AFIP Wednesday Slide Conference - No. 28
10 May 2000

Conference Moderator:
Dr. Daniela Ennulate, Diplomate, ACVP
Schering-Plough Research Institute
PO Box 32, 144 Route 94
Lafayette, NJ 07848-0032
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Case I - 3030/96 (AFIP 2694912)
Signalment: 2.5-year-old, female, Norwegian horse.
History: The horse had a history of diarrhea for longer than one week. The feces contained large numbers of small red nematodes up to 1cm in length. The animal showed reduced appetite, severe emaciation and a secondary hyperlipidemia. Therefore clinically a verminous colitis was diagnosed.

Over three days the horse was treated with electrolyte infusion, peristaltic and antiphlogistic agents, but the general condition remained bad, so the horse was euthanized, because of poor prognosis.
Case 28-1. Colon. Mucosal folds are swollen (edema). Abundant reddish-brown foci represent embedded nematode (Cyathostome) larvae.
Gross Pathology: The horse was partly necropsied by the veterinary surgeon and only parts of the large bowel were submitted for further microscopical examination. The gut wall of the large intestine was thickened due to a submucosal edema. On the luminal surface numerous submucosal and mucosal nodules, ranging from 6 mm in diameter to dark, tiny punctate lesions, could be detected.
Laboratory Results: PCV: 39.4%; pH of the blood: 7.24; BE: 13 mmol/l (metabolic acidosis).
Contributor's Diagnoses and Comments:
1. Colon: subacute multifocal moderate to severe granulomatous colitis with sections of nematode larvae in the lamina propria mucosa and tela submucosa.
2. Moderate submucosal edema.

Etiology: Larval cyathostomiasis
According to the stage of inflammation, focal or diffuse mucosal infiltrations with macrophages and neutrophils or parasitic granulomas dominate the lesions. The amount of eosinophils varied within the affected areas. In the submitted slides no eosinophils could be detected. The mucosal nodules consisted of larvae residing in dilated glandular crypts of mucosal cysts. The submucosal nodules contained parasites with a fibrous capsule surrounded by an intense inflammatory reaction, composed largely of macrophages and epithelioid cells, with fewer lymphocytes, plasma cells and neutrophils. As a residue of emigrated larval nematodes there was a focal accumulation of mononuclear cells in the mucosa. The intense mucosal edema was confirmed histologically. In addition some focal lymphangiectasia and medial hyperplasia of a few arteries accompanied the inflammatory reaction. In some sections, nematodes were found in lymph nodes, which could be interpreted as an incidental finding of aberrant larvae.
The most important helminthoses of horses are caused by nematodes, mainly by large strongyles (especially Strongylus vulgaris). Additionally members of the small strongyles are common nematode parasites of the colon and cecum in horses, usually present in mixed infestation (see slide). "Larval cyathostomiasis" has become more important recently due to the resistance of small strongyles against benzimidazoles.
The subfamily Cyathostominae, or small strongyles, includes eight genera of nematodes. Mainly the larvae have pathogenic significance. The larval stages (L3) migrate into the deep mucosa or submucosa of the large bowel (mainly cecum and ventral colon) from the gut lumen and enter the glands of Lieberkühn to molt and develop, before emerging into the lumen to molt again and mature. Larvae developing within cysts in the mucosal layer may alter these glands, with localized hypertrophy and hyperplasia of goblet cells. Local eosinophilia, edema and rupture of the muscularis mucosa are caused by the emergence of larvae, followed by infiltration of neutrophils and macrophages. Third or fourth-stage larvae may undergo hypobiosis or retarded development, only to mature sporadically as the adult population in the lumen turns over or is lost.
The disease "larval cyathostomiasis" is caused by maturation of large numbers of larvae leading to a leakage of the mucosal barrier. Only horses older than one year become ill and develop diarrhea, ill thrift or cachexia and hypoalbuminemia. However, these animals very often lack signs of eosinophilia. The mucosa is congested and edematous. If the mucosal damage is severe, there may be a fibrinous exudate on the eroded or ulcerated surface.
