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Canine hemangiosarcoma treated with standard chemotherapy and minocycline.

Standard treatments for canine hemangiosarcoma include surgery and chemotherapy with doxorubicin, but in spite of treatment most dogs with this disease die within 6 months of diagnosis. Tumor growth and metastasis are angiogenesis dependent. Antiangiogenic drugs such as minocycline may provide therapeutic benefits in cancer patients. The purpose of this prospective study was to evaluate the efficacy of chemotherapy with doxorubicin and minocycline, an antiangiogenic agent, in dogs with hemangiosarcoma. Eighteen dogs with histologically confirmed hemangiosarcoma of any stage were treated with doxorubicin, cyclophosphamide, and minocycline. Complete staging was performed before and during the treatment period to assess remission status and response to therapy. No statistically significant difference was found in survival between the dogs treated with chemotherapy and minocycline, and historical controls consisting of dogs that received chemotherapy alone. Postmortem examination revealed widespread metastasis, suggesting that minocycline is ineffective as a single antiangiogenic agent in canine hemangiosarcoma.

Angiogenesis Inhibitors↗

Hemangiosarcoma in 11 young horses.

Hemangiosarcoma is a rare neoplasm of horses and hemangiosarcoma in young horses might behave differently than in mature horses. The purpose of this study was to identify the characteristics of hemangiosarcoma occurring in horses < or = 3 years of age. Medical records from 1982 to 2004 were searched for horses < or = 3 years of age with a histopathologic diagnosis of hemangiosarcoma. Eleven records were identified. Thoroughbred and Thoroughbred crosses predominated. Age ranged from 9 days to 3 years. All horses presented with cutaneous or leg swellings or joint effusion. Physical examination findings included tachycardia, fever, and depression. Laboratory abnormalities included anemia (5/11), hyperfibrinogenemia (4/11), hypofibrinogenemia (3/11), thrombocytopenia (2/11), and neutrophilic leukocytosis (1/11). Ultrasonographic and radiographic evaluation was not diagnostic in any case. Antemortem histopathologic diagnosis was obtained in 10 cases. Six of 11 horses were euthanized. Surgical resection was performed in 5 horses, 2 of which were later euthanized. Diagnosis was confirmed histologically at postmortem examination in all euthanized horses. Two cases resolved spontaneously. Early histopathologic diagnosis may allow cure if the mass is localized and amenable to surgical resection. In cases where the horse is medically stable, and masses are not interfering with quality of life, a period of observation may be warranted.

Age Factors↗

Unusual metastatic behavior and clinicopathologic findings in eight cats with cutaneous or visceral hemangiosarcoma.

Eight cats with visceral or cutaneous hemangiosarcoma were evaluated, and unusual metastatic and clinicopathologic behavior was evident in each. Cutaneous hemangiosarcoma is generally believed to be locally aggressive and slow to metastasize. These 8 cats with cutaneous hemangiosarcoma, however, developed metastatic disease after initial surgical resection; only 1 had local regrowth of the tumor. All cats with visceral hemangiosarcoma had metastasis at the time of diagnosis, which is consistent with cats of other reports. Three of 8 cats had evidence of disseminated intravascular coagulation, including increased prothrombin time and partial thromboplastin time, decreased number of platelets, and anemia. These potential complications need to be considered when planning diagnostic and treatment protocols.

Abdominal Neoplasms↗

Subcutaneous hemangiosarcomas in a rhesus macaque (Macaca mulatta).

Hemangiosarcoma is a malignant tumor of vascular endothelial cell origin. The occurrence of hemangiosarcoma in nonhuman primates has been rarely documented. An adult male rhesus monkey was reported having a firm subcutaneous swelling, approximately 4.5 cm in diameter, on the ventral midline of the abdomen. Fine-needle aspiration, microbial culture, biopsy, radiographs, exploratory laparotomy, histopathology, immunohistochemistry, hematology, and serology were performed. A second subcutaneous mass approximately 4.5 x 4.0 x 2.7 cm developed on the ventral midline several weeks later. A fine-needle aspirate of the first mass consisted of numerous erythrocytes with few polymorphonuclear cells and lymphocytes. Histopathology showed foci of spindle-shaped cells surrounding the vascular spaces. Many spindle-shaped cells had prominent nucleoli, and mitotic figures could occasionally be seen. Immunohistochemical staining of the masses for Factor VIII-related antigen, an endothelial cell and tumor marker, yielded positive results. Both masses were consistent with hemangiosarcoma.

