RESUMO
OBJECTIVES: Angiosarcomas are rare malignant mesenchymal neoplasms of endothelial cell origin with a predilection to the ventral abdominal wall in cats. Larger case series describing this entity are lacking. METHODS: Two referral centre laboratory databases were searched for angiosarcoma of the ventral abdominal wall. Nine cases with a histological diagnosis were included. Immunohistochemistry (factor VIII and PROX-1 antibodies) was used to phenotype them as haemangiosarcoma or lymphangiosarcoma. RESULTS: All cats presented with a ventral abdominal mass, five of which were producing a serosanguinous discharge. Eight underwent tumour staging and pulmonary metastases were suspected in one cat (but not histologically confirmed). With histopathology alone, a diagnosis of angiosarcoma and lymphangiosarcoma was made in four and five cases, respectively. After immunohistochemistry, five cases had a haemangiosarcoma phenotype and four had a lymphangiosarcoma phenotype, including two cases of lymphangiosarcoma that were reclassified as hemangiosarcoma. Eight cats received treatment (either surgery with or without adjuvant therapies or medical management alone). Six cats were euthanased due to local disease progression. The median survival time for haemangiosarcoma was 166 days (range 137-381), and for lymphangiosarcoma it was 197 days (range 67-208). Two cats with haemangiosarcoma remained alive for a follow-up period of 329 and 580 days, respectively. CONCLUSIONS AND RELEVANCE: Feline ventral abdominal angiosarcomas are rare locally aggressive neoplasms. While histology often provides a diagnosis of angiosarcoma, immunohistochemistry is ultimately required to differentiate between haemangiosarcoma and lymphangiosarcoma phenotypes. Further studies are required to evaluate whether the different phenotypes have an impact on treatment response and outcome.
Assuntos
Parede Abdominal , Doenças do Gato , Hemangiossarcoma , Linfangiossarcoma , Sarcoma , Gatos , Animais , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/terapia , Hemangiossarcoma/veterinária , Linfangiossarcoma/diagnóstico , Linfangiossarcoma/veterinária , Sarcoma/veterinária , Agressão , Doenças do Gato/diagnóstico , Doenças do Gato/terapiaRESUMO
A 7-year-old intact Netherlands Dwarf rabbit with bloody discharge from the vulva underwent ovariohysterectomy. Grossly, both sides of the uterus were enlarged. Histologically, the tumour had formed protruded from the myometrial wall toward the serosa and was composed of irregular small capillaries with irregularly shaped structures and bundled proliferation of spindle-shaped cells. No tumour cells infiltrated the endometrium. The tumour cells were positive for CD31, and histological and immunohistochemical staining confirmed the diagnosis of haemangiosarcoma. Vascular tumours in the uterus of animals are uncommon, and only one case has been reported in the uterus of rabbits.
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Hemangiossarcoma , Neoplasias Uterinas , Feminino , Coelhos , Animais , Hemangiossarcoma/veterinária , Países Baixos , Neoplasias Uterinas/veterinária , Neoplasias Uterinas/patologia , Útero , EndométrioRESUMO
Haemangiosarcoma is a highly metastatic and lethal cancer of blood vessel-forming cells that commonly spreads to the brain in both humans and dogs. Dysregulations in phosphatase and tensin (PTEN) homologue have been identified in various types of cancers, including haemangiosarcoma. MicroRNAs (miRNAs) are short noncoding single-stranded RNA molecules that play a crucial role in regulating the gene expression. Some miRNAs can function as oncogenes or tumour suppressors, influencing important processes in cancer, such as angiogenesis. This study aimed to investigate whether miRNAs targeting PTEN were disrupted in canine haemangiosarcoma and its corresponding brain metastases (BM). The expression levels of miRNA-10b, miRNA-19b, miRNA-21, miRNA-141 and miRNA-494 were assessed in samples of primary canine cardiac haemangiosarcomas and their matched BM. Furthermore, the miRNA profile of the tumours was compared to samples of adjacent non-cancerous tissue and healthy control tissues. In primary cardiac haemangiosarcoma, miRNA-10b showed a significant increase in expression, while miRNA-494 and miRNA-141 exhibited downregulation. Moreover, the overexpression of miRNA-10b was retained in metastatic brain lesions. Healthy tissues demonstrated significantly different expression patterns compared to cancerous tissues. In particular, the expression of miRNA-10b was nearly undetectable in both control brain tissue and perimetastatic cerebral tissue. These findings can provide a rationale for the development of miRNA-based therapeutic strategies, aimed at selectively treating haemangiosarcoma.