Case 28-1. Colon. Multifocally expanding the mucosa, submucosa, and lamina propria there are multiple sections of nematode larvae representing several stages of development.
AFIP Diagnosis: Colon: Colitis, lymphoplasmacytic and granulomatous, chronic, multifocal, severe, with edema and mucosal and submucosal strongyle larvae, Norwegian horse, equine.
Conference Note: This case was reviewed by Chris H. Gardiner, PhD, our parasitology consultant. He agreed that the parasites are true strongyles, but was unable to further classify them.
In many areas, cyathostomes are now the main parasitic pathogen of the horse. This rise in prominence is a result of the marked decrease in prevalence of large strongyles caused by widespread use of modern anthelmintic compounds. Clinically normal horses can harbor tens of thousands of cyathostomes without apparent disease. Cyathostomes are pathogenic at times of both penetration and emergence from the large intestinal mucosa. Clinical disease occurs most often in young horses in the late winter and early spring when large numbers of larvae mature synchronously.
Contributor: Institut für Veterinär-Pathologie, Justus-Liebig-Universität Giessen; Germany.
1. Barker IK, Van Dreumel, Palmer N: The Alimentary System. In: Pathology of Domestic Animals, eds. Jubb KVF, Kennedy PC, Palmer N, vol. 2, 4th ed, pp. 281-283. Academic press, San Diego, Ca, 1993
2. Giles CJ, Urquhart KA, Longstaffe JA: Larval cyathostomiasis (immature Trichonema-induced enteropathy): A report of 15 clinical cases. Equi Vet J 17:196-201, 1985
3. Reinemeyer CR, Powell HS: Larval Cyathostomiasis in three horses in Tennessee. Amer Ass Vet Lab Diag 29:69-76, 1986
4. Reinemeier CR: Small Strongyles; recent advances. Vet Clin North Am 2:281-311, 1986
5. Schillinger D, Hasslinger MA: Benzimidazole resistance in small strongyles of horses - Occurrence in Germany and strategies for avoiding resistance. Revue Med Vet 145:119-124, 1994
6. Love S, Murphy D, Mellor D: Pathogenicity of cyathostome infection. Vet Parasitol 85:113-121, 1999
Case II - S99-1215 (AFIP 2686534)
Signalment: 22-day-old male quarter horse foal.
History: The foal showed signs of neonatal maladjustment syndrome and was in lateral recumbency with opisthotonus. He appeared to have cervical muscular pain and would seldom elevate his head. He was treated intensely, but remained weak and would drink milk from a pan but not nurse. He was outside grazing at the time of agonal collapse. The mare has had three foals, another of which died at birth.
Gross Pathology: There was evidence of normal recent feeding and some firm fecal balls in the colon. There was no body fat and marked serous atrophy, especially obvious in the coronary grooves. The ductus arteriosus was patent (>10mm). Left and right ventricular endocardium was opaque white and distinctly thickened to 2-3mm. Myocardium and skeletal muscle appeared grossly normal, as did all other organ systems.
Laboratory Results: Reported were persistent neutropenia, low thyroid values, and persistently elevated CK and AST values. No bacterial growth from CSF. Liver selenium 0.301 ppm wet wt, judged within normal limits, as were other heavy metal screen values.
Contributor's Diagnoses and Comments:
1. Skeletal and myocardial degeneration with intra- and extra-cellular basophilic bodies
2. Endocardial fibroelastosis
Cause - Metabolic myopathy
Although there is mild multifocal myocyte degeneration and necrosis, the predominate change is the presence of variably large, waxy, bluish, amorphous bodies, extracellular and in the sarcoplasm, especially striking in the Purkinje conduction system. These bodies are sometimes vaguely laminated and prove PAS-positive, diastase-resistant and are also prominent in the brain, where they are visible with H&E. They are iodine-positive and Congo red-negative. A few are identified in nerves within the muscle fascicles and they are present in splenic macrophages and hepatic Kupffer cells.
