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Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.

The rostral cranial fossa (RCF) consists of the sphenoid and ethmoid bones, which accommodate the olfactory bulbs and nerves along the recesses of the cribriform plate. Neoplasms located in the vicinities of the RCF can compress and/or invade the cribriform plate. Here we describe the clinical and pathologic findings of neoplasms involving the cribriform plate in 32 dogs and 17 cats autopsied over a 13-y period. The average ages of affected dogs and cats were 9.2 y and 9.7 y, respectively. No sex or breed predisposition was evident in dogs, but 13 of 18 cats were spayed females and 14 of 18 were domestic shorthair cats. The main clinical signs were seizures (10 cases) and epistaxis (5 cases) in dogs, and red-to-brown nasal discharge (5 cases) and seizures (4 cases) in cats. In dogs, the 22 sinonasal neoplasms included adenocarcinoma (14 cases), transitional carcinoma (4), squamous cell carcinoma (2), lymphoma (1), and histiocytic sarcoma (1); the 10 intracranial neoplasms consisted of high-grade gliomas (3 cases), psammomatous meningiomas (2), histiocytic sarcomas (2), olfactory neuroblastomas (2), and a meningeal granular cell tumor (1). In cats, the 14 sinonasal neoplasms included lymphoma (8 cases), adenocarcinoma (4), adenosquamous carcinoma (1), and squamous cell carcinoma (1); the 3 intracranial neoplasms consisted of oligodendroglioma (1), transitional meningioma (1), and olfactory neuroblastoma (1). [ABSTRACT FROM AUTHOR]

The National Cancer Institute-led multidisciplinary Comparative Brain Tumor Consortium (CBTC) convened a glioma pathology board, comprising both veterinarian and physician neuropathologists, and conducted a comprehensive review of 193 cases of canine glioma. The immediate goal was to improve existing glioma classification methods through creation of a histologic atlas of features, thus yielding greater harmonization of phenotypic characterization. The long-term goal was to support future incorporation of clinical outcomes and genomic data into proposed simplified diagnostic schema, so as to further bridge the worlds of veterinary and physician neuropathology and strengthen validity of the dog as a naturally occurring, translationally relevant animal model of human glioma. All cases were morphologically reclassified according to a new schema devised by the entire board, yielding a majority opinion diagnosis of astrocytoma (43, 22.3%), 19 of which were low-grade and 24 high-grade, and oligodendroglioma (134, 69.4%), 35 of which were low-grade and 99 were high-grade. Sixteen cases (8.3%) could not be classified as oligodendroglioma or astrocytoma based on morphology alone and were designated as undefined gliomas. The simplified classification scheme proposed herein provides a tractable means for future addition of molecular data, and also serves to highlight histologic similarities and differences between human and canine glioma.

On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed.

Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.

The diagnosis of primary and secondary CNS neoplasms of dogs and cats relies on histologic examination of autopsy or biopsy samples. In addition, many neoplasms must be further characterized by immunohistochemistry (IHC) for a more refined diagnosis in specific cases. Given the many investigations assessing the diagnostic and prognostic IHC profile of CNS neoplasms in the veterinary literature, it may be difficult for the diagnostic pathologist or pathology trainee to narrow the list of reliable diagnostic IHCs when facing a challenging case. Here we compile a comprehensive list of the most diagnostically relevant immunomarkers that should be utilized for the diagnostic support or confirmation of the most common primary and secondary CNS neoplasms of dogs and cats. [ABSTRACT FROM AUTHOR]

Leptomeningeal gliomatosis (LG) is characterized by extensive dissemination of neoplastic glial cells in the subarachnoid space either without an intraparenchymal glioma (primary LG or PLG) or secondary to an intraparenchymal glioma (secondary LG or SLG). Given the low frequency of LG in human and veterinary medicine, specific diagnostic criteria are lacking. Here, we describe 14 cases of canine LG that were retrospectively identified from 6 academic institutions. The mean age of affected dogs was 7.3 years and over 90% of patients were brachycephalic. Clinical signs were variable and progressive. Relevant magnetic resonance image findings in 7/14 dogs included meningeal enhancement of affected areas and/or intraparenchymal masses. All affected dogs were euthanized because of the poor prognosis. Gross changes were reported in 12/14 cases and consisted mainly of gelatinous leptomeningeal thickening in the brain (6/12 cases) or spinal cord (2/12 cases) and 1 or multiple, gelatinous, gray to red intraparenchymal masses in the brain (6/12 cases). Histologically, all leptomeningeal neoplasms and intraparenchymal gliomas were morphologically consistent with oligodendrogliomas. Widespread nuclear immunolabeling for OLIG2 was observed in all neoplasms. The absence of an intraparenchymal glioma was consistent with PLG in 3 cases. The remaining 11 cases were diagnosed as SLG. [ABSTRACT FROM AUTHOR]

