Prognostic factors and outcome in cats with thymic epithelial tumours: 64 cases (1999-2021).

OBJECTIVES: To describe the clinical presentation, treatment and outcomes of cats diagnosed with thymic epithelial tumours and to determine prognostic factors for survival and recurrence. MATERIALS AND METHODS: Clinical records of cats diagnosed with a thymic epithelial tumour between 1999 and 2021 at three referral institutions were retrospectively reviewed. RESULTS: Sixty-four cats were included. Paraneoplastic syndromes were present in nine cats and metastatic disease was seen in two cats, one at diagnosis and one at the time of recurrence. Median tumour diameter was 6 cm (range, 2 to 15) and a cystic appearance was described on imaging in 25 cats. Surgical excision was attempted in 54 cats with a perioperative mortality rate of 11%. Median survival time for cats surviving to hospital discharge was 897 days (range, 21 to 3322). The 1-, 2- and 5-year survival rates for surgically treated thymic epithelial tumour were 86%, 70% and 66%, respectively. Survival was longer for cats with Masaoka-Koga stage I and II tumours compared to stages III and IV (1366 days versus 454 days; P=0.002). Masaoka-Koga stage was the only significant prognostic factor detected on multi-variable analysis, with stage III and IV tumours associated with increased risk of death (hazard ratio: 5.67, 95% confidence interval: 1.29 to 24.91, P=.021). Tumour recurrence occurred in 11 cats at a median of 564 days (range, 93 to 1095); no significant prognostic factors for recurrence were identified. CLINICAL SIGNIFICANCE: Cats with thymic epithelial tumours had a good long-term prognosis following surgery. Tumour recurrence can occur late in the disease course and ongoing monitoring should therefore be considered. Masaoka-Koga stage may influence survival time and could be used to predict outcome.

Extracardiac adult-type rhabdomyoma-Report of two cases in dogs.

This report describes the cytologic, histopathologic, and immunohistochemical features of adult-type rhabdomyoma located within the subcutaneous tissue in a 14-year-old female Border Collie (thigh) and a 13-year-old male Mongrel (flank). In both cases, fine-needle aspiration biopsy revealed cluster-forming, epithelial-like polygonal cells with abundant foamy cytoplasm, and moderate to marked anisocytosis and anisokaryosis; therefore, an epithelial tumor was suspected. After surgical excision, tumors underwent histopathologic examination with additional immunohistochemistry. Both tumors were well-demarcated and located within the subcutaneous tissue in the vicinity of the cutaneous muscle. The tumor mass consisted of densely packed round or polygonal cells with distinct vacuolation of the cytoplasm. Tumor cells expressed vimentin, desmin, and NSE and were cytokeratin and α-SMA negative. Based on histologic features and immunophenotyping, adult-type rhabdomyoma was diagnosed in both cases. This study highlights that the cytologic features of rhabdomyoma can be misleading and may suggest an epithelial tumor.

Thymic epithelial tumours in 51 dogs: Histopathologic and clinicopathologic findings.

Canine thymic epithelial tumours (TET) are uncommon and little is known about their behaviour. Previous attempts at histologic classification have varied, and as such reliable prognostic information is unavailable. The aim of this retrospective multi-institutional study was to evaluate cases of canine TETs, irrespective of subtype, in order to identify useful histopathologic and clinicopathologic prognostic factors. Cases were included if the tumour arose from the cranial mediastinum and a diagnosis of TET was made on the basis of histopathology. Fifty-one dogs were included. In addition to clinicopathologic data, histology samples were reviewed for the following features: mitotic count, percentage of necrosis, presence of Hassall's corpuscles, lymphocytic infiltrate, cellular pleomorphism and vascular or capsular invasion. The median survival time for all dogs was 449 days. The 1- and 2-year survival rate was 52.6% and 26.3% respectively. On multivariable analysis surgical excision of the thymic tumour was associated with significantly prolonged survival; the presence of metastasis, myasthenia gravis and moderate or marked cellular pleomorphism were associated with significantly reduced survival. Additional studies are needed to further evaluate prognostic factors to aid treatment recommendations.

Immunocytochemical evaluation of epithelial-mesenchymal transition in epithelial tumors of dogs and cats.

