Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds.

Histiocytic sarcoma is an aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart affects flat-coated retrievers (FCRs) at unusually high frequency, with 20% developing the lethal disease. The similar clinical presentation combined with the closed population structure of dogs, leading to high genetic homogeneity, makes dogs an excellent model for genetic studies of cancer susceptibility. To determine the genetic risk factors underlying histiocytic sarcoma in FCRs, we conducted multiple genome-wide association studies (GWASs), identifying two loci that confer significant risk on canine chromosomes (CFA) 5 (Pwald = 4.83x10-9) and 19 (Pwald = 2.25x10-7). We subsequently undertook a multi-omics approach that has been largely unexplored in the canine model to interrogate these regions, generating whole genome, transcriptome, and chromatin immunoprecipitation sequencing. These data highlight the PI3K pathway gene PIK3R6 on CFA5, and proximal candidate regulatory variants that are strongly associated with histiocytic sarcoma and predicted to impact transcription factor binding. The CFA5 association colocalizes with susceptibility loci for two hematopoietic malignancies, hemangiosarcoma and B-cell lymphoma, in the closely related golden retriever breed, revealing the risk contribution this single locus makes to multiple hematological cancers. By comparison, the CFA19 locus is unique to the FCR and harbors risk alleles associated with upregulation of TNFAIP6, which itself affects cell migration and metastasis. Together, these loci explain ~35% of disease risk, an exceptionally high value that demonstrates the advantages of domestic dogs for complex trait mapping and genetic studies of cancer susceptibility.

A recurrent somatic missense mutation in GNAS gene identified in familial thyroid follicular cell carcinomas in German longhaired pointer dogs.

BACKGROUND: We previously reported a familial thyroid follicular cell carcinoma (FCC) in a large number of Dutch German longhaired pointers and identified two deleterious germline mutations in the TPO gene associated with disease predisposition. However, the somatic mutation profile of the FCC in dogs has not been investigated at a genome-wide scale. RESULTS: Herein, we comprehensively investigated the somatic mutations that potentially contribute to the inherited tumor formation and progression using high depth whole-genome sequencing. A GNAS p.A204D missense mutation was identified in 4 out of 7 FCC tumors by whole-genome sequencing and in 20 out of 32 dogs' tumors by targeted sequencing. In contrast to this, in the human TC, mutations in GNAS gene have lower prevalence. Meanwhile, the homologous somatic mutation in humans has not been reported. These findings suggest a difference in the somatic mutation landscape between TC in these dogs and human TC. Moreover, tumors with the GNAS p.A204D mutation had a significantly lower somatic mutation burden in these dogs. Somatic structural variant and copy number alterations were also investigated, but no potential driver event was identified. CONCLUSION: This study provides novel insight in the molecular mechanism of thyroid carcinoma development in dogs. German longhaired pointers carrying GNAS mutations in the tumor may be used as a disease model for the development and testing of novel therapies to kill the tumor with somatic mutations in the GNAS gene.

Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization.

Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.

Renal secondary hyperparathyroidism should be considered a differential diagnosis in forensic cases where animal abuse is suspected.

This case description reports an adult dog with multiple rib fractures that was initially suspected to be the victim of non-accidental trauma, but eventually was diagnosed with severe chronic interstitial nephritis and renal secondary hyperparathyroidism leading to fibrous osteodystrophy and multiple pathological fractures. The importance of the specific expertise of a dedicated expert panel on animal abuse is discussed. This case illustrates the significance of the identification of normal, pathological, and breed-related variations within an animal in addition to forensic expertise, emphasizing that the presence of multidisciplinary teams in an expert panel on animal abuse is crucial.

Clinical, ultrasonographic, and histopathologic findings in seven horses with Descemet's membrane detachment: A case series.

