Abstract
Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian ...elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation.
In psittacine birds, round cell neoplasms that originate from lymphocytes, plasma cells, histiocytes, or mast cells are sporadic and poorly described. The lack of morphological and ...immunohistochemical diagnostic criteria or grading schemes make specific diagnoses and prognoses challenging. We assessed cases of psittacine birds diagnosed with round cell neoplasia from 3 North American veterinary diagnostic laboratories to describe the diagnostic features of these tumors. For all cases, demographic data, anatomic distribution, histological features, and immunoreactivity for T (CD3) and B (Pax5 and MUM-1) cell markers were assessed using tissue microarrays and whole slide mounts. Thirty-eight psittacine birds representing 14 species were included. Tumors were mainly infiltrative and multicentric, were composed of homogenous sheets of round to polygonal cells, and commonly presented with a high mitotic count (average 21 mitoses per high-power field). Based on Pax5 immunoreactivity, B-cell lymphoma was most common (19/38 50%), and was significantly associated with involvement of the gastrointestinal and urogenital systems. Of the 38 cases, 6 (16%) were consistent with T-cell lymphoma, 3 (8%) with plasma cell tumor, and 3 (8%) were double-reactive for both B- and T-lymphocyte markers. This is the first study to describe morphologic and immunohistochemical features of round cell neoplasia in a large number of psittacine birds, and provides benchmark data for future studies aimed at elucidating the diagnosis and prognosis of these neoplasms. These data also provide useful information about reactivity of commercially available antibodies as lymphocyte markers in tissues of multiple psittacine species.
This study describes the clinical, gross, and histologic findings in 17 cases of aneurysms in bearded dragons (Pogona vitticeps). The clinical presentation ranged from incidental to sudden and ...unexpected death. The affected vasculature was predominantly arterial; however, based on the topographical locations of the lesions, gross structure, and drainage, some veins were likely involved. Magnetic resonance imaging and computerized tomography scans of 1 animal showed a large aneurysm of the internal carotid artery extending from near its aortic origin into the caudal head. Aneurysms were organized in 5 groups based on their anatomical locations: cephalic, cranial coelom (for all near the heart), caudal coelom (for the mesenteric vessels and descending aorta), limbs, and tail. The cranial coelomic region was the most prevalent location. Gross findings were large hematomas or red serosanguineous fluid filling the adjacent area, as most of the aneurysms (94%) were ruptured at the time of the study. The main histological findings were degenerative changes of the vessel walls characterized by moderate to severe disruption of the collagen and elastic fibers of the tunica media and adventitia (100%), followed by thickening of the intima with thrombi formation (54%) and dissecting hematoma of the vessel wall (47%). Vasculitis (29%), mineralization (6%), and lipid deposits (6%) in the vessel wall were observed occasionally. Based on these findings, the vascular dilations and ruptures observed in bearded dragons likely are associated with weakness of the vessel walls caused by degenerative changes in the intimal and medial tunics.
In a fluorescence polarization screen for the MYC–MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Kröhnke pyridine library. The K d of KJ-Pyr-9 for MYC ...in vitro is 6.5 ± 1.0 nM, as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC–MAX complex formation in the cell, as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC-driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells.
Sixteen whitespotted bamboo sharks (Chiloscyllium plagiosum) with histologically similar bacterial abscesses were submitted to Northwest ZooPath from nine zoo and aquarium institutions over a 17‐year ...period. These abscesses were characterized by inflammatory cell infiltrates and necrosis with intralesional small, Gram‐positive, acid‐fast negative, cocci bacteria. The clinical presentation, histologic findings, and culture results indicate that Enterococcus faecalis is a relatively common cause of these lesions in whitespotted bamboo sharks. This organism also provides a treatment challenge due to its inherent antibiotic‐resistant properties and ability to form biofilms, confounding the host's immune response. Enterococcus faecalis represents an important cause for abscess formation and cellulitis in captive whitespotted bamboo sharks.
Mammary gland neoplasms in macropods are uncommonly reported, and the morphological and immunohistochemical characteristics are incompletely described. The goal of this study was to describe the ...morphologic features of macropod mammary neoplasms and to determine the molecular subtypes of mammary carcinomas using a panel of antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p63, smooth muscle actin (SMA), and epidermal growth factor receptor (EGFR). Biopsy and necropsy specimens were examined from 21 macropods with mammary tumors submitted to Northwest ZooPath from 1996 to 2019. In accordance with the histologic classification of canine mammary tumors proposed by Goldschmidt and colleagues, tubulopapillary (2), tubular (10), and comedo-carcinomas (2), adenoma (1), lobular hyperplasia (3), fibroadenomatous hyperplasia (1), and mastitis (2) were diagnosed. Red kangaroos (Osphranter rufus) were most commonly diagnosed with mammary carcinomas (79% of all carcinomas). Seven carcinomas had lymphovascular invasion and 2 also had pulmonary metastases. Six of these 7 carcinomas were classified as grade 3. Immunohistochemistry (IHC) for all antibodies was performed on 9/14 carcinomas, and partial IHC was performed for 3 cases. All 12 carcinomas were immunoreactive for PR, 5 for ER, 9 for EGFR, and none for Her-2. Five of the 9 mammary carcinomas with complete IHC data were classified as luminal A subtype, and 4 were normal-like subtype. Accurate classification of mammary tumors in macropods based on morphology, immunohistological characteristics, and molecular subtype may be helpful in guiding clinical management, prognosis, and potential therapeutic targets.
