Dermoid cysts formation is a complication of wound pinch grafting in a horse: A case report.

OBJECTIVES: To describe dermoid cyst formation as an uncommon complication of the pinch grafting technique in horses. STUDY DESIGN: Case report. ANIMAL: A 8 year old Arabian gelding. METHODS: Clinical presentation, imaging, treatment, and histopathology records were reviewed. The horse originally presented due to delayed healing of a laceration to the distal aspect of the metatarsus. The wound was treated initially with debridement and it was allowed to fill with healthy granulation tissue prior to pinch grafting. Two months after grafting, the horse started to show self-mutilation behavior targeting the wound site. Ultrasonographic examination revealed the presence of cystic lesions in the subcutaneous tissue in the wound bed and adjacent to the long digital extensor tendon. RESULTS: Treatment involved surgical excision of the cysts, which resulted in a resolution of the self-mutilation episodes. The specimens were submitted for histopathological investigation, which revealed findings compatible with dermoid cyst formation, suspected to be secondary to the skin-grafting procedure. CONCLUSION: Dermoid cysts formation should be considered as a potential differential diagnosis for skin graft complications in horses.

Surgical removal of intra-articular loose bodies from the cervical articular process joints in 5 horses.

OBJECTIVE: To describe the surgical removal of intra-articular loose bodies (LBs) from the cervical articular process joints (APJs) in five horses and to describe the outcome of the surgery. STUDY DESIGN: Short case series. ANIMALS: Five client-owned horses with naturally occurring LBs within the cervical APJs. METHODS: Medical records were reviewed of horses that were diagnosed with LBs of the cervical APJs on computed tomography (CT), where the LBs were subsequently removed surgically. Details of case selection and surgical technique were reviewed along with postoperative complications and clinical outcome. Histopathology was performed on LBs in some cases. RESULTS: Surgery was performed on six APJs in five horses. Of the 14 LBs identified with CT, 13 were successfully removed from the C4/C5, C5/C6 and C6/C7 articulations. No surgical complications were encountered, and clinical signs of cervical dysfunction improved in all horses. All clinical cases returned to ridden work by 6 months post surgery. Histopathologic examination revealed the removed structures to be osteochondral or chondral loose bodies consisting of cartilaginous proliferation with or without ossification and central necrosis. CONCLUSIONS: Surgical removal of LBs is achievable from the cervical APJs and can result in the resolution of cervical pain. This procedure offers a new treatment option for management of selected horses with cervical pain, following thorough assessment and CT imaging.

Cross-species models of human melanoma.

Although transformation of melanocytes to melanoma is rare, the rapid growth, systemic spread, as well as the chemoresistance of melanoma present significant challenges for patient care. Here we review animal models of melanoma, including murine, canine, equine, and zebrafish models, and detail the immense contribution these models have made to our knowledge of human melanoma development, and to melanocyte biology. We also highlight the opportunities for cross-species comparative genomic studies of melanoma to identify the key molecular events that drive this complex disease.

Histological and Histopathological Features of the Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove in Thoroughbred Horses with Racing History.

Information regarding the histopathology of the proximal phalanx (P1) sagittal groove in racehorses is limited. Twenty-nine cadaver limbs from nine Thoroughbred racehorses in racing/race-training underwent histological examination. Histological specimens of the third metacarpal/metatarsal (MC3/MT3) parasagittal grooves and P1 sagittal grooves were graded for histopathological findings in hyaline cartilage (HC), calcified cartilage (CC), and subchondral plate and trabecular bone (SCB/TB) regions. Histopathological grades were compared between (1) fissure and non-fissure locations observed in a previous study and (2) dorsal, middle, and palmar/plantar aspects. (1) HC, CC, and SCB/TB grades were more severe in fissure than non-fissure locations in the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades were more severe in fissure than non-fissure locations in the P1 sagittal groove (p < 0.001). (2) HC, CC, and SCB/TB grades including SCB collapse were more severe in the palmar/plantar than the middle aspect of the MC3/MT3 parasagittal groove (p < 0.001). SCB/TB grades including SCB collapse were more severe in the dorsal and middle than the palmar/plantar aspect of the P1 sagittal groove (p < 0.001). Histopathology in the SCB/TB region including bone fatigue injury was related to fissure locations, the palmar/plantar MC3/MT3 parasagittal groove, and the dorsal P1 sagittal groove.