Abdominal Neoplasms↗

[Hemangiosarcoma of the liver with unusual expression of neuron-specific enolase (NSE)].

A 68-year-old male patient presented with unspecific decline of general health, multiple tumours in the liver discovered by ultrasound examination and a focus suggestive of tumour on chest x-ray. He was hospitalised because of suspected metastatic lung carcinoma. Laboratory analysis revealed a distinct elevation of serum neuron-specific enolase (NSE, 26,1 micro g/l). A CT scan of the abdomen confirmed the presence of multiple tumour foci in both hepatic lobes, while the lung, however, was found to be free of tumour on CT-examination. Bronchoscopy, gastroduodenoscopy and colonoscopy were unremarkable. Subsequently, an ultrasound guided fine-needle biopsy of the liver was performed. Histological examination disclosed hemangiosarcoma with unusual, though unequivocal expression of NSE in tumour cells. As even follow-up examinations were unable to trace out any extrahepatic primary tumour, the hemangiosarcoma was concluded to be of hepatic origin. The patient succumbed to his disease 6 months later, an autopsy was not performed. This case report of a NSE-producing primary hemangiosarcoma of the liver clearly outlines that a histological confirmation of an allegedly clear clinical diagnosis should always be performed because malignant tumours are capable of (co-)expressing so called tumour markers independently of their histogenesis.

Aged↗

Canine conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of 108 cases (1989-2004).

Canine conjunctival tumors of vascular endothelial origin are common, although under-reported. The purpose of this study was to evaluate the epidemiology of and potential risk factors for these tumors. This study evaluated 108 cases (70 hemangiomas, 38 hemangiosarcomas) from 8300 canine submissions between 1989 and 2004. Signalment, location, pigmentation, size, duration, diagnosis, margins, ancillary therapy, and geographic location were recorded. Follow-up information was available for 49 cases. Each case was matched with two unaffected controls and compared using logistic regression analysis. Average age upon presentation was 8.6 years; there was no sex predilection. Risk of conjunctival tumors was statistically different among breed groups (P = 0.0010), demonstrating a propensity to occur in groups likely to have increased outdoor activity. Primary involvement occurred within nonpigmented epithelium along the leading edge of the nictitating membrane (41/108) and temporal bulbar conjunctiva (33/108). The etiology remains unknown; however, the strong site predilection, involvement of nonpigmented epithelium, and development within specific breed classes strongly suggest ultraviolet (UV) light as a significant risk factor. In a full-logistic model including breed, gender, age, and UV exposure, UV was not a statistically significant variable (P = 0.1215). In a reduced-model including UV only, significance was approached (P = 0.0696) and posthoc contrast demonstrated a significant linear trend with increasing UV exposure (P = 0.0147). In separate analysis of risks associated with hemangiosarcoma, compared with hemangioma, breed was not significant while increasing UV exposure was significant (P = 0.0381). Early surgical therapy is recommended and may be curative; however, recurrence is possible and more likely with hemangiosarcomas (11/20).

Animals↗

Surgery and doxorubicin in dogs with hemangiosarcoma.

