Assessment of SOX10 expression in 437 canine neoplasms of different embryologic origins.

Several members of the SRY-related HMG-box (SOX) protein family are implicated in tumorigenesis, metastasis, and regulation of the tumor microenvironment. SOX10, which is involved in neural crest cell migration and differentiation, has long been recognized a sensitive and specific immunohistochemical (IHC) marker in the diagnosis of melanoma in humans. However, expression of SOX10 in other tumor types has infrequently been evaluated in humans until recently and has not been thoroughly investigated in the dog. Our aim was to characterize the expression of SOX10 in canine neoplasms to objectively assess its value as a diagnostic IHC marker. Immunohistochemistry for SOX10 was performed on 437 archived, formalin-fixed paraffin-embedded tissues from representative canine neoplasms of ectodermal (15 tumor types), mesodermal (13 tumor types), endodermal (8 tumor types), and mixed/unknown (7 tumor types) embryologic origin. Oral and cutaneous tumors of melanocytic origin were used as positive controls. Intense SOX10 immunolabeling was observed in most tumors of ectodermal origin, including consistent expression in mammary carcinomas, and gliomas. Embryonal and hair follicle neoplasms inconsistently exhibited strong nuclear immunolabeling. Oral fibrosarcomas and undifferentiated oral sarcomas both inconsistently exhibited moderate to strong nuclear immunolabeling. Neoplasms of mesodermal and endodermal origin lacked immunolabeling. Salivary carcinomas, representing an unknown/mixed embryologic origin, were strongly labeled. SOX10 expression is not limited to melanomas, but is expressed by canine tumors of diverse tissues and embryologic derivation. Importantly, expression of SOX10 by a subset of oral sarcomas impairs its value as a marker for spindle cell oral melanomas.

Combining ultrasound radiomics, complete blood count, and serum biochemical biomarkers for diagnosing intestinal disorders in cats using machine learning.

This retrospective analytical observational cohort study aimed to model and predict the classification of feline intestinal diseases from segmentations of a transverse section from small intestine ultrasound (US) image, complete blood count (CBC), and serum biochemical profile data using a variety of machine-learning approaches. In 149 cats from three institutions, images were obtained from cats with biopsy-confirmed small cell epitheliotropic lymphoma (lymphoma), inflammatory bowel disease (IBD), no pathology ("healthy"), and other conditions (warrant a biopsy for further diagnosis). CBC, blood serum chemistry, small intestinal ultrasound, and small intestinal biopsy were obtained within a 2-week interval. CBC and serum biomarkers and radiomic features were combined for modeling. Four classification schemes were investigated: (1) normal versus abnormal; (2) warranting or not warranting a biopsy; (3) lymphoma, IBD, healthy, or other conditions; and (4) lymphoma, IBD, or other conditions. Two feature selection methods were used to identify the top 3, 5, 10, and 20 features, and six machine learning models were trained. The average (95% CI) performance of models for all combinations of features, numbers of features, and types of classifiers was 0.886 (0.871-0.912) for Model 1 (normal vs. abnormal), 0.751 (0.735-0.818) for Model 2 (biopsy vs. no biopsy), 0.504 (0.450-0.556) for Model 3 (lymphoma, IBD, healthy, or other), and 0.531 (0.426-0.589), for Model 4 (lymphoma, IBD, or other). Our findings suggest model accuracies above 0.85 can be achieved in Model 1 and 2, and that including CBC and biochemistry data with US radiomics data did not significantly improve accuracy in our models.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

BACKGROUND: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. METHODS: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. RESULTS: Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. CONCLUSIONS: The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

Evaluation of the Use of Single- and Multi-Magnification Convolutional Neural Networks for the Determination and Quantitation of Lesions in Nonclinical Pathology Studies.

Digital pathology platforms with integrated artificial intelligence have the potential to increase the efficiency of the nonclinical pathologist's workflow through screening and prioritizing slides with lesions and highlighting areas with specific lesions for review. Herein, we describe the comparison of various single- and multi-magnification convolutional neural network (CNN) architectures to accelerate the detection of lesions in tissues. Different models were evaluated for defining performance characteristics and efficiency in accurately identifying lesions in 5 key rat organs (liver, kidney, heart, lung, and brain). Cohorts for liver and kidney were collected from TG-GATEs open-source repository, and heart, lung, and brain from internally selected R&D studies. Annotations were performed, and models were trained on each of the available lesion classes in the available organs. Various class-consolidation approaches were evaluated from generalized lesion detection to individual lesion detections. The relationship between the amount of annotated lesions and the precision/accuracy of model performance is elucidated. The utility of multi-magnification CNN implementations in specific tissue subtypes is also demonstrated. The use of these CNN-based models offers users the ability to apply generalized lesion detection to whole-slide images, with the potential to generate novel quantitative data that would not be possible with conventional image analysis techniques.

