The Veterinary Clinics of North America

Correlation of Nodal Mast Cells with Clinical Outcome in Dogs with Mast Cell Tumour and a Proposed Classification System for the Evaluation of Node Metastasis

Mast cell tumor (MCT) is a common canine cutaneous neoplasm with variable biological behavior. A 2-tier histologic grading system was recently proposed by Kiupel et al to reduce interobserver variation and eliminate prognostic uncertainty of the Patnaik system. This study compared the ability of these 2 grading systems to predict survival in a cohort of dogs with MCTs. However, surgical margins were unknown, and the risk of developing new/metastatic MCTs was not studied. Histologic grade was assessed according to both systems for 137 surgically resected cutaneous MCTs. The relationship between grade and survival was evaluated. According to the Patnaik system, 18 MCTs (13.1%) were classified as grade I, 83 (60.6%) as grade II, and 36 (26.3%) as grade III. Grade III was associated with a poorer prognosis (P < .001), but no significant difference between grades I and II was detected. Grading according to the Patnaik system was based on consensus grading among 3 pathologists, and interobserver variability was not considered. All grade I MCTs were low grade in the Kiupel system, and all grade III were high grade. Among grade II, 71 (85.6%) were low grade, and 12 (14.4%) were high grade, with a 1-year survival probability of 94% and 46%, respectively (P < .001). The 2-tier system had a high prognostic value and was able to correctly predict the negative outcomes of some grade II MCTs. Data also confirm that histologic grading cannot predict biological behavior of each MCT and should be supplemented with molecular methods for more accurate prognostication.

https://vet.sagepub.com/content/52/1/70.full.pdf+html

Histologic grading of canine mast cell tumor: is 2 better than 3?

Objective—To compare the Kiupel (2 categories) and Patnaik (3 categories) histologic grading systems for predicting the presence of metastasis at the time of initial examination in dogs with cutaneous mast cell tumors (MCTs). Design—Retrospective case series. Animals—386 client-owned dogs with cutaneous MCTs. Procedures—Medical records of dogs with newly diagnosed, histologically confirmed cutaneous MCTs that had undergone complete clinical staging were reviewed for clinical and histopathologic data. Results—All Patnaik grade 1 MCTs (n = 52) were classified as Kiupel low-grade MCTs, and all Patnaik grade 3 MCTs (43) were classified as Kiupel high-grade MCTs. Of the 291 Patnaik grade 2 MCTs, 243 (83.5%) were classified as Kiupel low-grade tumors, and 48 (16.5%) were classified as Kiupel high-grade MCTs. Dogs with Patnaik grade 3 MCTs were significantly more likely to have metastases at the time of initial examination than were dogs with grade 1 or 2 MCTs (OR, 5.46), and dogs with Kiupel high-grade MCTs wer...

Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009-2014)

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, rP = -0.610), history of tumor recurrence ( P < .0001, rP = -0.550), Patnaik ( P < .0001, rP = -0.380) and Kiupel grades ( P < .0001, rP = -0.500), predominant organization of neoplastic cells ( P < .0001, rP = -0.452), mitotic count ( P < .0001, rP = -0.325), Ki-67 labeling index ( P < .0001, rP = -0.414), KITr pattern ( P = .02, rP = 0.207), and c-KIT mutational status ( P < .0001, rP = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

https://journals.sagepub.com/doi/pdf/10.1177/0300985817747325

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

In preparing this document the Authors aimed to pool current information on canine and feline mast cell disease. The information was gathered from international studies and a emphasis was placed on material and opinion with a strong evidence base. We intend it to form the basis of our understanding in this disease at the current time and we anticipate that it will be particularly useful for the general practitioner. It should be emphasized that the authors are presenting this work from a European perspective.

/pdf/european-consensus-document-on-mast-cell-tumours-in-dogs-and-4ksvzt7rh3.pdf

European consensus document on mast cell tumours in dogs and cats.

OBJECTIVE
The objective of this study was to describe the clinical features, prognostic factors, and outcomes in dogs with surgically treated salivary gland carcinoma.


