Right-sided ureteral hemangiosarcoma in a paraplegic dog.

BACKGROUND: This study aims to describe a rare case of primary ureteral hemangiosarcoma, in which surgical intervention preserved the kidney and ureter after tumor removal. CASE PRESENTATION: A 13-year-old, neutered male dog, weighing 14 kg, mixed-breed, presented with apathy, anorexia, acute-onset vomiting, and abdominal discomfort during the physical examination. Ultrasonography and pyelography revealed a right-sided dilation of the renal pelvis and ureter due to complete obstruction in the middle third of the ureter. A mass obstructing the lumen of the right ureter was completely resected, and ureteral suturing was performed, preserving the integrity of the involved structures. Histopathology confirmed primary ureteral hemangiosarcoma. Due to the local and non-invasive nature of the mass, chemotherapy was not initiated. The patient's survival was approximately two years, and normal renal function was preserved throughout this period. CONCLUSIONS: Considering this type of tumor in the differential diagnosis of upper urinary tract obstructive disorders. Furthermore, the preservation of the ureter and kidney is a suitable therapeutic option after surgical resection of non-invasive tumors.

Tumor-associated macrophages in canine visceral hemangiosarcoma.

Canine hemangiosarcoma (HSA) is a highly malignant tumor derived from hematopoietic stem cells and commonly occurs in visceral organs or skin. Visceral HSAs are particularly aggressive and progress rapidly despite multimodal treatment. Tumor-associated macrophages (TAMs) play a central role in carcinogenesis, tumor progression, and metastasis in humans and murine models. In this retrospective study, we investigated the prevalence and phenotype of TAMs in privately owned, treatment-naïve dogs with naturally occurring HSA. We used CD204 as a general macrophage marker and CD206 as a marker for M2-polarized macrophages. Formalin-fixed paraffin-embedded tissues from HSAs in the spleen (n = 9), heart (n = 6), and other locations (n = 12) from 17 dogs were sectioned and immunohistochemically labeled with CD204 and CD206 antibodies. The mean number of log(CD204)- and log(CD206)-positive cells and the ratio of log(CD206/CD204)-positive cells were compared with normal surrounding tissues and between tumor locations. There were significantly more macrophages and M2 macrophages, and a higher ratio of M2 macrophages to total macrophages in tumor hot spots (P = .0002, P < .0001, and P = .0002, respectively) and in tumor tissues outside of hot spots (P = .009, P = .002, and P = .007, respectively) than in normal surrounding tissues. There were no significant differences between tumor locations, but there was a trend toward higher numbers of CD204-positive macrophages within the splenic tumors. There was no association between histological parameters or clinical stage and TAM numbers or phenotype. As in humans, TAMs in dogs with HSA have a predominantly M2-skewed phenotype. Dogs with HSA could serve as excellent models to evaluate new TAM-reprogramming therapies.

Immunohistochemical evidence of NF-kB activation in canine lymphomas, histiocytic sarcomas, hemangiosarcomas, and mast cell tumors.

Increased or constitutive activation of nuclear factor kappa B (NF-kB) is a feature of many chronic disease processes, including cancer. While NF-kB overactivation has been documented extensively in human oncology, there is a relative paucity of data documenting the same phenomenon in veterinary medicine. To assess NF-kB activity, antibodies to p65 and p100/p52, which are components of NF-kB heterodimers, were first validated for specificity and canine cross-reactivity via Western blot and labeling of immortalized cell pellets. Then, nuclear labeling for these antibodies was assessed via QuPath software in over 200 tumor tissue samples (10 hemangiosarcomas, 94 histiocytic sarcomas, 71 lymphomas, and 28 mast cell tumors) and compared to immunolabeling in appropriate normal tissue counterparts. Greater than 70% of spontaneous canine tumors evaluated in this study had more nuclear p65 and p100/p52 immunoreactivity than was observed in comparable normal cell populations. Specifically, 144/204 (70.58%) of tumors evaluated had positive p65 nuclear labeling and 179/195 (91.79%) had positive p100/p52 nuclear labeling. Surprisingly, greater nuclear p100/p52 reactivity was associated with a longer progression-free survival (PFS) and overall survival (OS) in canine lymphomas. These results provide support and preliminary data to investigate the role of NF-kB signaling in different types of canine cancer.