Intraneural perineurioma is an exceptionally rare neoplasm in animals. This case study comprises a series of three cases and a brief literature review focusing on canine intraneural perineurioma. The pathological and immunohistochemical findings are documented, revealing that canine intraneural perineurioma frequently a ects adult dogs aged between 3 and 10 years old, with a male predominance. Clinical signs associated with intraneural perineurioma in dogs include spinal pain, lameness, and paresis, resulting from the involvement of spinal nerve roots of the pelvic limbs, brachial plexus, or distal part of the median nerve. Most neoplasms had characteristic pseudo-onion bulb patterns on histopathology. Neoplastic perineurial cells, inmost cases, expressed laminin and claudin-1, and NF200 consistently highlighted the central axon. While the immunohistochemical (IHC) profile of intraneural perineurioma in veterinary medicine remains incompletely characterized, the available IHC data from all reported cases suggest that a combination of laminin and claudin- 1 immunomarkers, along with distinctive histological features, can assist in establishing a definitive diagnosis of intraneural perineurioma. [ABSTRACT FROM AUTHOR]

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 = <30% immunolabeling, 2 = 30–70% immunolabeling, 3 = >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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Intracranial neoplasia is relatively common in dogs and stereotactic radiotherapy, surgical debulking, or both, are the most successful treatment approaches. A key component of treatment planning involves delineating tumor margin on magnetic resonance imaging (MRI) examinations. How MRI signal intensity alterations relate to histological tumor margins is unknown. Objectives: Directly compare histological brain sections to MRI sequence images and determine which sequence alteration best correlates with tumor margins. Animals: Five dogs with glioma, 4 dogs with histiocytic sarcoma, and 3 dogs with meningioma. Methods: Retrospective cohort study. Histological brain sections were registered to in vivo MRI scan images obtained within 7 days of necropsy. Margins of signal intensity alterations (T2‐weighted, fluid‐attenuating inversion recovery [FLAIR], T1‐weighted and contrast enhancement) were compared directly to solid tumor and surgical margins identified on histology. Jacquard similarity metrics (JSM) and cross‐sectional areas were calculated. Results: In glioma cases, margins drawn around T2‐weighted hyperintensity were most similar to surgical margins (JSM, 0.66 ± 0.17) when compared to other sequences. In both meningioma (JSM, 0.57 ± 0.21) and histiocytic sarcoma (JSM, 0.75 ± 0.11) margins of contrast enhancement were most similar to surgical margins. Conclusions and Clinical Importance: Signal intensities correspond to tumor margins for different tumor types and facilitate surgical and radiation therapy planning using MRI images. [ABSTRACT FROM AUTHOR]

Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement. [ABSTRACT FROM AUTHOR]

Evasion of the immune response is an integral part of the pathogenesis of glioma. In humans, important mechanisms of immune evasion include recruitment of regulatory T cells (Tregs) and polarization of macrophages toward an M2 phenotype. Canine glioma has a robust immune cell infiltrate that has not been extensively characterized. The purpose of this study was to determine the distribution of immune cells infiltrating spontaneous intracranial canine gliomas. Seventy-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry for CD3, forkhead box 3 (FOXP3), CD20, Iba1, calprotectin (Mac387), CD163, and indoleamine 2,3-dioxygenase (IDO). Immune cell infiltration was present in all tumors. Low-grade and high-grade gliomas significantly differed in the numbers of FoxP3+ cells, Mac387+ cells, and CD163+ cells (P =.006,.01, and.01, respectively). Considering all tumors, there was a significant increase in tumor area fraction of CD163 compared to Mac387 (P <.0001), and this ratio was greater in high-grade tumors than in low-grade tumors (P =.005). These data warrant further exploration into the roles of macrophage repolarization or Treg interference therapy in canine glioma. [ABSTRACT FROM AUTHOR]