Epithelial-mesenchymal transition (EMT) plays a crucial role in metastasis of epithelial tumors; however, it is challenging to detect EMT by cytology. In the present study, EMT was visualized by fluorescence-immunocytochemistry (FICC). Air-dried smears from epithelial tumors of dogs (n=22) and cats (n=9) were stained using mouse monoclonal anti-E-cadherin and rabbit monoclonal anti-vimentin antibodies. Enzymatic immunohistochemistry (IHC) revealed that 51.6% (8/22 in dogs, 8/9 in cats) of the cases showed EMT. In dogs, FICC could detect EMT in 62.5% (5/8) of those cases. In cats, FICC could detect EMT in 100% (8/8) of the cases. In conclusion, the present FICC method could successfully detect EMT using conventional air-dried cytology smear slides.

Definitive-intent radiotherapy for sinonasal carcinoma in cats: A multicenter retrospective assessment.

Treatment of epithelial sinonasal tumours in cats is not commonly reported. In the newer reports, palliative radiation protocols have been described more often than definitive-intent protocols. In this multi-institutional retrospective study, we included 27 cats treated with single-modality radiotherapy. Cats were irradiated using 10 daily fractions of 4.2 Gy. Three cats (11.1%) experienced a complete clinical response and 17 (63%) had a partial clinical response. Stable clinical disease was noted in three cats (11.1%). Four cats (14.8%) showed progression within 3 months following treatment. The median time to progression for all cases was 269 days (95 % confidence intervals [CI]: 225; 314). The proportion of cats free of progression at 1 and 2 years was 24% (95% CI: 22%; 26%) and 5% (95% CI: 5%; 6%), respectively. None of the prognostic factors evaluated were predictive of outcome (anaemia, tumour volume at the time of staging, modified Adams stage, intracranial involvement, facial deformity, epistaxis, inappetence or weight loss). Median overall survival (OS) for all deaths was 452 days (95% CI: 334; 571). The proportion of cats alive at 1 and 2 years was 57% (95% CI: 37%; 77%) and 27% (95% CI: 25%; 29%), respectively. Surprisingly, cats with epistaxis had a longer median OS of 828 days (95% CI: 356; 1301) compared to 296 days (95% CI: 85; 508) in cats without epistaxis, (P = .04, Breslow). Radiation therapy used as a single modality for the treatment of feline sinonasal carcinoma improved clinical signs and was well tolerated but progression within a year was common.

Mediastinal lymphoma in dogs is homogeneous compared to thymic epithelial neoplasia and is more likely to envelop the cranial vena cava in CT images.

In order to identify CT signs that could be used to distinguish cranial mediastinal lymphoma and thymic epithelial neoplasia, a retrospective case-control study was done. Associations between CT signs and diagnosis were tested using binary logistic regression and results expressed as odds ratio and 95% confidence interval. Sixty-two dogs that had thoracic CT and confirmed diagnosis of lymphoma (n = 33) or thymic neoplasia (n = 29) were sampled. Thymic neoplasms included 24 thymomas and five thymic carcinomas. Dogs with thymic epithelial neoplasia were significantly older than dogs with lymphoma (median age 8.6 years versus 6.0 years, P = .007), but there were no significant differences in prevalence of clinical signs. Diagnosis of thymic epithelial neoplasia was associated with heterogeneous attenuation in pre- (odds ratio 23.3, 95% confidence interval, 4.5-121.1) and post-contrast (odds ratio 30.7, 95% confidence interval, 3.6-265.0) images. Conversely, envelopment of the cranial vena cava by the mass was less likely with thymic epithelial neoplasia than lymphoma (odds ratio 0.07, 95% confidence interval, 0.007-0.66). Greater standard deviation of Hounsfield unit values in post-contrast images was associated with thymic epithelial neoplasia (P = .005). Based on ROC analysis, SD > 17HU of the mass in post-contrast images had a sensitivity of 72% and specificity of 79% for thymic epithelial neoplasia. There were no significant differences in morphology, prevalence of calcification, mediastinal lymphadenopathy, cranial vena cava invasion, collateral vessels, or pleural fluid associated with these tumors. Thymic epithelial neoplasms tended to occur in older dogs and were heterogeneous in CT images, whereas mediastinal lymphoma was more homogeneous and more likely to envelop the cranial vena cava.

Diagnosis and Treatment of an Odontogenic Epithelial Tumor in a Dog With Features of Squamous Odontogenic Tumor.