Assuntos
Neoplasias Encefálicas , Doenças do Cão , Hemangiossarcoma , MicroRNAs , Humanos , Cães , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Hemangiossarcoma/genética , Hemangiossarcoma/veterinária , Doenças do Cão/genética , Encéfalo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/veterinária , Regulação Neoplásica da Expressão GênicaRESUMO
Background: Only 27 cases of equine conjunctival haemangiosarcoma have been reported in the literature over the past 37 years. Out of these, 22% of cases were lost to follow-up, 52% were euthanized, and 26% survived. A scarcity of cases and information is available for this rarely seen conjunctival tumour. Aim: To describe the clinical features, management, and outcome of conjunctival hemangiosarcoma in seven horses in the UK. Methods: Optivet medical records were reviewed for equine cases seen or advised on with a histopathological diagnosis of conjunctival haemangiosarcoma between January 2013 and March 2023. Medical records were accessed for details of signalment, history, management, and follow-up. Histopathology was used to confirm the diagnosis of haemangiosarcoma and assess the surgical margins. Immunohistochemistry was performed in a minority of cases with poorly differentiated solid tumours to support vascular lineage. Results: Seven eyes from seven horses (five geldings and two mares) with a mean age of 16 years and median of 18 years (range 10-21 years) met the criteria. Serosanguinous discharge was seen in six eyes. All eyes were managed surgically; 4 by exenteration and 3 by conjunctivectomy/keratectomy. Adjunctive cryotherapy was performed in two eyes. Metastatic disease in the ipsilateral parotid salivary gland, confirmed with histopathology, was seen in one horse. Surgical margins were clear in all but one eye. Solar elastosis was noted in five eyes. All horses were healthy at the last follow-up (0.2-5 years, mean 2.9 years, and median 2 years). Conclusion: Equine conjunctival haemangiosarcoma is rare. Serosanguinous ocular discharge is a common clinical sign. Early surgical excision is highly effective. Solar elastosis is a common histopathological feature, suggesting a role for UV-light in the pathogenesis.
Assuntos
Hemangiossarcoma , Doenças dos Cavalos , Cavalos , Animais , Masculino , Feminino , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/terapia , Hemangiossarcoma/veterinária , Margens de Excisão , Reino Unido/epidemiologia , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Doenças dos Cavalos/patologiaRESUMO
Haemangiosarcoma is a relatively common malignant tumour in dogs, and one of the primary outcomes of interest for the Golden Retriever Lifetime Study. This study collects longitudinal data and samples from a cohort of golden retrievers, with the aim of identification of nutritional, genetic, environmental, lifestyle and reproductive risk factors for cancers and other important diseases in dogs. This analysis describes the accumulating data and samples, which are available for use by researchers to fulfil the study's objectives. As of September 2022, 233/3044 dogs enrolled in the study had been diagnosed with haemangiosarcoma (7.65%), with an incidence rate of 1.10 cases per 100 dog-years. Visceral haemangiosarcoma was the most common, affecting 211/3044 study dogs (6.9%). One hundred and twenty eight visceral haemangiosarcoma diagnoses specified the presence of splenic tumours (60.7%) and 119 specified the presence of cardiac tumours (56.4%). The probability of remaining without a haemangiosarcoma diagnosis declined from 100% from approximately 4 years of age, to a 12 year probability of 91.1% in intact females (95% CI 84.4%-98.3%), 60.7% in neutered females (95% CI 41.6%-88.6%), 72.9% in intact males (95% CI 62.9%-84.6%) and 70.0% in neutered males (95% CI 53.4%-92.0%). The 1 year survival probability for visceral haemangiosarcoma was 1.42% (95% CI 0.37%-5.47%); for cutaneous haemangiosarcoma, it was 84.6% (95% CI 67.1%-99.99%). The accumulated data and samples are a considerable resource for further investigation of canine haemangiosarcoma and have a potential role in translational medicine.