Comparison of cone-beam and fan-beam computed tomography and low-field magnetic resonance imaging for detection of proximal phalanx dorsoproximal osteochondral defects.

BACKGROUND: Dorsoproximal osteochondral defects commonly affect the proximal phalanx, but information about diagnosis on computed tomography (CT) and magnetic resonance imaging (MRI) is limited. OBJECTIVES: To assess CT and MRI diagnoses of osteochondral defects, describe the lesions and compare sensitivity and specificity of the modalities using macroscopic pathology as gold standard. STUDY DESIGN: Cross-sectional study. METHODS: Thirty-five equine cadaver limbs underwent standing cone-beam CT (CBCT), fan-beam CT (FBCT), low-field MRI and pathological examination. CT and MR images were examined for proximal phalanx dorsomedial and dorsolateral eminence osteochondral defects. Defect dimensions were measured. Imaging diagnoses and measurements were compared with macroscopic examination. RESULTS: Fifty-six defects were seen over 70 potential locations. On CBCT and FBCT, osteochondral defects appeared as subchondral irregularity/saucer-shaped defects. On MRI, osteochondral defects were a combination of articular cartilage defect on dorsal images and subchondral flattening/irregularity on sagittal images. Subchondral thickening and osseous short tau inversion recovery hyperintensity were found concurrent with osteochondral defects. Compared with pathological examination, the sensitivity and specificity of diagnosis were 86% (95% confidence interval [95% CI] 75%-93%) and 64% (95% CI 38%-85%) for FBCT; 64% (95% CI 51%-76%) and 71% (95% CI 46%-90%) for CBCT; and 52% (95% CI 39%-65%) and 71% (95% CI 46%-90%) for MRI. Sensitivity of all modalities increased with defect size. Macroscopic defect dimensions were strongly correlated with CBCT (r = 0.76, p < 0.001) and moderately correlated with FBCT and MRI (r = 0.65, p < 0.001). Macroscopic measurements were significantly greater than all imaging modality dimensions (p < 0.001), potentially because macroscopy included articular cartilage pathology. MAIN LIMITATIONS: Influence of motion artefact could not be assessed. CONCLUSIONS: Osteochondral defects could be visualised using both CT and MRI with sensitivity increasing with defect size. Diagnostic performance was best using FBCT, followed by CBCT then MRI, but CBCT-measured defect size best correlated with macroscopic examination. MRI provided useful information on fluid signal associated with defects, which could represent active pathology.

The equine umbilical cord in clinically healthy pregnancies.

BACKGROUND: Excessive umbilical cord length (UCL) is associated with equine pregnancy loss. However, a lack of UCL reference values makes it difficult to define excessive UCL. Further, factors associated with differences in UCL are poorly understood. OBJECTIVES: To (i) report the total, allantoic and amniotic UCL in healthy term pregnancies in Thoroughbreds, (ii) describe the relationship between gestational age and UCL, fetal weight and crown rump length (CRL) using clinically normal pregnancies (CNPs) from mares dying during gestation, and (iii) identify associations between UCL and maternal age and parity, paternal age, and fetal sex. STUDY DESIGN: Cross-sectional. METHODS: Data including UCLs, fetal weight, CRL and maternal age, parity, paternal age and fetal sex were taken from CNPs from Thoroughbred mares dying during gestation (n = 32), and placentas from HTPs (n = 34) in England. Correlations were assessed using Spearman's rank with significant correlations estimated by locally weighted scatter plot smoothing (LOWESS). Regression plots were fitted to highly correlated variables to further assess and quantify relationships. Differences in UCL between categorical variables were assessed using Kruskall Wallis and Mann-Whitney U tests. RESULTS: The median total, amniotic and allantoic HTP UCLs were 53.5 cm (interquartile range [IQR] 16), 29.5 cm (IQR 7) and 25.0 cm (IQR 8) respectively. Gestational age and amniotic UCL were moderately correlated (rho = 0.53, p = 0.04), with LOWESS estimating an exponential increase followed by plateauing at around Day 200. Nonlinear associations were observed between fetal weight and gestational age and CRL (adjusted r2 = 0.98 and 0.95 respectively). A linear association was observed between gestational age and CRL: predicted CRL = -17.60 + 0.38 × gestational age, p < 0.001. MAIN LIMITATIONS: Limited availability of CNPs from mares dying during gestation. Estimated relationships can only approximate growth. CONCLUSIONS: This study provides important UCL and fetal size reference values, which may aid in assessing abnormalities. For the first time, associations between UCL and gestational age have been described.