An Angiomyomatous Hamartoma With Features of Vascular Transformation of Sinuses in the Mediastinal Lymph Node of a Beagle Dog.

Two similar benign, nonneoplastic vascular lesions have been described in the lymph nodes of humans and animals: angiomyomatous hamartoma (AMH), which is characterized by the replacement of lymphoid tissue by blood vessels, smooth muscle, and fibrous tissue, and vascular transformation of sinuses (VTS), which is considered a reactive transformation of lymph node sinuses into capillary-like vascular channels. We hereby report a lesion with features common to both lesions in the mediastinal lymph nodes of a 1-year-old beagle dog in a 1-month toxicity study. Grossly, enlargement and red discoloration were observed, while microscopically, the lesion was characterized by effacement of the lymph node parenchyma with replacement by mature blood vessels, smooth muscle, and fibrous tissue, associated with lymphoid atrophy, which is consistent with AMH. However, multifocal areas of anastomosing or plexiform capillary-like channels lined by normal to slightly plump endothelium, similar to those described for VTS, were also present. Immunohistochemistry analysis revealed abundant positive staining for smooth muscle actin and endothelial cells (von Willebrand factor/factor VIII) and the absence of proliferation (Ki67). In conclusion, these lesions most likely represent a mixture of both AMH and VTS.

Unusual Incidence and Location of Renaut Bodies in Beagle Dogs in a Nonclinical Study.

We identified the presence of Renaut bodies in an unusual location in Beagle dogs on a 3-month nonclinical toxicity study. These peculiar structures are commonly reported as a background finding in the sciatic nerve of dogs. In our study, however, they were also observed in autonomic nerves surrounding the adrenal gland, a location in which they have not been reported before. The incidence in both locations were 8 of 32 Beagle dogs in the sciatic nerve and 6 of 40 Beagle dogs around the adrenal gland in the dosing and/or recovery phases of the study.

Malignant transformation of an intraparenchymal hemangioma in the cervical spinal cord of a German shepherd dog.

An 8-year-old female spayed German shepherd dog was presented for evaluation of a 1-week history of right thoracic limb monoparesis. Magnetic resonance imaging (MRI) identified an intraparenchymal, T2 hypointense and T1 isointense, strongly heterogeneously contrast-enhancing mass with moderate internal susceptibility artifact on T2* images at the level of the cranial extent of the C5 vertebral body. Euthanasia was elected after a rapid neurologic decline in the 24 hours after MRI. Necropsy and histopathology identified an intraparenchymal hemangiosarcoma arising from a hemangioma in the cervical spinal cord, with no evidence of neoplastic disease in any other examined organs. The spectrum of vasoproliferative disorders in the central nervous system in veterinary species has been codified recently, but hemangiosarcoma is considered metastatic to the central nervous system. Herein we describe the clinical, imaging, and histologic findings in a dog with a novel primary location of hemangiosarcoma in the cervical spinal cord.

Bulging after DIEP Breast Reconstruction: New Insights Concerning Rectus Diastasis and Medial Perforator Harvest.

The aim of this study was to evaluate the association between flap harvest technique and occurrence of abdominal bulging. Methods: A retrospective analysis of 159 patients undergoing DIEP flap breast reconstruction between 2014 and 2021 in the University Medical Center Utrecht was conducted. Outcomes measured were preoperative rectus diastasis, flap weight, laterality of flap harvest (unilateral or bilateral), timing of the harvest (immediate or delayed), number of perforators harvested (single or multiple), and location of the harvested perforator (medial, lateral, or both). Results: In 159 patients, 244 DIEP flaps were performed, 16 of these donor-sites (6.6%) developed a clinically evident abdominal bulge. When preoperative rectus abdominis diastasis was found (n = 97), postoperative bulging occurred significantly more often (P < 0.01). Patients in whom the medial perforator artery was harvested for reconstruction (n = 114) showed less abdominal bulging than patients in whom the lateral (n = 92) was harvested (P = 0.02). Using single versus multiple perforators for the DIEP flap, bilateral versus unilateral reconstruction or timing of the operation showed no significant difference in outcome of bulging (P = 1.00, P = 0.78, P = 0.59, respectively). Conclusions: The incidence of bulging in our study cohort is comparable to the literature. Harvesting the medial perforator artery for the DIEP flap showed less abdominal bulging than using the lateral perforator artery in a DIEP flap breast reconstruction. Also, preoperative rectus diastasis was found to be an important risk factor for the occurrence of bulging.