Assuntos
Doenças do Cão , Neoplasias Cardíacas , Hemangiossarcoma , Neoplasias Cutâneas , Neoplasias Esplênicas , Humanos , Masculino , Feminino , Cães , Animais , Doenças do Cão/patologia , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/veterinária , Neoplasias Cutâneas/veterinária , Neoplasias Cardíacas/veterinária , Neoplasias Esplênicas/epidemiologia , Neoplasias Esplênicas/veterináriaRESUMO
A 4-month old, 200 kg, grey warmblood colt presented for a firm, non painful mass on the distal medial aspect of the left third metatarsus. Excisional biopsy revealed a diagnosis of haemangiosarcoma. Equine haemangiosarcoma is uncommon and only limited reports of successful treatment are available. The prognosis for survival is therefore considered to be poor. After two separate incidences of recurrence with incomplete excision of the tumour, intralesional treatment with cisplatin without excision or debulking was performed on three separate occasions. Intralesional cisplatin injection was performed at monthly intervals for three treatments. Four years post treatment with cisplatin, the horse remained in remission. This case report describes the diagnostic and treatment challenges for successful treatment of a primary haemangiosarcoma on the distal limb of a warmblood foal using intralesional cisplatin chemotherapy.
Assuntos
Hemangiossarcoma , Doenças dos Cavalos , Animais , Masculino , Cavalos , Cisplatino/uso terapêutico , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/veterinária , Hemangiossarcoma/diagnóstico , Prognóstico , Doenças dos Cavalos/diagnósticoRESUMO
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.
Assuntos
Doenças do Cão , Hemangiossarcoma , Animais , Encéfalo/patologia , Doenças do Cão/patologia , Cães , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/patologia , Hemangiossarcoma/veterinária , Imageamento por Ressonância Magnética/veterinária , Estudos RetrospectivosRESUMO
Haemangioma (HA) and haemangiosarcoma (HSA) are among the most common splenic neoplasms in dogs. The survival time in splenic HSA is short, probably due to the lack of proper biological markers allowing early detection. We investigated the serum angiopoietin-2 (Ang-2) concentrations in 9 healthy dogs and 40 dogs with abnormal splenic masses. The Ang-2 concentration differences were further compared in healthy dogs, dogs with splenitis, splenic HA and HSA. The results showed that the Ang-2 level in healthy dogs was significantly lower than in the splenitis and splenic HA cases. Moreover, the Ang-2 level was significantly higher in splenic HA than in splenic HSA. Conversely, no significant differences in Ang-2 level were recorded between healthy and splenic HSA dogs, and between splenitis and splenic neoplasms (HA and HSA). No significant correlations were observed between the Ang-2 level and (i) the clinical stage, (ii) histological growth pattern, and (iii) median survival time of splenic HSA dogs. In conclusion, serum Ang-2 concentration is a potentially useful biological marker for the discrimination of dogs with splenitis and splenic HA, as well as for the differentiation of splenic HA from its malignant form, HSA.
