Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Excision of a gastrointestinal stromal tumour in a dog using short-wave infrared fluorescence imaging and indocyanine green.

A 7-year-old castrated male Golden Retriever weighing 36.8 kg presented to the Veterinary Teaching Hospital with vomiting, anorexia and depression. After blood tests, radiographic, ultrasound and computed tomography examinations, a 7.85 × 5.90 × 8.75 cm mass was identified in the caecum. To visualise the tumour margin and improve the accuracy of tumour resection, intraoperative short-wave infrared imaging using indocyanine green was performed during surgery. An indocyanine green solution was injected intravenously as a bolus of 5 mg/kg 24 h before surgery. Tumour resection was performed with a 0.5 cm margin from the fluorescent-marked tissues. Histopathological examination revealed a diagnosis of a gastrointestinal stromal tumour (GIST) and the absence of neoplastic cells in the surgical margin, indicating a successful surgery. To our knowledge, this is the first case of a GIST resection in a dog using intraoperative short-wave infrared imaging.

Colonic gastrointestinal stromal tumor (GIST) presenting with colocolonic intussusception: A rare case report.

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing. Key clinical message: The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.

Tumeur stromale gastro-intestinale du côlon (GIST) présentant une invagination colocolique : un rapport de cas rare. Une femelle bouledogue anglais stérilisée de 8 ans a présenté des vomissements, une hyporexie et une diarrhée d'origine du gros intestin. L'échographie abdominale a révélé une masse colique focale avec une invagination située immédiatement oralement à la masse. L'intussusception englobait le côlon ascendant et transverse et était non réductible. La résection colique et l'anastomose ont été réalisées pour inclure l'intussusception et la masse colique. L'examen histopathologique de la masse a révélé un néoplasme à cellules fusiformes apparaissant dans la paroi musculaire du segment invaginé qui a oblitéré l'architecture normale. L'immunoréactivité cytoplasmique légère à modérée de la population de cellules tumorales pour le CD117 et l'actine des muscles lisses étaient compatibles avec un diagnostic de tumeur stromale gastro-intestinale. Le chien décrit ici est toujours vivant et exempt de maladie évolutive au moment de la rédaction.Message clinique clé :L'ensemble du tractus gastro-intestinal doit être évalué chez tout animal présentant des symptômes gastrointestinaux. Une tumeur stromale gastro-intestinale reste un diagnostic différentiel plausible, quel que soit le segment intestinal atteint, et l'intussusception associée à la tumeur est une constatation clinique rare mais urgente.(Traduit par Dr Serge Messier).

Probable paraneoplastic leukocytosis in a dog with a gastrointestinal stromal tumor.

A 9-year-old female spayed Boston Terrier presented for diagnostic investigation of lethargy, poor appetite, weight loss, and a marked leukocytosis. Significant muscle wasting and a palpable abdominal mass were present on physical examination. Abdominal imaging revealed the mass to be of small intestinal origin; consequently, an intestinal resection and anastomosis were performed without complication. The histopathologic diagnosis was a gastrointestinal stromal tumor, verified by immunohistochemical positivity to CD117 (KIT). Two weeks after discharge, the leukocytosis had resolved. Though the exact molecular mediator of the severe leukocytosis was undetermined, resolution following tumor removal suggests a paraneoplastic cause. To the authors' knowledge, this is the first reported case of probable paraneoplastic leukocytosis secondary to a gastrointestinal stromal tumor in the dog. Gastrointestinal tract imaging should be performed when this uncommon hematologic abnormality is present.

Canine gastrointestinal stromal tumours treated with surgery and imatinib mesylate: three cases (2018-2020).

