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Conference 1 C O N F E R E N C E 16 29 January 2020 18 August, 2021 Dr Joint Pathology CeJointnter Pathology Center Veterinary PatholVeterinaryogy Service Pathologys Services WEDNESDAY SLIDE CONFERENCE 2021-2022 WEDNESDAY SLIDE CONFER ENCE 2019-2020 Conference 1 C o n f e r e n c e 16 29 January 2020 18 August, 2021 Dr. Ingeborg Langohr, DVM, PhD, DACVP Professor Department of Pathobiological Sciences Louisiana S tate University School of Veterinary Medicine Baton RouJointge, L APathology Center Silver Spring, Maryland CASE I: CASE S1809996 1: 1 ((4152313JPC 4135077-00) ). Microscoptan/purple.ic Descr ipThetio n:medullary The inte rstitparenchymaium was within thedisrupted section isby diff dozensusel yof infilt brightra tedred btoy dull purple SignalmeSignalment:nt: A 3-mont h-old, male, mixed- moderate linesto lar thatge radiatednumbers from of pre thedomi levelna ofntl they renal crest breed pig 6(-Susmonth scrofa-old )male (intact) mastiff (Canis mononuclethroughar cell thes a lonmedulla.g with edema. There familiaris). is abunda nt type II pneumocyte hyperplasia History: This pig had no previous signs of lining alveolar septae and many of the illness, andHistory: was found dead. The patient was referred to a veterinary medicalalveola r spaces have central areas of Gross Patholteachingogy : hospitalApprox imfollowingately 70% an o facute, 1-dayne- crotic macrophages admixed with other the lungs,history primar ofily lethargy in the c andrani ainappetencel regions o fthat quicklymononucle ar cells and fewer neutrophils. the lobes, progressedwere patch toy obtundation. dark red, and Bloodwork firm performedOc casionally there is free nuclear basophilic comparedat to thethe rDVMmore norevealedrmal ar etooas ofhigh lun tog. read ALT, elevated ALP (805 U/L), hypoalbuminemia (2.7 Laboratorg/dL)y re suandlts: hypoglycemia Porcine reprodu (23 cmg/dL).tive PT and and respiraaPTTtory weresyndrome both prolonged (PRRS) PCat >100R wa secs and >300 positive frsec,om sprespectively.lenic tissue, Protein and P RandRS IHCbilirubin were was strongdetectedly immunore on a urineactive dipstick. within theA SNAP test for cytoplasmLeptosperosis of macroph awasges innegative. the aff eDespitected aggressive palliative therapy, the patient continued to lung tissue. Porcine influenza virus PCR, decline and euthanasia was elected. Figure 1-1. Liver, dog. The liver is diffusely friable and porcine cir covirus – 2 IHC, and mottled pale/bright red with a prominent reticular MycoplasGrossma hy opnpathology:eumoniae IHC were all pattern. (Photo courtesy of University of California, Davis negative. OnlySmall gross num belesionsrs of E.pertinent coli we rtoe the histologic Veterinary Medical Teaching Hospital, https://www.vetmed.ucdavis.edu/hospital). isolated fromfindings the candraniov caseentra discussionl lung with are provided. The aerobic cultentireure . length of the gastrointestinal tract Laboratory results: contained a small amount of intralumenal,Lu ng, pig (HE, 6X). There is diffuse consolidation of the lung. AtAmanita low magn (Liver):ification, aTraceirway adetectedre filled wit h watery, dark red to black ingesta and fecal exudate andAflatoxin the pleura a(Liver):nd interlo Nonebular cdetectedonnective material (melena). The intestinal mucosa wastiss ue are mMicrocystinsildly expanded. (Stomach contents): None detected mottled pale pink/red/dark purple. The hepatic parenchyma was diffusely friable and mottled pale/bright red with a prominent reticular pattern 1 (Image). The renal cortex was diffusely dull Microscopic description: multiple lobules. Lost hepatocytes are replaced by streams of extravasated red blood cells (hemorrhage), fibrin and karyorrhectic debris. Remaining individualized hepatocytes exhibit one or more of the following characteristics: cytoplasmic swelling, cytoplasmic vacuolation, cytoplasmic pigmentation, and nuclear pyknosis, karyorrhexis or karyolysis (degeneration and necrosis). Within the portal triads, portal collagen fibers are disrupted by increased clear space (edema), dissecting cords of hepatic progenitor cells (ductular reaction) and small numbers of lymphocytes and plasma cells. Scattered portal triads are additionally expanded by proliferating Figure 1-2. Liver, dog. A single section of liver is submitted collagenous stroma (fibrosis) that breaches the for examination. At subgross magnification, there is loss limiting plate and spans portal regions (bridging of normal plate architecture, diffuse loss of vital staining, and many lobules contain hemorrhage. There are portal fibrosis). numerous cracks and fissures present within the sample as a result of hepatocellular necrosis and loss of tissue cohesion. (HE, 5X) Contributor’s morphologic diagnosis: Liver: Massive hepatocellular necrosis with The slide contains one section of hepatic