STUDY DESIGN
Multi-institutional retrospective case series.


ANIMALS
Seventy-two client-owned dogs from 16 institutions with surgically excised salivary gland carcinoma.


METHODS
Medical records of dogs undergoing sialoadenectomy from January 1, 2000 to January 1, 2020 were reviewed for signalment, clinical signs, preoperative staging results, preoperative mass evaluation, complications, histopathologic diagnosis, local recurrence, metastatic disease, and survival times. Survival functions were estimated using the Kaplan-Meier estimator. Factors related to survival were individually tested using the log-rank test.


RESULTS
The overall median survival time (MST) associated with salivary carcinoma was 1886 days. Local recurrence occurred in 29/69 (42%) dogs with an overall disease-free interval (DFI) of 191 days. Metastatic disease occurred in 22/69 (31.9%) dogs, with an overall DFI of 299 days. Lymph node metastasis was present at the time of surgery in 11/38 (28.9%) dogs in which lymphadenectomy was performed at the time of surgery; these dogs had a shorter DFI at 98 days (P = .03) and MST at 248 days (P < .001).


CONCLUSION
The prognosis for dogs with salivary gland carcinoma treated surgically was more favorable than previously reported. Nodal metastasis was a negative prognostic factor for canine salivary gland carcinoma.


CLINICAL SIGNIFICANCE
Surgical intervention should be considered for dogs with salivary carcinoma.

Outcomes and clinical features associated with surgically excised canine salivary gland carcinoma: A multi-institutional, retrospective, Veterinary Society of Surgical Oncology study.

Simple Summary Although serum tumour markers offer an uncomplicated, non-invasive examination method and possible therapeutic options, they are still rarely used in veterinary medicine. Our marker of interest, the Ki-67 protein, can only be detected in the active phases of the cell cycle. Therefore, it is a suitable marker for assessing the proliferating cell fraction of an organism and can thus provide information about potentially present, rapid-growing tumour tissue. The purpose of our study was to determine whether Ki-67 could be considered as a possible tumour marker in canine serum for veterinary medicine. We measured serum concentrations of Ki-67 in dogs with various malignant tumours, such as carcinomas, sarcomas, and lymphomas. In the dogs with malignant tumours we determined significantly higher serum Ki-67 concentrations compared with healthy dogs and dogs with non-malignant diseases. No significant difference in serum Ki-67 concentration was observed between the different types of cancer or between benign and malignant mammary tumours. Our investigations also included some inflammatory parameters measured in blood, such as neutrophils, lymphocytes, and monocytes, with mixed results. The results of our study suggest that Ki-67 may be useful as a potential serum tumour marker, providing information about the presence of malignant diseases in a dog. Abstract Tumour markers are scarcely used in veterinary medicine, although they are non-invasive, contribute to a faster diagnosis and new therapeutic options. The nuclear protein Ki-67 is absent in G0-phase but is detectable throughout all active phases of the cell cycle. Consequently, it is used as a marker for the proliferating cell fraction of a cell population and thus could indicate neoplastic tissue present. Our study is designed to show whether Ki-67 can be considered as a potential canine serum tumour marker for veterinary medicine. We measured serum concentrations of Ki-67 in dogs with various malignant tumours (carcinomas (n = 35); sarcomas (n = 26); lymphomas (n = 21)) using a commercially available quantitative sandwich ELISA from mybiosource. Dogs with malignant tumours showed significantly higher serum Ki-67 concentrations compared to healthy dogs (n = 19) and non-neoplastic diseased dogs (n = 26). No significant difference in serum Ki-67 concentration was detected between carcinoma, sarcoma, and lymphoma, nor between mammary adenocarcinoma and adenoma. In our investigations we also included some inflammatory parameters measured in blood, such as neutrophils, lymphocytes, and monocytes, and gained mixed results. The results of our study suggest that Ki-67 may be useful as a potential serum tumour marker, providing information about the presence of malignancies in a dog.

