Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry.

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E-specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600-specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.

Retrospective evaluation of toceranib phosphate (Palladia) in the treatment of canine carcinomatosis and mesothelioma.

Canine carcinomatosis (CC) and mesothelioma (CM) are rare but aggressive neoplasms that historically have been associated with poor prognoses. There is limited information regarding treatment for CC and CM. The purpose of this retrospective study was to evaluate the efficacy and tolerability of toceranib phosphate (Palladia) in dogs with CC and CM. Cases were solicited from the American College of Veterinary Internal Medicine (ACVIM) Oncology listserv and retrospectively reviewed. For eligibility, a cytologic and/or histopathologic diagnosis of CC or CM was required. A total of 23 cases were included (CC = 14, CM = 8, both = 1). Eighty-two percent (19/23) of dogs presented with effusion. The best overall response rate (BORR) was 30.4% (13% complete response [CR], 17.3% partial response [PR]). Stable disease (SD) was appreciated in 14 dogs (60.8%) including the four dogs without effusion. The most common toceranib-related adverse events were either Grade 1 and 2 diarrhea or hyporexia. The median progression-free survival (PFS) was 171 days (range, 7-519 days) and overall median survival time (MST) was 301 days (range, 49-875 days) for all dogs. When evaluating dogs solely with effusion, the median PFS and overall MST were 171 days (range, 7-519 days) and 285 days (range, 49-875 days), respectively. This report demonstrates that toceranib is both well tolerated and a potential treatment for CC and CM. A randomised, controlled, prospective study would be needed to objectively assess the survival benefit of toceranib in the management of CC and CM, with and without effusion.

Diagnostic benefits of platelet-to-lymphocyte, neutrophil-to-lymphocyte, and albumin-to-globulin ratios in dogs with nasal cavity diseases.

BACKGROUND: A multimodal approach for diagnostic tests under anesthesia is required to diagnose nasal cavity pathology (NP) reliably in dogs. Blood test results may provide clues to the suspected NP. METHODS: This prospective blinded study assessed 72 dogs with chronic nasal discharge due to NPs, and 10 healthy dogs as the control group (CG). NPs were diagnosed using whole-body computed tomography (CT), upper airway endoscopy, examination of nasal mucosal swabs by bacterial and fungal culture, and histopathological examination of nasal mucosa biopsies. The exclusion criteria were the presence of any additional diseases or corticosteroid pre-treatment. In consideration of these exclusion criteria, 55 dogs entered the study. Dogs were classified into benign (benign tumors, idiopathic rhinitis (IR), and others) and malignant (carcinomas and sarcomas) NP groups. Blood count and blood chemistry tests were performed. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-to-globulin ratio (AGR) were calculated and compared. RESULTS: 25 dogs with malignant NP (13 and 12 with carcinomas and sarcomas, respectively) and 30 dogs with benign NP (seven with benign tumors,13 with IR, and 10 others) were included. In general, in dogs with NP there were only slight abnormalities in complete blood count. However, PLR was significantly higher in dogs with malignant NP (carcinoma and sarcoma) than in those with benign NP and in the CG. Compared with the CG, the NLR was significantly increased in all dogs with NP, and the AGR was mild but significantly lower, except in dogs with sarcomas and benign tumors. CONCLUSIONS: In dogs with nasal disease alone, there are usually no marked abnormalities in blood count. However, while mildly increased NLR and decreased AGR can be observed in almost all NPs, an increased PLR may indicate a malignant NP and can be used as an additional screening tool in dogs with nasal discharge due to nasal cavity pathology.

A pilot study investigating plasma pharmacokinetics and tolerance of oral capecitabine in carcinoma-bearing dogs.

BACKGROUND: Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. RESULTS: Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m[Formula: see text] by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC[Formula: see text] was 890 h[Formula: see text]ng/ml (range 750-1100 h[Formula: see text]ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. CONCLUSIONS: Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.

Homoharringtonine induces apoptosis of mammary carcinoma cells by inhibiting the AKT/mTOR signaling pathway.

