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Hemangiosarcoma of the spleen: report of a case and review of previously reported cases.

Splenic hamangiosarcomas are rare tumors, usually discovered at autopsy. In a few instances the diagnosis was made premortem, at the time of splenectomy for spontaneous rupture. The tumors usually present with abdominal pain, left upper guadrant mass and tenderness, and occasionally with a microangiopathic type of anemia. The histogenesis of the tumor is in dispute. Some authors feel that they are degenerations of hemangiomas. Others feel that they arise de novo in the spleen. There is not proven association of thorotrast administration or vinyl chloride exposure to the development of hemangiosarcomas in the spleen. The prognosis of the tumor is uniformly poor and most of the patients surviving laparotomy have followed a uniformly fatal clinical course. In a few cases treated with chemotherapy there has been no evidence of clinical benefit. The case report in this article presented with essentially all the features enumerated above.

Anemia↗

Hemangiosarcoma complicating Paget's disease of the bone.

An 87-year-old man with Paget's disease of the left humerus was found to have a Paget's sarcoma upon pathologic examination of the left upper limb, which was disarticulated for severe pain and recurrent fractures. The histologic type of this tumor, a hemangiosarcoma, was unique among Paget's sarcomas.

Aged↗

Hemangiosarcoma and hepatocellular carcinoma of the liver following vinyl chloride exposure. A report of two cases.

A report is given of the clinical and autopsy findings of two men who died from malignant liver neoplasm following occupational exposure to vinyl chloride. The first patient was a 44-year-old man with an hemangiosarcoma of the liver, the second patient a 67-year-old man with an hepatocellular carcinoma. So far an hepatocellular carcinoma due to vinyl chloride has not yet been observed in man. Its occurrence, however, has been suggested from the results of animal experiments. The connection of hepatocellular carcinoma with exposure to vinyl chloride is discussed.

Adult↗

[Primary renal hemangiosarcoma. Case report and review of the literature].

Primary hemangiosarcoma of the kidney is a very rare tumor for which only 23 case reports appear in the literature worldwide. An additional case of renal angiosarcoma in an adult is reported. The patient developed local tumor recurrence with multiple metastases within 4 weeks and died although there was no evidence of metastases at the time of nephrectomy.

Adult↗

Hepatic hemangiosarcoma in two ferrets (Mustela putorius furo).

Two ferrets were presented to the authors' clinic. Hemoperitoneum was diagnosed in one ferret, and an abdominal mass was palpated in the other. One ferret was euthanized and necropsied, and one ferret underwent exploratory laparotomy and liver lobectomy. In both cases, the histopathologic diagnosis was hepatic hemangiosarcoma.

Animals↗

Canine hemangiosarcoma originates from hematopoietic precursors with potential for endothelial differentiation.

OBJECTIVE: Two competing hypotheses can be formulated regarding the origin of canine hemangiosarcoma (HSA). One states HSA originates from differentiated vascular endothelial cells that undergo mutations which endow them with malignant potential. The other states HSA originates from transformed hemangioblastic stem cells. This study was designed to begin to distinguish between these possibilities, as well as to test if flow cytometry was sufficiently sensitive to detect malignant cells in blood samples from dogs with HSA. METHODS: We used multiparameter flow cytometry to examine expression of cell-surface determinants associated with hematopoietic precursors (c-kit, CD34, CD133, CD45) or with lineage-committed cells (CD3, CD11b, CD14, CD21, CD105, CD146, alphavbeta3-integrin) in HSA cell lines and in blood samples from healthy dogs or dogs with HSA. RESULTS: The data show that HSA cells coexpress surface markers associated with hematopoietic precursors and with commitment to endothelial lineage, providing a means to identify their presence in circulation and distinguish them from normal or malignant white blood cells. The percentage of cells that coexpressed these markers ranged from 0.5 to 1.25% for HSA dogs, and was less than 0.3% for unaffected dogs or dogs with HSA that had the tumors removed within 48 hours prior to obtaining samples. CONCLUSIONS: The results place the ontogeny of HSA with multipotential bone marrow-derived stem cells whose progeny arrest differentiation at the hemangioblast or angioblast stage. In addition, these expression patterns may assist to confirm an HSA diagnosis, monitor minimal residual disease, and detect the disease in early stages.