Prognostic impact of Ki-67 in canine splenic hemangiosarcoma: A preliminary study.

Canine splenic hemangiosarcoma has a high metastatic rate and short survival time. Currently, the main prognostic parameters are tumor stage and therapy, while data on histologic parameters, such as grade and Ki-67 expression, are scarce. The aims of this study were to compare two methods of assessment of Ki-67, verify their prognostic impact, and define a threshold value based on survival. Thirty-one cases of histologically diagnosed canine splenic hemangiosarcoma, which were treated with splenectomy and had full staging and follow-up information, were collected. Three were stage I, 17 stage II, and 11 stage III. The mean mitotic count (MC) was 23.9 (standard deviation [SD]: 22.1) and the median was 15 (range, 1-93). Immunohistochemistry for Ki-67 was performed, the Ki-67 labeling index (Ki-67LI) was assessed as a percentage of positive neoplastic nuclei per ≥500 cell, and the Ki-67 count (KI-67C) was defined as the average number of positive nuclei using a 1 cm2 optical grid performed in 5, 40× fields. The mean Ki-67LI and Ki-67C were 56.4% (SD: 38.7) and 27.2 (SD: 12.9) and medians were 51% (range, 8.2-55.2) and 26 (range, 5.5-148), respectively. Using a cut-off of 56% and 9, respectively, Kaplan-Meier survival curves showed an association of overall survival with Ki-67LI and MC. In addition to clinical stage, Ki-67LI maintained its prognostic value on multivariate analysis, supporting the role of Ki-67LI as an independent prognostic parameter. Based on these results, we propose a diagnostically applicable cut-off value of 56% for Ki-67LI as a prognostic parameter for canine splenic hemangiosarcoma.

Evaluating preoperative coagulation panels in dogs undergoing liver lobectomy for primary liver tumors: A multi-institutional retrospective study.

BACKGROUND: The objectives of this study were to: (i) Determine whether operable primary liver tumors were associated with prolongations in prothrombin time (PT) and activated partial thromboplastin time (aPTT) and (ii) determine if these secondary hemostatic abnormalities were more prevalent with specific liver tumors. STUDY DESIGN: Multi-institutional retrospective study. ANIMAL POPULATION: Dogs (n = 359) undergoing liver lobectomy for a primary liver tumor with a preoperative coagulation panel. METHODS: Data was identified via electronic medical record review at eight veterinary teaching hospitals. Baseline dog characteristics, coagulation panel values, platelet count, emergency versus non-emergency procedure, whether the dogs received transfusion(s) of a blood product, liver lobe removed, and histopathological diagnosis were extracted from the medical record. Chi-square analysis was used to compare categorical variables between groups. Continuous variables were assessed for normality using the Shapiro-Wilk test. RESULTS: A total of 74 of 359 dogs (20.6%) had a prolongation in either PT or aPTT preoperatively. A total of 20 of 359 dogs (5.6%) were found to have prolongation of both PT and aPTT. Hemangiosarcoma was the only histopathological diagnosis associated with concurrent prolongations of both PT and aPTT (p < .001) in 6/16 (37.5%) dogs. CONCLUSION: Coagulation panels including PT and aPTT are unlikely to detect substantial deficiencies in secondary hemostasis in most dogs with primary liver tumors except in dogs with a histopathological diagnosis of hemangiosarcoma. CLINICAL SIGNIFICANCE: PT and aPTT testing is low yield as an elective preoperative screening test in dogs with primary liver tumors except in dogs where there is a hemoabdomen or high suspicion for hepatic hemangiosarcoma.

Imaging diagnosis: Disseminated hemangiosarcoma in a Welsh pony.

A 16-year-old pony gelding presented with epistaxis and a head tilt. Referral skull radiographs suggested an ethmoid hematoma. Concurrent neurologic abnormalities prompted contrast-enhanced CT of the head and cranial neck, revealing numerous hyperattenuating masses throughout the brain and paranasal sinuses, along with a large osteolytic mass in the second cervical vertebra. The vertebral mass extended into the vertebral canal, causing focal extradural compressive myelopathy. These findings were inconsistent with ethmoid hematoma and metastatic hemangiosarcoma or malignant melanoma were prioritized as potential causes for the clinical signs. Postmortem examination confirmed the sinonasal, intracranial, and vertebral masses as hemangiosarcoma, and additionally revealed innumerable thoracoabdominal metastatic lesions and hemorrhagic foci. A final diagnosis of disseminated hemangiosarcoma was made. In this study, CT proved invaluable for evaluating the severity and characterizing regional disease and neural involvement, directly affecting case management decisions.

