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Xanthogranulomatosis is an inflammatory lesion characterized by lipid-containing macrophages, extracellular lipid, hemorrhage, and necrosis. We describe disseminated intracoelomic xanthogranulomatosis in 5 eclectus parrots ( Eclectus roratus) and 2 budgerigars ( Melopsittacus undulatus). Postmortem, clinicopathologic, and historical case material was reviewed. Ages ranged from 3 to 24 years; there were 5 males and 2 females. Table food was included in the diet of 3/5 cases, and animal products were included in 2/3 cases. Common clinicopathologic abnormalities included leukocytosis (4/5 cases) and elevated concentrations of bile acids (3/4 cases) and cholesterol within 6 months prior to death (2/4 cases). At postmortem examination, all 7 birds had grossly visible, irregular, soft, tan to yellow, amorphous plaques distributed on the surfaces of the viscera and body wall. Histologic evaluation and oil red O stain revealed xanthogranulomatous inflammation with phagocytized and extracellular lipid, necrosis, cholesterol clefts, fibrosis, and mineralization. Infectious agents were not identified with special stains in all cases. Concurrent hepatobiliary disease was present in 6/7 cases, and 6/7 had lipid accumulation within the parenchyma of various visceral organs. Five cases had atherosclerosis of great vessels. We describe a unique form of disseminated coelomic xanthogranulomatosis in 2 psittacine species. This condition should be recognized as a differential diagnosis in cases of disseminated coelomic mass formation and coelomic distension in psittacine birds, particularly in eclectus parrots and budgerigars.

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in domestic cats, but the cause is still largely elusive. While some viruses have been associated with this disease, none have been definitively implicated as causative. Recently, Rodent chaphamaparvovirus 1 was recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. A novel virus belonging to the same genus, Carnivore chaphamaparvovirus 2, was recently identified in the feces of cats with diarrhea. The goal of this study was to investigate the possible role of chaphamaparvoviruses including members of Rodent chaphamaparvovirus 1 and Carnivore chaphamaparvovirus 2 in the development of feline CKD. The presence of these viruses was retrospectively investigated in formalin-fixed paraffin-embedded feline kidney samples using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Cats were divided into 3 groups: normal ( N = 24), CKD ( N = 26), and immunocompromised ( N = 25). None of the kidney tissues from any of the 75 cats revealed the presence of chaphamaparvovirus DNA, RNA, or antigen. We conclude that viruses belonging to the chaphamaparvovirus genus are unlikely to contribute to the occurrence of feline CKD.

Increased doublecortin (DCX) immunolabeling at the tumor margins has been associated with tumor infiltration in human glioma and canine anaplastic meningioma. No association between DCX immunolabeling and glioma infiltration has been reported in dogs, to our knowledge. Here we compare the DCX immunolabeling in 14 diffusely infiltrating gliomas (gliomatosis cerebri) and 14 nodular gliomas with distinct degrees of tumor infiltration. Cytoplasmic DCX immunolabeling was classified according to intensity (weak, moderate, strong), distribution (1 = 70% immunolabeling), and location within the neoplasm (random or at tumor margins). Immunolabeling was detected in 6 of 14 (43%) diffusely infiltrating gliomas and 8 of 14 (57%) nodular gliomas. Diffusely infiltrating gliomas had moderate and random immunolabeling, with distribution scores of 1 (4 cases) or 2 (2 cases). Nodular gliomas had strong (6 cases) or moderate (2 cases) immunolabeling, with distribution scores of 1 (3 cases), 2 (3 cases), and 3 (2 cases), and random (6 cases) and/or marginal (3 cases) immunolabeling. Increased DCX immunolabeling within neoplastic cells palisading around necrosis occurred in 4 nodular gliomas. DCX immunolabeling was not increased at the margins of diffusely infiltrating gliomas, indicating that DCX should not be used as an immunomarker for glioma infiltration in dogs.

Digital microscopy (DM) is increasingly replacing traditional light microscopy (LM) for performing routine diagnostic and research work in human and veterinary pathology. The DM workflow encompasses specimen preparation, whole-slide image acquisition, slide retrieval, and the workstation, each of which has the potential (depending on the technical parameters) to introduce limitations and artifacts into microscopic examination by pathologists. Performing validation studies according to guidelines established in human pathology ensures that the best-practice approaches for patient care are not deteriorated by implementing DM. Whereas current publications on validation studies suggest an overall high reliability of DM, each laboratory is encouraged to perform an individual validation study to ensure that the DM workflow performs as expected in the respective clinical or research environment. With the exception of validation guidelines developed by the College of American Pathologists in 2013 and its update in 2021, there is no current review of the application of methods fundamental to validation. We highlight that there is high methodological variation between published validation studies, each having advantages and limitations. The diagnostic concordance rate between DM and LM is the most relevant outcome measure, which is influenced (regardless of the viewing modality used) by different sources of bias including complexity of the cases examined, diagnostic experience of the study pathologists, and case recall. Here, we review 3 general study designs used for previous publications on DM validation as well as different approaches for avoiding bias.