For this reason, and until molecular tools are readily available in veterinary medicine, there is an urgent need for more objective and precise means to morphologically classify and grade CNS neoplasms that would reduce intra- and interobserver disagreement when examining tumor samples. The Veterinary Cancer Guidelines and Protocols (VCGP) group has issued a protocol for CNS neoplasms of dogs and cats.[7] The document offers general guidelines that can be utilized in studies involving the biological behavior of primary and secondary CNS neoplasms. CNS tumors protocol: neoplasms of the central nervous system of dogs and cats, version 1.0. [Extracted from the article]

Background: Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. Objective: Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. Animals Thirteen dogs with DM and 13 aged‐matched controls. Methods: All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. Results: Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. Conclusions and Clinical Importance: Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition. [ABSTRACT FROM AUTHOR]

Endoparasitism remains a significant cause of morbidity and mortality in puppies and kittens. The ascarids of dogs and cats (Toxocara canis, Toxascaris leonina, Toxocara cati) cause significant pathology due to either larval migration or adult nematode burden within the gastrointestinal tract. This chapter will review the important pathologic events and lesions that are encountered during ascarid development in dogs and cats with emphasis given to the characteristic gross pathology lesions that are seen in affected animals. [ABSTRACT FROM AUTHOR]

A 7-y-old Black Russian Terrier dog was evaluated for chronic lameness of the right forelimb and concurrent weight loss. Clinical examination revealed a pigmented mass arising from digit 4 of the right forelimb; the digit was amputated and submitted for histologic evaluation. Histologically, the neoplasm was composed of ill-defined streams, sheets, and clusters of melanocytes admixed with a distinct population of malignant epithelial cells forming glands and nests. The diagnosis was a biphasic malignant melanoma adenocarcinoma, a rarely reported neoplasm in human medicine that has not been described in veterinary medicine, to our knowledge. [ABSTRACT FROM AUTHOR]

Meningiomas are the most commonly reported primary intracranial tumor in dogs and humans and between the two species there are similarities in histology and biologic behavior. Due to these similarities, dogs have been proposed as models for meningioma pathobiology. However, little is known about specific pathways and individual genes that are involved in the development and progression of canine meningioma. In addition, studies are lacking that utilize RNAseq to characterize gene expression in clinical cases of canine meningioma. The primary objective of this study was to develop a technique for which high quality RNA can be extracted from formalin-fixed, paraffin embedded tissue and then used for transcriptome analysis to determine patterns of gene expression. RNA was extracted from thirteen canine meningiomas–eleven from formalin fixed and two flash-frozen. These represented six grade I and seven grade II meningiomas based on the World Health Organization classification system for human meningioma. RNA was also extracted from fresh frozen leptomeninges from three control dogs for comparison. RNAseq libraries made from formalin fixed tissue were of sufficient quality to successfully identify 125 significantly differentially expressed genes, the majority of which were related to oncogenic processes. Twelve genes (AQP1, BMPER, FBLN2, FRZB, MEDAG, MYC, PAMR1, PDGFRL, PDPN, PECAM1, PERP, ZC2HC1C) were validated using qPCR. Among the differentially expressed genes were oncogenes, tumor suppressors, transcription factors, VEGF-related genes, and members of the WNT pathway. Our work demonstrates that RNA of sufficient quality can be extracted from FFPE canine meningioma samples to provide biologically relevant transcriptome analyses using a next-generation sequencing technique, such as RNA-seq. [ABSTRACT FROM AUTHOR]