Gadoxetate disodium (Gd-EOB-DTPA) contrast-enhanced magnetic resonance imaging for differentiation between benign and malignant splenic lesions in dogs.

Malignant splenic lesions in dogs are common, with hemangiosarcoma diagnosed most frequently, and there have been no consistent clinicopathologic, gross, or imaging characteristics identified that differentiate malignant from benign splenic lesions. Histopathology is required for definitive diagnosis, and given the poor long-term prognosis of malignant splenic lesions, a noninvasive tool to aid in diagnosis would be valuable. This prospective cohort study utilized gadoxetate disodium, a liver-specific contrast agent (Gd-EOB-DPTA; Eovist), to identify the general lesion and pre- and postcontrast signal characteristics of benign and malignant splenic and hepatic lesions in dogs with naturally occurring disease. Twenty-five dogs were enrolled, Eovist-enhanced MRI was performed, and dogs were taken to surgery for splenectomy and other organ biopsy. All histopathology and MRI studies were evaluated by a single pathologist and a single radiologist, respectively. The associations between the tumor type and numerous variables defined on MRI were evaluated using Fisher's exact tests, and the significance was identified at a P-value of .05. Malignant splenic masses were identified in 11/25 (44%) dogs, and 5/11 malignancies represented hemangiosarcoma. The presence of abdominal effusion (P = .017) and the presence of hepatic nodules on MRI (P = .009) were associated with splenic malignancy. There were no benign T2 hyperintense and no malignant T2 hypointense lesions (P = .021). Utilization of the T2 W MRI sequence may aid in the identification of malignant splenic lesions, particularly when accompanied by abdominal effusion and hepatic lesions.

Computed tomographic findings in canine and feline heart base tumors (25 cases).

Tumors located at the heart base are rare in dogs and cats and aortic body tumors (chemodectoma/paraganglioma), hemangiosarcoma, ectopic thyroid carcinoma, lymphoma, and other uncommon neoplasia can be found at that location. The objective of this retrospective case series was to describe the CT characteristics of canine and feline heart base tumors. CT studies of 21 dogs and four cats with histologically or cytologically confirmed heart base tumors were reviewed for size, location, shape, margination, contrast enhancement, adjacent neovascularization, invasion, mass effect, cavitary effusions, and metastasis. Neuroendocrine tumors (15 aortic body tumors, three ectopic thyroid carcinoma, and three nonspecific neuroendocrine) were more commonly observed than hemangiosarcoma (4) and were frequently located between the cranial vena cava and aortic arch (12/21; 57%) and or dorsal to the pulmonary trunk bifurcation/pulmonary arteries (10/21; 48%). Hemangiosarcoma was more commonly found cranioventral to the aortic arch and cranial to the right auricular appendage (3/4; 75%). Mediastinal and peritumoral neovascularization was associated with 16/21 (76%) neuroendocrine tumors but none of the hemangiosarcoma. Median postcontrast attenuation in Hounsfield units (HU) was higher in neuroendocrine (110 HU) than in hemangiosarcoma (51 HU). Pericardial effusion was frequently observed with hemangiosarcoma (3/4; 75%) and infrequently in neuroendocrine (3/21; 14%). In four cases (all neuroendocrine), concurrent cranial mediastinal masses were present. CT provides useful information regarding the characteristics of heart base tumors, indicating differences between the appearance of neuroendocrine tumors and hemangiosarcoma. However, no differences were found between aortic body tumors and ectopic thyroid carcinoma.

Ultrasonographic and CT-scan findings of splenic active chylous effusion and postlymphangiography enhancement in a cat with chylothorax associated with splenic angiosarcoma.

