Sensitivity of canine hematological cancers to BH3 mimetics.

BACKGROUND: Inhibition of antiapoptotic B-cell lymphoma 2 (BCL2) proteins by small molecule Bcl-2 homology 3 (BH3) mimetics causes rapid induction of apoptosis of human hematological cancers in vitro and in vivo. OBJECTIVES: Assess in vitro sensitivity of non-neoplastic lymphocytes and primary hematological cancer cells from dogs to venetoclax (VEN) or the dual BCL2/ B-cell lymphoma-extra-large (BCLxL) inhibitor, navitoclax (NAV), and evaluate the association between BCL2 protein expression and VEN sensitivity. ANIMALS: Nine client-owned dogs without cancer and 18 client-owned dogs with hematological cancer. METHODS: Prospective, nonrandomized noncontrolled study. Lymphocytes isolated from peripheral blood, lymph node, or bone marrow from dogs were incubated with BH3 mimetics for 24 hours. Viable cells were counted using flow cytometry and half maximal effective concentration (EC50 ) was calculated. BCL2 protein from whole cell lysates was assessed via immunoblots. RESULTS: Nodal B and T lymphocytes were more sensitive to VEN than circulating lymphocytes (P = .02). Neoplastic T lymphocytes were sensitive to VEN (mean EC50 ± SD = 0.023 ± 0.018 µM), whereas most non-indolent B cell cancers were resistant to killing by VEN (mean EC50 ± SD = 288 ± 700 µM). Unclassified leukemias showed variable sensitivity to VEN (mean EC50 ± SD = 0.49 ± 0.66 µM). Detection of BCL2 protein was not associated with VEN sensitivity. CONCLUSION AND CLINICAL IMPORTANCE: Neoplastic canine T lymphocytes are sensitive to VEN in vitro. Quantification of BCL2 protein alone is insufficient to predict sensitivity to VEN.

Response of canine thyroid carcinomas to radioiodine.

Radioactive iodine (131 I) has previously been reported to prolong survival in dogs with thyroid carcinoma. This study aimed to describe tumour response and progression-free interval (PFI) in dogs with thyroid carcinomas treated with 131 I. Secondary aims were to describe overall survival time (OST) and prognostic factors. A bi-institutional retrospective review of records identified 66 dogs with thyroid carcinoma treated with 131 I from January 2010 to April 2020. Response was described using RECIST or a subjective response assessment where specific tumour measurements were not available. Forty-eight dogs (72.7%) were treatment naïve and 18 dogs (27.3%) had received prior therapy at the time of 131 I treatment. Objective responses were available for 34 dogs and subjective responses for 58 dogs. The overall response rate was 35.3% (four complete and eight partial responses). Improvement of clinical signs was seen in 76.2% of dogs (32/42). Kaplan-Meier-estimated median PFI (95% confidence interval [CI]) was 301 (217-578) days and OST (95% CI) was 564 (421-865) days. Prior therapy was associated with a lower hazard for progression (hazard ratio [HR] 0.260 95% CI 0.123-0.548, p = .0004). Treatment of thyroid carcinoma using 131 I can effectively alleviate clinical signs and reduce disease burden in a proportion of dogs.

Suspected pancreatic carcinoma needle tract seeding in a cat.

CASE SUMMARY: A 15-year-old male neutered domestic longhair cat was referred for investigation of a pancreatic nodule. Fine-needle aspiration of the nodule was performed on two occasions, 2 weeks apart, and cytology revealed pyogranulomatous inflammation and moderately dysplastic exocrine pancreatic epithelium, suspicious for neoplasia. Thoracic radiographs were unremarkable and a partial pancreatectomy was performed. On histopathology, the nodule was diagnosed as a moderately differentiated pancreatic adenocarcinoma. Two weeks after surgery, a firm subcutaneous nodule was detected on the left ventrolateral abdomen. Cytology of the nodule was suggestive of pancreatic carcinoma and needle tract seeding was suspected. With palliative treatment, the cat lived a further 136 days. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this represents the first report of suspected transabdominal needle tract seeding of pancreatic carcinoma following fine-needle aspiration in veterinary medicine. Veterinarians should consider this when discussing risks of pancreatic fine-needle aspiration with owners and should attempt to minimise the number of needle aspirations where possible.

Cutaneous non-epitheliotropic T-cell lymphoma associated with a fracture site in a cat.

CASE SUMMARY: A 7-year-old male neutered domestic shorthair cat presented for investigation of a swelling over the right forelimb. Radiographs of the right forelimb revealed significant lysis and soft tissue swelling surrounding a previously implanted surgical plate, used to repair a fracture of the distal radius 5 years prior. The implant was removed, and a biopsy was collected. Histopathological analysis and immunohistochemistry diagnosed a non-epitheliotropic T-cell cutaneous lymphoma. Staging confirmed multiple regional lymph node involvement. The cat was started on a CHOP-based protocol (vincristine, doxorubicin, cyclophosphamide and prednisolone). At week 4, the disease progressed both locally and within the regional lymph nodes. The primary lesion became severely ulcerated and the cat was euthanased, 42 days post-diagnosis. RELEVANCE AND NOVEL INFORMATION: This is the first report of a cutaneous non-epitheliotropic lymphoma developing at the site of a previous traumatic fracture and metal implant. The cat's response to chemotherapy was poor and euthanasia was performed owing to progressive disease. More investigation is required to understand the role that malignant transformation could have at sites of chronic inflammation, bone fractures and surgical implants.