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.

First Evidence of Familial Transmission of Hereditary Gastrointestinal Polyposis Associated with Germline APC Variant in Jack Russell Terriers.

Jack Russell terriers (JRTs) with gastrointestinal (GI) neoplastic polyps have been recently reported to harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT], in the heterozygous state, which indicates that this disease is an autosomal dominant hereditary disorder. Many individual cases of this disease have been observed in clinical practice; however, familial transmission has not been demonstrated due to the difficulty in tracing the family members of household dogs, especially after the disease's onset in adulthood. Recently, we encountered two cases of GI polyposis in maternal half sisters. These two cases facilitated the identification of additional relatives spanning three generations, including parents, full and half siblings of the dam (aunt and uncle), littermate and non-littermate siblings, and a nephew. Genetic analysis revealed that 11 of the 14 examined JRTs in this family carried the heterozygous germline APC variant, and eight dogs with the variant already had a current and/or past medical history of GI neoplastic polyps. Some cases in the family showed significantly more severe disease phenotypes than those initially reported, suggesting that the severity of this disease can vary considerably among individuals. Moreover, familial aggregation of severe cases suggested that the genetic modifier involved in increasing severity may have been transmitted in this family in addition to the germline APC variant. Furthermore, in addition to this family, we reported two other families of JRTs affected by hereditary GI polyposis that consisted of five full and half siblings and a mother-daughter pair, respectively. These findings unequivocally establish the transgenerational transmission of hereditary GI polyposis associated with the germline APC variant in JRT lineages.

Clinical and Pathological Diagnosis of Hereditary Gastrointestinal Polyposis in Jack Russell Terriers.

Hereditary GI polyposis in JRTs is a novel hereditary disease characterized by the development of solitary and multiple polypoid tumors, predominantly in the stomach and/or colorectum. Our recent study indicated that JRTs with GI neoplastic polyps harbor an identical germline variant in the APC gene, c.[462_463delinsTT], in a heterozygous state. Unlike sporadic cases, dogs afflicted with hereditary GI polyposis can be expected to have a prolonged survival time, as hereditary tumors are noninvasive. Since the discovery of this disease, the number of newly diagnosed cases in Japan has increased, allowing us to update the clinical and pathological features and provide a large number of diagnostic images. The present clinical case series study employing various diagnostic imaging techniques revealed that some of the cases harbored tumors in the small intestine in addition to the stomach and colorectum. Moreover, although rare, hereditary GI cancers can progress to the advanced stage and develop systemic metastasis, similar to sporadic GI tumors. These findings indicate that there is a wider range of variation in disease severity than was initially recognized. Our results can contribute to the accurate diagnosis of hereditary GI polyposis in clinical practice, pathological examinations, and future research.

Molecular epidemiological study of germline APC variant associated with hereditary gastrointestinal polyposis in dogs: current frequency in Jack Russell Terriers in Japan and breed distribution.

BACKGROUND: Cases of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) have increased in Japan since the late 2000s. We recently demonstrated that JRTs with GI polyps heterozygously harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT]; therefore, this is an autosomal dominant hereditary disease. We conducted a molecular epidemiological study to explore the current frequency of the APC variant in JRTs in Japan and the breed distribution of this disease. RESULTS: Peripheral blood samples from 792 JRTs were collected at 93 veterinary hospitals in Japan in 2020. Using an established polymerase chain reaction-restriction fragment length polymorphism assay, the germline APC variant was detected in 15 JRTs, with an overall frequency of 1.89%. The frequency was not significantly different for sex, age, and coat type criteria. Notably, the variant carriers had a current or previous history of GI neoplastic polyps, providing further evidence of the association of the germline APC variant with GI polyposis. Pedigree analysis of carrier dogs revealed that the germline APC variant was no longer confined to a few specific families but was widely spread among JRTs in Japan. Furthermore, some ancestors of the carriers were from Australia or New Zealand, suggesting the possible presence of carriers in countries other than Japan. Next, we retrospectively investigated the germline APC variant status of dogs with GI epithelial tumors using genomic DNA samples extracted from archived pathological specimens (28 purebred dogs of 14 breeds and four mixed-breed dog), as well as those stored in a canine genome bank (38 dogs of 18 breeds and a mixed-breed dogs). In total, 66 purebred dogs of 25 breeds, including another four JRTs, and five mixed-breed dogs were examined. While three variant carriers were found in JRTs, the germline APC variant was not detected in any of the other breeds. CONCLUSION: The current frequency of the germline APC variant was approximately 2% in JRTs in Japan and the frequency remained roughly flat during the last 15 years. In addition, hereditary GI polyposis associated with the variant was virtually specific to JRTs.