Counting mitotic figures (MF) in hematoxylin and eosin–stained histologic sections is an integral part of the diagnostic pathologist’s tumor evaluation. The mitotic count (MC) is used alone or as part of a grading scheme for assessment of prognosis and clinical decisions. Determining MCs is subjective, somewhat laborious, and has interobserver variation. Proposals for standardizing this parameter in the veterinary field are limited to terminology (use of the term MC) and area (MC is counted in an area measuring 2.37 mm2). Digital imaging techniques are now commonplace and widely used among veterinary pathologists, and field of view area can be easily calculated with digital imaging software. In addition to standardizing the methods of counting MF, the morphologic characteristics of MF and distinguishing atypical mitotic figures (AMF) versus mitotic-like figures (MLF) need to be defined. This article provides morphologic criteria for MF identification and for distinguishing normal phases of MF from AMF and MLF. Pertinent features of digital microscopy and application of computational pathology (CPATH) methods are discussed. Correct identification of MF will improve MC consistency, reproducibility, and accuracy obtained from manual (glass slide or whole-slide imaging) and CPATH approaches.

Subungual keratoacanthoma (SK) is a digital neoplasm that has rarely been reported in dogs and carries an excellent prognosis following surgical removal. Radiographic features of canine SK have only been briefly discussed in two prior case reports. Both articles described extensive distal phalangeal osteolysis, a feature more commonly associated with malignant digital neoplasms (e.g., subungual squamous cell carcinoma (SCC) or melanoma). This retrospective case series aimed to further characterize radiographic findings of histologically confirmed canine SK. Seven dogs met the inclusion criteria, with a total of seven affected digits. All seven digits (100%) had osteolysis of the distal phalanx's ungual process and crest, as well as regional soft tissue swelling. Osteolysis of the ungual process was severe in all cases, with complete destruction in six of seven digits (86%). Partial ungual crest geographic and expansile osteolysis was noted in four of seven digits (57%), while two digits (28%) had complete ungual crest destruction. Seven of seven digits (100%) had a radiographically thickened claw, and two of seven digits (28%) had associated lysis of the distal aspect of the middle phalanx. Based on these findings, an osteolytic subungual mass should not be considered pathognomonic for malignant neoplasia. Observing the imaging features previously described should prompt veterinarians to consider SK as a differential diagnosis.

CASE DESCRIPTION A 15-year-old 0.412-kg (0.906-lb) sexually intact male eclectus parrot (Eclectus roratus) was evaluated because its owners found it lethargic and dyspneic at the bottom of its cage. CLINICAL FINDINGS The parrot was thin and had generalized muscle wasting, diffuse feather loss, pale mucous membranes, and melena. The coelomic cavity was distended and soft on palpation, with coelomic effusion suspected. Results of a CBC indicated leukocytosis with left shift heterophilia, including toxic heterophils, lymphopenia, and anemia. Plasma biochemical analyses revealed severe hyperamylasemia. TREATMENT AND OUTCOME Radiography revealed no evidence of a metallic foreign body but severe loss of coelomic detail, suggestive of a coelomic mass, coelomic effusion with coelomitis, or both. Ultrasonography and CT revealed severe accumulation of coelomic fluid; a large, heterogeneous, irregularly marginated, and moderately vascularized mass in the caudal aspect of the coelomic cavity; and multiple hepatic, coelomic, and pulmonary nodules. On the basis of a poor prognosis, the parrot was euthanized. Necropsy results confirmed exocrine pancreatic adenocarcinoma, with disseminated metastases in the liver, gastrointestinal tract, coelomic cavity, and lungs. CLINICAL RELEVANCE In birds, pancreatic adenocarcinoma is rarely reported but should be considered a differential diagnosis for hyperamylasemia, coelomic mass, coelomic effusion, or abnormal gastrointestinal signs, alone or in combination. Ultrasonography and CT can be useful in further evaluating such patients and should be considered in the diagnostic plan.

