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CASE I – N00-94 (AFIP 2741633)
Signalment: 9-year-old, female, Tennessee Walking Horse, equine
History: This animal had a history of chronic weight loss, severe respiratory problems and anorexia. The animal also had a loose, greenish stool for two days and was eventually euthanized.
Gross Pathology: A yellowish discoloration of subcutaneous and mesenteric fat was observed. Approximately two liters of a yellowish–brown fluid was within the peritoneal cavity. The pleural cavity also had increased yellow fluid and the lungs were meaty and bright red. A thick, white, stringy material covered the tracheal mucosa. Ecchymotic hemorrhages were seen in the uterine body and horns. Mesenteric lymph nodes were enlarged and edematous. There were multiple gastric erosions and jejunal ulcers present. The spleen and liver were slightly enlarged and firm. The liver had a small white nodule within the median lobe.
Laboratory Results: Serology: a titer of 1:4 for the virus of equine viral arteritis (EVA) was detected. There was no prior history of vaccination against EVA in this animal.
Contributor’s Diagnosis and Comment: Panarteritis, lymphocytic/plasmacytic, diffuse, severe with segmental fibrinoid necrosis.
Diffusely, there is lymphoplasmacytic perivascular cuffing of adventitial (vasa vasorum), mesenteric, epineural and endoneural arterioles. Many small arteries have segmental, fibrinoid necrosis of the tunica media and a few have recognizable thrombi. Some arterial walls are hypertrophied and many associated nerve fiber bundles are vacuolated and disorientated, and mildly infiltrated with lymphocytes and plasma cells. A section of lymph node (on some slides) has subcapsular sinuses and cortical areas that are expanded by hemorrhage and edema. There is random necrosis of individual lymphocytes.
Equine viral arteritis is a cosmopolitan infectious disease of horses characterized by panvasculitis, edema and hemorrhage in affected tissue. Major targets of viral replication include blood vessels, lung, intestine, kidney and reproductive system. Equine viral arteritis is caused by an arterivirus that is an RNA, enveloped member of the family Arteriviridae, along with the porcine reproductive and respiratory syndrome virus, simian hemorrhagic fever virus, and lactate dehydrogenase elevating virus.
AFIP Diagnosis: Large artery with adjacent adipose tissue, fibrous tissue and nerve bundle: Vasculitis, necrotizing, chronic, multifocal, severe, with chronic, fibrosing perivascular and perineural inflammation and edema, Tennessee walking horse, equine.
Conference Comment: The clinical manifestations of EVA resemble those of many of the febrile hemorrhagic fevers. The fatal sequence of necrotizing panvasculitis, increased vascular permeability, and hemorrhage and edema of the subcutaneous tissues, lymph nodes, and viscera can be seen along with lymphoid necrosis, renal tubular necrosis, abortion, and inflammation of male accessory reproductive glands.
Infection typically involves viral replication in respiratory epithelium and alveolar macrophages. Localization in bronchial lymph nodes is followed by replication in endothelium and circulating monocytes with subsequent systemic distribution. At approximately 10 days post-infection, the most severe damage occurs with necrosis of the tunica media of small muscular arteries.
Abortion in EVA may occur as a result of decreased blood flow through edematous endometrium or alterations in vascular tone caused by various inflammatory mediators. Ischemia and placental hypoxia, combined with the local release of prostaglandins, may trigger premature chorionic detachment and expulsion of the fetus. In the infected fetus, viral antigen often can be identified within the trophoblastic epithelium.
Infections with equine herpesvirus 1, the orbivirus of African horse sickness, the paramyxovirus of Hendra disease, and Getah virus can have similar clinical and histopathological findings. These diseases can usually be differentiated with available ancillary procedures.
In this case, conference participants did not believe that the morphologic changes present in the examined tissues and the titer of 1:4 were diagnostic of EVA. Most preferred a differential diagnosis consisting of EVA, the diseases listed above, and other infectious and immune mediated diseases.
