The Armed Forces Institute of Pathology

Department of Veterinary Pathology

WEDNESDAY SLIDE CONFERENCE

2000-2001

 

CONFERENCE 30

16 May 2001

 

Conference Moderator: LTC Dale Dunn

Chief, Division of Veterinary Pathology

Armed Forces Institute of Pathology

Washington, DC 20306-6000

 

CASE I – 990-18956 (AFIP 2741026)

 

Signalment: 14-year-old, gelding American paint horse (Equus caballus), equine.

 

History: Horse presented for acute hind-limb paresis, incontinence and ataxia.  The horse was humanely destroyed following a tentative clinical diagnosis of cauda equina neuritis.

 

Gross Pathology: An approximately 20 cm segment of the sacral spinal cord and cauda equina is expanded by an irregular, lobulated, firm, tan to gray mass that incorporates the dura and nerve roots.  On section this tissue expands the dura without gross evidence of medullary involvement.  No other gross lesions are identified in the remainder of the CNS or other organ systems.

 

Laboratory Results: Not available.

 

Contributor’s Diagnosis and Comment: Spinal cord and cauda equina: Radiculomeningomyelitis, chronic, granulomatous, segmental, severe, with intralesional nematodes, equine, American paint horse.  (Myelitis is not present in all of the sections)

Etiology: Halicephalobus gingivalis

 

Halicephalobus gingivalis (Micronema deletrix) is a free-living nematode of the superfamily Rhabditoidea and family Rhabditidae.  This nematode has a rhabditiform esophagus with a corpus, isthmus and valved bulb.  The parthenogenetic female is didelphic with reflexed ovaries.  H. gingivalis is a sporadic cause of granulomatous gingivitis, nephritis, and meningoencephalitis in the equine.  The route of entry is thought to be from fecal-contaminated skin abrasions or lacerations; however, the pathogenesis, life cycle, and routes of entry are poorly understood.  The parasite may initially involve nasal and oral cavities with subsequent hematogenous dissemination.  This case is unusual in that both gross and histologic lesions were restricted to the posterior spinal cord and cauda equina.

 


AFIP Diagnosis: Sacral spinal cord, meninges, and nerve roots: Meningitis and polyradiculitis, granulomatous, multifocal, moderate, with rhabditoid nematode adults, larvae, and eggs, etiology consistent with Halicephalobus gingivalis (H. deletrix), horse, American paint, equine.

 

Conference Comment: While there are a few reports of infection in man (all fatal), most reports of Halicephalobus infection have been in horses.  Other rhabditoid nematodes reported to infect the horse, mainly the integument, include Strongyloides westeri and Cephalobus spp.  Strongyloides westeri larvae are associated with cutaneous penetration, but adults and eggs are typically not found in the skin.  Histomorphologic features that distinguish Cephalobus spp. include a blunt tail and subtle differences in the shape of the esophagus.  Cephalobus has been reported in the mammary gland of a mare.

 

Contributor: Colorado State University, Department of Pathology, 200 West Lake Street, Ft. Collins, CO 80523

 

References: 1.  Anderson RC, Linder KE, Peregrine AS: Halicephalobus gingivalis (Stefanski, 1954) from a fatal infection in a horse in Ontario, Canada with comments. Parasite 5:255-261, 1998

2.  Greiner EC, Calderwood-Mays MB, Smart GC, Weisbrode SE: Verminous mastitis in a mare caused by a free-living nematode. J Parasitol 77(2):320-322, 1991

3.  Kinde H, Mathews M, Ash L, St. Leger J: Halicephalobus gingivalis (H. deletrix) infection in two horses in southern California. J Vet Diag Inv 12:162-165, 2000

4.  Shadduck JA, Ubelaker J, Telford VQ: Micronema deletrix meningoencephalitis in an adult man. Am J Clin Pathol 72(4):640-643, 1979

 

 

 


CASE II – A00-238 (AFIP 2738719)

 

Signalment: 4-year-old, male rhesus macaque (Macaca mulatta).

 

History: This animal was one of a group used to evaluate the pathogenic effects of genetically modified strains of simian immunodeficiency virus (SIV) as part of a vaccine development study.  Approximately 8 months after SIV inoculation, the animal was noted to have respiratory difficulty and severe diarrhea.  Euthanasia was performed.

 

Gross Pathology: At necropsy, there was approximately 5 ml of clear fluid in the peritoneal cavity.  The body of the pancreas was white, firm, and markedly enlarged.  Portions of the pancreas were adherent to the greater curvature of the stomach, distal duodenum and transverse colon.  Diffusely, the wall of the jejunum was mildly thickened and mesenteric lymph nodes were prominent.  Lung lobes were partially collapsed, resilient to firm, and pale tan.