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intraobserver discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying or classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, computer-assisted review by pathologists may ensure reliability. In the present study, we compared partial (MC-ROI preselection) and full (additional visualization of MF candidates and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole-slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MFs, and improving classification against imposters. The interobserver consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected hotspot MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study demonstrate that computer assistance may lead to more reproducible and accurate MCs in ccMCTs.

Xanthogranulomatosis is an inflammatory lesion characterized by lipid-containing macrophages, extracellular lipid, hemorrhage, and necrosis. We describe disseminated intracoelomic xanthogranulomatosis in 5 eclectus parrots (

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms.

Density of mitotic figures in histologic sections is a prognostically relevant characteristic for many tumours. Due to high interpathologist variability, deep learning-based algorithms are a promising solution to improve tumour prognostication. Pathologists are the gold standard for database development, however, labelling errors may hamper development of accurate algorithms. In the present work we evaluated the benefit of multi-expert consensus (n = 3, 5, 7, 9, 11) on algorithmic performance. While training with individual databases resulted in highly variable F1 scores, performance was notably increased and more consistent when using the consensus of three annotators. Adding more annotators only resulted in minor improvements. We conclude that databases by few pathologists and high label precision may be the best compromise between high algorithmic performance and time investment.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website ( www.vetcancerprotocols.org ), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass ( P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases ( P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

A 15-year-old 0.412-kg (0.906-lb) sexually intact male eclectus parrot (The parrot was thin and had generalized muscle wasting, diffuse feather loss, pale mucous membranes, and melena. The coelomic cavity was distended and soft on palpation, with coelomic effusion suspected. Results of a CBC indicated leukocytosis with left shift heterophilia, including toxic heterophils, lymphopenia, and anemia. Plasma biochemical analyses revealed severe hyperamylasemia.Radiography revealed no evidence of a metallic foreign body but severe loss of coelomic detail, suggestive of a coelomic mass, coelomic effusion with coelomitis, or both. Ultrasonography and CT revealed severe accumulation of coelomic fluid; a large, heterogeneous, irregularly marginated, and moderately vascularized mass in the caudal aspect of the coelomic cavity; and multiple hepatic, coelomic, and pulmonary nodules. On the basis of a poor prognosis, the parrot was euthanized. Necropsy results confirmed exocrine pancreatic adenocarcinoma, with disseminated metastases in the liver, gastrointestinal tract, coelomic cavity, and lungs.In birds, pancreatic adenocarcinoma is rarely reported but should be considered a differential diagnosis for hyperamylasemia, coelomic mass, coelomic effusion, or abnormal gastrointestinal signs, alone or in combination. Ultrasonography and CT can be useful in further evaluating such patients and should be considered in the diagnostic plan.

Astract Canine mammary carcinoma (CMC) has been used as a model to investigate the pathogenesis of human breast cancer and the same grading scheme is commonly used to assess tumor malignancy in both. One key component of this grading scheme is the density of mitotic figures (MF). Current publicly available datasets on human breast cancer only provide annotations for small subsets of whole slide images (WSIs). We present a novel dataset of 21 WSIs of CMC completely annotated for MF. For this, a pathologist screened all WSIs for potential MF and structures with a similar appearance. A second expert blindly assigned labels, and for non-matching labels, a third expert assigned the final labels. Additionally, we used machine learning to identify previously undetected MF. Finally, we performed representation learning and two-dimensional projection to further increase the consistency of the annotations. Our dataset consists of 13,907 MF and 36,379 hard negatives. We achieved a mean F1-score of 0.791 on the test set and of up to 0.696 on a human breast cancer dataset., Measurement(s) Mitotic Figure • Slide Image • non-mitotic structures • anatomical phenotype annotation Technology Type(s) Pathology Report • hematoxylin and eosin stain • machine learning Factor Type(s) breast cancer tissue Sample Characteristic - Organism Canis Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.13182857

Xanthogranulomatous disease is a rare condition, which can be caused by infection, inflammation, hemorrhage, immunologic disease, or inherited lysosomal disorders. It is characterized by non-intracellular lipid and cholesterol deposits among an inflammatory infiltrate of vacuolated macrophages and giant cells. The diagnosis of xanthogranulomatous disease is challenging, with nonspecific imaging findings often misinterpreted as aggressive neoplastic processes in humans. In this retrospective case series study, we describe the diagnostic imaging characteristics of a disseminated xanthogranulomatous condition identified in five eclectus parrots (Eclectus roratus). Decreased serosal detail and celomic distension were present in all three birds radiographed, with multifocal variably sized celomic mineralization (3/3 birds), and extracelomic mineralized masses (1/3 birds). Celomic effusion with foci of celomic mineralization and hepatomegaly were identified in all birds (3/3) imaged with ultrasound. Finally, a mineralized mural ventricular mass was present in one of three patients imaged with CT, multifocal celomic mineralization with moderate to severe celomic effusion in two of three patients, diffuse severe proventricular and intestinal dilation in all three patients, and atherosclerosis of the major arterial trunks in all three patients. Veterinary radiologists should be aware of this inflammatory condition in birds, especially in eclectus parrots, and should be able to recognize the imaging features of xanthogranulomatous inflammation.

