Non‐functional metastatic thyroid carcinoma with oesophageal invasion and ulceration in a cat

Veterinary Record Case Reports · 2024

• Medicine
• Pathology
• Internal medicine

Abstract An adult, male, neutered, domestic shorthair cat was presented with a 2‐month history of dysphagia and a movable cervical mass. Cytology of the cervical mass was consistent with carcinoma. Thoracic radiographs revealed pleural effusion, cardiomegaly, diffuse patchy interstitial pattern and pulmonary nodules. Fluid analysis of the pleural effusion was consistent with marked septic neutrophilic inflammation, and Pasteurella multocida was isolated. Contrast‐enhanced cervical and thoracic computed tomography scan revealed a cervical mass in the region of the right thyroid lobe, with circumferential invasion of the oesophageal wall and well‐defined pulmonary nodules consistent with distant metastases. Oesophago‐gastroscopy was performed and revealed a proximal, oesophageal, mural mass causing severe intraluminal obstruction. Humane euthanasia was elected. Postmortem examination with histology and immunohistochemistry confirmed a thyroid carcinoma with oesophageal invasion and pulmonary metastases. The oesophageal mucosa was extensively disrupted and ulcerated by the thyroid carcinoma. Additionally, echocardiogram and postmortem examination confirmed cardiomyopathy and congestive heart failure.

Atypical multiple myeloma in 3 young dogs

Veterinary Pathology · 2022 · 4 citations

• Pathology
• Biology
• Medicine

Three dogs under 12 months old were diagnosed with atypical multiple myeloma (MM), having an aggressive multifocal anaplastic round cell sarcoma in bone marrow, viscera, and/or peripheral blood, which were confirmed by cytology and immunohistochemistry to be of plasma cell origin. The intramedullary sarcomas caused myelophthisis, osteolysis, and hypercalcemia. Complete or free light chain monoclonal gammopathy in the serum and/or urine was demonstrated by protein electrophoresis and immunofixation. The polymerase chain reaction for antigen receptor rearrangement assay performed on 2 cases identified a clonally rearranged immunoglobulin gene. Neoplastic cells lacked expression of CD45, CD3, CD18, CD21, CD34, and MHCII by flow cytometry. Immunohistochemistry revealed MUM1 immunoreactivity of the neoplastic cells. Combining all data, the diagnosis was MM. An aggressive form of MM in young dogs should be a differential diagnosis for patients with an immunoglobulin-productive, B cell-clonal, CD45-negative, MUM1-positive discrete cell neoplasm arising from the bone marrow.

Identification of a naturally-occurring canine model for early detection and intervention research in high grade urothelial carcinoma

Frontiers in Oncology · 2022 · 19 citations

• Medicine
• Oncology
• Internal medicine

Background: Early detection and intervention research is expected to improve the outcomes for patients with high grade muscle invasive urothelial carcinoma (InvUC). With limited patients in suitable high-risk study cohorts, relevant animal model research is critical. Experimental animal models often fail to adequately represent human cancer. The purpose of this study was to determine the suitability of dogs with high breed-associated risk for naturally-occurring InvUC to serve as relevant models for early detection and intervention research. The feasibility of screening and early intervention, and similarities and differences between canine and human tumors, and early and later canine tumors were determined. Methods: STs (n=120) ≥ 6 years old with no outward evidence of urinary disease were screened at 6-month intervals for 3 years with physical exam, ultrasonography, and urinalysis with sediment exam. Cystoscopic biopsy was performed in dogs with positive screening tests. The pathological, clinical, and molecular characteristics of the "early" cancer detected by screening were determined. Transcriptomic signatures were compared between the early tumors and published findings in human InvUC, and to more advanced "later" canine tumors from STs who had the typical presentation of hematuria and urinary dysfunction. An early intervention trial of an oral cyclooxygenase inhibitor, deracoxib, was conducted in dogs with cancer detected through screening. Results: (n=1). Transcriptomic signatures including druggable targets such as EGFR and the PI3K-AKT-mTOR pathway, were very similar between canine and human InvUC, especially within luminal and basal molecular subtypes. Marked transcriptomic differences were noted between early and later canine tumors, particularly within luminal subtype tumors. The deracoxib remission rate (42% CR+PR) compared very favorably to that with single-agent cyclooxygenase inhibitors in more advanced canine InvUC (17-25%), supporting the value of early intervention. Conclusions: The study defined a novel naturally-occurring animal model to complement experimental models for early detection and intervention research in InvUC. Research incorporating the canine model is expected to lead to improved outcomes for humans, as well as pet dogs, facing bladder cancer.

Phase I/II Trial of Vemurafenib in Dogs with Naturally Occurring, <i>BRAF</i> -mutated Urothelial Carcinoma

Molecular Cancer Therapeutics · 2021 · 25 citations

• Cancer research
• Medicine
• Internal medicine

-mutated canine InvUC offers an important complementary animal model to improve BRAF-targeted therapies in humans.

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

Frontiers in Oncology · 2020 · 127 citations

• Medicine
• Bioinformatics
• Oncology

There is a great need to improve the outlook for people facing urinary bladder cancer, especially for patients with invasive urothelial carcinoma (InvUC) which is lethal in 50% of cases. Improved outcomes for patients with InvUC could come from advances on several fronts including emerging immunotherapies, targeted therapies, and new drug combinations; selection of patients most likely to respond to a given treatment based on molecular subtypes, immune signatures, and other characteristics; and prevention, early detection, and early intervention. Progress on all of these fronts will require clinically relevant animal models for translational research. The animal model(s) should possess key features that drive success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). Experimental animal models, while essential in bladder cancer research, do not possess these collective features to accurately predict outcomes in humans. These key features, however, are present in naturally-occurring InvUC in pet dogs. Canine InvUC closely mimics muscle-invasive bladder cancer in humans in cellular and molecular features, molecular subtypes, immune response patterns, biological behavior (sites and frequency of metastasis), and response to therapy. Thus, dogs can offer a highly relevant animal model to complement other models in research for new therapies for bladder cancer. Clinical treatment trials in pet dogs with InvUC are considered a win-win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. In addition, the high breed-associated risk for InvUC in dogs (e.g., 20-fold increased risk in Scottish Terriers) offers an unparalleled opportunity to test new strategies in primary prevention, early detection, and early intervention. This review will provide an overview of canine InvUC, summarize the similarities (and differences) between canine and human InvUC, and provide evidence for the expanding value of this canine model in bladder cancer research.