Mammary tumour is the most common type of tumour in dogs, especially in unneutered female dogs. Homoharringtonine (HHT) is a natural alkaloid that can be used to treat various types of human tumour. However, the inhibitory effect and mechanism of HHT on canine mammary carcinomas (CMC) remain unclear. This study aimed to evaluate the inhibitory effect of HHT on CMC in vitro and determine its underlying molecular mechanism. The effects of HHT on the cytotoxicity of CMC U27 cells were evaluated by the cell counting kit-8, wound healing, and Transwell assays. HHT-induced apoptosis of U27 cells was detected by JC-1 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Moreover, the gene expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were analysed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the protein expression of protein kinase B/mammalian target of rapamycin (AKT/mTOR) and mitochondrial apoptosis proteins were determined by western blotting. Furthermore, mammary tumour-bearing mouse models were established using 4T1 cells to evaluate the therapeutic effect of HHT. It was found that HHT could significantly down-regulated the protein expression of p-AKT, p-mTOR, and Bcl-2, and up-regulated the protein expression of P53, Bax, cleaved caspase-3, and cleaved caspase-9. In addition, HHT significantly suppressed both tumour volume and mass in mammary tumour mice. In conclusion, HHT damages CMC cells by inhibiting the AKT/mTOR signalling pathway and inducing mitochondrial apoptosis. Such findings lay a theoretical foundation for the clinical treatment of CMC and provide more options for clinical medication.

Fluoroscopy-guided fine-needle aspiration of deep-seated pulmonary masses in dogs and cats appears safe and accurate.

OBJECTIVE: Deep-seated pulmonary lesions can be difficult to sample safely. The objective of this study was to determine the relative safety and accuracy of fluoroscopy-guided fine-needle aspiration of deep-seated pulmonary lesions regardless of their size and depth. ANIMALS: Client-owned animals; 5 dogs and 5 cats. CLINICAL PRESENTATION: Pulmonary lesion locations were determined on dorsoventral and lateral views using fluoroscopy. The lateral thoracic wall was aseptically scrubbed, and an indelible marker was used to mark the point of entry of the needle for sampling. The path of a 22-gauge needle attached to a syringe was followed using fluoroscopic guidance. Mass volume (Vma) and distance from skin and pleura to lesion (DSK-L and DPL-L) were recorded. RESULTS: In dogs, mean Vma was 137.2 cm3 (range, 6.3 to 426.2 cm3). Mean DSK-L was 71 mm (range, 37 to 101 mm) and DPL-L was 33 mm (range, 16 to 71 mm). Exfoliative cytology results were consistent with carcinoma in 4 dogs and lymphoma in 1 dog. A minor postprocedural complication was noted in 1 dog. In cats, the mean Vma was 2.4 cm3 (range, 1.6 to 3.7 cm3). Mean DSK-L was 42 mm (range, 20 to 75 mm) and DPL-L was 21 mm (range, 12 to 32 mm). Cytology results were consistent with pulmonary carcinoma in 2 cats, inflammation in 2 cats, and necrotic debris in 1 cat. CLINICAL RELEVANCE: Fluoroscopy-guided fine-needle aspiration of pulmonary masses is a safe and accurate technique to obtain cytologic samples irrespective of the size and depth of the lesions.

Expression patterns of aquaporins 1, 3, 5 in canine mammary gland carcinomas.

Aquaporins (AQPs) are water channel proteins, and the expression of AQPs in carcinoma cells has received much attention over the last 15 years. In the veterinary field, however, little is known about the expression of AQPs. In the present study using immunohistochemistry, we examined the expression of AQP1, AQP3, and AQP5 in canine mammary gland carcinomas. The 27 samples comprised 10 grade I, 12 grade II, and 5 grade III samples (See Materials and Methods section for grade classification method). AQP1 was expressed in only 2 of the grade III carcinomas, and the expression was limited to spindle-shaped cells in the solid structure and on the outside of the solid mass. AQP3-positive cells were observed in 20 of 22 grade I and II samples. On the other hand, among grade III carcinomas, AQP3 was expressed only in spindle-shaped cells in 1 sample. AQP5 was expressed in all grade I and II carcinomas but not in the grade III tumors. In addition, enhanced expression of basolateral AQP3 and apical AQP5 was observed in lobular hyperplastic cells. These results suggest that the expression patterns of AQP3 and AQP5 can be of help for judging the grading of canine mammary tumors and that AQP1 is likely to be involved in metastasis. Moreover, AQP3 and AQP5 might be relevant to lactation in female dogs.

