, and protein gene product 9.5. Ultrastructurally, the large polygonal cells were characterized by abundant cytoplasm that included compressed Golgi cisternae and rough endoplasmic reticula and abundant intermediate filaments. A discontinuous basement membrane surrounded the spindle cells. Metastatic foci were found in the lungs, kidney, pancreas, urinary bladder, and adrenal glands. The morphological, immunohistochemical, and ultrastructural characteristics of the tumor cells were consistent with those of ganglioneuroma. The tumor was presumed to originate from the intramural parasympathetic ganglia in the right atrium.

A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata.

Using novel antibodies of high avidity to--and specificity for--the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by α- and ß-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all adherens junctions of these tumors contained, in addition, another major armadillo protein Pkp2, hitherto known as an obligatory and characteristic constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2 in a series of noncardiac myxomata studied in parallel. Therefore, we conclude that this acquisition of Pkp2, which we have recently also observed in some mesenchymally derived cells growing in culture, can also occur in tumorigenic transformations in situ. We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents.

Cardiac angioleiomyoma in 44 cattle in Japan (1982-2009).

A retrospective study was performed on primary cardiac tumors found in 44 cattle during meat inspection in Japan, using histology, immunohistochemistry, and electron microscopy. The age of affected cattle ranged from 10 to 129 months; 82% were less than 3 years old. In 38 hearts, the tumor was solitary; the remaining 6 hearts had multiple masses. All tumors were subendocardial and involved the papillary muscles and/or cardiac valves. Two histologic patterns were recognized; both included giant cells. Pattern 1 was characterized by interlacing fascicles of spindle-shaped cells; pattern 2 resembled cavernous hemangioma. The 2 patterns coexisted and were linked by transitional zones. Given the immunohistochemical reactivity and ultrastructure, the spindle-shaped cells were identified as smooth muscle cells and the giant cells as endothelial cells. Single cell and multicellular angiogenesis by giant cells was observed. The tumors were classified as cardiac angioleiomyoma. Subendocardial multipotential mesenchymal cells, persistent tissue of the endocardial cushion, or valvular interstitial cells were suspected as the origin.

Myocardial adenomatoid tumor in eight cattle: evidence for mesothelial origin of bovine myocardial epithelial inclusions.

The adenomatoid tumor is an uncommon benign lesion, thus far described only in humans. Adenomatoid tumors typically arise in the genital tract, exceptionally in the heart, and usually represent an incidental finding. Microscopically, they are constituted by epithelioid cells that form tubular structures and anastomosing channels within a fibrous stroma. Mesothelial origin of these lesions is suggested by their immunohistochemical characteristics. In cattle, previously reported myocardial epithelial inclusions are morphologically similar in that the cells are immunoreactive for both cytokeratins and vimentin, and bear surface microvilli. Myocardial lesions found incidentally at slaughter in 8 cattle histologically resembled the so-called bovine myocardial epithelial inclusions and had morphologic and immunohistochemical features consistent with human adenomatoid tumor. All lesions were in the left ventricular myocardium, adjacent to the epicardium, and composed of epithelioid cells that formed cords and tubules, and were immunoreactive for pan-cytokeratins, cytokeratin 5/6, vimentin, calretinin, Wilms' tumor 1 suppressor gene, and CD30 antigen. By electron microscopy, numerous long slender microvilli were associated with desmosomes and tonofibrils. The immunohistochemical and ultrastructural features were considered consistent with mesothelial origin. These lesions, corresponding to the previously described myocardial epithelial inclusions in cattle, might be considered embryologic rests and could represent the bovine counterpart of the human adenomatoid tumor.

Cambios electrocardiogáficos y arritmias en pacientes pediátricos con rabdomioma / Electrocardiographical changes and arrhythmias in pediatric patients with rabdomiome