A 9-year-old standard poodle presented for a comprehensive oral health assessment and treatment, at which time a left rostral mandibular swelling was recognized. The mass was biopsied and eventually excised by a left rostral mandibulectomy en bloc resection. Histopathology supported the diagnosis of a benign, intraosseous, epithelial tumor that was otherwise unclassified. The clinical, radiological, and histological features of this case are similar to those reported for squamous odontogenic tumor (SOT) in humans. This case study relays the diagnosis, treatment, and follow-up of the first SOT-like tumor in a dog.

Histologic and immunohistochemical characterization of thymic epithelial tumours in the dog.

Thymic epithelial tumour (TET) histologic subclassification has not been well described in the veterinary literature as it has in humans. The objective of this study was to identify and describe TET subtypes in dogs and to determine the utility of immunohistochemistry (IHC) in differentiating these subtypes. Samples were reviewed and classified according to a modified World Health Organization (WHO) criteria for human tumours of thymic origin. Signallment, presenting signs, treatment and survival data was collected from medical records. Histologic review confirmed the same subtypes as described in humans. Presence of high stage disease, pleomorphism, mitotic figures and capsular invasion was more common in atypical thymomas and thymic carcinomas than in thymomas. IHC was performed for GLUT-1, CD5, CD117 and CK8/18; however, this was not useful in classifying the tumours.

Thymic Carcinoma with Cartilage Formation in a Dog.

An 11-year-old female Chihuahua exhibited respiratory distress and a computed tomography scan showed a large mass in the anterior thoracic cavity. During surgery, it was found that the mass was strongly adherent to surrounding tissue. A histopathological examination of a biopsy sample from the mass revealed proliferation of atypical epithelial cells and cartilage formation admixed with mature lymphocytes. Immunohistochemically, the tumour cells, as well as the normal canine thymic epithelial cells, were positive for pan-cytokeratin (CK), CK5/6, CK19, p63 and bone morphogenetic protein (BMP) 6. Foci of cartilage tissue were formed in association with the neoplastic epithelial tissue. In the normal canine thymus, the subcapsular epithelial cells are positive for both CK19 and BMP6. These findings indicate that the cartilage element within the tumour developed from CK19-positive neoplastic epithelial cells, which were derived from the thymic subcapsular epithelium. This case represents a novel variant of canine thymic epithelial tumour that exhibits cartilage differentiation.

Salivary Gland Epithelial-Myoepithelial Carcinoma with High-Grade Transformation in a Dog.

An 8-year-old male neutered standard dachshund was presented with a slowly growing mass in the left submandibular salivary gland. Histopathological examination revealed a tumour that was composed of bilayered duct-like structures with an inner layer of ductal cells and an outer layer of clear cells. Both inner and outer cells in the greater part of the tumour exhibited low to moderate atypia and low mitotic activity. However, a focal area towards the periphery showed enhanced cellular atypia and mitotic activity in tumour cells. Immunohistochemically, the outer layer of clear cells expressed myoepithelial markers, while the inner layer cells were positive for a luminal epithelial marker. No local recurrence or lymph node or distant metastasis was observed 18 months following surgery. Based on the morphology and immunohistochemical findings, a final diagnosis of epithelial-myoepithelial carcinoma with high-grade transformation was made.

On the apparent rarity of epithelial cancers in captive chimpanzees.

Malignant neoplasms arising from epithelial cells are called carcinomas. Such cancers are diagnosed in about one in three humans in 'developed' countries, with the most common sites affected being lung, breast, prostate, colon, ovary and pancreas. By contrast, carcinomas are said to be rare in captive chimpanzees, which share more than 99% protein sequence homology with humans (and possibly in other related 'great apes'-bonobos, gorillas and orangutans). Simple ascertainment bias is an unlikely explanation, as these nonhuman hominids are recipients of excellent veterinary care in research facilities and zoos, and are typically subjected to necropsies when they die. In keeping with this notion, benign tumours and cancers that are less common in humans are well documented in this population. In this brief overview, we discuss other possible explanations for the reported rarity of carcinomas in our closest evolutionary cousins, including inadequacy of numbers surveyed, differences in life expectancy, diet, genetic susceptibility, immune responses or their microbiomes, and other potential environmental factors. We conclude that while relative carcinoma risk is a likely difference between humans and chimpanzees (and possibly other 'great apes'), a more systematic survey of available data is required for validation of this claim.

Perioperative Mortality and Long-Term Survival in 80 Dogs and 32 Cats Undergoing Excision of Thymic Epithelial Tumors.

