Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer.

BACKGROUND: In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. RESULTS: Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. CONCLUSION: Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

Identification of an ectopic periorbital lymph node in two horses.

Background: To describe the clinical presentation and treatment of an ectopic periorbital lymph node in two young horses. Case Description: Two warm-blood horses were presented at the equine clinic of the University of Liège with a periorbital non-painful mass. Differential diagnosis included neoplasm (lymphoma), (sterile) abscess, cyst, ectopic lacrimal gland tissue, hematoma, adipose tissue, or ectopic lymphoid tissue. Information collected included physical and ophthalmic examination findings, results of the ocular and periocular ultrasound, surgical procedure, histopathology, and follow-up. Masses of 2 × 2 cm and 3 × 2 cm subcutaneous, ovoid, smooth, and firm mass were observed in the zygomatic region of the head. On ultrasound, the mass appeared as a hypoechoic subcutaneous structure. Cytology showed a mixed lymphocytic cell population. No abnormal mitotic activity was observed. Histopathology revealed a chronic markedly reactive lymph node. Conclusion: To the authors' knowledge, this is the first description of periorbital ectopic lymph nodes in veterinary medicine. Ectopic lymph nodes should therefore be included in the differential diagnosis of periocular masses in animals. Surgery was easily performed and was curative.

Feline maculopapular cutaneous mastocytosis: a retrospective study of 13 cases and proposal for a new classification.

CASE SERIES SUMMARY: Cutaneous mastocytosis is a disorder rarely reported in veterinary dermatology and usually described as 'urticaria pigmentosa'. This study aimed to evaluate the diagnosis, treatment and outcome of 13 affected cats, selected from the files of a private referral dermatology practice within a period of 14 years. Breeds of the affected individuals included Sphynx (n = 9), Devon Rex (n = 2) and Sphynx/Devon Rex crossbreeds (n = 2). Females (n = 9) were over-represented and the median duration of clinical signs prior to diagnosis was 8 months. The clinical presentation of these 13 cats was compared with cases reported in the veterinary literature and classified according to the current human consensus on cutaneous mastocytosis. Three clinical forms could be distinguished in cats: (1) large papular lesions and wheals, typically localised to the head, shoulders, ventral neck and axillae, and which may spontaneously resolve (termed polymorphic maculopapular cutaneous mastocytosis); (2) erythematous dermatitis, characterised by small maculopapular lesions often associated with crusts and with a poorer prognosis (termed monomorphic maculopapular cutaneous mastocytosis); and (3) more chronic dermatitis characterised by lichenification and hyperpigmentation, similar to the human condition 'urticaria pigmentosa' (termed pigmented maculopapular cutaneous mastocytosis). Histopathology was performed in eight cases and revealed a superficial-to-deep dermatitis characterised by infiltrates of mast cells and eosinophils. The response to various treatments, including antihistamines, steroids and ciclosporin, was variable. RELEVANCE AND NOVEL INFORMATION: This article reports 13 new cases of feline cutaneous mastocytosis, confirming the clinical presentation and apparent breed predisposition. The feline maculopapular cutaneous mastocytosis seems to be clinically very close to the human form. This study proposes a new classification system for the feline disease based on the current human consensus, clinical presentation and prognosis, with three different subforms: polymorphic maculopapular cutaneous mastocytosis with eventual spontaneous regression; monomorphic maculopapular cutaneous mastocytosis with chronic evolution; and pigmented maculopapular cutaneous mastocytosis.

Cutaneous epitheliotropic T-cell lymphoma in the cat: a review of the literature and five new cases.

Cutaneous epitheliotropic T-cell lymphoma (CETL) is characterized by cutaneous infiltration of neoplastic T lymphocytes with a specific tropism for the epidermis and adnexal epithelium. This disease is reported very rarely in the cat. Clinical data were collected from an informal discussion with veterinary dermatologists through the Vetdermlist (vetderm@lists.ncsu.edu). In parallel, case archives of two European diagnostic histopathology laboratories (Institut de Pathologie et Génétique/Bio.be Gosselies, Belgium and the School of Veterinary Sciences, University of Bristol, UK) were reviewed. Fifteen cases with a good clinical description were selected, and five sets of skin biopsies were available for review. Cutaneous epitheliotropic T-cell lymphoma generally affects older cats with no apparent sex or breed predisposition. Solitary or multiple lesions were reported without predilection for any particular location. The lesions consisted of erythematous plaques or patches, scaly alopecic patches and nonhealing ulcers or nodules, which sometimes mimicked an eosinophilic plaque. Pruritus was rarely reported. No lesions affecting the oral mucosa were observed. Clinical diagnosis of CETL is more challenging in cats than in dogs. Final diagnosis must be based on histopathological examination of skin biopsy samples. The characteristic lesions of feline CETL are similar to those reported in the dog, but involvement of the adnexal glands was not observed in this series (n=5). The neoplastic T cells were generally small to medium in size. The survival time of cats with CETL seems to be more variable than that of affected dogs. Too few cases have been evaluated to permit clear recommendations to be made with respect to treatment.