Following the conference, this case was evaluated in consultation with Dr. Fabio Del Piero at the University of Pennsylvania, New Bolton Center. Lung, kidney, and lymphoid tissue were tested for the presence of equine arteritis virus antigen (EAV Ag) and equine herpesvirus-1 antigen (EHV-1 Ag) using indirect immunoperoxidase histochemistry on formalin-fixed tissues. The first monoclonal antibody recognizes a 30 kD structural protein of EAV; the monoclonal for EHV-1 identifies a structural glycoprotein. The tissues were negative for EAV and EHV-1 Ag. While these negative results do not exclude the possibility of an unusual presentation of EVA or a particular strain of virus that is not recognized by the monoclonal antibody, Dr. Del Piero considered this unlikely.
Contributor: Tuskegee University, School of Veterinary Medicine, Department of Pathobiology, Tuskegee, AL 36088
References: 1. Del Piero F: Equine viral arteritis. Vet Pathol 37:287-296, 2000
2. Timoney PJ, McCollum WH: Equine viral arteritis. Vet Clin North Amer Eq Pract 9:295-309, 1993
3. Estes PC, Cheville NF: The ultrastructure of vascular lesions in equine viral arteritis. Amer J Path 58:235-252, 1970
CASE II – 96199 (AFIP 2738850)
Signalment: Seventeen-year-old, female, cynomolgus macaque (Macaca fascicularis)
History: Incidental histologic finding in ovaries collected for experimental reasons
Gross Pathology: None provided.
Laboratory Results: None provided.
Contributor’s Diagnoses and Comment: Ovary - 1. Moderate multifocal paraovarian endometriosis.
2. Multiple paraovarian cysts (tubal/Müllerian)
3. Ectopic ovarian tissue, minimal, focal, within mesovarium (some sections)
4. Focal fibrous ovariofimbrial adhesion (some sections).
Ovarian endometriosis was an incidental finding upon histologic examination of the ovaries, and was not grossly apparent. Endometriosis was bilateral but limited to the ovaries. The endometriotic lesions consist of both glands and stroma, and some contain blood and/or cellular debris. Other small cystic structures near the ovarian hilus are considered Müllerian duct cysts because they are partially bounded by smooth muscle, lack endometrial-type stroma, and are lined by ciliated epithelium. The prominent rete ovarii is considered normal for a macaque. Other minor lesions, such as ectopic ovarian tissue within the mesovarium and focal adhesion of the ovary to the fimbria, were discovered during sectioning for this conference and thus are only apparent in some sections.
Endometriosis is common in macaques. Dioxin exposure has been associated with endometriosis in rhesus macaques. Endometriosis in rhesus monkeys occurs most commonly on the uterine serosa and in the posterior pelvic cul-de-sac, and affected animals can be identified by measurement of serum CA-125 concentrations.
Ectopic or remnant ovarian tissue occurs rarely in animals necropsied at our institution, but occasionally interferes with studies involving ovariectomy to induce estrogen deficiency. Ectopic ovarian tissue is not well documented in macaques.
“Ovarian remnant syndrome” is a well-documented entity in veterinary medicine and has been diagnosed in women when estrogen-dependent disease conditions have persisted after ovariectomy. True ectopic ovarian tissue is rarely identified and is usually discovered when neoplasms have arisen in the ectopic ovarian tissue.
AFIP Diagnosis: Ovary and mesovarium: Endometriosis, multifocal, with paraovarian cysts, cynomolgus monkey (Macaca fascicularis), nonhuman primate.
Conference Comment: Endometriosis has only been reported in human and nonhuman primates. The condition often involves the ovary, but may be seen in uterine serosa and adjacent pelvic structures, urinary bladder, lymph nodes, liver and lung. Ectopic endometrial tissue responds to cyclic hormonal stimulation, just as normal endometrium does, and therefore undergoes the cyclic menstrual changes with periodic bleeding. Organizing hemorrhage can cause extensive fibrous adhesions between uterine tubes, ovaries, and other structures. This finding can possibly make it difficult to differentiate endometriosis from retroperitoneal fibromatosis on gross examination. The ovaries may contain large cystic spaces filled with brown blood debris to form so-called chocolate cysts.