Animals↗

Biological and molecular characterization of a canine hemangiosarcoma-derived cell line.

Canine hemangiosarcoma (HSA) is a devastating disease. Investigation of novel therapies has been limited by the limited availability of canine HSA-derived cell lines. We report the development of a canine HSA-derived cell line, DEN-HSA, which recapitulates features of angiogenic endothelium. DEN-HSA cells were derived from a spontaneous HSA arising in the kidney of a dog. DEN-HSA displayed surface molecules distinctive of endothelial histogenesis, including factor VIII-related antigen, ICAM-1 and alpha(v)beta3 integrin. In vitro, DEN-HSA formed microvascular tube-like structures on Matrigel, and proliferated in response to a variety of angiogenic growth factors. The cells expressed mRNA and protein specific for bFGF and its receptors, and VEGF and its receptors, among others. DEN-HSA conditioned medium evoked a marked angiogenic response in a murine corneal pocket assay, indicating potent proangiogenic activity of substances secreted by this cell line. This research confirms the DEN-HSA cell line as endothelial in origin, suggests the presence of angiogenic growth factor autocrine loops, and offers the potential to utilize DEN-HSA cells for the study of novel therapies that modulate endothelial proliferation.

Angiogenic Proteins↗

Primary hemangiosarcoma of the mediastinum.

A case of a 44-year-old female who had an intrathoracic mass that was found to be a hemangiosarcoma of the anterior mediastinum is reported. Radical surgical incision through a right anterior thoracotomy was performed, followed by post-operative radiotherapy. Since this is a rare tumor at this location, the clinical and radiological findings, the histopathological appearances and its therapeutic management are discussed. Radiologists, surgeons and oncologists should in the differential diagnosis of a mediastinal mass include that of a tumor of vascular origin, even if it is rare. Radical excision followed by post-operative radiotherapy, especially in cases where the tumor has been partially excised, is the treatment of choice.

Adult↗

Hemangiosarcoma in dogs and cats.

Hemangiosarcoma (HSA, including angiosarcoma and malignant hemangioendothelioma) is a highly malignant tumor derived from the endothelial cell line and is characterized by early and aggressive metastasis. HAS is a common tumor type in dogs, but is rare in other species. Treatment options include surgery, chemotherapy, and possibly radiation, but survival times are invariably short (usually < 1 year), except for patients with superficial dermal HSAs. Further options to treat this tumor type are currently being investigated.

Animals↗

[Primary sternal hemangiosarcoma].

We describe a 22-year-old man with a bone mass in the middle and lower third of the sternum with no signs of respiratory deterioration. After biopsy by incision established a diagnosis of hemangiosarcoma, appropriate resection and repair of the thoracic wall was scheduled. An adequate amount of tissue for analysis must be obtained to allow choice of a surgical technique that will assure the best prognosis in malignant tumors of the sternum and assignation of the most appropriate mechanical ventilation procedure.

Adult↗

Histopathologic studies on myeloproliferative sarcoma virus (MPSV) induced leukemias and hemangiosarcoma in Jar-2 rats.

It is well known that MPSV induces myeloproliferative syndrome (MPS) in mice. Intravenous one shot inoculation of myeloproliferative sarcoma virus (MPSV) with Friend murine leukemia virus (F-MuLV) as a helper in newborn Jar-2 rats (on the second neonatal day) yielded hematopoietic malignancies in all the treated rats (25/25 rats) after 2 weeks' latency. MPS appeared from the 14th day in 14 rats. In the midst of the myeloproliferative field of the spleen and bone marrow, myeloblastic or myeloblastic-erythroblastic foci were observed. From 19th day, acute myeloblastic leukemia occurred in 3 rats and erythroleukemia in 8 rats. MPSV induced first MPS which remained as such or later developed into acute leukemia. Myelofibrosis as seen in mice was not observed. In addition, hemangiosarcoma of the brain, spinal cord and spleen appeared in 15 rats from the 24th day, and were often multiple. MPSV can yield the tumor only in newborn rats, and target cells of MPSV are not only hematopoietic cells but also endothelial cells of the brain, spinal cord and occasionally spleen.

Animals↗

[Cardiac hemangiosarcoma in a dog].