Assuntos
Doenças do Cão , Hemangioma , Hemangiossarcoma , Neoplasias Esplênicas , Angiopoietina-2 , Animais , Doenças do Cão/diagnóstico , Cães , Hemangioma/veterinária , Hemangiossarcoma/veterinária , Neoplasias Esplênicas/veterináriaRESUMO
Haemoperitoneum secondary to ruptured splenic tumours can be either benign or malignant in origin. The majority of previous studies of canine haemoperitoneum have been retrospective, which are associated with well-recognized biases, such as the potential to underappreciate the diversity of outcomes in a complex presentation such as haemoperitoneum. This study seeks to prospectively define perioperative morbidity and mortality of haemoperitoneum in dogs secondary to ruptured splenic masses. Forty dogs with haemoperitoneum secondary to a ruptured splenic mass met the inclusion criteria. As expected, the cohort predominately consisted of older large breed dogs. All dogs underwent preoperative staging and had a splenectomy performed. Histopathologic analysis was performed on the splenic mass, as well as any possible metastatic lesions that were noted intra-operatively. Perioperative care outside of splenectomy was delivered in specialty practices using current conventional approaches to care (eg, transfusions and anti-arrhythmic medications). Fifteen dogs (37.5%) had benign splenic tumours and were cured with surgery alone, whereas 62.5% had malignant disease (most often haemangiosarcoma [HSA]). Surgical outcomes were highly favourable in the vast majority of dogs. Indeed, 38 dogs (95%) survived and were discharged after a median hospitalization of 39.5 hours. Independent predictors of longer hospitalization times included receiving a transfusion and the development of an arrhythmia. Although small, this cohort defines distinctive and optimistic perspectives for dogs with haemoperitoneum from splenic tumour rupture. These favourable outcomes from this prospective study are sufficient to ask if larger prospective studies should be conducted to better inform owners during this challenging cancer emergency presentation.
Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/patologia , Hemangiossarcoma/veterinária , Neoplasias Esplênicas/veterinária , Ruptura Esplênica/veterinária , Animais , Doenças do Cão/cirurgia , Cães , Feminino , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Hospitais Veterinários , Fígado/patologia , Masculino , Estudos Prospectivos , Esplenectomia/veterinária , Neoplasias Esplênicas/epidemiologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia , Ruptura Esplênica/epidemiologia , Ruptura Esplênica/patologia , Ruptura Esplênica/cirurgia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
We previously reported that eBAT, an EGF-targeted angiotoxin, was safe and it improved the overall survival for dogs with splenic haemangiosarcoma when added to the standard of care in a single cycle of three administrations in the minimal residual disease setting. Our objective for the SRCBST-2 trial was to assess whether increased dosing through multiple cycles of eBAT would be well tolerated and would further enhance the benefits of eBAT. Eligibility was expanded to dogs with stage 3 haemangiosarcoma, provided that gross lesions could be surgically excised. The interval between eBAT and the start of chemotherapy was reduced, and the experimental therapy was expanded to three cycles, each administered at the biologically active dose (50 µg/kg) on a Monday/Wednesday/Friday schedule following splenectomy, and scheduled 1 week prior to the first, second and fifth doxorubicin chemotherapy. Twenty-five dogs were enrolled; six experienced acute hypotension with two requiring hospitalization. Self-limiting elevation of ALT was observed in one dog. A statistically significant survival benefit was not seen in this study in eBAT-treated dogs compared with a Contemporary comparison group of dogs with stages 1-3 haemangiosarcoma treated with standard of care alone. Our results indicate that repeated dosing cycles of eBAT starting 1 week prior to doxorubicin chemotherapy led to greater toxicity and reduced efficacy compared with a single cycle given between surgery and a delayed start of chemotherapy. Further work is needed to understand the precise mechanisms of action of eBAT in order to optimize its clinical benefits in the treatment of canine haemangiosarcoma and other tumours. IACUC Protocols 1110A06186 and 1507-32804A.