A 12-year-old domestic shorthair cat was presented with relapsing noncardiogenic chylothorax. CT-lymphangiography of the thorax confirmed bilateral pleural effusion without evidence of an underlying intra-thoracic origin. Abdominal CT-lymphangiography revealed a 2.6 cm diameter splenic mass surrounded by chylous effusion actively collecting during ultrasonographic assessment. Following splenectomy, histopathological analysis revealed that the splenic mass exhibited characteristics indicative of splenic angiosarcoma. This case report highlights the utility of advanced thoracic and abdominal imaging, notably CT-lymphangiography, in the diagnostic evaluation of chylothorax in cats. The identification of a splenic mass encased in chylous effusion should prompt a proactive case management strategy.

Obstructive cardiac myxosarcoma of the right ventricular outflow tract with pulmonary embolism and concurrent right atrial hemangiosarcoma in a dog.

A 13-year-old spayed female rottweiler crossbreed dog was presented with an 8-day history of abnormal gait and collapse associated with excitement or physical activity. A cardiac gallop was noticed on thoracic auscultation, and a 1st-degree atrioventricular block and sinus tachycardia were noted on an electrocardiogram. Echocardiography identified a hypoechoic, irregularly marginated luminal mass in the right ventricle at the level of the pulmonic valves. Postmortem gross examination confirmed the presence of a soft, polypoid, and botryoid mass (9 × 3 × 3 cm) with a smooth and glistening surface attached to the endocardium of the right ventricular outflow tract and extending to the pulmonary artery. The histological findings were consistent with the diagnosis of myxosarcoma with pulmonary embolism. In addition, the dog in this report had a right atrial hemangiosarcoma and a cutaneous hemangioma unrelated to her clinical findings. Key clinical message: Cardiac myxosarcomas are very rare neoplasms in dogs and concomitant primary heart tumors of different histogenesis are even rarer in dogs. To the authors' knowledge, this is the first report of coexistent myxosarcoma and hemangiosarcoma in the heart of a dog. Cardiac myxosarcomas should be considered in the differential diagnosis of intracavitary heart masses associated with signs of cardiac obstruction and failure.

Myxosarcome cardiaque obstructif de la voie d'éjection du ventricule droit avec embolie pulmonaire et hémangiosarcome auriculaire droit concomitant chez un chien. Une chienne croisée rottweiler stérilisée âgée de 13 ans a été présentée avec une histoire de démarche anormale et d'effondrement associés à l'excitation ou à l'activité physique depuis 8 jours. Un galop cardiaque a été noté à l'auscultation thoracique, un bloc auriculo-ventriculaire du 1er degré et une tachycardie sinusale ont été notés à l'électrocardiogramme. L'échocardiographie a permis d'identifier une masse luminale hypoéchogène et irrégulièrement marginalisée dans le ventricule droit au niveau des valvules pulmonaires. L'examen macroscopique post-mortem a confirmé la présence d'une masse molle, polypoïde et botryoïde (9 × 3 × 3 cm) avec une surface lisse et brillante attachée à l'endocarde de la voie d'éjection du ventricule droit et s'étendant jusqu'à l'artère pulmonaire. Les résultats histologiques concordaient avec le diagnostic de myxosarcome avec embolie pulmonaire. De plus, la chienne dans ce rapport présentait un hémangiosarcome auriculaire droit et un hémangiome cutané sans rapport avec ses résultats cliniques.Message clinique clé :Les myxosarcomes cardiaques sont des néoplasmes très rares chez le chien et les tumeurs cardiaques primaires concomitantes d'histogenèse différente sont encore plus rares chez le chien. À la connaissance des auteurs, il s'agit du premier rapport de myxosarcome et d'hémangiosarcome coexistant dans le cœur d'un chien. Les myxosarcomes cardiaques doivent être pris en compte dans le diagnostic différentiel des masses cardiaques intracavitaires associées à des signes d'obstruction et d'insuffisance cardiaque.(Traduit par Dr Serge Messier).

HEMANGIOSARCOMA IN RED WOLVES (CANIS RUFUS) AND GRAY WOLVES (CANIS LUPUS) IN HUMAN CARE: SIX CASES.