La incidencia de tumores cardíacos en pediatría es menor de 0,1%, en su mayoría son de carácter benigno y másde la mitad rabdomiomas. La historia natural de estos tumores es de regresión y la mayoría no produce síntomas. No es infrecuente la asociación con cambios electrocardiográficos, dependiendo de la localización tumoral, y ocasionalmente su presentación concomitante con taquicardias ventriculares, bloqueos aurículo-ventriculares y supraventriculares por vías anómalas.Revisamos nuestra experiencia en pacientes diagnosticados con rabdomioma asociados a arritmias y suevolución. 18 pacientes, nueve de ellos varones diagnosticados con tumoración cardíaca y etiquetados como rabdomioma por imagenología, a una edad media de 7,7 meses (uno prenatalmente). 22% (4) presentaban esclerosis tuberosa asociada. La media de seguimiento es de 17 años. De los 18 pacientes, siete presentaban bloqueo de rama derecha (dos aislado, tres con bloqueo aurículo-ventricular de primer grado, dos con bloqueo aurículo-ventricular de segundo grado y extrasístoles ventriculares), tres debutaron con taquicardia o fibrilación ventricular, uno con bradicardia neonatal y siete con preexcitación intermitente (cuatro con taquicardia supraventricular), cinco fallecieron durante meses posteriores al diagnóstico, dos de ellos tempranamente en relación con arritmias ventriculares incontrolables, uno por problemas hemodinámicos obstructivos previo a cirugía y dos en el postoperatorio inmediato (ninguno de ellos tenía el diagnóstico de esclerosis tuberosa). De los 13 pacientes restantes, seis requirieron ser intervenidos por obstrucción tumoral. En uno se implantó un marcapasos AAI por disfunción sinusal evolutiva postoperatoria y en un paciente persiste preexcitación electrocardiográfica, sin taquicardia y en tratamiento con betabloqueantes, y en dos bloqueo de rama derecha, uno de ellos asociado a bloqueo aurículo ventricular de primer grado...

The incidence of cardiac tumors in children is < 0,1%; most of them are benign and more than half of them arerhabdomyosarcoma. The majority regresses without symptoms. Frequently, depending on the tumors location, electrocardiographic changes can be seen, occasionally with ventricular tachyarrhythmia, auricular-ventricular blockage and supraventricular tachyarrhythmia due to accessory pathways. Our experience with patients who had rhabdomyosarcoma with arrhythmias and their evolution is described in thispaper. 18 patients were included, nine boys with the diagnosis of rhabdomyosarcoma through image with an age average of 7,7 months old (one was done prenatal). Four patients (22%) had tuberous sclerosis associated. Follow–up was done for an average of 17 years. Of the 18 patients, seven had sinoatrial block (two isolated, three with first degree AV block, two with second degree block and ventricular extrasystoles), three started with VT/VF, one had neonatal bradyarrhythmia and seven with intermitent preexcitement (four with SVT), five died months after the diagnosis, two died prematurelydue to uncontrollable ventricular arrhythmias, one had preoperative hemodynamic problems and two diedinmedialtely after surgery (none had tuberous sclerosis). Of the 13 patients left, six needed surgery due to tumoralobstruction. One patient needed a cardiac pacing and another patient persist with electrocardiographicpreexcitation, without tachyarrhythmia who is treated with â-blockers. Two have sinoatrial block, one of them firstdegree block. Of the rest three were operated and 16 had tumoral regression.Electrocardiographic alterations and arrythmias associated to tumors are frequent, malignant arrythmias can befatal but most of them dissapear when surgery of the tumor is practiced.

Cardiac myxoma cells exhibit embryonic endocardial stem cell features.

The origin of myxoma, the most frequent tumour of the heart, remains uncertain. Previous phenotypic characterizations have shown heterogeneous results and the most recent hypothesis suggests that cardiac myxoma originates from a primitive pluripotential cardiogenic cell. We investigated the expression of actin isoforms in 30 left atrial myxomas by immunohistochemistry and in eight consecutive tumours by RT-PCR. alpha-Smooth muscle actin (alpha-SMA) protein and/or transcripts were detected in all cases, whereas alpha-cardiac actin was observed in few cases and alpha-skeletal actin was always absent. Besides classical features, vessel-like structures were characterized by cells expressing CD34 and, less frequently, alpha-SMA. Confocal microscopy showed focal co-expression of CD34 and alpha-SMA in myxoma cells, suggesting a gradual loss of stem endothelial markers and the acquisition of myocytic antigens. In order to confirm this hypothesis, early cardiac differentiation markers were also investigated. RT-PCR documented the presence of transcripts for Sox9 (100%), Notch1 (87.5%), NFATc1 (37.5%), Smad6, metalloproteinases 1 and 2 alone or in variable combinations and the absence of ErbB3 and WT1. Myxoma cells maintained phenotypic heterogeneity in vitro, including the expression of alpha-SMA and the presence of stress fibres. These findings document in cardiac myxoma cells phenotypic markers of the embryonic endothelial-to-mesenchymal transformation that precedes terminal differentiation of endocardial cushions, supporting the hypothesis that cardiac myxoma cells may derive from adult developmental remnants.