Localized pleural mesothelioma in a dog.

Malignant mesotheliomas with localized growth are extremely rare in dogs. A 9-year-old male dog presented with a localized tumour that originated from the parietal pleura and had polypoid growth in the thoracic cavity. Histological examination revealed that the tumour consisted of tubular formations with scattered cysts and minimal papillary growth pattern. Neoplastic cells were immunopositive for mesothelial markers (calretinin and Wilms' tumour gene 1) and negative for carcinoma markers (thyroid transcription factor 1 and tumour protein 63). The animal was alive with no recurrence or metastasis/dissemination 11 months after surgery. To the best of our knowledge, this is the first report of a localized mesothelioma in a dog without metastasis/dissemination and highlights the value of mesothelial markers for an accurate diagnosis.

Usability of serum hedgehog signalling proteins as biomarkers in canine mammary carcinomas.

BACKGROUND: The hedgehog signalling pathway has been implicated in tumourigenesis and progression of many tumour types. This pathway has recently emerged as a therapeutic target, and inhibitors of hedgehog signalling have gained considerable attention. In dogs, the roles of hedgehog signals in several types of tumours have been investigated, but their relationship with canine mammary gland tumours (MGTs) has not been established. This study aimed to evaluate the expression of sonic hedgehog (SHH) and glioma-associated oncogene 1 (GLI-1) in the serum and mammary tumour tissues of dogs. RESULTS: SHH and GLI-1 protein expression levels were significantly higher in MGT tissues than in normal mammary gland tissues, as well as in malignant MGT specimens than in benign MGT specimens. Serum levels of SHH and GLI-1 were higher in MGT patients than in healthy controls (p < .001 and .001, respectively). Serum SHH level showed a statistically significant relationship with metastatic status (p = .01), and serum GLI-1 level showed a statistically significant relationship with histologic grade (p = 0.048) and metastatic status (p = 0.007). Serum hedgehog signalling protein levels were not significantly associated with breed size, sex, tumour size, or histologic type. CONCLUSIONS: Hedgehog signalling protein expression in canine MGT tissue and serum differed according to the histological classification (benign and malignant) and metastatic status, indicating a relationship between the hedgehog signalling pathway and canine MGT. Thus, the hedgehog signalling pathway may serve as a new biomarker and therapeutic target in canine MGT patients.

Platelet count and MCHC as independent prognostic markers for feline mammary carcinomas.

Mammary neoplasms are common in felines species and represent a significant disease for its unfavorable prognosis. Changes in the blood count and serum biochemical profile of these patients have potential as non-invasive prognostic markers prior to mastectomy, however, they are poorly described in literature. In this study univariate and multivariate analyses were performed using these factors to determine the effect of each parameter on the one-year survival time after the surgical procedure in these animals. The median overall survival (OS) and the disease-free survival (DFS) were 365 and 242 days, respectively. In univariate analysis, values within the reference range of monocyte, platelet and creatinine counts were identified as significant prognostic factors for OS and only creatinine was significant for DFS (P < 0.05). In the multivariate analysis, platelets and mean corpuscular hemoglobin concentration (MCHC) remained independent prognostic factors for OS. The results presented suggest that monocytes, platelets and creatinine may be important non-invasive pre-surgical prognostic markers, and that platelet count and MCHC are independent prognostic markers for feline mammary carcinomas (FMC). The correlation between such alterations is of important relevance for veterinary oncology, and prospective studies are needed to validate their clinical use and that platelet count and MCHC are independent prognostic markers for FMC. The results found in this study can also be studied in human medicine, regarding blood markers in human breast cancer (HBC).

Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium.

