Clinical and pathologic features of acute bovine liver disease in Australia

Acute bovine liver disease (ABLD) is a sporadic hepatic disease affecting cattle in southern Australia, characterized histologically by striking periportal hepatocellular necrosis. The cause of ABLD is unknown; however, the seasonality and acute presentation of outbreaks suggest mycotoxin involvement. We describe here the clinical and pathologic findings of ABLD in 45 naturally affected cattle from 13 outbreaks occurring from 2010 to 2019 in Victoria, Australia. Outbreaks occurred in herds located along the southern coastal plain of Victoria and were observed most frequently in lactating dairy cattle. Clinical signs commonly included a combination of mild photosensitization, progressive neurologic signs, and hypogalactia, which preceded death by ≤ 48 h. All affected animals had marked elevations in activities of glutamate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transferase. At autopsy, the most common lesions were serosal petechiae and/or gastrointestinal hemorrhage, and hepatomegaly with a pronounced hepatic reticular pattern. The principal histologic lesion was widespread—severe periportal hepatocellular coagulative necrosis and erythrocyte pooling—which often extended to massive necrosis. Lesions in other organs were uncommon. Our study of ABLD suggests involvement of a potent hepatotoxin that is either directly cytopathic or requires bioactivation by periportal-specific enzymes.

Samples sizes required to accurately quantify viral load and histologic lesion severity at the maternal–fetal interface of PRRSV-inoculated pregnant gilts

Porcine reproductive and respiratory syndrome virus (PRRSV) is transmitted vertically, causing fetal death in late gestation. Spatiotemporal distribution of virus at the maternal–fetal interface (MFI) is variable, and accurate assessment of viral concentration and lesions is thus subject to sampling error. Our objectives were: 1) to assess whether viral load and lesion severity in a single sample of endometrium (END) and placenta (PLC), collected near the base of the umbilical cord (the current standard), are representative of the entire organ; and 2) to compare sampling strategies and evaluate if spatial variation in viral load can be overcome by pooling of like-tissues. Spatially distinct pieces of END and PLC of 24 fetuses from PRRSV-2–infected dams were collected. PRRSV RNA quantified by RT-qPCR was compared in 5 individual pieces per fetus and in respective pools of tissue and extracted RNA. Three distinct pieces of MFI were assessed for histologic severity. Concordance correlation and kappa inter-rater agreement were used to characterize agreement among individual samples and pools. The viral load of individual samples and pools of END had greater concordance to a referent standard than did samples of PLC. Larger pool sizes had greater concordance than smaller pool sizes. Average viral load and lesion severity did not differ by location sampled, and no technical advantages of pooling tissues versus RNA extracts were found. We conclude that multiple pieces of MFI tissues must be evaluated to accurately assess lesion severity and viral load. Three pieces per fetus provided a reasonable balance of cost and logistic feasibility.

Helicobacter pylori infection and chronic gastritis; use of the Updated Sydney System in histopathological evaluation of gastritis

Objective Helicobacter pylori is a major cause for chronic gastritis and further it is associated with development of peptic ulcer disease and gastric cancer. Therefore, the objective of this study was to classify gastritis according to the updated Sydney system guidelines and find the association of H. pylori with each of graded variable. Number of 152 dyspeptic patients who underwent upper gastro-intestinal endoscopy at a Teaching Hospital were enrolled. Of the 2 biopsies collected one was used for PCR to detect H. pylori. The other biopsy was fixed in formalin followed by paraffin embedding and stained with H&E stain. Gastritis was classified microscopically according to the updated Sydney system. Results : Gastritis was reported over a wide age group ranging from 18-84 years with a mean age of 51 years. Based on histological findings, 12% of patients were diagnosed as H. pylori associated chronic active gastritis. There was no significant association between each graded variable and H. pylori positivity. Of the 152 dyspeptic patients 34 were positive by PCR for H. pylori infection. All the dyspeptic patients with H. pylori infection had chronic active gastritis, suggesting an etiologic role of the bacterium in the histologic lesion.

Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach

FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.

FSGS: Diagnosis and Diagnostic Work-Up

Focal segmental glomerulosclerosis is a histologic lesion, rather than a clinical disease. FSGS is common cause of nephrotic syndrome in both adults and children worldwide. In the United States it is the most common primary glomerular disease resulting in end-stage renal disease and recent reports have suggested that its incidence might be on the rise. Currently the incidence is estimated to be 7 per million. The podocyte is the cellular target cell in FSGS and in recent years substantial insight in the pathogenesis and genetics of FSGS have accumulated. Furthermore the discovery of potential novel biomarkers to diagnose FSGS and monitor disease activity has renewed interest in this disease. In this review article we will focus on the clinical presentation and diagnosis of FSGS.

Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

Sarcocystis sp.-Associated Meningoencephalitis in a Bald Eagle (Haliaeetus Leucocephalus)

Protozoal meningoencephalitis is uncommon in raptors. An adult female bald eagle ( Haliaeetus leucocephalus) was euthanized after several months of treatment for progressive neurologic signs. The predominant histologic lesion was lymphoplasmacytic and histiocytic meningoencephalitis involving the cerebrum and cerebellum. There was a marked segmental loss of granular cells and Purkinje cells, as well as segmental atrophy of the molecular layer in the cerebellum. Protozoal merozoites and schizonts were observed in the gray matter of the cerebellum. Ultrastructurally, the merozoites were classified as a species of Sarcocystis due to the lack of rhoptries. Immunohistochemistry of the agent revealed a positive reaction for Sarcocystis neurona, while sections were negative for Toxoplasma gondii and Neospora caninum. Sarcocystis sp. infection should be considered as a differential diagnosis in bald eagles with chronic neurologic disease.