Although the pathogenesis of endometriosis has not been fully elucidated, three theories may each have some validity. The metaplastic theory proposes that endometriosis represents endometrial differentiation of coelomic epithelium. The regurgitation or implantation theory proposes that endometrium is regurgitated through the Fallopian tubes at menstruation and implants in various locations. The vascular or lymphatic dissemination theory possibly explains extrapelvic or intranodal implants; it proposes that endometrial tissue disseminates via the blood or lymphatics.
Spontaneous endometriosis in rhesus macaques is an excellent model of human endometriosis. Cancer antigen-125 (CA-125), a surface glycoprotein of Müllerian duct origin, has been shown to be elevated in the blood of women and rhesus macaques with this condition. This easily measurable, circulating marker, while not specific for endometriosis, can be utilized as a non-invasive adjunct to select animals for laparoscopic examination in endometriosis research.
Contributor: Wake Forest University School of Medicine, Department of Pathology, Section on Comparative Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040
References: 1. Heller DS, Harpaz N and Breakstone B: Neoplasms arising in ectopic ovaries: a case of Brenner tumor in an accessory ovary. [Review] [16 refs.]. Int J Gyn Path 9:185-1899, 1990
2. Lafferty HW, Angioli R, Rudolph J, Penalver MA: Ovarian remnant syndrome: experience at Jackson Memorial Hospital, University of Miami, 1985 through 1993 [see comments]. [Review] [23 refs.]. Amer J Obstet & Gyn 174:641-645, 1996
3. Mercer LJ, Toub DB, Cibils LA: Tumors originating in supernumerary ovaries: A report of two cases. [Review] [9 refs.]. J Repro Med 32:932-934, 1987
4. Miller DM: Ovarian remnant syndrome in dogs and cats: 46 cases (1988-1992). J Vet Diagn Invest 7:572-574, 1995
5. Rier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL: Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin [see comments]. Fund & Appl Tox 21:433-441, 1993
6. Rippy MK, Lee DR, Pearson SL, Bernal JC, Kuehl TJ: Identification of rhesus macaques with spontaneous endometriosis. J Med Primatol 25:346-355, 1996
CASE III – 20040-00 (AFIP 2741433)
Signalment: Four-week-old crossbred pigs (Sus scrofa domesticus)
History: These nursery pigs had severe respiratory distress with weight loss that had been unresponsive of a variety of antimicrobial agents. Of 100 pigs in the group, half were affected.
Gross Pathology: There was marked, diffuse, tan discoloration of the lungs. The cranial lung lobes were dark tan and firm. No other gross lesions were seen.
Laboratory Results: Immunohistochemical tests for porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV-2) were positive in parallel sections of lungs. ELISA for PRRS virus on serum was positive. Haemophilus parasuis was isolated from the lungs of a pen mate of this pig.
Contributor’s Diagnosis and Comment: Pneumonia, severe, subacute, diffuse, histiocytic, neutrophilic, bronchointerstitial.
Normal alveolar architecture is partially obscured by large numbers of histiocytes in alveoli. Numerous aggregates of neutrophils and karyorrhectic and granular proteinic debris are also present in alveolar spaces. Many airway lumens are filled with neutrophils and bronchi contain small intraepithelial aggregates of neutrophils. Cuffs of mixed mononuclear inflammatory cells and eosinophils are observed surrounding many airways and arterioles. As noted in the photomicrographs, there is positive immunohistochemical staining for the presence of PRRSV and PCV-2 in parallel sections of lung. Other lesions observed in this pig were lymphoid depletion of germinal centers in the tonsil with granulomatous inflammation. Many macrophages contained botryoid clusters of basophilic intracytoplasmic inclusion bodies, consistent with what is seen in cases of postweaning multisystemic wasting syndrome (PMWS).