OBJECTIVE: To describe ultrasonography as a diagnostic method of in vivo Descemet's membrane detachment (DMD) in horses. ANIMALS STUDIED: Seven horses (three Icelandic horses, two Dutch Warmblood horses, one Appaloosa, and one Welsh Pony), presenting with moderate-to-severe focal or diffuse corneal edema, in whom DMD was suspected on ultrasonographic examination and confirmed with histopathology, were studied. PROCEDURE: A retrospective analysis of case records of horses with suspected DMD was performed. RESULTS: Median age at presentation was 14 years (range 11-24). Clinical signs in eyes with DMD were unilateral in all horses and included blepharospasm and epiphora (6/7), buphthalmos (5/7), moderate-to-severe focal or diffuse corneal edema (7/7), corneal epithelial bullae (4/7), corneal neovascularization (4/7), Haab's striae (2/7), corneal endothelial precipitates (1/7), fibrin in the anterior chamber (1/7), focal cataract (2/7), and pigment deposits on the anterior lens capsule (1/7). During transpalpebral ultrasonography, a distinct linear echogenic structure was noted in the anterior chamber, initially diverging from, and later running parallel to, the posterior lining of the cornea in all eyes studied. In all cases, the cornea was severely thickened and echogenic, consistent with edema, and DMD was suspected. In all horses, the clinical signs progressed and the affected eye was eventually enucleated. Histopathology revealed DMD (7/7), spindle cell proliferation (4/7), Descemet's membrane reformation (3/7), and inflammation of the anterior uvea (5/7). Overall incidence was 1.04%. CONCLUSIONS: Ultrasonography is an adequate tool in diagnosing DMD in horses. Descemet's membrane detachment should be included in the differential diagnosis in horses with dense focal or diffuse corneal edema.

Progressive retrocorneal pigmentation in dogs: A clinical report of 34 cases.

OBJECTIVES: To describe the signalment, ophthalmic examination findings, and follow-up of dogs affected with a previously unreported retrocorneal pigmentary lesion. MATERIALS AND METHODS: Retrospective record evaluation spanning 2009-2019. RESULTS: Retrocorneal pigmentary lesions were described in 34 patients (46 eyes). German Shepherds (n = 7), Jack Russel terriers (n = 5), and terrier crosses (n = 4) made up 16/34 (47.1%) of the cases. The mean age was 13.5 years (range 1.4-14.2 years), and 16/30 (53.3%) dogs were female. Most dogs were affected unilaterally (22/34 (64.7%)), the others bilaterally, and 5/34 (14.7%) were referred for it while the others were incidentally diagnosed. The lesions affected the ventral, peripheral, inner cornea and had a round/undulated leading edge. The number of corneal clock hours affected was known for 41/46 (89.1%) eyes and involved 1-3 clock hours in 32/41 (78.1%) eyes, 4-6 in 6/41 (14.6%), 7-9 in 2/41 (4.9%), and 10 in 1/41 (2.4%). The central cornea was affected in 9/46 (19.6%) eyes, and in 5/9 (55.6%), the median corneal clarity score was G2 (scale: G0-G4). The commonest additional findings included free-floating uveal cysts (11/34 dogs, 32.4%), cataracts (6/34 dogs, 17.6%), and primary glaucoma (5/34 dogs, 14.7%). Gonioscopy was available in 16/34 (47.1%) dogs and was normal except in primary glaucoma cases. Follow-up was documented in 13/34 (38.2%) dogs with a mean follow-up of 17 months (range: 5-26 months). Lesion progression was documented in 6/13 (46.2%) dogs. CONCLUSIONS: Retrocorneal pigmentation occurs as a slowly progressive lesion of older dogs that could impact vision. Histological studies of affected eyes are warranted.

Resection of urachal anomalies in dogs with recurrent lower urinary tract disease.

OBJECTIVE: To determine whether surgical removal of urachal anomalies improves the outcomes of dogs with recurrent lower urinary tract disease (LUTD) and bacterial urinary tract infection (BUTI). STUDY DESIGN: Retrospective study. ANIMALS: Thirty-three dogs with urachal anomalies and recurrent LUTD or BUTI. METHODS: Medical records of dogs with LUTD or BUTI and a diagnosis of urachal anomaly treated by partial cystectomy were reviewed. A minimum follow-up of 9 months was required for inclusion. RESULTS: Median age at onset of clinical signs was 12 months (range, 1 month to 10 years). Urachal anomalies were detected with histopathology in 20 of 28 (71%) dogs. At a median follow-up of 22 months (range, 9-114), 21 of 28 (64%) dogs were free of signs of LUTD. Nine (27%) dogs exhibited reduced signs of LUTD; in three (9%) dogs, no clinical improvement was observed. Among the 25 dogs with confirmed preoperative BUTI, 22 clinically improved with surgery. CONCLUSION: Partial cystectomy reduced the long-term severity of clinical signs and risk of recurrence of LUTD or BUTI in dogs with confirmed or suspected urachal anomalies. CLINICAL SIGNIFICANCE: Partial cystectomy should be considered as an adjunct to the treatment of LUTD and BUTI in dogs.

Instrumented cervical fusion in nine dogs with caudal cervical spondylomyelopathy.