Large-scale retrospective studies allow for identification of disease trends, such as predisposing factors, typical clinical signs, and range of histologic lesions, which cannot be determined in ...individual case reports. Lesions of the endocrine pancreas of ferrets are extensively reported; however, there are no in-depth investigations of lesions in the exocrine pancreas. This retrospective analysis presents the histologic features, clinical signs, and concurrent diseases of lesions in the exocrine pancreas of ferrets. Seventy-seven lesions were reported and included acinar cell hyperplasia (n = 32), chronic pancreatitis (n = 16), acute pancreatitis (n = 13), acinar cell adenoma (n = 5), acinar cell carcinoma (n = 4), acinar cell atrophy (n = 3), presumptive acinar cell hypoplasia (n = 2), and lymphoma (n = 2). Our results demonstrate that acinar cell hyperplasia and chronic pancreatitis can both cause grossly visible pancreatic nodules. Hyperplasia was not associated with neoplastic transformation. In addition, acinar cell adenoma was slightly more common than carcinoma, which is contrary to most reports of neoplasia in ferrets. Our findings also suggest that acute pancreatitis can be a sequela to pancreatic biopsy and that there may be an association between chronic pancreatitis and diabetes mellitus in ferrets. Finally, zinc toxicosis was found to be an unlikely cause of pancreatitis in these ferrets based on zinc tissue concentration testing in a subset of cases.
Chromatophoromas are neoplasms that develop from the dermal pigment-bearing and light-reflecting cells (chromatophores) in the skin of reptiles, fish, and amphibians. Seventeen cutaneous ...chromatophoromas were identified from 851 bearded dragon submissions (2%) to a private diagnostic laboratory in a 15-y period. No sex predilection was found. Ages ranged from 9 mo to 11 y. Chromatophoromas most commonly were single, raised, variably pigmented masses or pigmented scales on the trunk, and less commonly the extremities or head. Microscopically, iridophoromas, melanophoromas, mixed chromatophoromas, and nonpigmented chromatophoromas were identified. Neoplasms were often ulcerated and invaded deep into the subcutis and muscle. Most commonly, nuclear atypia was mild-to-moderate, and mitotic count was low. Six neoplasms had abundant, periodic acid-Schiff–positive, mucinous stroma. Histologic examination was often adequate to diagnose chromatophoromas in bearded dragons given that 11 of 17 had some degree of pigmentation, although it was often scant. IHC for S100 and PNL2 could be helpful to diagnose poorly pigmented neoplasms. No lymphatic invasion or metastases at the time of excision were noted in any of the cases. Follow-up data were available for 6 cases, with no reports of recurrence or neoplasia-related death. Two cases had elevated mitotic counts and nuclear pleomorphism, which has been associated with metastasis in other reports of bearded dragon chromatophoromas. In general, it appears that aggressive surgical excision is often curative, but monitoring may be warranted for cases in which tumors had high mitotic count and nuclear pleomorphism.
Mesothelioma has been reported frequently in large felids. These neoplasms present a diagnostic challenge given their highly variable morphology that mimics carcinomas or sarcomas at different ...locations. Our goal was to characterize mesotheliomas morphologically and immunohistochemically to determine if a panel of antibodies could be used to more accurately support the diagnosis of these neoplasms in large felids. Mesotheliomas from 6 large felids, including 4 clouded leopards, 1 Bengal tiger, and 1 cheetah, were immunohistochemically labeled for vimentin, E-cadherin, pancytokeratin, Wilms tumor 1 (WT1), MUC-1, and calretinin. The mesotheliomas of the 4 clouded leopards and the tiger were of the epithelial subtype; the mesothelioma from the cheetah was biphasic. All 6 mesotheliomas had strong immunohistochemical labeling for vimentin, E-cadherin, and pancytokeratin. All cases had cytoplasmic labeling for WT1, and 2 also had nuclear labeling. The 3 mesotheliomas with distinct papillary fronds were weakly positive for MUC-1. These and one other epithelial mesothelioma were also positive for calretinin. Our study demonstrates that the morphologic and immunohistochemical phenotypes of mesothelioma that have been identified in humans and domestic species can occur in large felids, and a panel of pancytokeratin, vimentin, WT1, and calretinin can be utilized to support the diagnosis of these neoplasms.
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