Unique cytologic and imaging features of a lumbosacral oligodendroglioma in a cat.

A 12-y-old castrated male domestic longhaired cat had progressive paraparesis and neurolocalization of L4-S3. MRI revealed a circumscribed intradural-extraparenchymal mass from L5 to S1 that was T2 and short tau inversion recovery hyperintense and strongly contrast-enhancing. Cytologic interpretation of a blind fine-needle aspirate obtained through the L5-L6 space was a tumor of probable mesenchymal origin. A pair of suspect neoplastic cells was seen on a cytocentrifuged preparation of the atlanto-occipital CSF sample, despite a normal nucleated cell count (0 × 106/L) and total protein (0.11 g/L) with only 3 RBCs × 106/L. Clinical signs progressed despite increasing doses of prednisolone and cytarabine arabinoside. Repeat MRI on day 162 demonstrated tumor progression from L4 to Cd2 vertebral segments with intraparenchymal extension. Surgical tumor debulking was attempted, but an L4-S1 dorsal laminectomy revealed diffusely abnormal neuroparenchyma. Intraoperative cryosection favored lymphoma, and the cat was euthanized intraoperatively 163 d following presentation. Postmortem examination was performed, and the final diagnosis was a high-grade oligodendroglioma. This case illustrates the cytologic, cryosection, and MRI features of a unique clinical presentation of oligodendroglioma.

Spontaneous Pituitary Neoplasm in Two Female Geriatric Southern Giant Pouched Rats (Cricetomys ansorgei).

Southern giant pouched rats (Cricetomys ansorgei) are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively small size makes them useful working animals for various applications in humanitarian work. At our institution, a breeding colony of Southern giant pouched rats is maintained to study their physiology and utility as scent detectors. This case report describes the occurrence of spontaneous pituitary neoplasms with distinct clinical presentations in 2 geriatric (approximately 7.5 y old) wild-caught female Southern giant pouched rats. The first pouched rat displayed vestibular deficits, including left-sided head tilt, ataxia, disorientation, and circling. MRI revealed a large, focal heterogeneous mass arising from the pituitary fossa. The second pouched rat presented with polyuria, polydipsia, and hyperglycemia but no neurologic signs. Examination after euthanasia revealed a prolactin (PRL)-expressing pituitary carcinoma and adenoma in the first and second pouched rat, respectively, associated with mammary hyperplasia in both animals. This is the first report of spontaneous PRL-producing pituitary tumors in Southern giant pouched rats.

Comparison of anti-Müllerian hormone and inhibin immunolabeling in canine and equine granulosa cell tumors.

Granulosa cell tumors (GCTs) are common ovarian neoplasms in the mare and bitch that can be challenging to diagnose on histopathology. Inhibin has long been the standard immunohistochemical (IHC) marker for GCTs; however, anti-Müllerian hormone (AMH) has not been evaluated widely as an IHC marker in the bitch and mare. We compared the efficacy of AMH and inhibin as IHC markers in canine and equine GCTs. We selected retrospectively 18 equine and 15 canine cases. All equine tumors were dominated by a cystic pattern; canine tumors often had solid patterns. Both inhibin and AMH had similar punctate cytoplasmic patterns of immunolabeling, although labeling intensity was variable; distribution and intensity of labeling were unrelated to the histomorphologic pattern. Labeling for AMH occurred in 12 of 15 canine and 18 of 18 equine cases. Labeling for inhibin occurred in 15 of 15 canine and 18 of 18 equine cases. AMH in equine GCTs often had stronger immunolabeling than inhibin, and granulosa cells were labeled more extensively. Inhibin and AMH performed comparably in bitches, but AMH had more diffuse immunolabeling than inhibin in mares.