OBJECTIVE: To examine perioperative mortality, long-term survival, causes of death, and prognostic factors for dogs and cats undergoing surgical excision of thymic epithelial tumors (TETs). STUDY DESIGN: Multi-institutional case series. ANIMALS: Eighty dogs and 32 cats. METHODS: Follow-up information was obtained for dogs and cats that underwent surgical excision of a TET between 2001 and 2012. RESULTS: Perioperative mortality was 20% in dogs and 22% in cats. No independent risk factors for perioperative mortality were identified. The estimated median survival time for all dogs was 1.69 years (95% CI 0.56-4.32) and the 1- and 4-year survival rates were 55% (95% CI 44-67) and 44% (95% CI 32-56). The estimated median survival time for all cats was 3.71 years (95% CI 0.56-unestimatable) and the 1- and 4-year survival rates were 70% (95% CI 53-87) and 47% (95% CI 0-100). Of animals that survived to discharge, 42% of dogs and 20% of cats eventually died of TET-related causes. The presence of paraneoplastic syndromes (hazard ratio [HR] 5.78, 95% CI 1.64-20.45, P = .007) or incomplete histologic margins (HR 6.09, 95% CI 1.50-24.72, P = .01) were independently associated with decreased survival in dogs. No significant predictors of survival were identified in cats. Conclusions regarding the effect of chemotherapy or radiation therapy could not be made. CONCLUSIONS: While there is substantial risk of perioperative death in dogs and cats undergoing surgery for TETs, many animals that survive to discharge have prolonged survival. Survival is significantly decreased in dogs with paraneoplastic syndromes or incomplete histologic margins.

Uncovering molecular events associated with the chemosuppressive effects of flaxseed: a microarray analysis of the laying hen model of ovarian cancer.

BACKGROUND: The laying hen model of spontaneous epithelial ovarian cancer (EOC) is unique in that it is the only model that enables observations of early events in disease progression and is therefore also uniquely suited for chemoprevention trials. Previous studies on the effect of dietary flaxseed in laying hens have revealed the potential for both amelioration and prevention of ovarian cancer. The objective of this study was to assess the effect of flaxseed on genes and pathways that are dysregulated in tumors. We have used a bioinformatics approach to identify these genes, followed by qPCR validation, immunohistochemical localization, and in situ hybridization to visualize expression in normal ovaries and tumors from animals fed a control diet or a diet containing 10% flaxseed. RESULTS: Bioinformatic analysis of ovarian tumors in hens led to the identification of a group of highly up-regulated genes that are involved in the embryonic process of branching morphogenesis. Expression of these genes coincides with expression of E-cadherin in the tumor epithelium. Levels of expression of these genes in tumors from flax-fed animals are reduced 40-60%. E-cadherin and miR200 are both up-regulated in tumors from control-fed hens, whereas their expression is decreased 60-75% in tumors from flax-fed hens. This does not appear to be due to an increase in ZEB1 as mRNA levels are increased five-fold in tumors, with no significant difference between control-fed and flax-fed hens. CONCLUSIONS: We suggest that nutritional intervention with flaxseed targets the pathways regulating branching morphogenesis and thereby alters the progression of ovarian cancer.

Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here the most comprehensive survey of the chicken blood proteome to date.

Neoplasms of the urinary tract in fish.

The veterinary literature contains scattered reports of primary tumors of the urinary tract of fish, dating back to 1906. Many of the more recent reports have been described in association with the Registry of Tumors in Lower Animals, and most of the spontaneous neoplasms of the kidney and urinary bladder are single case reports. In rare instances, such as described in nephroblastomas of Japanese eels and tubular adenomas/adenocarcinomas of Oscars, there is suggestion of a genetic predisposition of certain populations to specific renal neoplasms, environmental carcinogenesis, or potentially an unknown infectious etiology acting as a promoter. Hematopoeitic neoplasms have been infrequently described as primary to the kidney of a variety of fish species, and therefore those case reports of renal lymphoma and plasmacytic leukemia are addressed within the context of this review.

The hen as a model of ovarian cancer.

The domestic laying hen is the only non-human animal that spontaneously develops ovarian cancer with a high prevalence. Hens ovulate prolifically, and this has made the hen intuitively appealing as a model of this disease in light of epidemiological evidence that ovulation rate is highly correlated with the risk of human ovarian cancer. As in women, ovarian cancer in the hen is age-related and it is also grossly and histologically similar to that in humans. In both women and hens, the cancer metastasizes to similar tissues with an accumulation of ascites fluid. Some aggressive ovarian cancers in women arise from cells in the oviduct; this is intriguing because ovarian cancers in the hen express an oviductal protein that is normally absent in the ovary.