This case represents a common presentation of porcine respiratory disease and PMWS in swine. Often, there is concurrent infection with PRRSV and PCV-2 resulting in a complex disease process. There are often multiple bacterial infections present in association with these cases of dual viral infection. A synergistic effect has been demonstrated between PCV-2 and porcine parvovirus, and a synergistic effect between PRRSV and PCV-2 has been postulated.
AFIP Diagnosis: Lung: Pneumonia, bronchointerstitial, necrosuppurative and histiocytic, subacute to chronic, diffuse, severe, with intrahistiocytic amphophilic to basophilic intracytoplasmic inclusion bodies.
Conference Comment: Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in 5–12-week-old piglets characterized by progressive weight loss, tachypnea, dyspnea, and jaundice. Clinically, PMWS can be difficult to differentiate from porcine reproductive and respiratory syndrome (PRRS), which is caused by an arterivirus.
Porcine circoviruses (PCV-1 and PCV-2) are non-enveloped, noncytopathic viruses with a unique single-stranded circular DNA genome that replicate in a variety of different cells. PCV-1 appears to be non-pathogenic and was originally identified as a contaminant of porcine cell cultures. Some studies have indicated that PCV-2 infection may be a widespread, often asymptomatic infection in swine herds. Similarly, porcine parvovirus (PPV) is thought to be endemic in pigs worldwide. It causes abortion and fetal death, but has only rarely been associated with any other disease.
Recent research has shown that concurrent infection of PCV-2 and PPV produced lesions similar to naturally occurring cases of PMWS in gnotobiotic pigs. These results have provided evidence that PPV may act synergistically with PCV-2 as an important cofactor in the development of naturally occurring PMWS. Questions have also been raised regarding the possibility that many of the pathologic features that have been attributed to PRRSV could, in fact, be caused by infection or coinfection with PCV-2.
Further research of these disease syndromes is needed to fully understand the contributory roles that each virus plays in pathogenesis and disease expression in swine herds.
Contributor: University of Nebraska, Veterinary Diagnostic Center, Fair Street and East Campus Loop, Lincoln, NE, 68583-0907
References: 1. Ellis JA, Bratanich A, Clark EG, Allan G, Meehan B, Haines D, Harding J, West KH, Krakaowka S, Konoby C, Hassard L, Martin K, McNeilly F: Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome. J Vet Diagn Invest 12:21-27, 2000
2. Ellis J, Krakowka S, Lairmore M, Haines D, Bratanich A, Clark E, Allan G, Konoby C, Hassard L, Meehan B, Martin K, Harding J, Kennedy S, McNeilly F: Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic pigs. J Vet Diagn Invest 11:3-14, 1999
3. Ellis JA, Krakowka S, Allan G, Clark E, Kennedy S: “The clinical scope of porcine reproduction and respiratory syndrome virus infection has expanded since 1987”: An alternative perspective. Vet Pathol 36(3):262-265, 1999
4. Harding JCS, Clark EG: Recognizing and diagnosing postweaning multisystemic wasting syndrome (PMWS). Swine Hlth Prod 5(5):201-203, 1997
CASE IV – 00-4825 (AFIP 2741369)
Signalment: Tissue is from a 2-year-old, male, domestic shorthair cat.
History: The owners of this cat purchased an Easter lily (Lilium longiflorum) on the Saturday preceding Easter Sunday, and placed the plant in a common living room. Several hours later the owners noticed that the plant had been knocked over and multiple leaves were fragmented, missing portions and had multiple bite marks. Within 3 hours the household cat was listless and vomiting. The owners took the cat to a local practitioner where over the next 24 hours oliguria and adynamic ileus were noted. A presumptive diagnosis of acute renal failure was made and the owners elected euthanasia.