Forty-six dogs with histologically confirmed hemangiosarcoma of various locations other than skin were used in a prospective study to determine the efficacy of adjuvant doxorubicin (30 mg/m2 IV q 3 weeks for 5 treatments) 10 to 14 days after the tumor was partially or completely excised. Analysis of the data included information on variables that were hypothesized to influence response to therapy, disease-free interval (DFI), or survival time (ST). Other information collected included age, gender, breed, weight, prior therapy, type of surgery, location of the primary tumor, presence of metastases, number of doses of doxorubicin, response to doxorubicin therapy (complete or partial response), and the following histological criteria: overall differentiation, nuclear pleomorphism, percent necrosis, mitotic score, total histological score, and grade. Surgery outcome (complete versus incomplete surgical excision) markedly influenced survival times (P < .001). Twenty percent of the dogs rendered free of disease were alive at 1 year, whereas none of the dogs that had residual tumor after surgery were alive at 1 year. Most of the histological criteria (nuclear pleomorphism, mitotic score, grade, overall differentiation) had marked (P < .05), or close to marked, independent associations with ST for dogs that had complete tumor removal. Results from analysis of DFI were generally similar to those of ST in dogs with complete excision of the tumor. Twenty-seven of the 46 dogs (58.7%) had all clinical evidence of tumour successfully removed. Logistic regression analysis of surgical outcome (ability to remove all visible tumor) suggested that age of the subject was the only factor markedly influencing surgical outcome (P = .017). As age increased, the probability of success increased. Those dogs that had previous treatment for their hemangiosarcoma tended (P = .08) to have a shorter DFI and ST. Therefore, complete removal of all evidence of tumor followed by 5 doses of doxorubicin may be an effective treatment for dogs with hemangiosarcoma. Dogs that had all tumor successfully removed had a mean and median ST of 267 and 172 days, respectively. Dogs with incomplete tumor removal had a mean and median ST of 172 and 60 days, respectively. Similarly, prognostic variables such as the ability to completely excise all evidence of tumor, histological criteria, and age of the patient are potentially important prognostic variables for predicting outcome.

Animals↗

Primary cardiac hemangiosarcomas induced by 1,3-butadiene in B6C3F1 hybrid mice.

Proliferative vascular lesions of the heart were found in mice exposed chronically to 1,3-butadiene by inhalation with an overall incidence of 30% in males and 43% in females. Based on histological criteria, the lesions were subclassified as endothelial hyperplasia with an incidence of 7% in males and 13% in females and hemangiosarcoma with an incidence of 23% and 30%, respectively. A dose-relationship for both lesions was observed in females, but not in males. The absence of a dose response in males was most likely due to the lower survival rate for high-dose animals (14%) when compared to the lower-dose animals (22%). Endothelial hyperplasia was characterized by widened vascular spaces lined by a single layer of plump endothelial cells. When cellular pleomorphism and piling up of endothelial nuclei were observed, the lesion was diagnosed as hemangiosarcoma. Ultrastructural examination of hemangiosarcomas revealed lumen formation, intercellular junctions and cytoplasmic filaments. Pinocytotic vesicles which are 1 of the characteristics of endothelial cells could not be identified with certainty. Weibel-Palade bodies were not detected in the neoplastic endothelium. Metastatic lesions were observed in liver, lung and kidney. To date, 1,3-butadiene is the only carcinogen reported that induces proliferative vascular lesions in the heart of mice.

Animals↗

Case report: spontaneous hemangiosarcoma in the pancreas of a Fischer rat.

Spontaneous hemangioma or hemangiosarcoma is sometimes found in the viscera and soft tissue of rats and mice. However, there is no report of the tumor occurring in the pancreas of rats. We report a pancreatic hemangiosarcoma in a 109-wk-old, male Fischer 344 rat, which was used in the control group of a carcinogenicity study. The tumor destroyed and compressed the normal pancreatic tissue and displayed a high density in terms of the numerous capillaries and strands of endothelial tumor cells. A reticulin stain revealed a dense network formation. The frequency of proliferating cell nuclear antigen-positive staining showed active proliferation of the tumor cells. Immunohistochemically, some of the tumor cells stained positive with factor VIII-related antigen, and ultrastructurally, Weibel-Palade bodies were rarely observed in the cytoplasm of the tumor cell. From these findings, the tumor was diagnosed as a hemangiosarcoma that occurred naturally in the pancreas.

Animals↗

Epithelioid variant of hemangioma and hemangiosarcoma in the dog, horse, and cow.