The specific biochemical abnormality remains to be identified at this time but this appears to be a deficiency of a glycogen branching enzyme leading to inherited hypoglycemia, sepsis, cardiomyopathy and rhabdomyolysis in neonatal quarter horses. The fibroelastosis (proven with elastic stains) and PDA have apparently not been reported as parts of this syndrome.
Another recent report characterizing amylopectinosis in quarter horses shows many similarities, but not the crystals nor staining in the tongue in this present foal. That report suggested a form of glycogen storage disease, Type IV.
Case 28-2. Multifocally myocardial muscle fibers are expanded by variably sized, round, basophilic inclusions.
AFIP Diagnoses:
1. Heart, cardiomyocytes and Purkinje fibers: Amphophilic to basophilic intrasarcoplasmic inclusions, diffuse, numerous, quarter horse, equine.
2. Heart: Endocardial fibroelastosis, diffuse, moderate.
3. Skeletal muscle: Degeneration and necrosis, individual myofibers, multifocal, few, with scattered amphophilic to basophilic intrasarcoplasmic inclusions.
Conference Note: Two similar conditions in the horse have been recently reported, amylopectinosis (Render JA et al.) and equine polysaccharide storage myopathy (EPSSM) (Valentine BA et al.). There is abnormal accumulation of polysaccharides in both conditions, characterized by cytoplasmic inclusions that are PAS positive, diastase resistant and Congo red negative.
Amylopectinosis is described only in neonatal quarter horses. Amylopectin is similar to glycogen, but differs by having fewer a 1, 6 linked branch points and longer unbranched a 1, 4-linked chain segments. Although studies have not yet identified a specific defect in glycolytic or glycogenolytic pathways, the similarities to human type IV glycogen storage disease (caused by a deficiency of glycogen branching enzyme) cannot be denied. In amylopectinosis, cytoplasmic inclusions stain blue to black when treated with iodine, indicating a large amount of long unbranched chains. Inclusions are found in multiple tissues, including skeletal muscle (especially the tongue), cardiomyocytes, nerves, brain and spinal cord. Amylopectin must be differentiated from corpora amylacea and Lafora bodies, which have similar staining characteristics.
In contrast, EPSSM has been described in various horse and pony breeds and is characterized by repeated bouts of exertional rhabdomyolysis and generalized muscle atrophy in animals 8 months of age and older. Cytoplasmic inclusions are PAS positive, amylase resistant, and are found in skeletal muscle only.
Contributor: California Veterinary Diagnostic Laboratory- San Bernardino, 105 W Central Avenue, Box 5579, San Bernardino, CA 92412.
1. Render JA, Common RS, Kennedy FA, Jones MZ, Fyfe JC: Amylopectinosis in Fetal and Neonatal Quarter Horses. Vet Pathol 36:157-160, 1999
2. Valberg SJ, Hiraragi H, Ward TL, Rush B, Kinde H, Mickelson JR: Glycogen branching enzyme deficiency: an emerging cause of neonatal mortality in foals (abstract). J Vet Internal Med 12:234, 1998
3. Valentine BA, McDonough PP, Chang YF, Vonderchek: Polysaccharide storage myopathy in Morgan, Arabian, and Standardbred related horses and Welsh-cross ponies. Vet Pathol 37:193-196, 2000
Case III - TAMU 97-1 (AFIP 2594829)
Signalment: 14-year-old, thoroughbred, female, equine
History: The mare had a two-month history of tail rubbing and loss of hair around the tail head. There was a progressive atrophy of the muscles of the rump and mild ataxia. The skin around the tail had lost sensation and the mare was fecal incontinent.
Gross Pathology: The mare was euthanized, and at necropsy, the rectum was distended to 25 cm diameter. The urinary bladder was full of urine and turbid, gritty sediment. The spinal cord from the last lumbar nerves caudally was surrounded by brown-red fibrous tissue that coated the nerves of the cauda equina.