OBJECTIVE: To report the long-term outcome of nine dogs treated for caudal cervical spondylomyelopathy (CCSM) with surgical spinal fusion. STUDY DESIGN: Short case series. ANIMALS: Nine large-breed dogs. METHODS: Medical records of dogs treated for disc-associated CCSM (2013-2016) were reviewed. The surgery objective was spinal distraction by implantation of a SynCage and fixation with two Unilock plates. Follow-up included the Helsinki pain score questionnaire, neurological grading, radiography, computed tomography (CT), and micro-CT (µCT) with subsequent histopathology (two dogs). RESULTS: Clinical follow-up was obtained between 9 and 51 months (27.4 ± 13.4 months). The Helsinki pain score and neurological Griffith score improved (P < .01) in all dogs and in eight of nine dogs, respectively. According to CT, the volume of bone (mean ± SD) through the cage was 79.5% ± 14.3%, including compact bone (53.0% ± 23.4%). Subsidence was seen in one of nine dogs. Implant failure was evident in four dogs, and plates were removed in two dogs. In seven of nine dogs, infraclinical pathology was observed in adjacent segment, associated with implants engaging adjacent intervertebral discs. Radiographic evidence of bony fusion between vertebral bodies was noted in all dogs. Spinal fusion was confirmed by µCT and histopathology in two cervical spine segments that became available at 22 and 40 months postoperatively. CONCLUSION: Instrumented spinal fusion in dogs with disc-associated CCSM resulted in owner satisfaction and radiographic evidence of interbody spinal fusion in all dogs. CLINICAL SIGNIFICANCE: The fusion distraction technique reported here can be used to achieve spinal fusion with a good long-term outcome.

Leukoencephalomyelopathy in cats linked to abnormal fatty acid composition of the white matter of the spinal cord and of irradiated dry cat food.

Four outbreaks of leukoencephalomyelopathy in colonies of SPF cats on a long-term diet of irradiated dry cat food were observed in the Netherlands between 1989 and 2001. As a primary defect in myelin formation was suspected to be the cause of the disease and myelin consists mainly of lipids and their fatty acids, we investigated the fatty acid composition of the white matter of the spinal cord of affected and control cats and of irradiated and non-irradiated food. The irradiated food had low levels of alpha-linolenic acid compared to linoleic acid as well as a high total omega-6:omega-3 ratio of 7:1 in the irradiated and of 2:1 in the non-irradiated food. The white matter of the spinal cord showed low levels of linoleic acid and absence of alpha-linolenic acid in affected cats as well as absence of lignoceric and nervonic acid in both affected and control cats. These abnormalities in fatty acid composition of the white matter of the spinal cord may reflect an increased need for alpha-linolenic acid as a substrate for longer chain omega-3 fatty acids to compose myelin and thus indicate a particular species sensitivity to dietary deficiency in omega-3 polyunsaturated fatty acids, particularly alpha-linolenic acid in cats. Our findings indicate that abnormalities in fatty acid metabolism in myelin play an essential role in the pathogenesis of this acquired form of leukoencephalomyelopathy in cats.

Pathological Findings in the Pituitary Glands of Dogs and Cats.

With the exception of classic functional adenomas in dogs and horses, pituitary lesions are infrequently described in the veterinary literature. Approximately 10% of pituitary glands from asymptomatic humans contain abnormalities, but the equivalent proportion in small animals is unknown. Pituitary glands from 136 dogs and 65 cats collected during routine necropsies were examined to determine the prevalence of pituitary lesions and their histopathological diagnosis. Lesions were characterized in sections stained with hematoxylin and eosin, periodic acid-Schiff (PAS), Gordon and Sweet's and reticulin stains, and immunohistochemistry for adrenocorticotropic hormone (ACTH), growth hormone, melanocyte stimulating hormone-α, and prolactin. Pituitary abnormalities were identified in 36 of 136 (26.4%) dogs and 10 of 65 (15.3%) cats. Cystic changes were the most common lesion, occurring in 18 (13.2%) dogs and 8 (12.3%) cats. Pituitary neoplasia was detected in 14.1% (12/85) of middle-aged and old dogs; 1 (1.5%) cat had pituitary nodular hyperplasia. PAS and reticulin stains helped differentiate ACTH-immunoreactive adenomas from hyperplastic nodules: adenomas contained PAS-positive intracytoplasmic granules and loss of the normal reticulin network. One dog had a pituitary carcinoma with infiltration into the thalamus. Other pituitary abnormalities included secondary metastases (2 dogs) and hypophysitis (4 dogs, 1 cat). In most cases, the lesion appeared to be subclinical and could be considered incidental, whereas clinical manifestations were apparent in only 4 dogs (2.9%) and none of the cats with pituitary lesions. Pituitary abnormalities are common in dogs and cats, and their clinical relevance requires further investigation.