An unexpected cause of a recurrent cerebral hemorrhage.

A 4-year-old previously healthy boy presented with a non-traumatic right parietal hemorrhage. A second life-threatening left cerebral hemorrhage occurred three weeks later and was decompressed with a craniotomy. Transthoracic echocardiography revealed a hypermobile elongated tumor of the mitral valve. The cardiac tumor was successfully resected three weeks after the craniotomy. Histological examination of the cardiac tumor revealed a papillary lesion of spindle cells with smooth muscle cell differentiation. In view of the histological findings and the clinical symptoms, a cellular myofibroblastic tumor was considered the most likely diagnosis in our patient. Although a cardiac tumor is a rare cause of a cerebral hemorrhage, a cardiac evaluation is recommended in pediatric patients with a cerebral hemorrhage of unknown etiology.

Angiosarcoma of the heart: structural and ultrastructural study.

BACKGROUND: Primary cardiac tumours are rare. Nearly 70% of primary cardiac tumours are benign, the majority of which are represented by myxomas. The most frequent primary cardiac neoplasm is the angiosarcoma that represents 31% of primary cardiac malignant. We report a particular clinical case of cardiac angiosarcoma, its light and transmission electron microscopic aspects and a review of the recent literature. METHODS: A 52 years old man died for a severe right ventricle filling deficit caused by an intracavitary tumour originated from the right atrial anterolateral wall. The fragments obtained from autoptic tumoral cardiac tissue were processed for light and electron microscopy. The section were stained with haematoxilineosin, Masson trichromic and Gomori method. An immunohistochemical study for vimentin, Factor VIII related antigen and peroxidase-conjugated lectin from Ulex Europaeus was also performed using the unlabed peroxidase-antiperoxidase method. RESULTS: The hematoxylin-eosin staining showed that the tumoral mass was composed by a well-differentiated histotype characterized by numerous vascular areas in which neoplastic cells were loosely and irregularly arranged to form incomplete vessels or anastomized blood-filled vascular channels. On the other hand, some less-differentiated solid areas were present and irregularly surrounded the differentiated vascular areas. Results of Ulex Europeaeus Agglutinin I labelling were positive in both solid and vascular areas of the tumour although the positive reaction was less evident in the solid zones Factor VIII related antigen positive cells were less numerous and mainly found in vascular areas. The observation by electron microscopy showed the lack of evident pinocytotic vesicles, the presence of thin and delicate cytoplasmatic processes, Weibel-Palade bodies, and also the disarrangement of the extracellular fibrous matrix. CONCLUSION: The light microscopy observation and immunohistochemical study underscore that is not easy to obtain information about the level of differentiation of this tumour. The presence of blood-filled lumina and the identification of typical markers of endothelial cells seems to indicate a well-differentiated nature. However, the ultrastructural findings seem to indicate a less differentiated nature.

Fibroelastoma papilífero: experiência de uma instituição / Cardiac papillary fibroelastoma: experience of an institution

Os tumores cardíacos primários do coração são raros, com uma prevalência entre 0,0017 por cento e 0,19 por cento dos estudos de autópsia não selecionados. Cerca de 75 por cento são tumores benignos e quase a metade são mixomas. Os restantes se dividem entre rabdomiomas, lipomas e fibroelastomas. Os mixomas são os tumores cardíacos mais comuns na idade adulta e os rabdomiomas, os mais comuns da população pediátrica. O fibroelastoma papilífero (FEP) é um tumor benigno do coração, relativamente raro, correspondendo a aproximadamente 8 por cento dos tumores cardíacos. São os que mais comumente acometem as valvas cardíacas . No passado, consistiam de achados de necropsia ou eram encontrados em procedimentos cirúrgicos ao acaso. O diagnóstico in vivo era esporádico². Com o aprimoramento das técnicas de ecocardiografia, o FEP tem sido diagnosticado com maior freqüência. São, geralmente, descritos como uma massa móvel, pedunculada, bem delimitada e com predileção pelo endocárdio valvar. A proposta terapêutica, quando pedunculados, é a ressecção cirúrgica, visando a prevenção de fenômenos embólicos cerebrais, pulmonares, coronarianos ou periféricos1,3. Serão apresentados cinco casos diagnosticados em nossa instituição, no período de agosto de 1995 a junho de 2004.

Cardiac plasmacytoma.