OBJECTIVES: Gastrointestinal stromal tumours (GISTs) are described in dogs and are histologically diagnosed with the aid of immunohistochemistry to allow differentiation from leiomyomas/leiomyosarcomas. These tumours express c-kit and in some cases could harbour mutations in KIT coding gene. MATERIALS AND METHODS: Dogs with a diagnosis of GIST previously confirmed with histopathology and immunohistochemistry were considered for inclusion. Medical records were reviewed for clinical signs at presentation, results of diagnostic tests, tumour location and treatment. To be included, patients had to undergo staging procedures and treatment with imatinib alone or in combination with surgery. Immunohistochemistry and KIT mutational analysis were performed assessing all included cases. RESULTS: Three cases were included. All cases underwent staging procedures and surgical excision. Tumours were located in the stomach (two cases) or caecum (one case). KIT mutational status was assessed and the presence of a 54-base pair deletion in exon 11 was identified in one case. Following surgery, imatinib was used to treat recurrent, metastatic or residual disease and resulted in complete response and stable disease in the macroscopic setting and no evidence of recurrence in the microscopic setting. Follow-up time was 890, 120 and 352 days, respectively. CLINICAL SIGNIFICANCE: Surgical and medical treatment resulted in a positive outcome in these cases of canine GIST. Imatinib treatment was well tolerated and resulted in a measurable response and a low spectrum of toxicities. Further studies on the tolerability and efficacy of imatinib in solid tumours and GIST are warranted to define its effectiveness and safety.

CT features of gastrointestinal spindle cell, epithelial, and round cell tumors in 41 dogs.

There is sparse published information on computed tomographic (CT) characteristics of canine gastrointestinal tumors. The purposes of this multi-center, retrospective, descriptive study were to describe the CT features of histologically-confirmed canine gastrointestinal spindle cell, epithelial, and round cell tumors and, when available, describe the corresponding ultrasound findings. The inclusion criteria were as follows: availability of pre-and post-contrast CT study, and a histopathological diagnosis of the lesions. Recorded parameters were tumor size, location, gastrointestinal wall layers involvement, lesion's growth and enhancement patterns, tumor margination, presence of stenosis, mineralization, ulcerations, lymphadenopathy, or other lesions in the abdomen/thorax. When available, ultrasound images were evaluated. Forty-one dogs met the inclusion criteria and had the following histological diagnoses: 21/41 (51%) spindle cells (7 leiomyomas, 14 leiomyosarcomas/gastrointestinal stromal tumors (GISTs)), 13/41 (32%) epithelial (adenocarcinoma), and 7/41 (17%) round cell (lymphoma) tumors. The growth pattern was concentric, eccentric, and mixed in epithelial, spindle cell, and round cell tumors, respectively. Spindle cell tumors had the largest main volume and involved the outer gastrointestinal layer with an unaffected inner layer. Leiomyosarcomas/GISTs showed irregular margins compared to leiomyomas. Only lymphomas showed multifocal gastrointestinal involvement. Nine carcinomas and six spindle cell tumors caused partial stenosis with secondary sub-obstruction. Mineralizations were more frequent in spindle cell tumors (10/21) and absent in lymphomas. Lymphadenomegaly was widespread in lymphomas, regional in leiomyosarcomas-GISTs and adenocarcinomas, and absent in leiomyomas. The reported CT features may be useful in prioritizing the differential diagnosis between spindle cell, epithelial, and round cell tumors, similar to those reported on ultrasound.

Gastrointestinal stromal tumor (GIST) presenting as a multilocular cystic intra-abdominal mass in a dog.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm described in humans, dogs, and cats. A hallmark of diagnosis for GISTs is positive immunohistochemical labelling with c-Kit (CD117). The differentiation of GIST from other mesenchymal neoplasms of the gastrointestinal tract is pivotal to allow for initiation of appropriate treatment. In humans, cystic GIST has been described, though this has not been reported in dogs. In humans, the cystic form of GIST has been associated with a favorable prognosis. In the present paper, we report a case of multilocular cystic GIST in a dog, which has not previously been described in this species. CASE PRESENTATION: A ten-year-old, male-entire Maltese terrier mix breed dog presented with a large cystic mural mass of the duoedenum and orad jejunum. Histopathology and positive immunohistochemical staining with CD117 confirmed a diagnosis of GIST. No evidence of metastasis was detected on routine staging with abdominal sonography and thoracic radiography at the time of diagnosis. Surgical resection was performed and toceranib therapy was initiated post-operatively. Metastasis was documented 251 days after surgery on computed tomography. Due to clinical deterioration, the patient was humanely euthanised 370 days after surgical excision. CONCLUSIONS: There are few differential diagnoses for large multilocular cystic intra-abdominal masses in dogs. This case presents a previously undescribed presentation of gastrointestinal stromal tumor in the dog as a predominantly multilocular cystic mass. It remains unclear if the cystic form of GIST may represent a favorable prognosis in dogs.