Assuntos
Quimioterapia Adjuvante/veterinária , Doenças do Cão/tratamento farmacológico , Fator de Crescimento Epidérmico/farmacologia , Hemangiossarcoma/veterinária , Neoplasias Esplênicas/veterinária , Animais , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Quimioterapia Adjuvante/métodos , Doenças do Cão/patologia , Cães , Doxorrubicina/uso terapêutico , Feminino , Hemangiossarcoma/tratamento farmacológico , Masculino , Neoplasias Esplênicas/tratamento farmacológico , Neoplasias Esplênicas/patologia , Resultado do TratamentoRESUMO
AIMS: A wide range of post-radiotherapy (RT) vascular lesions can occur, ranging from benign lymphangiomatous papules of the skin (BLAPs), to atypical vascular lesions (AVLs) and post-RT angiosarcomas (ASs). The relationship between benign and malignant post-RT breast lesions and their prognostic features are still controversial. The aims of this study were to investigate the relationship between benign and malignant mammary post-RT vascular lesions and to define post-RT AS prognostic features. METHODS AND RESULTS: Seventy-four post-RT vascular lesion cases were obtained and stained with antibodies against CD34, CD31, D2-40, Ki67, and c-Myc. Mutational analysis was performed by deep sequencing for the following genes: KRAS, NRAS, HRAS, BRAF, PIK3CA, TP53, NOTCH1, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, hTERT, and PTPRB. Post-RT AS cases were graded according to a previously reported breast AS grading system. AVL cases showed a low number of HRAS and hTERT mutations, whereas post-RT AS cases showed a high frequency of EGFR, TP53, HRAS and hTERT mutations. On follow-up, all BLAP and AVL patients were alive with no evidence of disease. Post-RT AS 5-year overall survival declined with the increase in grade, as follows: 85.7% for grade 1, 83.3% for grade 2, and 40.4% for grade 3. CONCLUSIONS: Our findings confirm that BLAP and AVL have a good prognosis, and that post-RT AS prognosis is strongly related to histological grading. On molecular analysis, AVL and post-RT AS shared HRAS and hTERT mutations, suggesting a relationship between the two lesions.
Assuntos
Neoplasias Induzidas por Radiação/patologia , Radioterapia/efeitos adversos , Malformações Vasculares/patologia , Adulto , Idoso , Mama/patologia , Neoplasias da Mama/patologia , Análise Mutacional de DNA , Feminino , Seguimentos , Hemangiossarcoma/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Oncogenes/genética , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Neoplasias Cutâneas/patologia , Telomerase/genética , Telomerase/metabolismoRESUMO
Prediction of the likely histopathological diagnosis of canine splenic masses can guide appropriate decision-making. This study explores the predictive effect of breed and clinical presentation on the diagnosis of a canine splenic mass. Records from the Royal Veterinary College, United Kingdom (2007-2017) were reviewed. Dogs with a histopathologic or cytologic diagnosis from a splenic mass, or imaging findings consistent with disseminated metastatic disease, were included. Signalment, physical examination, haematology results, imaging findings and pathology reports were recorded. Breeds were grouped according to several permutations of their phenotype and then by clustering of breeds based on single nucleotide polymorphism analysis. Binary logistic regression was performed to identify predictors of malignancy and haemangiosarcoma. Two hundred and eighty-eight dogs were identified: 27% female and 63% male, 21% entire and 79% neutered; German Shepherd was the most common breed (11%). Median age was 10 years and median bodyweight 25 kg. Thirty-eight percent of dogs presented with haemoabdomen; a splenic mass was found incidentally in 28%. Sixty percent had a malignant tumour of which haemangiosarcoma comprised 66%. On multivariable analysis, genotype-based breed group (P = .004), haemoabdomen (P < .001) and neutrophil count (P = .025) predicted malignancy, and genotype-based breed group (P < .001) and haemoabdomen (P < .001) predicted haemangiosarcoma. Genotype-based breed group and occurrence of haemoabdomen may have predictive value to diagnose malignant splenic masses and more specifically haemangiosarcoma. The effect of genotype-based breed grouping was a superior predictor of the diagnosis of a canine splenic mass lesion compared with all phenotype-based groupings tested.