A 9-y-old male Boxer dog developed a mandibular skin tumor, which histologically had a locally invasive growth pattern composed of bilayered structures of inner eosinophilic cuboidal tumor cells and outer clear polygonal tumor cells with cytoplasm containing glycogen granules. Both cell populations gradually changed from low-grade morphologic features to highly anaplastic ones. Immunohistochemically, the eosinophilic tumor cells were positive for cytokeratin 8, a useful marker for luminal epithelial cells. In contrast, the clear tumor cells expressed several myoepithelial markers, including α-smooth muscle actin, p63, and cytokeratin 14. Based on these histologic and immunohistochemical characteristics, we diagnosed this apocrine sweat gland tumor as a carcinoma-and-malignant myoepithelioma with high-grade transformation of both luminal and myoepithelial cells. Our case may be a helpful reference for the histogenesis of carcinoma-and-malignant myoepithelioma, in which both the luminal epithelial and myoepithelial components are malignant.

Abdominal hernia as a rare manifestation of feline mammary gland carcinoma: a case report.

A 15-year-old, spayed female, Scottish Straight cat without any traumatic history was presented with swollen abdomen and diagnosed as an abdominal wall hernia. Abdominal ultrasound revealed thickened, irregular, and hypoechoic change of abdominal wall muscle adjacent to defect. During the herniorrhaphy, multiple nodules were identified in the subcutaneous tissue around the defect. Histological examination of the nodular tissue was performed, and it was confirmed as mammary gland tumor. After the surgery, metastatic changes of the pancreas were identified, and pleural effusion and ascites were also confirmed. The patient deteriorated rapidly and died 78 days after the surgery. This is the first case presenting abdominal wall hernia induced by malignant tumor in veterinary medicine.

Biphasic pleural mesothelioma in a goat.

An 8-year-old Saanen goat doe was seen for inappetence, tachycardia, and intermittent bluish-grey discoloration of the oral mucous membranes. On physical examination, the goat was mildly tachypneic and tachycardic, with reduced sounds auscultated on the left side of the thorax. Euthanasia was elected. Necropsy revealed an infiltrative, multinodular mass within the left thoracic cavity and innumerable small, tan nodules disseminated across the pleura of the lungs, thoracic walls, and diaphragm. Upon histologic examination, the mass was composed of highly pleomorphic, fusiform to polygonal cells. Neoplastic cells exhibited positive immunoreactivity for both cytokeratin and vimentin, consistent with a diagnosis of biphasic pleural mesothelioma. Key clinical message: Mesothelioma has rarely been described in the goat but should be considered as a differential diagnosis for thoracic masses in small ruminants, along with thymoma; metastatic neoplasia; carcinomatosis; and granulomatous lesions caused by parasites, bacteria, and fungi.

Mésothéliome pleural biphasique chez une chèvre. Une chèvre Saanen âgée de 8 ans a été vue pour de l'inappétence, une tachycardie et une décoloration gris bleuâtre intermittente des muqueuses buccales. À l'examen physique, la chèvre était légèrement tachypnéique et tachycardique, avec des sons réduits auscultés du côté gauche du thorax. Il a été décidé d'euthanasier l'animal. L'autopsie a révélé une masse multinodulaire infiltrante dans la cavité thoracique gauche et d'innombrables petits nodules brun clair disséminés à travers la plèvre pulmonaire, les parois thoraciques et le diaphragme. À l'examen histologique, la masse était composée de cellules hautement pléomorphes, fusiformes à polygonales. Les cellules néoplasiques ont présenté une immunoréactivité positive pour la cytokératine et la vimentine, compatible avec un diagnostic de mésothéliome pleural biphasique.Message clinique clé:Le mésothéliome a rarement été décrit chez la chèvre mais doit être considéré comme un diagnostic différentiel des masses thoraciques chez les petits ruminants, avec le thymome, la néoplasie métastatique, la carcinomatose et les lésions granulomateuses causées par des parasites, des bactéries et des champignons.(Traduit par Dr Serge Messier).

Metastatic carcinoma of unknown origin in a dog.

Although cancer of unknown primary origin (CUP) is well-described in the human literature, it is not as well-understood within veterinary medicine. This case report represents one of few focused on describing CUP in a dog. Key clinical message: Metastatic CUP should be considered as a differential diagnosis despite being a rare disease entity that is infrequently reported within the veterinary literature.