Gastrointestinal stromal tumors with Kit gene mutation in 4 guinea pigs (Cavia porcellus).

Gastrointestinal stromal tumors (GISTs) have been rarely reported in guinea pigs. We aimed to characterize the clinical and pathological features of GISTs in 4 guinea pigs and investigate the presence of mutations in exon 11 of the KIT proto-oncogene receptor tyrosine kinase (Kit) gene. Two subjects were male and 2 were female; 2 were 6 years old, 1 was 7 years old, and 1 was of an unknown age. Three cases had primary gastric tumors, whereas 1 had a primary small intestinal tumor. All cases had tumors that extended from the submucosa to the serosa with extraluminal growth. A gastric tumor had gastric, pancreatic, and cecal metastases. Histologically, the tumors were sharply demarcated and composed of spindle cells arranged in bundles, intermixed with small amounts of collagenous stroma. The tumor cells had mild atypia with few mitotic figures (0-5/50 high power fields, 7.95 mm2) and were immunolabeled for KIT and Discovered-on-GIST 1 (DOG1). All cases had mutations in exon 11 of the Kit gene. These findings indicate that GISTs in guinea pigs are similar to those in humans and dogs. GISTs in guinea pigs are potentially malignant submucosal tumors with KIT- and DOG1-immunolabeling, exon 11 KIT mutations, and the possibility of metastasis.

Gastrointestinal stromal tumour lacking mutations in the KIT and PDGFRA genes in a cat.

Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.

Needle rinse cell blocks as an ancillary technique: Diagnostic and clinical utility in gastrointestinal neoplasia.

BACKGROUND: Fine-needle aspirate (FNA) cytology is often the first-choice method for diagnosing gastrointestinal nodular lesions. The FNA material can be converted to histopathology specimens by a needle rinse cell block (NRCB) technique, allowing ancillary studies to refine the cytologic diagnosis. Despite use in human pathology, NRCB has never been applied to canine or feline gastrointestinal neoplasia. OBJECTIVE: This study described NRCB methodology and its diagnostic utility in specific cases of neoplastic gastrointestinal lesions. METHODS: Needle rinses with saline were performed after ultrasound-guided FNAs of two intestinal lymphomas (canine and feline) and a canine gastrointestinal stromal tumor (GIST). The NRCB was prepared using the cell tube block technique and processed for paraffin embedding. Routine immunohistochemistry protocols (using CD3, PAX-5, and Ki-67 for lymphoma cases and vimentin, desmin, S-100, and KIT markers for GIST) were applied to NRCB sections, and the results were compared with matched tissue biopsies. RESULTS: NRCBs with adequate cell numbers, preservation, and good separation of blood were obtained. The diagnosis and immunophenotyping were confirmed in both cases of lymphoma in NRCBs. In the GIST, the immunolabeling of the neoplastic cells in NRCB was completely concordant with the tissue biopsy. CONCLUSIONS: The described methodology is suitable for veterinary settings, having few technical requirements and low invasiveness. The presented cases of gastrointestinal neoplasia highlight the utility of NRCBs as a platform to conduct ancillary studies and refine the cytologic diagnosis.

Incidental diagnosis of a spindle cell type gastrointestinal stromal tumor in a dog with ethylene glycol intoxication.