/pdf/utility-of-serum-ki-67-as-a-marker-for-malignancy-in-dogs-19deopab.pdf

Utility of Serum Ki-67 as a Marker for Malignancy in Dogs

Organoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period. This cMTC N°2 organoid line was further compared to the primary tumor regarding morphology and IHC expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, calcitonin, synaptophysin, vimentin, Ki-67, cyclooxygenase-2 (COX-2), P-glycoprotein and vascular endothelial growth factor (VEGF). Quality control of the cMTC N°2 organoid line was achieved by a single nucleotide polymorphism (SNP) array of the organoids, primary tumor and healthy blood cells of the same dog. The effect of carboplatin, meloxicam and toceranib phosphate (TOC) on cMTC N°2 organoids' viability was evaluated. The cMTC N°2 organoid line was cultured for 94 days and showed similar histological features with the primary tumor. Immunolabeling for TTF-1, thyroglobulin, calcitonin and VEGF was similar between the primary tumor and cMTC N°2 organoids. Compared to the primary tumor, organoids showed higher immunolabeling for vimentin and Ki-67, and lower immunolabeling for synaptophysin, COX-2 and P-glycoprotein. The SNP genotype was similar for each chromosome between healthy blood cells, primary tumor and cMTC N°2 organoids. Carboplatin, meloxicam and TOC had no effect on cMTC N°2 organoid cell viability within achievable in vivo concentration range. In conclusion, the cMTC N°2 organoid line is a promising first milestone towards an established in vitro organoid model to explore pathophysiology and new treatment modalities in cMTC. This article is protected by copyright. All rights reserved.

https://biblio.ugent.be/publication/01GPDBNKV77HFKY5JXXBR82REV/file/01GPDBSQZTFPCEK3HFYXM0TREP.pdf

Organoids of patient-derived medullary thyroid carcinoma: the first milestone towards a new in vitro model in dogs.

Reports on canine frontal sinus carcinomas (FSCs) are scarce. This retrospective review of 41 dogs with FSC (2001-2022) describes demographic and clinical characteristics of canine FSC and reports the clinical experience and overall survival following treatment with toceranib phosphate (TOC) and meloxicam in 10 cases. Median age at diagnosis was 10.6 years (range: 6.5-15.4 years). There was a male-to-female-ratio of 2.4:1. The most common breeds were Jack Russell Terriers (JRT) (n=7; 17.1%) and Rottweilers (n=3, 7.3%). Mesocephalic breeds (70.6%) were most commonly affected, brachycephalics accounted for 8.8%. The most frequent clinical signs included skull deformation dorsomedial to the eye (87.5%), pain/head-shyness (40.0%), ocular (22.5%)/nasal (17.5%) discharge, and exophthalmos (17.5%). Duration of symptoms prior to diagnosis varied from a few days to 9 months. There were no neurological signs at initial presentation despite imaging evidence of osteolysis of the lamina interna of the frontal bone in most dogs (69.4%). In 11.5%, pulmonary changes suggestive of metastasis or concurrent primary pulmonary neoplasia were present. Tumour types included squamous cell carcinoma (58.5%), unspecified carcinoma (29.3%), and adenocarcinoma (9.8%). Ten dogs were treated with TOC (median 2.8mg/kg EOD or 3 times/week) and meloxicam (0.1mg/kg, EOD) (TOC-M), resulting in subjective regression of skull deformity in 8/10 (80.0%) patients. Overall median survival time with TOC-M was 183.5 days (range: 120-434 days). FSCs typically present with skull deformation, but no overt neurological signs. Male dogs and JRT may be overrepresented. The use of TOC-M in FSC appears promising and warrants further prospective evaluation. This article is protected by copyright. All rights reserved.

M. Kessler

Papers

European consensus document on mast cell tumours in dogs and cats.

Outcomes and clinical features associated with surgically excised canine salivary gland carcinoma: A multi-institutional, retrospective, Veterinary Society of Surgical Oncology study.

Utility of Serum Ki-67 as a Marker for Malignancy in Dogs

Organoids of patient-derived medullary thyroid carcinoma: the first milestone towards a new in vitro model in dogs.

Frontal sinus carcinoma in 41 dogs (2001-2022).