Canine ovarian tumors: an immunohistochemical study with HBME-1 antibody.

The morphology of ovarian tumors is characterized by a variety of histological features causing diagnostic difficulties. In human medicine, HBME-1 (Hector Battifora mesothelial epitope)-1 is one of the immunohistochemical markers employed in the diagnosis of ovarian epithelial tumors. The aim of the current study was to investigate the reliability of the marker HBME-1 in canine ovaries, granulosa cell tumors, and epithelial ovarian neoplasms to determine whether this marker could be included in an immunohistochemical panel for differential diagnoses of canine ovarian tumors. Samples were obtained from 4 normal ovaries, 10 granulosa cell tumors, and 18 epithelial ovarian tumors. After formalin fixation and paraffin embedding, tissue sections were stained with hematoxylin and eosin and probed immunohistochemically for the HBME-1 marker. Granulosa cells and related tumors were consistently negative for HBME-1. Normal ovarian surface epithelium and 17 out of 18 ovarian epithelial tumors were positive for HBME-1. The results suggested that HBME-1 would be a useful marker for the differential diagnosis of ovarian tumors in the dog.

AE1/AE3, vimentin and p63 immunolocalization in canine mammary gland tumours: roles in differentiation between luminal epithelial and myoepithelial lineages.

Mammary tumors are by far the most common tumors in female dogs and effective treatment relies on prompt and accurate diagnostic procedures. Canine mammary tumors may originate from various cell types, such as luminal epithelial, myoepithelial and stromal cells. This study aimed to differentiate luminal epithelial and myoepithelial lineages, using specific markers including AE1/AE3, Vimentin, and p63. Such data can be useful for prognosis. Canine mammary tumors were collected by surgical resection and tissue samples were investigated using the avidin-biotin-immunoperoxidase method with used primary antibodies against AE1/AE3, vimentin, and p63. Luminal epithelial-origin tumors were found to be immunoreactive with AE1/AE3 and vimentin monoclonal antibody, while myoepithelial-origin tumors were positive for p63 and vimentin . In addition, canine mixed tumors showed reactivity with all three antibodies. In summary, AE1/AE3, p63 and vimentin can be used as specific immunohistochemical markers to distinguish lumino-epithelial and myoepithelial lineages of canine mammary tumors.

Calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle.

BACKGROUND: Calpain 3 (Capn3), also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). Recent experimental studies have hypothesized a pro-apoptotic role of Capn3 in some melanoma cell lines. So far the link between calpain3 and tumors comes from in vitro studies. The objective of this study was to describe Capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle. METHODS AND FINDINGS: Here we describe, for the first time in veterinary and comparative oncology, the activation of Capn3 in twelve urothelial tumor cells of the urinary bladder of cattle. Capn3 protein was initially identified with nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC-MS/MS) in a co-immunoprecipitation experiment on E2F3, known to be a transcription factor playing a crucial role in bladder carcinogenesis in humans. Capn3 expression was then confirmed by reverse transcription polymerase chain reaction (RT-PCR). Finally, the Ca(2+)-dependent proteolytic activity of Capn3 was assayed following ion exchange chromatography. Morphologically, Capn3 expression was documented by immunohistochemical methods. In fact numerous tumor cells showed an intracytoplasmic immunoreactivity, which was more rarely evident also at nuclear level. In urothelial tumors, bovine papillomavirus type 2 (BPV-2) DNA was amplified by PCR and the expression of E5 protein, the major oncogenic protein of BVP-2, was detected by western blotting, immunohistochemistry, and immunofluorescence. E2F3 overexpression and pRb protein downregulation were shown by western blotting. CONCLUSION: The role of capn3 protein in urothelial cancer of the urinary bladder remains to be elucidated: further studies would be required to determine the precise function of this protease in tumor development and progression. However, we suggest that activated Capn3 may be involved in molecular pathways leading to the overexpression of E2F3, which in turn could be responsible for urothelial tumor cell proliferation also in cattle, though other mechanisms are likely to exist. If further studies corroborate the important role of Capn3 in urothelial tumors of the urinary bladder, cattle with urinary tumors may prove useful as animal model for bladder carcinogenesis.

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence.

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty-six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.