Canid alphaherpesvirus 1 (CHV) causes morbidity and mortality in susceptible puppies. While the neuropathology of experimentally infected puppies has been detailed, characterization of naturally acquired infections is limited. The aim of this study was to describe the histologic, immunohistochemical, and in situ hybridization features of CHV encephalitis in the dog. Six female and 11 male puppies ranging in age from stillborn to 57 days old were included. Histologically, lesions included multifocal glial nodules (16/17, 94%), meningeal infiltrates (15/17, 88%), and cerebellar cortical necrosis (6/9, 67%); however, robust inflammation was not a significant feature in any of the cases. Immunohistochemistry for CD3, CD20, MAC387, and Iba1 was performed. Although T cells predominated over B cells, the overall number of cells was small in all cases both within the glial nodules and the meninges. In 16 of 16 (100%) cases, glial nodules were diffusely immunoreactive for Iba1; however, limited or no immunoreactivity for MAC387 was present. In situ hybridization directed at the CHV thymidine kinase gene revealed CHV nucleic acid in the granule neurons of the cerebellar folia (8/9; 89%), endothelial cells in the meninges and parenchyma (12/17, 71%), and individual randomly distributed neurons (6/17, 35%). These results clarify the pathology of naturally acquired CHV infection and indicate that developing cerebellar granule neurons are an important site of viral replication. [ABSTRACT FROM AUTHOR]

Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord. All dogs had a presumptive clinical diagnosis of intraparenchymal neoplasia or myelitis based on history, advanced imaging, and cerebrospinal fluid analysis. Euthanasia was elected in all cases because of poor outcome despite anti-inflammatory or immunosuppressive treatment or because of poor prognosis at the time of diagnosis. Tumor location during autopsy ranged from C1 to L6, with no clear predilection for a specific spinal cord segment. The diagnosis was based on histopathology and the immunohistochemistry expression of glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, neuron-specific enolase, synaptophysin, and Ki-67. Diagnoses consisted of 4 cases of oligodendroglioma, 2 cases of gliomatosis cerebri, and 1 astrocytoma. This case series further defines the clinicopathologic features of canine spinal glioma and highlights the need for comprehensive immunohistochemistry in addition to routine histopathology to confirm the diagnosis of these tumors. [ABSTRACT FROM AUTHOR]

The article evaluates canine brains for evidence of Borrelia (B.) burgdorferi infection. The findings revealed that almost half of the dogs with B. burgdorferi-infected ticks had mild to moderate lymphoplasmacytic choroid plexitis. The researchers concluded that B. burgdorferi does not have a role in the etiopathogenesis of canine central nervous system pathology.

OBJECTIVE To characterize the association between peritoneopericardial diaphragmat-ic hernia (PPDH) or congenital central diaphragmatic hernia (CCDH) and ductal plate malformations (DPMs) in dogs and cats. ANIMIALS 18 dogs and 18 cats with PPDH or CCDH and 19 dogs and 18 cats without PPDH or CCDH. PROCEDURES Evaluation of clinical details verified PPDH or CCDH and survival times. Histologic features of nonherniated liver samples were used to categorize DPM. Immunohistochemical staining for cytokeratin- 19 distinguished bile duct profiles per portal tract and for Ki-67—assessed cholangiocyte proliferation. Histologic features of herniated liver samples from PPDH or CCDH were compared with those of pathological controls (traumatic diaphragmatic hernia, n = 6: liver lobe torsion, 6; ischemic hepatopathy, 2). RESULTS DPM occurred in 13 of 18 dogs with the proliferative-like phenotype pre-dominating and in 15 of 18 cats with evenly distributed proliferative-like and Caroli phenotypes. Congenital hepatic fibrosis DPM was noted in 3 dogs and 2 cats and renal DPM in 3 dogs and 3 cats. No signalment, clinical signs, or clinicopathologic features discriminated DPM. Kaplan Meier survival curves were similar in dogs and cats. Bile duct profiles per portal tract in dogs (median. 5.0; range, 1.4 to 100.8) and cats (6.6; 1.9 to 11.0) with con-genital diaphragmatic hernias significantly exceeded those in healthy dogs (1.4; 1.2 to 1.6) and cats (2.3; 1.7 to 2.6). Animals with DPM lacked active cholangiocyte proliferation. Histologic features characterizing malformative bile duct profiles yet without biliary proliferation were preserved in herni-ated liver lobes in animals with DPM. CONCLUSIONS AND CLINICAL RELEVANCE DPM was strongly associated with PPDH and CCDH. Because DPM can impact health, awareness of its coexistence with PPDH or CCDH should prompt biopsy of nonherniated liver tissue during surgical correction of PPDH and CCDH. [ABSTRACT FROM AUTHOR]