Comparison of cone-beam and fan-beam computed tomography and low-field magnetic resonance imaging for detection of palmar/plantar osteochondral disease in Thoroughbred horses.

BACKGROUND: Palmar/plantar osteochondral disease (POD) of the metacarpal/tarsal condyles is a common pathological finding in racehorses. OBJECTIVE: To compare diagnoses, imaging details, and measurements of POD lesions between cone-beam computed tomography CT (CBCT), fan-beam CT (FBCT), and low-field magnetic resonance imaging (MRI) using macroscopic pathology as a gold standard. STUDY DESIGN: Cross-sectional study. METHODS: Thirty-five cadaver limbs from 10 horses underwent CBCT, FBCT, MRI, and macroscopic examination. CT and MR images were examined for presence of POD, imaging details of POD, and measurements of POD dimensions and areas. Imaging diagnoses, details, and measurements were compared with macroscopic examination and between modalities. RESULTS: Forty-eight POD lesions were seen over 70 condyles. Compared with macroscopic examination the sensitivity and specificity of diagnosis were 95.8% (CI95 = 88%-99%) and 63.6% (CI95 = 43%-81%) for FBCT, 85.4% (CI95 = 74%-94%) and 81.8% (CI95 = 63%-94%) for CBCT, and 69.0% (CI95 = 54%-82%) and 71.4% (CI95 = 46%-90%) for MRI. Inter-modality agreement on diagnosis was moderate between CBCT and FBCT (κ = 0.56, p < 0.001). POD was identified on CT as hypoattenuating lesions with surrounding hyperattenuation and on MRI as either T1W, T2*W, T2W, and STIR hyperintense lesions or T1W and T2*W heterogeneous hypointense lesions with surrounding hypointensity. Agreement on imaging details between CBCT and FBCT was substantial for subchondral irregularity (κ = 0.61, p < 0.001). Macroscopic POD width strongly correlated with MRI (r = 0.81, p < 0.001) and CBCT (r = 0.79, p < 0.001) and moderately correlated with FBCT (r = 0.69, p < 0.001). Macroscopic POD width was greater than all imaging modality (p < 0.001). MAIN LIMITATIONS: Effect of motion artefact in live horse imaging could not be assessed. CONCLUSIONS: All imaging modalities were able to detect POD lesions, but underestimated lesion size. The CT systems were more sensitive, but the differing patterns of signal intensity may suggest that MRI can detect changes associated with POD pathological status or severity. The image features observed by CBCT and FBCT were similar.

Three-Dimensional Imaging and Histopathological Features of Third Metacarpal/Tarsal Parasagittal Groove and Proximal Phalanx Sagittal Groove Fissures in Thoroughbred Horses.

Fissure in the third metacarpal/tarsal parasagittal groove and proximal phalanx sagittal groove is a potential prodromal pathology of fracture; therefore, early identification and characterisation of fissures using non-invasive imaging could be of clinical value. Thirty-three equine cadaver limbs underwent standing cone-beam (CB) computed tomography (CT), fan-beam (FB) CT, low-field magnetic resonance imaging (MRI), and macro/histo-pathological examination. Imaging diagnoses of fissures were compared to microscopic examination. Imaging features of fissures were described. Histopathological findings were scored and compared between locations with and without fissures on CT. Microscopic examination identified 114/291 locations with fissures. The diagnostic sensitivity and specificity were 88.5% and 61.3% for CBCT, 84.1% and 72.3% for FBCT, and 43.6% and 85.2% for MRI. Four types of imaging features of fissures were characterised on CT: (1) CBCT/FBCT hypoattenuating linear defects, (2) CBCT/FBCT striated hypoattenuated lines, (3) CBCT/FBCT subchondral irregularity, and (4) CBCT striated hypoattenuating lines and FBCT subchondral irregularity. Fissures on MRI appeared as subchondral bone hypo-/hyperintense defects. Microscopic scores of subchondral bone sclerosis, microcracks, and collapse were significantly higher in locations with CT-identified fissures. All imaging modalities were able to identify fissures. Fissures identified on CT were associated with histopathology of fatigue injuries.