Carcinome métastatique d'origine inconnue chez un chien. Bien que le cancer d'origine primaire inconnue (CUP) soit bien décrit dans la littérature humaine, il n'est pas aussi bien compris en médecine vétérinaire. Ce rapport de cas représente l'un des rares à s'intéresser à la description du CUP chez un chien.Message clinique clé:Le CUP métastatique doit être considéré comme un diagnostic différentiel bien qu'il s'agisse d'une entité de maladie rare rarement rapportée dans la littérature vétérinaire.(Traduit par Dr Serge Messier).

Upregulation of miR-21 and pro-inflammatory cytokine genes IL-6 and TNF-α in promoting a pro-tumorigenic microenvironment in canine mammary carcinomas.

This study evaluated the gene expression of the pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in canine mammary tumors (CMTs), and correlated them with gene expression of miRNAs expected to regulate the secretion of pro-inflammatory cytokines within the tumor microenvironment (TME). Furthermore, gene expression of cytokines and miRNAs involved in tumor cell proliferation and invasion (i.e. miR-21; miR-124; miR-145) were correlated with tumor proliferation index (Ki67 index) to determine the prognostic value in CMTs. Twenty-six canine mammary samples were used, including 22 CMTs and 4 control samples. MiR-21, IL-6 and TNF-α were upregulated in mammary carcinomas compared with controls (p < 0.05). MiR-146b was downregulated in CMTs compared with control cases (p < 0.05). IL-6 expression showed a significant positive correlation with miR-21 and a negative correlation with miR-146b; while, TNF-α gene expression was positively correlated with miR-21 and miR-145 in mammary carcinomas. In carcinomas, the Ki67 index correlated positively with gene expression of IL-6 and miR-21 and negatively correlated with miR-145 and miR-146b. Specifically, gene expression of IL-6 and miR-21 was positively correlated with ki67 index >33.3%, whereas, expression of miR-145 and miR-146b was negatively correlated with ki67 index <33.3%. Results reinforce the concept of interaction between tumor cells and inflammatory cells within the TME, with a central role of IL-6 and TNF-α. Since the upregulation of miR-21 reflects the gene overexpression of interleukins and the high proliferation index of tumor cells, this miRNA may be considered a biomarker with prognostic value in CMTs.

Plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases.

The aim of this study was to evaluate the plasma levels of chemokines CCL2 and CXCL12 in female dogs with malignant mammary gland tumours without and with metastases. The concentrations of CCL2 and CXCL12 were determined in 25 female dogs with malignant mammary gland tumours (15 without metastases and 10 with metastases) and 10 healthy control animals using a specific canine ELISA assay. The mean plasma concentrations of CCL2 and CXCL12 were significantly higher (p<0.05) in the metastatic group compared to the control group. Moreover, the concentrations of these chemokines were markedly higher in the dogs with metastases than in those without metastases; however, a statistically significant difference was not found. The concentrations of both tested chemokines were numerically increased in the dogs with grade 2 and grade 3 carcinomas compared to the dogs with grade 1 carcinomas but the differences did not reach statistical significance. In conclusion, the results of our study demonstrate that plasma concentrations of chemokines CCL2 and CXCL12 are significantly increased in the dogs with metastatic malignant mammary gland tumours compared to the healthy dogs and show an upward trend compared to those without metastases. However, clarifying whether the increase of these chemokines is a cause or an effect of metastasis in female dogs with malignant mammary gland tumours as well as their potential role in metastatic process requires further research.

Topoisomerase IIα immunoexpression in feline mammary carcinomas: A correlation with Ki67 immunoexpression and the mitotic count.

The aim of the study was to compare the immunohistochemical expression of topoisomerase IIα protein (Topo IIα) with Ki67 expression and mitotic count in feline mammary carcinomas (FMCs). Topo IIα is considered as a proliferation indicator as well as a molecular target of anthracycline chemotherapy. The studied material included 70 FMCs from female cats treated with mastectomy. Primary mouse monoclonal antibodies directed against Topo IIα and Ki67 were used in immunohistochemical reactions. The number of mitotic figures was counted at 400× magnification in a field of 2.37 mm2. Immunohistochemical reaction for Topo IIα occurred in cell nuclei. The Topo IIα index ranged from 6.12% to 54.60% and was positively correlated with the values of the Ki67 index (r = 0.7193) and the mitotic count (r = 0. 2858). This indicates the potential possibility of use of the immunohistochemical expression of Topo IIα to assess the rate of proliferation in FMCs. The wide range of expression of Topo IIα in individual tumorus found in the conducted studies allows us to hypothesize that its assessment could be used as a predictive marker in chemotherapy of FMCs with the use of anthracyclines. However, this requires confirmation in clinical trials.