Assuntos
Doenças do Cão/genética , Hemangiossarcoma/veterinária , Neoplasias Esplênicas/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Genótipo , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Baço , Esplenectomia/veterinária , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/patologia , Reino UnidoRESUMO
A nine-year-old female desexed Great Dane presented with a painful, proliferative, soft red putative neoplastic vascular mass on the nictitating membrane. Three 7-day cycles of the topical cytotoxic drug mitomycin C 0.04%, applied four times daily to the lesion using a low-dose alternate-week pulse therapy, brought about rapid remission of the lesion. The lesion was still in remission at time of euthanasia some 13 months later.
Assuntos
Doenças do Cão/tratamento farmacológico , Mitomicina , Membrana Nictitante , Administração Tópica , Animais , Antibióticos Antineoplásicos/uso terapêutico , Cães , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/veterináriaRESUMO
Splenectomy followed by adjuvant chemotherapy is commonly used to treat canine splenic haemangiosarcoma (HSA), although it is unclear if different treatment protocols may have a similar efficacy. The objective of this retrospective study was to assess outcome in dogs with stage I and II splenic HSA treated with either first-line adjuvant anthracycline (AC) or metronomic (MC)-based chemotherapy protocols, by comparing median time to progression (TTP) and median survival time (MST). Medical records of nine institutions were searched for dogs diagnosed with stage I and II splenic HSA that underwent adjuvant treatment with AC- or MC-based protocols following splenectomy. Patients treated with MC following AC were included in an additional group (AMC). Ninety-three dogs were included: 50 in the AC group, 23 in the AMC group and 20 in the MC group. The overall MST was 200 days (range 47-3352) and the overall median TTP was 185 days (range 37-1236). The median TTP of stage I dogs was significantly longer compared to stage II dogs (338 vs 151 days, respectively, P = .028). When adjusting for treatment type, the MST was 154 days for the AC group (range 47-3352 days), 338 days for the AMC group (range 79-1623 days) and 225 days for the MC group (range 57-911 days). The difference in MST and median TTP was not found to be statistically significant between treatment groups. This study suggests that adjuvant MC in canine splenic HSA may result in a similar outcome when compared to other treatment protocols. Further studies are warranted to confirm these findings.
Assuntos
Antraciclinas/farmacologia , Antineoplásicos/farmacologia , Doenças do Cão/tratamento farmacológico , Hemangiossarcoma/veterinária , Administração Metronômica , Animais , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/veterinária , Doenças do Cão/patologia , Cães , Feminino , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/patologia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Haemangiosarcoma (HSA) is a malignant tumour of vascular endothelial cells. It is common in dogs, but rare in other species, and may arise in any tissue. A dermal location of canine HSA has been associated with short survival and recurrence after surgical excision. Solar radiation has been proposed as a predisposing factor in shorthaired dogs with light skin pigmentation. There are no studies relating the expression of immunohistochemical markers to survival of dogs with cutaneous haemangiosarcoma (cHSA). Such data could contribute to establishing prognostic factors and new therapies based on the expression of target molecules. The aim of this study was to evaluate biomarkers and overall survival (OS) of dogs with cHSA, therefore helping to understand the biological behaviour of this neoplasm and determine prognostic factors. Sixty samples of canine cHSA were evaluated for the expression of factor VIII (FVIII), cyclo-oxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and caspase-3 (Casp-3) by immunohistochemistry. The results were related to OS of animals through the model of competitive risks. In addition, the relationships between age, sex, breed, tumour invasiveness, histological differentiation scoring, mitotic rate and tumour size were correlated with the OS of the dogs. Markers expression was positive in 80-100% of the samples, predominantly with weak to moderate labelling intensity for FVIII, COX-2, and VEGF, but with strong expression of PCNA and Casp-3. The median OS of dogs was 12 months. The variables of dog age, tumour invasiveness, histological differentiation scoring, mitotic rate and tumour size were not related to the survival rate. Some predisposed breeds (i.e. pitbull, boxer, Basset hound and Dalmatian) showed greater OS than non-predisposed breeds. Dogs affected by other concomitant primary neoplasms had a longer survival curve than those with only cHSA, while the females of the former group had lower OS than males. The labelling indices of FVIII, COX-2, VEGF, PCNA and Casp-3 had no relationship to OS, neither did the labelling intensity of FVIII, COX-2 and VEGF. However, the expression of COX-2 and VEGF is frequent in canine cHSA so these possible therapeutic targets should be investigated further.