Wolves are commonly housed in zoological institutions and captive breeding facilities that are essential for maintaining genetic diversity and for the recovery of declining populations. Neoplasia is a common cause of mortality in wolves, but hemangiosarcoma has not previously been described. This condition was diagnosed in four red wolves (Canis rufus) and two gray wolves (Canis lupus) housed at five different institutions between 2008 and 2018. Animals were 11-16 yr of age at the time of presentation. Clinical signs included loss of body condition, abdominal distension, lethargy, weakness, ataxia, and hyporexia. Three animals were mildly anemic. All animals were humanely euthanized within an average of 3 d from onset of clinical signs. Two animals had primary splenic tumors, two had pelvic tumors with one originating from the aorta, and one had a cranial mediastinal mass. Diagnosis was made on postmortem histologic examination in all cases. Four wolves had evidence of metastases with foci in the lungs, lymph nodes, mesentery, liver, subcutis/skeletal muscle, kidney, adrenal, and thyroid gland. Hemangiosarcoma should be considered in geriatric wolves presenting with nonspecific signs, particularly if abdominal distension, free peritoneal fluid, or anemia is present.

Machine learning application identifies novel gene signatures from transcriptomic data of spontaneous canine hemangiosarcoma.

Angiosarcomas are soft-tissue sarcomas that form malignant vascular tissues. Angiosarcomas are very rare, and due to their aggressive behavior and high metastatic propensity, they have poor clinical outcomes. Hemangiosarcomas commonly occur in domestic dogs, and share pathological and clinical features with human angiosarcomas. Typical pathognomonic features of this tumor are irregular vascular channels that are filled with blood and are lined by a mixture of malignant and nonmalignant endothelial cells. The current gold standard is the histological diagnosis of angiosarcoma; however, microscopic evaluation may be complicated, particularly when tumor cells are undetectable due to the presence of excessive amounts of nontumor cells or when tissue specimens have insufficient tumor content. In this study, we implemented machine learning applications from next-generation transcriptomic data of canine hemangiosarcoma tumor samples (n = 76) and nonmalignant tissues (n = 10) to evaluate their training performance for diagnostic utility. The 10-fold cross-validation test and multiple feature selection methods were applied. We found that extra trees and random forest learning models were the best classifiers for hemangiosarcoma in our testing datasets. We also identified novel gene signatures using the mutual information and Monte Carlo feature selection method. The extra trees model revealed high classification accuracy for hemangiosarcoma in validation sets. We demonstrate that high-throughput sequencing data of canine hemangiosarcoma are trainable for machine learning applications. Furthermore, our approach enables us to identify novel gene signatures as reliable determinants of hemangiosarcoma, providing significant insights into the development of potential applications for this vascular malignancy.

Intensity-modulated radiotherapy and chemotherapy for canine right atrial tumors: A retrospective study of seven dogs.

Most primary cardiac tumors in dogs are located in the right atrium/atrial appendage, with hemangiosarcoma being the most common. The aims of this retrospective, case series were to describe outcomes for seven dogs with right atrial tumors treated with hypofractionated intensity-modulated radiotherapy and concurrent vinblastine and propranolol. One dog had a complete response, four dogs had partial responses and two dogs had stable disease after treatment. Effusions resolved in all dogs. Median progression-free survival was 290 days. Five dogs died from metastatic disease, one dog from unrelated neoplasia, and one dog is alive. Median overall survival was 326 days. Three dogs with confirmed hemangiosarcoma survived 244, 326, and 445 days. Two dogs developed clinically significant, but nonfatal, cardiac arrhythmias. One dog that received three courses of radiation had subclinical myocardial and arterial fibrosis at necropsy. Hypofractionated chemoradiotherapy was well tolerated and may provide clinical benefit in dogs with right atrial tumors.

Can CT texture analysis parameters be used as imaging biomarkers for prediction of malignancy in canine splenic tumors?

Splenic hemangiosarcoma has morphological similarities to benign nodular hyperplasia. Computed tomography (CT) texture analysis can analyze the texture of images that the naive human eye cannot detect. Recently, there have been attempts to incorporate CT texture analysis with artificial intelligence in human medicine. This retrospective, analytical design study aimed to assess the feasibility of CT texture analysis in splenic masses and investigate predictive biomarkers of splenic hemangiosarcoma in dogs. Parameters for dogs with hemangiosarcoma and nodular hyperplasia were compared, and an independent parameter that could differentiate between them was selected. Discriminant analysis was performed to assess the ability to discriminate the two splenic masses and compare the relative importance of the parameters. A total of 23 dogs were sampled, including 16 splenic nodular hyperplasia and seven hemangiosarcoma. In each dog, total 38 radiomic parameters were extracted from first-, second-, and higher-order matrices. Thirteen parameters had significant differences between hemangiosarcoma and nodular hyperplasia. Skewness in the first-order matrix and GLRLM_LGRE and GLZLM_ZLNU in the second, higher-order matrix were determined as independent parameters. A discriminant equation consisting of skewness, GLZLM_LGZE, and GLZLM_ZLNU was derived, and the cross-validation verification result showed an accuracy of 95.7%. Skewness was the most influential parameter for the discrimination of the two masses. The study results supported using CT texture analysis to help differentiate hemangiosarcoma from nodular hyperplasia in dogs. This new diagnostic approach can be used for developing future machine learning-based texture analysis tools.