Epithelioid hemangiomas, hemangioendotheliomas, and angiosarcomas are well recognized histologic variants of endothelial tumors in humans that in the past have been confused with neoplasms of epithelial or histiocytic origin. We describe 12 epithelioid endothelial vascular tumors in 8 dogs, 3 horses, and 1 cow that share microscopic features with these tumors in humans. Ten tumors were located within the dermis and subcutis, 1 in the gastrocnemius tendon, and 1 in the skeletal muscle of the thigh. Key histologic features were the plump, epithelioid appearance of neoplastic endothelial cells and occasional cytoplasmic vacuolation, which rarely contained a single erythrocyte. Patterns of epithelioid endothelial cell growth ranged from conventional vasoformative structures to glandlike acini and short ducts to solid, sheetlike arrangements. All tumors were positive for endothelial markers: 12/12 (100%) were positive for von Willebrand factor with variable intensity and distribution and 9/9 (100%) were positive for CD31. All 12 were negative for cytokeratin. We subdivided these tumors into epithelioid hemangiomas (n = 3) and hemangiosarcomas (n = 9) based on conventional morphologic criteria, growth pattern (invasive or not), and metastasis (known in 1 case at the time of biopsy). Additional follow-up information obtained by a written questionnaire was available for 6/12 (50%) animals and revealed local recurrence in 3 animals (1 epithelioid hemangioma and 2 epithelioid hemangiosarcoma) and regional metastasis in 3 animals (all epithelioid hemangiosarcomas). This series represents a novel group of vascular tumors in domestic animals of which there are only 3 previous cases reported in the veterinary literature.

Animals↗

Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids.

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.

Animals↗

Disseminated hemangiosarcoma in the horse: 35 cases.

Thirty-five cases of disseminated hemangiosarcoma (21 clinical cases and 14 previously reported cases) were reviewed to describe the disease in horses. Hemangiosarcoma occurred in mature, particularly middle-aged horses, with no apparent sex predilection. Thoroughbreds seemed to be overrepresented (13 cases) but a true breed predilection could not be established. The respiratory and musculoskeletal systems were most commonly affected and presenting complaints included dyspnea (26%), subcutaneous or muscular swelling (24%), epistaxis (17%), and lameness (12%). Heart and respiratory rates were usually increased and mucous membrane color was frequently pale or icteric. Capillary refill time and rectal temperature were often normal. Anemia (88%), neutrophilic leukocytosis (62%), and thrombocytopenia (48%) were common. Examination of tissue samples collected by fine-needle aspirate or biopsy established an antemortem diagnosis in 4 horses. The diagnosis was made during postmortem examination in the remaining 31 horses. The lung and pleura (77%), skeletal muscle (46%), and spleen (43%) were most commonly affected. A primary site of tumor involvement could be identified in 22 horses. Hemangiosarcoma should be included as a differential diagnosis for horses with evidence of hemorrhage into body cavities, skeletal muscle, or subcutaneous locations.

Animals↗

Occurrence of hemangiosarcomas in beagles with internally deposited radionuclides.

In a series of related experiments to evaluate the relative toxicity of inhaled radionuclides, beagles were exposed to aerosols containing relatively soluble (chloride) or relatively insoluble (fused clay) forms of 144-Ce and 90Sr. With the solubled 144-CeCl3, significant radiation doses were delivered to the lungs, liver, and skeleton whereas, after 90-SrCl2 exposure, the radiation dose was delivered predominantly to the skeleton. In dogs exposed to 144-Ce and 90-Sr in fused clay particles, radiation doses were delivered mostly to the lungs and tracheobronchial lymph nodes. In most dogs dying within 2 years after exposure, deaths were attributable to nonneoplastic radiation-induced lesions in the target organ systems. At later times after exposure, neoplasms were the major cause of death, again occurring mostly in target organs or the adjacent tissues. Lung liver, and bone-related neoplasms, including five hepatic hemangiosarcomas, developed after 144-CeCl3 exposure. Among the bone-related sarcomas seen in dogs exposed to 144-CeC3 or 90-SrC2, the incidence of hemangiosarcomas was over 40%. Among the 20 dogs dying with pulmonary neoplasms after exposure to 144-Ce or 90Sr in fused clay particles, all had hemangiosarcomas and several also had other neoplasms. This high after exposure and differs from results in other laboratories where beagles have been exposed to both alpha and beta-emitting radionuclides.

Aerosols↗

[A case of renal capsular hemangiosarcoma].