Assuntos
Biomarcadores Tumorais/análise , Doenças do Cão/mortalidade , Hemangiossarcoma/veterinária , Neoplasias Cutâneas/veterinária , Animais , Cães , Feminino , MasculinoRESUMO
Vascular tumours of the liver represent an underrated chapter of medical and surgical hepatology. These tumours cover a wide spectrum ranging from the frequent and most benign hepatic haemangioma (HH), via the rare and intermediately aggressive hepatic epithelioid haemangioendothelioma (HEHE) to the rare and most malignant hepatic haemangiosarcoma (HHS). In contrast to the treatment algorithms for hepatocellular and cholangiocellular cancer, the diagnostic and therapeutic approaches to HEHE and HHS are not well developed. The related uncertainty is explained by their rare occurrence and their protean clinical, morphological (imaging) and histopathological presentation and behaviour. This article gives an update about these particular tumours based on the analysis of the recent literature and of the studies on vascular tumours published by the European Liver Intestine Transplantation Association (ELITA)-European Liver Transplant Registry (ELTR). It focuses also on the place of liver transplantation (LT) in the respective therapeutic algorithms. The differential diagnosis between these vascular and other tumour types may be very difficult. Correct diagnosis is of utmost importance and is based on a high index of clinical suspicion and on the integration of clinical, radiological, histological [including immunohistochemistry (IHC) and molecular biology findings]. Surgery, be it partial or total hepatectomy (LT), should be proposed whenever possible, because it is the therapeutic mainstay. In HEHE, LT provides excellent results, with long-term disease-free survivals (DFS) reaching 75%. Good results can be obtained even in case of (frequent) extrahepatic spread. Based on the extensive ELITA-ELTR study a HEHE-LT prognostic score has been proposed in order to estimate the risk of recurrence after LT. In contrast, results of surgery and LT are extremely poor for HHS, for the almost invariably rapid recurrence (within 6 months) and related death within 2 years. LT remains a contraindication for HHS. Due to the still important recurrence rate after surgical resection (25% in HEHE and almost 100% in HHS), there is an urgent need to develop pharmacological treatments targeting angiogenic and non-VEGF angiogenic pathways. To date, some prospective pilot studies and case reports have shown some short-term stabilisation of the disease in small groups of patients. In order to make progress, combination of surgery, anti-angiogenic and immunotherapy seems worthwhile. To complete the panel of vascular liver tumours, infantile haemangioendothelioma, haemangiopericytoma, nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN) are also discussed.
RESUMO
CASE SUMMARY: A 12-year-old entire domestic shorthair was evaluated for a 5 week history of intermittent vomiting, loss of appetite and weight loss. Abdominal ultrasound revealed a multi-lobulated heterogeneous mass adjacent to the mesenteric vessels. Cytology from fine-needle aspirates was non-diagnostic. Histopathology from a Tru-cut biopsy was consistent with haemangiosarcoma. The cat was treated with metronomic chemotherapy using oral cyclophosphamide. The cat remained clinically well and was euthanased 10 months after diagnosis owing to development of a haemoabdomen. RELEVANCE AND NOVEL INFORMATION: Prognosis of feline abdominal haemangiosarcoma is generally poor and limited information on treatment is available in the veterinary literature. The use of metronomic chemotherapy with oral cyclophosphamide in this cat provided a 10 month period of good-quality life.