The case of a 11 year-old mix breed dog is being described. It initially presented for watery diarrhea and inappetence. During the diagnostic workup, the dog developed a sustained ventricular tachycardia. Echocardiography showed a mass extending from the wall of the right ventricle which filled up the ventricle almost completely. Histopathologic examination of the mass after euthanasia of the dog revealed a hemangiosarcoma.

Animals↗

Canine malignant hemangiosarcoma as a model of primitive angiogenic endothelium.

Hemangiosarcoma (HSA) is a common untreatable cancer of dogs that resembles human angiosarcoma. Detailed studies of these diseases have been historically hindered by the paucity of suitable reagents. Here, we show that expression of CD117 (c-Kit) can distinguish primitive (malignant) from mature (benign) proliferative endothelial lesions, and we describe eight independent cell lines derived from canine HSA explants. Endothelial origin was confirmed by sustained expression of surface CD105 (endoglin), CD146 (MUC18), and CD51/CD61 (alpha(v)beta(3) integrin). The cell lines showed anchorage-independent growth and were motile and invasive when cultured on a basement membrane matrix. They required endothelial growth factors for growth and survival, and they could be induced to form tubular structures resembling blood vessels when cultured under low calcium conditions. The formation of vessel-like structures was blocked by nicotine, and restored by FK506, suggesting that 'nuclear factor of activated T cells' activity prevents differentiation of these cells. In summary, these cell lines represent a unique and novel resource to improve our understanding of endothelial cell biology in general and canine HSA in particular.

Animals↗

Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice.

We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal strongly inhibited the progression of established H5V cell-induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life-threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma-associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10(10) infectious units/animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN gamma-expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular tumors and that autonomous parvovirus-based vectors can be considered potent tools for cancer gene therapy purposes.

Animals↗

Mucinous cystadenocarcinoma in combination with hemangiosarcoma in the ovary.

The ovary is the sixth most frequent site of cancer in women in Denmark with an incidence of approximately 600 cases per year. Carcinomas predominate whereas sarcomas are rare. We describe a case of the combination mucinous cystadenocarcinoma and hemangiosarcoma in a 37-year old woman, who had a right-sited oophorectomy because of a cyst. Clinically there was no suspicion of malignancy. The macro- and microscopic findings are described as well as the immunohistochemical stainings performed to confirm the diagnosis. The case shows the importance of careful sampling at the macroscopic examination, especially from areas with a striking appearance.

Adult↗

Analysis of vascular endothelial growth factor (VEGF) and a receptor subtype (KDR/flk-1) in the liver of rats exposed to riddelliine: a potential role in the development of hemangiosarcoma.

Riddelliine alters hepatocellular and endothelial cell kinetics and function including stimulating an increase in hepatocytic vascular endothelial growth factor (VEGF) in the absence of increased serological levels of VEGF (NYSKA et al. 2002). The objective of this study was to further assess hepatic VEGF and KDR/flk-1 synthesis and expression by hepatic cells under riddelliine treatment conditions. Forty-two male F344/N rats were dosed by gavage with riddelliine (0, 1.0, and 2.5 mg/kg/day) for 6 weeks. Seven animals/group were sacrificed after 8 consecutive daily doses; remaining rats were terminated after 30 daily doses, excluding weekends. Hepatic tissues were evaluated by immunohistochemistry and in situ hybridization. The results showed that VEGF mRNA expression was observed in control and treated animals; however, qualitative differences were noted. Treated animals exhibited VEGF mRNA in clustered, focal hepatocytes and bile duct epithelium, whereas VEGF mRNA in hepatocytes from vehicle control rats was distributed evenly across all hepatocytes. Results evaluating the distribution of the VEGF cognate receptor, KDR/flk-1 showed that randomly distributed, rare sinusoidal endothelium, including those demonstrating karyomegaly and cytomegaly expressed KDR/flk-1. Phosphorylation of KDR/flk-1 at pTyr996 and pTyr1054/1059, but not pTyr951, was also detected, evidence that endothelial cell KDR/flk-1 was activated. These results suggest that both hepatocytes and endothelial cells are targets of riddelliine-induced injury. We speculate that damage to both populations of cells may lead to dysregulated VEGF synthesis by hepatocytes and activation of KDR/flk-1 by endothelium leading to the induction of sustained endothelial cell proliferation, culminating in the development of hepatic hemangiosarcoma.

Administration, Oral↗