Contributor's Diagnosis and Comments: Chronic, extradural, fibrosing, granulomatous neuritis and perineuritis, Büngner band formation, demyelinating, neuropathy (neuritis of the cauda equina).
The sections submitted tried to demonstrate that the reaction is extra dural, and at the level of the section, it is asymmetric in involvement of the extradural nerve roots. Although there is a mild microgliosis with an occasional degenerated axonal fiber, the spinal cord is minimally affected; however, the perineurium is thickened by fibrous connective tissue and an infiltration by lymphocytes, macrophages, plasma cells and neutrophils with a rare multinucleated macrophage. The circumferential wraps of sheath cells (Büngner's bands) are impressive. Nerves are compressed and demyelinated. Less-affected nerves have cuffed vessels.
The gross and histologic observations in this case of neuritis of the cauda equina are typical of published cases. The presenting complaints indicated disease in the lumbar and sacral areas and the gross lesions reflected that. There was a ganglioneuritis of the trigeminal and cervical ganglia, but no other lesions were noted in the CNS. The fibrous tissue surrounding the cauda equina prevented separation of nerves; yet, the reaction stopped at the dura. This condition affects adult horses of many breeds. Because antibodies to P2 myelin have been commonly reported to be present in these animals, this disease is thought to represent an allergic neuritis similar to human Guillain-Barré syndrome. A test for P2 antibodies was not run in this horse. The etiology of this condition is not known. Equine adenovirus was isolated (after multiple passages) from two, reported cases of equine cauda equina neuritis.
Case 28-3. The outlines of degenerate nerve sheaths are surrounded by an infiltrate of lymphocytes, plasma cells, rare foreign body giant cells supported by fibrous connective tissue.
AFIP Diagnosis: Spinal cord, nerve roots: Polyradiculoneuritis, lymphoplasmacytic, histiocytic, fibrosing, multifocal, mild to severe, thoroughbred, equine.
Conference Note: Neuritis of the cauda equina has often been compared to Guillain-Barré syndrome and experimental allergic neuritis. Similarities include demyelinating changes in the proximal roots associated with infiltrating mononuclear cells and macrophages that strip away segments of the myelin sheaths. It is unclear whether circulating antibodies against P2 myelin protein represent the cause of the disease or a consequence of antigen release during myelin destruction. The chronic, unremitting course, intense granulomatous inflammation of the extradural roots and prevalence of axonal degeneration in neuritis of the cauda equina also differ from the previously mentioned immune-mediated diseases.
Contributor: College of Vet Medicine, Texas A&M University, College Station, TX 77843-4467.
1. Edington N, Wright JA, Patel JR, Edwards GB, Griffiths L: Equine adenovirus 1 isolated from cauda equina neuritis. Res Vet Sci 37:252-254, 1984
2. Fordyce PS, Edington N, Bridges GC, Wright AJ, Edwards GB: Use of an ELISA in the differential diagnosis of cauda equina neuritis and other equine neuropathies. Eq Vet J 19:55-59, 1987
3. Kadlubowski M, Ingram PL: Circulating antibodies to the neuritogenic myelin protein, P2, in neuritis of the cauda equina of the horse. Nature 293:299-300, 1981
4. Summers BA, Cummings JF, de Lahunta A: Veterinary Neuropathology, pp. 432-434. Mosby-Year Book, Inc., Baltimore, MD, 1995
5. Wright JA, Fordyce P, Edington N: Neuritis of the cauda equina in the horse. J Comp Pathol 97:667-675, 1987
Case IV - UCD2 (AFIP 2714532)
Signalment: One-month-old, male, thoroughbred foal
History: This foal was born three weeks prematurely and had a history of dyspnea with ataxia, aspiration pneumonia and labored breathing. The foal presented to the Veterinary Medical Teaching Hospital, bright, alert and responsive but icteric. Twenty-four hours after presentation the PCV dropped from 22 to 10. Occult blood was present in the feces and the foal was weakly Coombs' positive. The animal was given a transfusion with washed red blood cells from the mare. The foal was hypoxic and was given nasal oxygen. Blood glucose ranged from 50 to 60 despite a continuing good appetite. Radiographs revealed hypoplastic cuboidal bones in the tarsus and carpus. The foal was treated with ampicillin, amikacin®, Ranitidine®, Sucralfate®, Banamine®, dexamethasone, vitamin E, fluid and dextrose.