Characterization of alkaline phosphatase cytochemistry in canine neoplastic and non-neoplastic pulmonary mass aspirates.

BACKGROUND: Distinguishing primary and secondary pulmonary neoplasms can be challenging via cytology, and a rapid, inexpensive diagnostic tool to differentiate these neoplasms is unavailable. Alkaline phosphatase cytochemistry (ALP-CC) has been used to identify primary pulmonary carcinomas in human patients, and we hypothesized it could be applied to canine lung aspirates. OBJECTIVE: We aimed to characterize ALP-CC expression in fine-needle aspirate (FNA) samples of canine pulmonary neoplastic and non-neoplastic tumors. METHODS: A retrospective case search was conducted to identify cases with contemporaneous cytology and histopathology reports from pulmonary lesions, including neoplastic and non-neoplastic etiologies. Slides prepared from pulmonary aspirates were stained for ALP-CC activity, and the percentage of ALP-CC-positive primary pulmonary epithelial tumors was determined. To characterize the ALP-CC expression in non-neoplastic cellular constituents of pulmonary FNA samples, mesothelial cells were also evaluated. RESULTS: Forty-eight canine cases met the inclusion criteria. ALP-CC-positive cells were seen in both neoplastic and non-neoplastic lesions. In non-neoplastic lesions, pulmonary epithelial cells were ALP-CC positive. Eighty-nine percent of primary pulmonary epithelial neoplasms were ALP-CC positive, and no ALP-CC positivity was noted in mesothelial cells. ALP-CC-positive neoplastic cells were seen in a metastatic amelanotic melanoma. CONCLUSIONS: Primary pulmonary epithelial neoplasms are frequently ALP-CC positive, but such positivity is not restricted to this tumor type. Non-neoplastic pulmonary epithelial cells can be ALP-CC positive, whereas mesothelial cells are negative.

Retrospective study evaluating the efficacy of stereotactic body radiation therapy for the treatment of confirmed or suspected primary pulmonary carcinomas in dogs.

Canine primary pulmonary carcinomas (PCCs) are commonly treated with surgery with overall median survival times (MST) around a year; however, due to extent of disease, prognosis, or client preference, alternative treatments have been considered. Stereotactic body radiation therapy (SBRT) has been utilized in human cancer patients for local control of lung tumours as a surgical alternative. Twenty-one PCCs in 19 dogs that received SBRT for local control were retrospectively evaluated. Dogs were staged according to the canine lung carcinoma stage classification (CLCSC) system with three as Stage 1, five as Stage 2, three as Stage 3, and eight as Stage 4. Overall MST was 343 days with 38% of patients alive at 1 year. Stage did not significantly impact survival time (p = .72). Five (26%) dogs had lymphadenopathy and MST was not significantly different from dogs without lymphadenopathy (343 vs. 353 days; p = .54). Five out of 18 evaluable dogs (28%) experienced acute lung VRTOG effects and 2 of 12 dogs (17%) experienced late lung VRTOG effects. Median lung dose, V5, V20, and D30 to the lung did not correlate significantly with the development of adverse radiation events. Twelve dogs had follow-up imaging and the best response included a complete response (17%), partial response (42%), and stable disease (42%). Progressive disease was noted in seven dogs a median of 229 days after SBRT. SBRT was documented to be a safe and effective alternative to surgery and may have survival advantages for Stage 3 or 4 dogs according to the CLCSC.

Stereotactic radiotherapy outcomes for intraventricular brain tumours in 11 dogs.

Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011-2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)-diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33-1593 days). The survival time for two pathology-diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short-lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation-specific complications are possible due to the small dataset and limited follow-up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long-term survivors are noted.