A 69-year-old white woman presented with a 3-month history of progressive dyspnea, orthopnea, fatigue and weakness. Clinical, diagnostic imaging and echocardiographic investigations suggested an occult primary cancer with metastasis to the heart. The patient's condition deteriorated gradually, and she died 2 months later. At autopsy, a malignant tumor encasing the heart and a 1-cm solitary tumor nodule in the lower lobe of the left lung were found. Histologic and electron microscopic studies revealed a plasmacytoma predominantly involving the epicardium and a small solitary plasmacytoma located in the left lung. The two tumors were further confirmed by immunohistochemical studies that showed monoclonal IgG expression and kappa light chain restriction.

Myxosarcoma of the right ventricle: an immunohistochemical and ultrastructural study.

BACKGROUND: Myxosarcoma is an unusual form of primary cardiac malignancy with few reports in the literature. Although these tumours occur in a similar anatomical distribution to cardiac myxoma, the relationship between these two tumours is uncertain due largely to the limited studies available that characterise the morphological features of myxosarcoma. MATERIALS AND METHODS: The clinical and pathological features, including immunohistochemical and ultrastructural studies of cardiac myxosarcoma, in a 58-year-old male who died eight months after onset of symptoms are reported. RESULTS: At presentation the tumour was sited in the right ventricle and at post-mortem was found to have extended into the right atrium, pulmonary infundibulum, pulmonary artery, pericardium and pleural cavities. Histologically the tumour was composed of spindle and stellate cells within a myxoid stroma. Ultrastructural studies showed abundant intermediate filaments and vacuoles within the tumour cell cytoplasm, without any evidence of muscle differentiation. Immunohistochemical staining for vimentin and myoglobin was positive, while there was negative expression of desmin, smooth muscle actin, factor VIIIa, CD34, CD68, S-100 protein, bcl-2 and for epithelial markers. CONCLUSION: Comparison of the morphological findings from the present case with the limited data available suggests that myxosarcoma is not a single tumour entity but a group of tumours of diverse histogenesis.

[Heart myxoma histogenesis in the light of its histological and ultrastructural features]. / Predstavleniia o gistogeneze miksomy serdtsa v svete ee gistologicheskikh i ul'trastrukturnykh osobennostei.

In 168 cases of heart myxoma histological and electron-microscopic examination have revealed signs of embryonal endothelium capable of vasoformation and glycoprotein and glycosaminoglycanes synthesis in myxoma cells. Neither differentiation of myxomas cells up to mature endotheliocytes no signs of malignant transformation was found. According to the authors, heart myxoma is a true benign dysontogenetic tumor originating from embryonal endothelium. The term myxoma does not reflect morphological entity of the tumor and the authors suggest to call it embryonal endocardial endothelioma.

Cardiac sarcoma showing bone formation and neurogenic markers: report of a case.

A 54 year-old Japanese female with cardiac insufficiency was found to have a left atrial mass and smaller masses on the mitral valve. Excisional surgery of the masses and mitral valve replacement were carried out. In spite of intensive post-operative radiation therapy, the patient died of intra-atrial recurrence and brain metastases after 8 months. Tumour cells were spindled to oval, were positive for vimentin, S100 protein and neurone specific enolase. Laminin and fibronectin were also demonstrated. Bone formation and myxoid areas were present. An ultrastructurally identifiable stromal component, possibly responsible for laminin and fibronectin staining, was also present. The merits of the two main diagnostic possibilities - a mesenchymal/fibroblastic sarcoma showing bone and aberrant S100 protein, and a malignant peripheral nerve sheath tumour with bone - were discussed. In practical terms, the tumour was given the diagnosis of unclassifiable sarcoma of the left atrium. Atrial sarcomas showing neural markers and bone formation are exceedingly rare, and this report adds a further exceptionally uncommon case to the literature.

[Diagnosis and treatment of biatrial myxomas of the heart]. / Diagnostika i lechenie biatrial'nykh miksom serdtsa.

Of the multiple myxomas of the heart (MH) the bilateral myxomas were revealed in 57.1%. Of 4 patients before the operation the correct diagnosis was established only in one. Meticulous data on clinical signs, diagnosis and surgical treatment peculiarities of patients with bilateral MH were adduced. Morphological peculiarities of the tumor were analyzed. Special attention was paid to the necessity of clinical and surgical guard toward revelation of undiagnosed tumors, the choice of optimal approaches to the heart cavities while performing radical operation. Basing on results of histological studying of operational specimen it was established that MH is originated from transformed vessels of interatrial septum.