A 6-year-old castrated male American Pit Bull Terrier dog was presented for evaluation of acute onset of tonic-clonic seizures, anorexia, and vomiting. On physical examination, neurologic signs, such as generalized proprioceptive ataxia, salivation, circling to the right, and absent patellar reflexes bilaterally, were noted. A complete blood cell count revealed mild hemoconcentration and an inflammatory leukogram, while a chemistry panel showed severe azotemia, marked hypochloremia, and a severe titrational metabolic acidosis, suggesting possible ethylene glycol intoxication. However, an irregularly round, small mass was identified in the large intestine on abdominal ultrasound. Additionally, bilateral hyperechoic renal cortices with medullary rim sign were suggestive of acute nephritis or tubular necrosis. The cytologic evaluation of a fine-needle aspiration biopsy of the abdominal mass revealed a large population of mesenchymal cells, suggesting the presence of neoplasia. Due to the worsening of symptoms, the dog was humanely euthanized. Necropsy confirmed ethylene glycol intoxication, and the incidental finding of a neoplastic intestinal mass was diagnosed as spindle cell sarcoma. Immunohistochemical staining showed strong, diffuse positivity for CD117, smooth muscle actin, and S-100, indicating the final diagnosis of a spindle cell type gastrointestinal stromal tumor (GIST). This report briefly discusses the classifications of nonlymphoid, nonangiogenic intestinal mesenchymal tumors, characteristics of GISTs, and the importance of the immunohistochemical classification of mesenchymal tumors of the gastrointestinal tract.

Prognostic factors for dogs with surgically resected gastrointestinal stromal tumors.

Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.

Outcome, prognostic factors and histological characterization of canine gastrointestinal sarcomas.

Canine gastrointestinal sarcomas, a group of tumours that includes leiomyosarcomas (LMSAs), gastrointestinal stromal tumours (GISTs) and other rarer sarcomas, comprise about 10-30% of all gastrointestinal tumours. This study aims to characterize the histologic characteristics and clinical behaviour in order to identify prognostic factors predictive of outcome. A single institution database search for surgically treated gastrointestinal sarcomas yielded 47 cases with adequate tissue remaining for histologic analysis and 42 cases available for analysis of clinical outcome. Tumours were then prospectively evaluated for mitotic count, necrosis, haemorrhage and inflammation, as well as categorized via immunohistochemical (IHC) staining for smooth muscle actin, c-KIT and DOG-1. IHC analysis defined 32 tumours as GISTs, 14 as LMSAs and one as a sarcoma not otherwise specified. For both GISTs and LMSAs, the overall median survival time (MST) is 1024 days (range 31-1456), which did not differ statistically between tumour types (p = .92). The overall metastatic rate of GISTs in this study was 32.1% (n = 9) which was not significantly different to that of LMSAs at 15.3% (n = 2, p = .45). In multivariate analysis, mitotic count under 9 in GIST patients and complete surgical excision in all tumour types correlated with improved MST. For patients with GISTs, the intensity of c-KIT staining also correlated positively with survival, with an MST of 250 days in cases with weak staining and an MST of 1418 days in cases with moderate or strong c-KIT staining (p = .005).

Management of a feline gastric stromal cell tumour with toceranib phosphate: a case study.

BACKGROUND: A fifteen-year old, female spayed domestic longhaired cat was presented for a routine vaccination during which an incidental abdominal mass was palpated. After further inquiry, occasional vomiting was reported to occur once every few weeks to months, associated with no other gastrointestinal signs. CASE REPORT: Ultrasonography revealed a gastric mass. Histopathology and immunohistochemistry confirmed a CD117 positive, smooth muscle actin and desmin negative neoplasm, consistent with a gastrointestinal stromal cell tumour (GIST). Treatment was initiated with toceranib phosphate resulting in stable disease for over eighteen months, and the patient was still alive at the time of writing. CONCLUSION: GISTs are rare in cats and this is the first report of medical management of feline GIST using toceranib.

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting. OBJECTIVES: To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value. ANIMALS: Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib. METHODS: Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs. RESULTS: Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

Canine Gastrointestinal Spindle Cell Tumors Efficiently Diagnosed by Tissue Microarray-Based Immunohistochemistry.