RESUMO
Haemangiosarcoma (HSA) has an aggressive biological behaviour and carries a poor prognosis, with less than 10% of treated dogs surviving longer than 1 year. In this retrospective study a varied metronomic chemotherapy (MC) regimen preceded by adjuvant doxorubicin-based maximum-tolerated dose chemotherapy (MTDC) was compared with MTDC, in terms of efficacy [time to metastasis, (TTM) and survival time (ST)] and safety in dogs with biologically aggressive HSA. Dogs were eligible if they had no metastasis after MTDC and received either no further chemotherapy or MC maintenance. Twelve dogs received MTDC, and 10 received MC thereafter. Median TTM and ST were significantly longer for dogs receiving MTDC-MC (not reached versus 150 days, P = 0.028; and not reached versus 168 days, P = 0.030, respectively). Treatment was well tolerated. MTDC followed by MC is safe and suggests improved TTM and ST in dogs with surgically removed, biologically aggressive HSA that are treated in the microscopic setting.
Assuntos
Doenças do Cão/terapia , Substituição de Medicamentos/veterinária , Hemangiossarcoma/veterinária , Administração Metronômica , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Terapia Combinada/veterinária , Doenças do Cão/mortalidade , Cães , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Hemangiossarcoma/mortalidade , Hemangiossarcoma/terapia , Masculino , Estudos RetrospectivosRESUMO
Canine haemangiosarcoma (HSA), like human angiosarcoma, is an uncommon malignant vascular endothelial cell tumour associated with a poor prognosis. The peroxiredoxin (PRDX) family of peroxidases, which comprises six members in mammals (PRDX1-6), might contribute to cancer cell survival in the face of oxidative stress as these proteins exhibit frequent upregulation in cancer cells. In this study, we investigated the expression levels of PRDX6 in spontaneously arising primary canine HSAs by immunohistochemical analysis, identifying marked expression of this protein. Both PRDX6 mRNA and protein were overexpressed in HSA cell lines compared with normal canine endothelial cells, although some variation was observed between the different HSA cell lines. Small interfering RNA-induced downregulation of PRDX6 promoted apoptosis in the HSA cell lines. The observation that PRDX6 suppression increased the cytotoxicity of these cells suggests that PRDX6 might play an important cytoprotective role.
Assuntos
Apoptose/fisiologia , Biomarcadores Tumorais/análise , Doenças do Cão/patologia , Hemangiossarcoma/veterinária , Peroxirredoxina VI/biossíntese , Animais , Western Blotting , Linhagem Celular Tumoral , Cães , Feminino , Técnicas de Silenciamento de Genes , Imuno-Histoquímica , Masculino , Peroxirredoxina VI/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Primary heart tumours affect less than 1% of dogs. Due to their rare incidence, every research showing the frequency of cardiac tumours is valuable. Routine diagnostics is often complemented with immunohistochemical analysis. This study was conducted on 110 patient records from all veterinary faculties in Poland from dogs diagnosed with heart tumours between 1970 and 2014. The dogs' age, breed and sex with tumour localisation and histopathological diagnosis were analysed. Because of its most common incidence, samples of haemangiosarcoma underwent further examination with assessment of the expression of cell markers that have not been evaluated earlier (i.e. minichromosome maintenance proteins and beta-catenin). We noted 111 tumours including 88.3% malignant and 10.8% benign ones. Haemangiosarcoma and aortic body tumour were the most frequent cardiac neoplasms in the dogs examined (45.9% and 27.9% of all tumours, respectively). Immunohistochemical analysis of haemangiosarcoma showed a positive expression of all markers examined. CD31, vimentin, and beta-catenin showed a positive reaction in all 11 samples examined. At least one proliferative marker (Ki-67, MCM-3 or MCM-7) showed a positive reaction in each sample. MCM-3 showed a higher expression than the two other proliferative markers (P = 0.006), but only Ki-67 showed a positive correlation with the mitotic index (P > 0.05, r = 0.89). Although beta-catenin, MCM-3 and MCM-7 showed a positive reaction in the haemangiosarcomas examined, their usefulness as diagnostic and prognostic factors should be a topic of further research.