Gross Pathology: Bilateral perirenal edema and minimal urine within the bladder were the only significant findings. The gastrointestinal tract was not opened.
Laboratory Results: No ancillary laboratory tests were performed.
Contributor’s Diagnosis and Comment: Acute tubular necrosis, disseminated, severe with cellular and protein casts
There is widespread degeneration/necrosis of the epithelial cells lining multiple tubules (likely proximal tubules). Affected cells are swollen and have vacuolated to granular eosinophilic cytoplasm, and vesicular to pyknotic nuclei. Numerous tubules lack epithelial cells, although basement membranes are intact. Rare tubules are lined by severely flattened epithelial cells or by hyperbasophilic cells with large hyperchromatic nuclei (regenerative cells). Occasional mitotic figures are noted in the areas of attenuated epithelium. Affected tubules often contain protein casts and, less often, accumulations of cellular debris. Medullary tubules variably contain abundant proteinaceous fluid with intermixed protein and cellular casts. These histopathologic findings, taken together with the history, clinical signs, and gross findings strongly suggest Easter lily toxicity.
Although the exact amount of plant material necessary to induce nephrotoxicity is not known, consumption of less than one leaf is known to produce severe toxicosis. The toxic principle is likewise unknown, but is present in both leaves and flowers. Common presenting signs are vomiting (minutes to hours post ingestion) and anorexia. Renal failure subsequently develops within 48 to 96 hours post ingestion and is attributed to acute renal tubular epithelial cell necrosis. Death due to renal failure or euthanasia commonly occurs by 3 to 6 days post exposure. Clinical intervention (decontamination and fluid diuresis), if initiated within 6 hours post exposure can prevent mortality. The cat may be predisposed to Easter lily toxicity, as attempts to produce a similar syndrome in rats and rabbits have been unsuccessful.
AFIP Diagnosis: Kidney: Necrosis, tubular, acute, diffuse, with regeneration, tubular protein and granular casts, domestic shorthair, feline.
Conference Comment: Nephrotoxic acute tubular necrosis is a reversible lesion that is usually characterized by extensive necrosis of primarily proximal tubular epithelial cells but with preservation of tubular basement membranes. Preservation of basement membranes is necessary to provide the framework for epithelial regeneration. The loss of detached tubular epithelial cells and necrotic debris into the lumen can cause luminal tubule obstruction, increased intratubular pressure, decreased glomerular filtration rate, and oliguria.
Although not reported in this case, electrolyte and serum chemistry alterations occurring in acute renal disease include hyperphosphatemia, hyperkalemia, and metabolic acidosis. Measurement of urine specific gravity is a good indicator of renal tubular function. A cat with a random specific gravity of >1.035 is presumed to have adequate concentrating ability. Urine specific gravity <1.008 indicates some renal water-balance function; solute is being reabsorbed in excess of water. Glucosuria, also, could be seen due to inefficient reabsorption of glucose in the proximal tubules, but is not a reliable indicator of proximal tubular function.
Contributor: Washington State University, Department of Veterinary Microbiology and Pathology, P.O. Box 647040, Pullman, WA 99164-7040
References: 1. Volmer PA: Easter lily toxicosis in cats. Vet Med 94:331, 1999
2. Hall JO: Nephrotoxicity of Easter lily (Lilium longiflorum) when ingested by the cat. Proceedings of the 10th Annual Meeting of the American College of Veterinary Internal Medicine, p. 804, 1992
3. Groff RM, Miller JM, Stair JO, Knight MW, Buck WB: Toxicoses and toxins. In: Feline Practice, ed. Norsworthy GD, p. 564. Lippincott Co., Philadelphia, PA, 1992
4. Gulledge L, Boos D, Wachsstock R: Acute renal failure in a cat secondary to Tiger lily (Lilium tigrinum) toxicity. Fel Pract 25:38-39, 1997
*Sponsored by the American Veterinary Medical Association, the American College of Veterinary Pathologists and the C. L. Davis Foundation.
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