We report herein a case of renal capsular hemangiosarcoma. A 68-year-old man was admitted to our hospital for treatment of a retroperitoneal tumor identified incidentally on abdominal computed tomography (CT) for follow-up of superficial bladder tumor. The tumor was about 7cm in diameter, positioned between the right kidney and the liver. Right nephrectomy was performed under a diagnosis of renal capsular tumor. Pathological diagnosis was hemangiosarcoma and positive surgical margins were suspected. Radiotherapy was performed postoperatively to a total dose of 50 Gy. Hemangiosarcoma frequently occurs in the skin, but is rare in the retroperitoneal cavity. Neither metastasis nor recurrence has been seen as of 19 months postoperatively.

Aged↗

N-nitroso-2,6-dimethylmorpholine-induced hemangiosarcomas in the livers of randombred guinea pigs.

The carcinogenic effect of N-nitroso-2,6-dimethylmorpholine (DMNM) was studied in randombred guinea pigs after repeated administration of this compound by gavage. DMNM was administered at two dose levels (14 and 28 mg/kg body wt) weekly for 23 weeks. All animals were observed until their death or termination of the experiment at 54 and 37 weeks for the 14- and 28-mg dose levels, respectively. At 14 mg, 67% of the animals developed hemangiosarcomas of the liver and 60% developed cholangiomas between 36 and 54 weeks. In addition, a poorly differentiated malignant mesenchymal tumor was observed in 1 animal. At 28 mg, liver hemangiosarcomas were observed in 82% of the animals between 26 and 37 weeks. In addition, in 18% of the animals, bronchioalveolar adenoma (1 animal), hepatocellular carcinoma (1 animal), and malignant lymphoma (1 animal) were also induced. Metastases of hemangiosarcomas to lungs, mesenteries, and lymph nodes were observed in 3 animals of each group.

Animals↗

Primary hemangiosarcoma of the spleen with angioscintigraphic demonstration of metastases.

A case of primary hemangiosarcoma of the spleen in a 48-year-old woman is presented. Twenty-eight months after splenectomy the patient developed a severe anemia of the microangiopathic type, thrombocytopenia, and a leukoerythroblastic peripheral blood picture. In contrast to x-ray and conventional 99mTc-methylene-diphosphonate (MDP) bone scintigraphy, which showed only a few minor focal changes in the spine and ribs, angioscintigraphy with in vitro labeled 99mTc-erythrocytes revealed extensive pathologic accumulations throughout the spine, femurs, and the liver, indicating the presence of extremely vascular metastases. Autopsy 15 months later confirmed the scintigraphic findings. Angiography with 99mTc-labeled erythrocytes seems to be useful for monitoring metastases from hemangiosarcomas.

Anemia↗

Development of hemangiosarcomas in B6C3F1 mice fed 2-methyl-1-nitroanthraquinone.

Subcutaneous hemangiosarcomas developed in 97% of 172 B6C3F1 mice of both sexes fed either 0.03% or 0.36% 2-methyl-1-nitroanthraquinone in the diet. There was no significant relationship to dose or sex. In addition similar vascular tumors occurred in the mesentery of 14 mice. 2-Methyl-1-nitroanthraquinone is carcinogenic in B6C3F1 mice when given in food. One of 97 control mice had a splenic hemangiosarcoma.

Animals↗

Enormous hemangiosarcoma of the heart.

This report describes a 26-year-old patient with hemangiosarcoma of the heart and summarizes the clinicopathological features in previous reports of patients with cardiac angiosarcoma. The patient was admitted to our hospital because of a syncope and one episode of nocturnal dyspnea and hemoptysis. In his history he complained of progressive weakness and loss of weight over the past 2 months. Echocardiography and computed tomography of the chest showed inhomogeneous masses in the pericardial cavity completely surrounding the heart and involving the ascending aorta and the superior vena cava. Histological examination of the tissue obtained from the mass by fine needle technique revealed a poorly differentiated malignant tumor of mesenchymal origin. Exploratory thoracotomy followed by tumor biopsies showed an inoperable cardiac hemangiosarcoma of enormous size with multiple metastases in both lungs. Palliative tumor resection was not performed. During the postoperative course the patient still required controlled ventilation. After 3 days of cytostatic chemotherapy no regression of tumor mass was seen by chest radiography. Cardiorespiratory insufficiency was progressive, and the patient died within 3 weeks after admission.

Adult↗