Identification of Heterotopic Mineralization and Adjacent Pathology in the Equine Fetlock Region by Low-Field Magnetic Resonance Imaging, Cone-Beam and Fan-Beam Computed Tomography.

Heterotopic mineralization in equine distal limbs has been considered an incidental finding and little is known about its imaging features. The study aimed to identify heterotopic mineralization and adjacent pathology in the fetlock region with cone-beam (CB) computed tomography (CT), fan-beam (FB) CT, and low-field magnetic resonance imaging (MRI). Images from 12 equine cadaver limbs were examined for heterotopic mineralization and adjacent pathology and verified by macro-examination. Retrospective review of the CBCT/MR images from 2 standing horses was also included. CBCT and FBCT identified twelve mineralization's with homogeneous hyperattenuation: oblique-sesamoidean-ligament (5) without macroscopic abnormality; deep-digital-flexor-tendon (1) and suspensory-branch (6) with macroscopic abnormalities. MRI failed to identify all mineralization's, but detected suspensory branch splitting, and T2 and STIR hyperintensity in 4 suspensory-branches and 3 oblique-sesamoidean-ligaments. Macro-examination found corresponding disruption/splitting and discoloration. All modalities identified 7 ossified fragments showing cortical/trabecular pattern: capsular (1), palmar sagittal ridge (1), proximal phalanx (2) without macroscopic abnormality, and proximal sesamoid bones (3). On MRI, fragments were most identifiable on T1 images. All abaxial avulsions had suspensory-branch splitting on T1 images with T2 and STIR hyperintensity. Macro-examination showed ligament disruption/splitting and discoloration. Suspensory-branch/intersesamoidean ligament mineralization's were identified by CBCT in standing cases; 1 had associated T2 hyperintensity. Both CT systems were generally superior in identifying heterotopic mineralization's than MRI, while MRI provided information on soft tissue pathology related to the lesions, which may be important for management.

First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c.2032G>A.

BACKGROUND: Warmblood Fragile Foal Syndrome Type 1 (WFFS) is an autosomal recessive disorder reported previously only in warmbloods and thought to be caused by a variant in the gene procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1, c.2032G>A, p.Gly678Arg). Given the presentation of this Thoroughbred case, we hypothesised that a similar genetic mechanism caused this phenotype. OBJECTIVES: To describe the pathological and genetic findings on a foal presenting to a veterinary practice in the UK with skin lesions similar to other Ehlers-Danlos Syndromes, including those documented for warmbloods with WFFS. STUDY DESIGN: A single case report describing a genetic investigation. METHODS: A Thoroughbred foal presenting as dystocia was euthanised for multiple skin lesions and developmental abnormalities. DNA extracted from the foal was tested for the PLOD1 variant (c.2032G>A, p.Gly678Arg) using the commercially available assay. To confirm causality and further interrogate potential novel causes of Ehlers-Danlos Syndrome, 1799 functional candidate genes, including PLOD1, were analysed using whole genome sequencing data generated from DNA extracted from the foal's muscle. These data were compared to 34 control samples from at least 11 other breeds. Variants were prioritised for further evaluation based on predicted impact on protein function. RESULTS: Post-mortem evaluation concluded that this foal suffered from a condition of collagen dysplasia. The foal was homozygous for the c.2032G>A PLOD1 variant. Only two other missense variants identified from whole genome sequencing data were also computationally predicted to be deleterious to protein function, (NPHP3 c.1253T>C, p.Leu418Pro, EPDR1 c.154G>C, p.Glu52Gln). Neither of these genes have been linked to similar phenotypes, or Ehlers-Danlos Syndrome in humans or other species and thus further investigation of these variants as the cause of EDS was not warranted. MAIN LIMITATIONS: This study is a single case report in the Thoroughbred with no additional cases from this breed yet identified to replicate this finding. CONCLUSIONS: Given the clinical presentation similar to WFFS, homozygosity for the PLOD1 variant, and absence of another more plausible causal variant from the WGS experiment, we conclude that PLOD1 c.2032G>A is the likely cause of this foal's condition. This is the first documented evidence of fragile foal syndrome caused by the PLOD1 variant in a breed outside of warmbloods, the Thoroughbred. We therefore recommend a change in the name of this disorder to fragile foal syndrome type 1 (FFS) and utilisation of genetic testing in Thoroughbreds to avoid producing affected foals.