Gene expression profiles of beta-adrenergic receptors in canine vascular tumors: a preliminary study.

Beta adrenergic receptors (ß-AR) play a key role in regulating several hallmark pathways of both benign and malignant human and canine tumors. There is scarce information on the expression of ß-AR in canine vascular tumors. Therefore, the purpose of the present research work was to study the mRNA expression levels of the three subtypes of the ß-AR genes (ADRB1, ADRB2, ADRB3) in hemangiosarcoma (HSA) and hemangioma (HA), as well as in vascular hamartomas (VH) from dogs.Fifty samples (n = 50) were obtained from 38 dogs. Twenty-three animals had HSA, eight animals HA and seven animals VH. HSA were auricular (n = 8), splenic (n = 5), cutaneous (n = 6), auricular and splenic (n = 2), cutaneous-muscular (n = 1) and disseminated (n = 1). There were seven cases of HSA that were divided into primary tumor and secondary (metastatic) tumor. Skin and muscle samples with a normal histological study were used as control group. ADRB gene expression was determinate in all samples by real-time quantitative PCR. Results showed that ADRB1, ADRB2 and ADRB3 were overexpressed in HSA when compared to the control group. ADRB2 was overexpressed in HA when compared to the control group. HSA express higher values of ADBR1 (p = 0.0178) compared to VH. There was a high inter-individual variability in the expression of the three subtypes of ADBR. No statistically significant difference in the expression of ADBR genes were observed between HSA primary when compared to metastatic or in different anatomical locations. In conclusion, canine HSA overexpress the three ß-AR subtypes and canine HA ß2-AR. High variability was observed in ß-AR mRNA levels amongst HSA cases.

Retrospective evaluation of canine primary, multicentric, and metastatic intraocular neoplasia.

OBJECTIVE: To provide an updated characterization of the prevalence of primary, multicentric, and metastatic intraocular tumors in the canine patient. PROCEDURES: Medical records databases from 4 veterinary referral hospitals were reviewed from 1999 to present to identify dogs with a diagnosis of intraocular neoplasia histopathologically confirmed following enucleation or necropsy. RESULTS: One hundred seventy-two dogs with 173 intraocular neoplasms met the inclusion criteria. Primary intraocular neoplasms were the most common tumors in the study (128); the two most common types were melanocytic neoplasia (90), followed by iridociliary neoplasia (33). There were 28 cases of intraocular involvement secondary to round cell neoplasia, with 18 cases of lymphoma, seven histiocytic sarcomas, and three undifferentiated round cell neoplasms. There were 17 cases of metastatic intraocular neoplasia, with hemangiosarcoma being the most common (9). CONCLUSIONS: The majority of intraocular tumors in dogs arise from the ocular tissues. However, the eye may also be involved in patients with multicentric neoplasia, and, less commonly, as a site for metastatic disease. Ocular screening for patients with multicentric neoplasia should be considered during staging, and ocular signs should be viewed with suspicion in dogs with neoplasia in other sites.

MRI features of canine hemangiosarcoma affecting the central nervous system.