Transobturator vaginal tape inside out for treatment of urethral sphincter mechanism incompetence in female dogs: cadaveric study and preliminary study in continent female dogs.

OBJECTIVES: (1) To describe a surgical technique adapted from the "transobturator vaginal tape inside-out" (TVT-O) used in women and to define the trajectory of the tape on canine cadavers, and (2) to determine the urodynamic and morphological effects of the TVT-O in continent bitches. STUDY DESIGN: Cadaveric and experimental in vivo study. ANIMALS: Fresh female canine cadavers (n=12) and spayed female Beagle dogs (2). METHODS: (1) TVT-O was inserted in 12 cadavers. Dissection was performed and distances between the tape and neighboring structures were recorded. (2) TVT-O was inserted in 2 continent female Beagle dogs. Urethral pressure profilometry and vaginourethrograms were performed preoperatively, immediately after surgery, and 2, 4, and 6 months postoperatively. Histopathology was performed 6 months after surgery. RESULTS: (1) TVT-O tape was consistently located in a perineal space before entering the obturator foramina and was located at a safe distance from major neurovascular structures including the femoral vessels and obturator nerve. (2) TVT-O was performed without any surgical or postoperative complications in 2 continent bitches. Histopathologic examination of the tissues surrounding the tape revealed a mild fibroblastic proliferation with a mild to minimal lymphoplasmacytic inflammatory infiltration. CONCLUSIONS: TVT-O is a feasible and accurate procedure that can be performed in continent bitches with a low risk of complications.

Canine cutaneous epitheliotropic T-cell lymphoma: a review of 30 cases.

This retrospective study reviewed the clinical, histological and immunohistochemical features of 30 European cases of canine cutaneous epitheliotropic T-cell lymphoma (CETL). The clinical presentation was highly variable and was not associated with the disease subtype. Diffuse erythema (86.6%) with scaling (60%) and focal hypopigmentation (50%) were the most common lesions. The skin was uniformly involved but muco-cutaneous junctions or mucosae were affected in 50% of cases. The median age at diagnosis was 10 years (SD 2.79, range 4-15) and the median time between onset and final diagnosis was 5 months (SD 3.79, range 0-12). Five cases occurred in Bichon Frises. There was no evidence of a previous history of chronic dermatitis in any cases. Histologically, the follicular epithelium was affected in 86.7% of cases. One case with mainly follicular disease was considered folliculotropic mycosis fungoides (MF), but no follicular mucinosis was observed. Epidermal Pautrier's microabscesses were uncommon (23.3%). Sweat glands were infiltrated in 70% of cases. Immunohistochemistry confirmed T-cell neoplasia in all cases. B cells infiltrated as individual cells or formed linear bands or ectopic follicles at the base of the neoplasm. Ki67 labelling revealed a range of proliferation indices but did not correlate with severity. A final diagnosis of classical MF was made in 40% of the dogs, MF d'emblé in 36.7%, generalized Pagetoid reticulosis in 20% and localized Pagetoid reticulosis in one case (Woringer-Kolopp Pagetoid reticulosis). The median survival time after diagnosis was 6 months and this did not change appreciably with therapy (lomustine or prednisolone).

Inflammatory pseudotumours of the urinary bladder in dogs resembling human myofibroblastic tumours: a report of eight cases and comparative pathology.

Eight cases of inflammatory myofibroblastic tumours (IMT) of the urinary bladder in dogs are described, including their clinical, imaging, morphological, and histopathological aspects. Old small breed female dogs were more commonly affected. Haematuria was the main clinical sign, often associated with dysuria and crystalluria. The IMT appeared as single or multiple, polypoid, firm masses, measuring 1-7 cm. Histologically, the masses were well delineated, covered by a benign hyperplastic urothelium and diffusely infiltrated by a mixed inflammatory component. The cells were spindle-shaped, adopting a fascicular, pallisading or whirling organisation and were vimentin and variably desmin and actin positive. The nuclei were globular, containing open chromatin and prominent nucleoli. Mild to moderate pleomorphism and little mitotic activity were present. These morphological features are compatible with human myofibroblastic inflammatory tumours.