Intervertebral Disc Degeneration in Warmblood Horses: Morphology, Grading, and Distribution of Lesions.

Equine intervertebral disc degeneration is thought to be rare and of limited clinical relevance, although research is lacking. To objectively assess pathological changes of the equine intervertebral disc and their clinical relevance, description of the normal morphology and a practical, biologically credible grading scheme are needed. The objectives of this study are to describe the gross and histological appearance of the equine intervertebral discs and to propose a grading scheme for macroscopic degeneration. Spinal units from 33 warmblood horses were grossly analyzed and scored. Of the 286 intervertebral discs analyzed, 107 (37%) were assigned grade 1 and grade 2 (considered normal) and were analyzed histologically. A nucleus pulposus and an annulus fibrosus could be identified macroscopically and histologically. Histologically, the nucleus pulposus was composed of a cartilaginous matrix and the annulus fibrosus of parallel collagenous bands. A transition zone was also histologically visible. Intra- and inter-observer reliability scores were high for all observers. Higher grades were associated with greater age. Gross changes associated with equine intervertebral disc degeneration (grades 3-5)-that is, yellow discoloration, cleft formation (tearing), and changes in consistency of the nucleus pulposus-were largely similar to those in humans and dogs and were most prevalent in the caudal cervical spine. Equine intervertebral disc degeneration was not associated with osteophyte formation. Changes of the vertebral bone were most common in the thoracolumbar spine but were not correlated with higher grades of intervertebral disc degeneration. Thus, changes of the vertebral bone should be excluded from grading for equine intervertebral disc degeneration.

The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs.

Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I-III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.

Inflammatory profiles in canine intervertebral disc degeneration.

BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. RESULTS: PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. CONCLUSIONS: PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.

CD200 receptor controls sex-specific TLR7 responses to viral infection.

Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200(-/-) mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R.

Estimated incidence rate and distribution of tumours in 4,653 cases of archival submissions derived from the Dutch golden retriever population.

BACKGROUND: A genetic predisposition for certain tumour types has been proven for some dog breeds. Some studies have suggested that this may also be true for the Golden retriever breed. The present study aimed to examine a possible existence of a tumour (type) predisposition in the Dutch population of Golden retrievers by evaluating annual estimated incidence rates compared to incidence rates from previous publications. A second aim was to evaluate whether incidences of various tumours differed as related to the diagnostic method chosen, being either cytology or histology. RESULTS: Tumours submitted to Utrecht University during the period 1998-2004 diagnosed either by means of cytology (n = 2,529) or histology (n = 2,124), were related to an average annual Dutch kennel club population of 29,304 Golden retrievers.Combining individual tumours from both the cytological and the histopathological data-set resulted in an annual estimated incidence rate of 2,242 for 100,000 dog-years at risk regarding tumour development in general.The most common cytological tumor diagnoses were 'fat, possibly lipoma' (35%), mast cell tumour (21%) and non-Hodgkin lymphoma (10%). The most commonly diagnosed tumours by histology were mast cell tumour (26%), soft tissue sarcomas (11%) and melanoma (8%). Both the cytological and histopathological data-sets, showed variation; in patient age distribution, age of onset and incidence of various tumours. CONCLUSION: Comparing our data with previous reports in non-breed-specified dog populations, the Golden retriever breed shows an increased risk for the development of tumours in general, as well as an increased risk for the development of specific tumour types, including the group of soft tissue sarcomas. Variations in age, location and incidence of various tumours were observed between the two data-sets, indicating a selection bias for diagnostic procedure.

Distichiasis in a ferret (Mustela putorius furo).

A 4-year-old intact male ferret was presented to the Ophthalmology Service of the Department of Clinical Sciences of Companion Animals of Utrecht University with chronic blepharospasm, epiphora, and conjunctivitis of the right eye. Examination of the eye revealed mild conjunctivitis and three hairs protruding from the openings of meibomian glands in the upper eyelid, providing the clinical diagnosis of distichiasis. The distichia were removed by transconjunctival unipolar electrocautery. Recovery was uneventful, but the original signs recurred 10 weeks after surgery. Ophthalmic examination revealed another distichia at a different location in the same eyelid and it was removed by full-thickness wedge excision. Histopathological examination failed to reveal the exact origin of the distichia. To our knowledge, this is the first reported case of distichiasis in a ferret.