Hemangiosarcoma is the most common metastatic tumor involving the brain in dogs but detailed published descriptions of the magnetic resonance imaging (MRI) features are lacking. The objective of this multi-center, retrospective case series study was to describe MRI characteristics of canine hemangiosarcoma affecting the central nervous system (CNS). Medical records of seven referral institutions were retrospectively reviewed. Dogs were included if they had a histopathologically confirmed diagnosis of hemangiosarcoma affecting the CNS and undergone an MRI of the brain and/or vertebral column. Lesions were independently evaluated by two observers. Twenty dogs met the inclusion criteria and one dog had both intracranial and intramedullary hemangiosarcoma. Consistent MRI features included heterogeneous (17/21) lesions in all sequences with mainly mixed signal intensity (12/21), presence of susceptibility artifact on T2*w (15/16), associated moderate to severe perilesional edema (21/21), and moderate to strong (20/21) heterogeneous (14/21) or ring-like (6/21) contrast enhancement. Intracranial hemangiosarcoma was frequently multiple and intra-axial, affecting consistently the telencephalon and no differences in MRI features were found between primary and metastatic hemangiosarcoma. This is the first MRI description of primary intracranial hemangiosarcoma and primary intracranial epithelioid hemangiosarcoma. Vertebral hemangiosarcomas were segmental poorly marginated polyostotic and highly aggressive lesions invading the thoracic vertebral canal and paraspinal tissues. Epidural hemangiosarcomas were single and well-marginated lesions in the thoracolumbar and/or lumbar region. Intramedullary hemangiosarcomas were cervical, metastatic in origin, and frequently (3/4) accompanied by intracranial lesions. These described MRI features will aid early identification of hemangiosarcoma guiding subsequent diagnostics and therapeutics.

Addressing Delicate and Variable Cancer Morphology in Spectral Histopathology Using Canine Visceral Hemangiosarcoma.

Spectral histopathology has shown promise for the classification and diagnosis of tumors with defined morphology, but application in tumors with variable or diffuse morphologies is yet to be investigated. To address this gap, we evaluated the application of Fourier transform infrared (FTIR) imaging as an accessory diagnostic tool for canine hemangiosarcoma (HSA), a vascular endothelial cell cancer that is difficult to diagnose. To preserve the delicate vascular tumor tissue structure, and potential classification of single endothelial cells, paraffin removal was not performed, and a partial least square discrimination analysis (PLSDA) and Random Forest (RF) models to classify different tissue types at individual pixel level were established using a calibration set (24 FTIR images from 13 spleen specimens). Next, the prediction capability of the PLSDA model was tested with an independent test set (n = 11), resulting in 74% correct classification of different tissue types at an individual pixel level. Finally, the performance of the FTIR spectropathology and chemometric algorithm for diagnosis of HSA was established in a blinded set of tissue samples (n = 24), with sensitivity and specificity of 80 and 81%, respectively. Taken together, these results show that FTIR imaging without paraffin removal can be applied to tumors with diffuse morphology, and this technique is a promising tool to assist in canine splenic HSA differential diagnosis.

Characterizing circulating nucleosomes in the plasma of dogs with hemangiosarcoma.

BACKGROUND: Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay. Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC. RESULTS: Dogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease. CONCLUSIONS: Plasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.

A Review of Proliferative Vascular Disorders of the Central Nervous System of Animals.

In disease, blood vessel proliferation has many salient roles including in inflammation, when granulation tissue fills superficial defects, or in the recanalization of an occluded blood vessel. Sometimes angiogenesis goes awry-granulation can be exuberant, and plexiform proliferation of vascular components can contribute to pulmonary hypertension. This review focuses on the diverse manifestations of pathologic vascular overgrowth that occur in the brain, spinal cord, and meninges of animals from birth until old age. Entities discussed include systemic reactive angioendotheliomatosis in which glomeruloid vascular proliferations are encountered in various organs including the central nervous system (CNS). The triad of CNS vascular malformations, hamartomas, and benign vascular proliferations are an especially fraught category in which terminology overlap and the microscopic similarity of various disorders makes diagnostic classification incredibly challenging. Pathologists commonly take refuge in "CNS vascular hamartoma" despite the lack of any unique histopathologic features and we recommend that this diagnostic category be abandoned. Malformative lesions that are often confusing and have similar features; the conditions include arteriovenous malformation, cavernous angioma, venous angioma, and capillary telangiectases. Meningioangiomatosis, a benign meningovascular proliferation with dual components, is a unique entity seen most commonly in young dogs. Last, accepted neoplastic conditions range from lower-grade locally acquired growths like hemangioblastoma (a tumor of mysterious interstitial stromal cells encountered in the setting of abundant capillary vasculature proliferation), the rare hemangioendothelioma, and the highly malignant and invariably multifocal metastatic hemangiosarcoma. Additionally, this review draws on the comparative medical literature for further insights into this problematic topic in pathology.