Gross Pathology: The animal was icteric. Petechiation was present on the tongue, gingiva and esophageal mucosa. Both lungs were diffusely wet, heavy and firm on palpation. On incision they were moderately to markedly wet. The spleen was approximately 2-3 times normal size and was firm. There were multiple renal infarcts.
Laboratory Results: WBC: 85,000 one week prior to presentation. Dropped to 4200 forty-eight hours after hospitalization. Post mortem cultures of the lungs and liver revealed large numbers of Candida lusitaniae-like organisms
Contributor's Diagnosis and Comments: Lung: Severe diffuse subacute interstitial pneumonia with intralesional yeasts (Candida lusitaniae).
Organisms were also found in the thymus, spleen, and liver. Additionally there was evidence of erythrophagocytosis in the spleen as well as disseminated intravascular coagulopathy. Systemic yeast infections have been observed in neonatal foals, especially those with complex medical problems or prematurity. Factors that increase the risk of systemic candidiasis include intravenous catheters, urinary catheters, endotracheal tubes, and multiple antibiotic therapy. Systemic Candida infections are also problematic in premature or ill human infants. Infections can either begin with colonization of endotracheal tubes or be a result of ascending infection from the lower genital tract of the mother. In one study, progression of local, tracheal colonization by Candida to systemic infection was most frequent in very low birth weight infants. In humans ascending intra-amniotic infections by a variety of organisms, including Candida, are major causes of preterm labor and premature rupture of the membranes. Theoretically this foal could have become infected by such a route; however, culture of the mare revealed no Candida species and thus it is most likely that this foal became infected as a result of debilitation.
Case 28-4. Occasional foreign body giant cells, macrophages and cell debris within alveoli and alveolar septa. Scattered macrophages contain multiple 3-4um basophilic organisms.
AFIP Diagnoses:
1. Lung: Pneumonia, interstitial, granulomatous, diffuse, severe, with numerous intrahistiocytic yeasts, thoroughbred, equine.
2. Lung, blood vessels: Fibrin thrombi, with yeasts.
Conference Note: Conference participants considered a broad differential diagnosis that included Histoplasma capsulatum, Cryptococcus neoformans, Blastomycetes dermatitidis, Sporothrix schenckii, Coccidioides immitis, Leishmania sp., Toxoplasma gondii, and Neospora caninum. Candida spp. can be identified in tissue when yeasts, hyphae and pseudohyphae are all present. In cases where all three structures are not present, culture is required for definitive diagnosis. Yeasts, hyphae and pseudohyphae are clearly evident in sections stained with GMS and PAS.
Along with pneumonia, systemic candidiasis may cause synovitis, panophthalmitis, meningitis, glossitis, osteomyelitis and cystitis.
Contributor: The University of California, Davis VM-PMI, 1 Shields, Davis, California, 95616.
1. Mazor M, Chiam W, Shinwell ES, Glezerman M: Asymptomatic amniotic fluid invasion with Candida albicans in preterm premature rupture of membranes: Implications for obstetric and neonatal management. Acta Obstetrica et Gyneco Scandin 72(1):52-54, 1993
2. Reilly L, Palmer JE: Systemic candidiasis in four foals. J of the Amer Vet Med Assoc 205(3):464-466, 1994
3. Rowen JL, Rench M, Kozinetz C, Adams J, Baker C: Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates. The J Ped 124(5):789-794, 1994
J Scot Estep, DVM
Captain, United States Army
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202) 782-2615; DSN: 662-2615
* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.
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