ductular reaction, hydropic degeneration, portal parenchyma in which massive necrosis is fibrosis and portal to portal bridging fibrosis. characterized by dissociation of hepatic cords to complete loss of hepatocytes across all zones of Figure 1-3. Liver, dog: Throughout the section, there is diffuse massive necrosis with hepatocellular individualization, rounding up, cytoplasmic vacuolation, and nuclear pyknosis and karyolysis. (HE, 400X) Figure 1-4. Liver, dog. There is moderate ductular reaction in response to widespread hepatocellular necrosis. (HE, 310X) Contributor’s comment: 0.5 mg/kg, which may be contained within 20 g The constellation of the patient’s age, clinical of Amanita mushrooms.5 Therefore, one history, bloodwork abnormalities and hepatic mushroom cap can provide a lethal dose to dogs. lesions were most concerning for a toxic etiology. Evaluation of numerous treatment options has Fresh samples of hepatic parenchyma were remained fruitless as the mortality rates in dogs submitted for toxicological analysis. A trace of remains high. Interestingly, studies have revealed amanitin was detected, therefore confirming remarkable variance in species sensitivity.4 For ingestion of Amanita phalloides, which is also instance, the rate of gastrointestinal absorption is known as the death cap or death angel mushroom. much greater in dogs than in mice and rabbits. Furthermore, rats appear to be relatively resistant Amanitin poisoning is classically divided into to amanitin’s toxic effects. four consecutive clinical stages, although each stage may not be evident in each case. Following Amanitin’s mechanism of action primarily stems ingestion, the first stage is characterized by from the toxin’s ability to inhibit RNA approximately 8 to 12 hours of no clinical polymerase II. Ceased transcription and abnormalities. The patient will then develop decreased protein synthesis eventually leads to severe gastrointestinal signs including vomiting cell death. Cells with high metabolic rate, such as and bloody diarrhea. The third stage of toxicity is hepatocytes, crypt cells and proximal convoluted characterized by brief clinical improvement, tubules, are the most severely affected, thus referred to as a “false recovery”, and quickly explaining the classic triad of hepatic failure, followed by the 4th stage, which is characterized gastroenteritis and renal failure, respectively. In by multi-organ failure. The liver and kidneys addition to inhibition of RNA polymerase II, appear to be most severely affected within this amanitin may induce hepatocellular apoptosis, fourth stage, as evidenced by striking thus compounding hepatocellular death and derangements in bloodwork and urinalysis. hepatic failure.2 Patients typically die within 12 to 84 hours Given the patient’s clinical history and the following ingestion of the lethal dose. The lethal hepatic lesions, top differential diagnoses dose (LD) for dogs is estimated to be around included blue-green algae poisoning (microcystins) and aflatoxin. However, no pursued until development of gastrointestinal microcystins were detected within the patient’s signs or multi-organ failure.1 A recent study stomach content nor was any aflatoxin detected evaluating 59 cases of α-amanitin toxicosis in within the fresh samples of hepatic parenchyma. dogs found upon presentation, alanine transferase activity (ALT) was mildly to markedly increased Contributing Institution: in 97% of dogs, hypoglycemia in 78% and University of California coagulation times were increased in 91%.1 Davis Veterinary Medical Teaching Hospital Although the signs of liver failure are not specific 1 Garrod Drive to α-amanitin toxicosis, early onset Attn: Anatomic Pathology Service hypoglycemia was found to be a distinguishing Davis, CA 95616 biochemical abnormality and its identification https://www.vetmed.ucdavis.edu/hospital helped distinguish affected dogs from those with other causes of gastroenteritis; however, JPC diagnosis: differential diagnoses should also include xylitol Liver: Hepatocellular necrosis, massive, diffuse, toxicosis, severe anaphylaxis, sepsis, and with ductular reaction and stromal collapse. portosystemic shunt.1 JPC comment: During necropsy, the liver is often swollen, The contributor provides an excellent overview without any other significant abnormalities and is of the pathogenesis and clinical progression of histopathologically characterized by massive amanitin toxicosis following ingestion of hepatocellular necrosis with collapse of hepatic Amanita phalloides. cords and acute tubular necrosis in dogs that develop renal failure. 4 A. phalloides is found worldwide due to the importation of trees from its native Europe. An Confirmatory diagnosis at select veterinary ectomycorrhizal fungus, A. phalloides shares a toxicology
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