Sweat gland hamartoma resembling human syringocystadenoma papilliferum in two young cats.

Syringocystadenoma papilliferum, a hamartoma with mostly sweat gland, but also follicular infundibular elements, is described on the flank and head of two young cats. Clinically, lesions were cutaneous plaques characterized by irregular but sharply demarcated borders and a roughened, hyperpigmented surface. Complete surgical excision in one case was curative. Histologically, the lesion was limited to the superficial dermis and consisted of coalescing units of proliferating sweat glands. The proliferation was tubular or papillary, and may have been epitrichial, opening within dilated hypertrophied follicular infundibuli, or atrichial. Three types of epithelium were observed, recapitulating the formation of the follicular-sweat gland unit with infundibular, ductal and secretory epithelia. The glands reacted positively for alpha cytokeratin 8 and were supported by fibrous tissue with a plasmacytic, lymphocytic and neutrophilic infiltrate. As in humans, this lesion may be classified within the hamartoma-nevus-type category.

Histology of two rice bodies isolated from the stifle of an adult draught horse stallion.

In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.

Use of autogenous fascia lata graft for perineal herniorrhaphy in dogs.

OBJECTIVE: To evaluate the effectiveness of a herniorrhaphy technique, using an autogenous fascia lata graft (FLG) for perineal hernia (PH) repair in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Twelve dogs with PH. METHOD: PHs were repaired with FLG harvested from the dog's ipsilateral thigh and sutured directly into the perineal defect. Correction of associated conditions, and castration were performed. Surgical time, pain, inflammation, pattern of defecation, lameness, hospitalization time, postoperative complications, and owner satisfaction were recorded. Histopathologic examination was performed in 1 dog euthanatized 10 months after repair. RESULTS: Hernia did not recur (mean follow-up, 5.8 months). Lameness was the most frequent minor complication, and was resolved within a few days. Transient rectal prolapse occurred in 2 dogs with bilateral PH. The mean (+/-SD) hospitalization was 1.8+/-0.9 days, and the surgical time was 76.5+/-9.8 minutes. Histopathologic examination in 1 dog revealed perfect integration of FLG into adjacent tissues without substantial tissue reaction. CONCLUSIONS: FLG reconstruction of PH is a simple, effective method of treatment. CLINICAL RELEVANCE: FLG can be used without major complications for primary repair of PH, as an augmentation procedure when the internal obturator muscle is thin or friable, or when herniation has recurred after another repair technique.

Magnetic resonance imaging findings in the equine deep digital flexor tendon and distal sesamoid bone in advanced navicular disease--an ex vivo study.

We describe the abnormal magnetic resonance (MR) imaging findings in the deep digital flexor tendon (DDFT) and distal sesamoid bone in horses with radiographic changes compatible with navicular syndrome. Thirteen postmortem specimens were examined using a 1.5-T magnetic field, with spin echo (SE) T1-weighted, turbo SE (TSE) proton density-weighted (with and without fat saturation), and fat saturation TSE T2-weighted sequences. The limbs were then dissected to compare the MR findings with the gross assessment and histologic examination of the DDFT and distal sesamoid bones. Tendonous abnormalities were detected by MR imaging in 12 DDFTs and confirmed at necropsy. Most tendon lesions were located at the level of the distal sesamoid bone and the proximal recess of the podotrochlear bursa. Tendon lesions were classified based on their MR imaging features as core lesions, dorsal lesions, dorsal abrasions, and parasagittal splits. Areas of increased MR signal in the DDFTs were characterized by tendon fiber disturbance and lack of continuity of the collagen fibers, foci of edema, hemorrhages, and formation of lakes containing eosinophilic plasma-like material or amphophilic material of low density. Bone marrow signal alterations in the distal sesamoid bone were seen in all digits. Two main phenomena were responsible for the abnormal signal, respectively, in T1-weighted (decreased signal) and in T2-weighted fat-suppressed images (increased signal): a decrease in the fat marrow content in the trabecular spaces and an increase in the fluid content. Histologic examination revealed foci of bone marrow edema, hemorrhage, necrosis, and fibrosis. Cyst formation and trabecular abnormalities (disorganization, thinning, remodelling) were also observed in areas of abnormal signal intensity. Increased bone density because of trabecular thickening induced a decrease in signal in all sequences.