Complete surgical removal of a very enlarged pituitary corticotroph adenoma in a dog.

A 13 yr old castrated male vizsla was referred to the authors' institute because of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in width. Medical therapy was initiated with trilostane. Despite adequate control of the hypercortisolemia, the polyuria and polydipsia persisted and the dog developed neurologic signs due to the pituitary mass effect. Pituitary transsphenoidal debulking surgery was performed and immunocytochemistry confirmed a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem examination revealed an empty fossa without pituitary remnants and the presence of a malignant pheochromocytoma in the right adrenal gland. This case report demonstrates, for the first time, that a large pituitary adenoma in the dog may be treated successfully by pituitary surgery.

Pathologic Changes in and Immunophenotyping of Polymyositis in the Dutch Kooiker Dog.

Earlier, we described a breed-specific inflammatory myopathy in Dutch Kooiker dogs (Het Nederlandse Kooikerhondje), one of the nine Dutch breeds. The disease commonly manifests itself with clinical signs of difficulty walking, muscle weakness, exercise intolerance, and/or dysphagia. In nearly all dogs' creatine kinase (CK) activity was elevated. Histopathology reveals the infiltration of inflammatory cells within the skeletal muscles. The objective of this study was to further investigate and characterize the histopathological changes in muscle tissue and immunophenotype the inflammatory infiltrates. FFPE fixed-muscle biopsies from 39 purebred Kooiker dogs were included and evaluated histopathologically according to a tailored classification scheme for skeletal muscle inflammation. As in other breed-related inflammatory myopathies, multifocal, mixed, and predominantly mononuclear cell infiltration was present, with an initial invasion of viable muscle fibres and the surrounding stroma leading to inflammation, necrosis, and tissue damage. Immunophenotyping primarily revealed lymphohistiocytic infiltrates, with CD3+ T-cells being the predominant inflammatory cell type, accompanied by CD8+ cytotoxic T-cells. The concurrent expression of MHC-II class molecules on myofibres suggests their involvement in initiating and maintaining inflammation. Additionally, CD20+ B-cells were identified, though in lower numbers compared to T-cells, and IBA-1-positive macrophages were frequently seen. These findings suggest a breed-specific subtype of polymyositis in Kooiker dogs, akin to other breeds. This study sheds light on the immune response activation, combining adaptive and innate mechanisms, contributing to our understanding of polymyositis in this breed.

Equine sarcoidosis: clinical signs, diagnosis, treatment and outcome of 22 cases.

BACKGROUND: Equine sarcoidosis may present as a generalized or localized exfoliative dermatitis and/or as a granulomatous inflammation of multiple organs. OBJECTIVES: To report the clinical signs, diagnosis, treatment and outcome for 22 horses with histologically confirmed sarcoidosis. ANIMALS: Twenty-two horses of different breeds, between 3 and 17 years of age. METHODS: Diagnosis was based on clinical signs and histopathological findings. RESULTS: The following three forms of equine sarcoidosis were identified: generalized (13.6%), partially generalized (18.2%) and localized (68.2%). High-dose systemic corticosteroids were used as the initial treatment in all three forms, followed by lower doses for a variable number of weeks. No local treatment was prescribed. Case outcome was variable; one of three cases of generalized sarcoidosis was euthanized immediately and the remaining two were euthanized after 2-3 months of unsuccessful treatment; all four cases of partially generalized sarcoidosis deteriorated despite treatment and were euthanized after 3.5-12 months; two cases with localized disease showed no response or insufficient response to treatment and were euthanized; four cases recovered fully with or without treatment, and one showed partial recovery without treatment; and eight cases improved whilst receiving prednisolone but required continuous low doses to maintain remission. CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the different forms of sarcoidosis based on history, clinical appearance and histopathology assisted in making an informed choice between treatment and euthanasia and prevented unnecessary local treatment. Equine sarcoidosis should be included in the differential diagnosis of a localized exfoliative dermatitis of unknown origin.

Equine sarcoidosis.

Equine sarcoidosis seems to be an emerging problem. As more horses are referred for dermatologic disease, equine sarcoidosis should be considered in any case of exfoliative and/or nodular skin disease with or without systemic involvement, including generalized granulomatous disease affecting most internal organs. Multiple breeds are affected with mares being predisposed. Affected horses are typically 3 years or older. The prognosis for generalized granulomatous disease is generally poor, whereas the prognosis for the localized cutaneous form is favorable but may require lifelong treatment.