Laparoscopic partial pancreatectomy has been performed in experimental canine studies and has been evaluated in human medicine but has not been reported in a clinical veterinary case. The authors present a 9 yr old field spaniel with weakness and hypoglycemia with insulin levels and Amended Insulin: Glucose Ratio results equivocal for a pancreatic insulinoma. Multiple abdominal ultrasounds did not detect the tumor, yet dual-phase computed tomographic angiography revealed the presence of a focal hypoattenuating nodule in the left lobe of the pancreas. A 3-port laparoscopic approach to the abdomen confirmed a 1.5-cm mass in the mid-left limb of the pancreas, and resection of the mass was performed with a bipolar vessel-sealing device. The surgery was performed without complication, and the dog became normoglycemic within 4 hr following surgery. Final histopathology results revealed pancreatic neuroendocrine carcinoma of the β cells. Recurrence of hypoglycemia was noted 18 mo postoperatively; however, repeat computed tomographic angiography did not reveal pancreatic abnormalities and fine needle aspirates of liver nodules did not suggest metastatic disease. Medical management was elected and the patient was euthanized 28 mo after surgery due to refractory hypoglycemic seizures.

OBJECTIVE To assess causes of splenomegaly and postsurgical outcomes in small-breed (ie, < 16-kg [< 35.2-lb]) dogs that underwent splenectomy and evaluate associations among malignant disease, hemoperitoneum, and survival time in these patients. DESIGN Retrospective case series. ANIMALS 45 client-owned dogs. PROCEDURES Medical records of 2 veterinary facilities were reviewed to identify small-breed dogs that underwent splenectomy and had a histologic diagnosis recorded. Data analyzed included signalment, diagnosis, presence or absence of hemoperitoneum, and survival time. RESULTS 21 dogs had malignant neoplasia and 24 had benign splenic diseases. Hemangiosarcoma was the most common malignancy (14/21 [67%] dogs) and lymphoid nodular hyperplasia, hematoma, or extramedullary hematopoiesis (alone or in combination) was most commonly diagnosed in dogs with benign disease (17/24 [71%]). Wheaton Terriers were significantly more likely to have malignant splenic disease than were dogs of other breeds. Malignant splenic disease and the presence of hemoperitoneum had significant negative associations with survival time. Malignant disease was not significantly associated with the presence of hemoperitoneum. CONCLUSIONS AND CLINICAL RELEVANCE Causes for splenomegaly and survival times were similar to those previously reported for populations that primarily included large-breed dogs. There were approximately equal numbers of benign and malignant causes for splenomegaly in this population. Results suggested that Wheaton Terriers with splenomegaly had a higher likelihood of malignant neoplasia than other breeds and that hemoperitoneum may not be a significant predictor of malignancy in small-breed dogs. However, further research including a larger number of dogs is needed to confirm these findings. (J Am Vet Med Assoc 2017;250:1148–1154)

An adult female scarlet macaw ( Ara macao ) was referred for evaluation of increased respiratory noise. Previous treatment with antibiotic agents by the referring veterinarian did not improve clinical signs. Upon presentation, when manually restrained, the patient became severely tachypneic with increased respiratory effort. Standing whole-body radiographic images revealed a soft tissue mass at the cranial aspect of the cardiac silhouette, but the origin of the mass could not be ascertained because of superimposed structures. Owing to the birdʼs significant respiratory compromise and concern for risks of general anesthesia, a standing computed tomography (CT) scan was performed without sedation to further assess the origin of the suspected mass. The CT images showed the presence of a large infiltrative intracoelomic soft tissue mass with adjacent keel osteolysis. After attempts at supportive care with nebulization, antibiotic therapy, and antifungal agents, the patientʼs condition declined and was subsequently euthanized. The results of the postmortem examination confirmed a large intracoelomic neoplasm with involvement of the keel, lungs, and adjacent air sacs. The mass was diagnosed as a primary respiratory adenocarcinoma, believed to have originated from the intraosseous air sac epithelium, with local pulmonary, air sac, and intracoelomic metastasis.