Incidence and causes of pregnancy loss after Day 70 of gestation in Thoroughbreds.

BACKGROUND: Pregnancy loss after Day 70 of gestation manifests as abortion, stillbirth or perinatal death. While previous studies have reported the diagnoses of laboratory submissions, none have quantified the incidence and causes of abortions, stillbirths and perinatal mortality at a population level. OBJECTIVES: To report the incidence and causes of pregnancy loss after Day 70 of gestation in a cohort of Thoroughbreds. STUDY DESIGN: Retrospective cohort study. METHODS: Outcomes of Day 70 pregnancies were collected from eight Thoroughbred farms over the 2013-2017 breeding seasons. Stud, veterinary and laboratory records were supplemented with publicly available data. Cause of loss was categorised using custom criteria. RESULTS: Data were collected on 3,586 pregnancies from 1,802 mares. The incidence risk of a pregnancy failing to produce a live foal at 24 hours post parturition was 7.3% (95% confidence interval (CI) 6.5-8.2, equating to 7.3 cases per 100 Day-70 pregnancies). The incidence of pregnancy loss between Day 70 and 300 of gestation, Day 301-315 and stillbirth/perinatal death was 4.0% (95% CI 3.4-4.7), 0.3% (95% CI 0.2-0.6) and 1.4% (95% CI 1.1-1.9) respectively. Of the pregnancy losses where tissue was available, 61.1% were submitted for post-mortem examination. The incidence risk of loss due to umbilical cord-related pathologies was 1.5% (95% CI 1.1-1.9), 0.4% (95% CI 0.2-0.6) for noninfectious placental disease and 0.3% (95% CI 0.2-0.6) for both infectious placentitis and Equine Herpesvirus infection. No primary diagnosis was made in 11.2% of the cases which underwent full post-mortem examination. MAIN LIMITATIONS: It was not possible to differentiate between intra-partum stillbirth and early post-partum death. CONCLUSION: Pregnancy loss after Day 70 of gestation is a significant source of loss in the Thoroughbred with umbilical cord-related pathologies being the most commonly diagnosed cause. Reporting the incidence of pregnancy loss at a population level with clear case definitions will allow for accurate global comparisons.

Equine renal hemangiosarcoma: clinical presentation, pathologic features, and pSTAT3 expression.

Hemangiosarcoma is an uncommon tumor in horses. We characterized 3 cases of equine renal hemangiosarcoma, focusing on clinical and pathologic features, and describe occurrence of the epithelioid variant of hemangiosarcoma in one of these cases. Nuclear expression of phosphorylated STAT3 (pSTAT3) was assessed to analyze potential inappropriate STAT3 activation as a component of tumor pathogenesis. Clinical signs in the 3 horses included insidious weight loss, followed in one case by serosanguineous nasal discharge and terminal epistaxis, and nonspecific signs of abdominal pain. Two of the hemangiosarcomas had a classical histopathologic appearance; in the other, neoplastic cells were polygonal and were arranged in densely packed sheets, resembling the epithelioid variant. Cross-reactivity of a pSTAT3 antibody was established by demonstration of pSTAT3 expression in the epithelium of glabrous skin by immunoblotting and immunohistochemistry. In the epithelioid hemangiosarcoma, ~40% of neoplastic cells exhibited nuclear pSTAT3 expression, but in the other 2 cases, expression was weak and variable in the neoplastic population, although stromal cell pSTAT3 activity was evident in pulmonary metastases in one case.