Tissue microarray (TMA) is a time- and cost-saving technique allowing the simultaneous immunohistochemical evaluation of multiple tissue samples. The aim of this study was to assess the efficacy of TMA at classifying canine gastrointestinal spindle cell tumors as gastrointestinal stromal tumor (GIST), smooth muscle tumor (SMT), and non-GIST/non-SMT based on the expression of α-smooth muscle actin (α-SMA), desmin, and CD117. Thirty-four cases were investigated on TMAs, sampling 2 cores each. Immunohistochemistry was performed on TMAs and full sections, and the results were compared. Comparing full sections, TMA specificity and sensitivity were 100% and 93.8%, respectively, for α-SMA; 100% and 80.8% for desmin; and 100% and 100% for CD117. TMA allowed the identification of 6 of 6 GISTs, 25 of 26 SMTs, and 2 of 2 non-GIST/non-SMTs. One SMT was misdiagnosed as non-GIST/non-SMT. Based on these results, TMA-based immunohistochemistry is efficient at diagnosing canine gastrointestinal spindle cell tumors and might be applied on large caseloads in a research setting.

Gastrointestinal spindle cell tumor of the rumen with metastasis to the liver in a goat.

Many neoplasms have been reported in goats; however, neoplasia of the rumen is rarely reported. A 9-y-old castrated male pygmy goat was presented with a history of respiratory stertor, fever, and anorexia. A respiratory diagnostic work-up including skull and thorax radiographs and endoscopy revealed minor enlargement of the arytenoids but no other abnormal findings. After a month of little improvement on symptomatic treatment and worsening general health, the goat was euthanized. On autopsy, the forestomachs, liver, spleen, diaphragm, and the ventral and lateral aspects of the cranial third of the walls of the peritoneal cavity were adhered to one another by fibrinous and fibrous adhesions. Numerous firm, white, up to 2 cm diameter nodules were found throughout the liver. A large sessile mass extended from the rumen wall into the lumen. The rumen mass was a gastrointestinal stromal tumor with metastasis to the liver.

A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells.

Overexpression of KIT is one of the mechanisms that contributes to imatinib resistance in KIT mutation-driven tumors. Here, the mechanism underlying this overexpression of KIT was investigated using an imatinib-sensitive canine mast cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS cells by their continuous exposure to increasing concentrations of imatinib. Neither a secondary mutation nor upregulated transcription of KIT was detected in rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and KIT overexpression were found in rCoMS1 cells. These events were suppressed by withdrawal of imatinib and were re-induced by re­treatment with imatinib. These findings suggest that imatinib elicited overexpression of KIT via suppression of its ubiquitination. These results also indicated that imatinib-induced overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting that the imatinib-induced decrease in KIT ubiquitination could be mediated by upregulation and/or activation of deubiquitinating enzyme(s). It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation.

Intestinal gastrointestinal stromal tumor in a cat.

A 12-year-old, 3.6-kg, spayed female domestic shorthaired cat had a 2-month history of anorexia and weight loss. Abdominal ultrasonography and computed tomography revealed an exophytic mass originating from the jejunum with very poor central and poor peripheral contrast enhancement. On day 14, surgical resection of the jejunum and mass with 5-cm margins and an end-to-end anastomosis were performed. Histopathological examination revealed the mass was a transmural, invasive cancer showing exophytic growth and originating from the small intestinal muscle layer. Immunohistochemical analysis of tumor cells revealed diffuse positivity for KIT protein and negativity for desmin and S-100. The mass was diagnosed as a gastrointestinal stromal tumor (GIST). Ultrasonographic findings indicated the tumor probably metastasized to the liver and omentum, as seen in humans and dogs. The owner rejected further treatment at the last visit on day 192. To our knowledge, this is the first report of intestinal tumor and metastasis in feline GIST and its imaging features.

Successful treatment of a metastatic, gastrointestinal stromal tumour in a dog with toceranib phosphate (Palladia).

A ten-year-old, female-entire English springer spaniel presented with a large intra-abdominal mass but no other clinical signs. Gastrointestinal stromal tumour of the caecum with widespread abdominal metastasis was confirmed. Treatment with toceranib phosphate resulted in complete response, despite the absence of exon-8 or exon-11 c-kit mutation. There was no clinical evidence of tumour recurrence nine months after diagnosis.