 

Laboratory Results: Immunohistochemical labeling with a monoclonal antibody, recognizing all 41 serotypes of human adenovirus, revealed many immunoreactive cells in acini surrounding foci of pancreatic necrosis.  Positive staining was also present in the epithelium of pancreatic ducts, and fewer individual immunoreactive nuclei were scattered randomly in the remainder of the exocrine pancreatic lobules.  No adenoviral immunoreactive nuclei were identified in the mucosa of the gastrointestinal tract or lung.  In the lamina propria of the gastrointestinal tract, and within the pulmonary interstitium, there were occasional individual macrophages with coarsely granular, intracytoplasmic labeling that represented immunoreactive debris in phagolysosomes.  Virus isolation and serologic typing were not performed.

 

Contributor’s Diagnoses and Comment: 1.  Pancreas: Severe, diffuse, chronic-active, necrotizing pancreatitis, with multifocal hemorrhage and intranuclear inclusion bodies (adenovirus).

2.  Duodenum: Mild, diffuse, suppurative and proliferative enteritis. 

 

There is moderate to marked, diffuse degeneration of exocrine pancreatic cells, with few cells containing visible zymogen granules.  Most cells are shrunken and contain glassy eosinophilic cytoplasm and central, euchromatic nuclei.  Occasionally, acinar cells contain large, central nuclei with marginated chromatin and glassy, amphophilic to basophilic intranuclear inclusion bodies.  There are many foci in which pancreatic acinar cells are lost, with replacement by nodular aggregates of many intact and degenerative neutrophils, fewer macrophages and lymphocytes, and moderate amounts of granular cellular and karyorrhectic debris.  Ductal epithelial cells are variably shrunken, and rare individual cells contain intranuclear inclusion bodies.  Several duct lumina contain aggregates of neutrophils and cellular debris.  The interlobular septa are markedly thickened by severe edema, fibrin, many intact and degenerative neutrophils, fewer macrophages, lymphocytes and plasma cells, fibrosis, and frequent foci of mild hemorrhage.  Diffusely, moderate numbers of lymphocytes and plasma cells, and small numbers of intact neutrophils infiltrate the peripancreatic adipose tissue. 

          In the section of adjacent duodenum, the villi are separated by proprial infiltrates of moderate numbers of macrophages, lymphocytes and fewer plasma cells, occasional neutrophils, and few multinucleated giant cells.  There are aggregates of hemosiderin-laden macrophages in the lamina propria of the superficial villus tips, foci of congestion, and few individual villi with mild, superficial mucosal hemorrhage.  There are increased numbers of mitotic figures in the superficial epithelium.  Mucosal-associated lymphoid tissue is prominent. 

          Transmission electron microscopic examination of exocrine pancreatic cells revealed few intracytoplasmic zymogen granules.  Many cells are undergoing degeneration.  Nuclei of infected cells contain latticework arrays of icosahedral, 80-nm diameter, mature virus particles and scattered electron dense, irregular granules of immature virus, consistent with an adenovirus.  Small marginal clumps of chromatin are present in karyorrhectic nuclei.  There are frequent virus particles free in the cytoplasm.

Other significant gross and histopathologic lesions in this animal are characteristic of SIV infection and include thymic atrophy, splenomegaly with lymphoid follicular dysplasia, lymph node sinus histiocytosis with multinucleated giant cells, and lymphoid nodules in the bone marrow.  Opportunistic infections include severe Pneumocystis carinii pneumonia, and moderate jejunal cryptosporidiosis.  Mild to moderate, suppurative and proliferative gastritis, enteritis, and typhlocolitis are present, for which the etiopathogenesis is undetermined.  Importantly, epithelial cells infected with adenovirus are not identified by immunohistochemistry in these tissues. 

          The family Adenoviridae comprises over 100 members, and is divided into two genera: Mastadenovirus, affecting mammals and marsupials, and Aviadenovirus, which infect birds.  Adenoviruses are nonenveloped, and contain linear, double-stranded DNA that is contained within an icosahedral protein capsid ranging between 70-100 nm in diameter.  Viral replication occurs in the nucleus of host cells, resulting in characteristic inclusion bodies visible by light microscopy.  Species-specific adenoviruses have been isolated from many mammals, including humans and nonhuman primates, and most often result in pneumonia or enteritis.  At least 27 strains are recognized to infect nonhuman primates, and were studied extensively for their ability to immortalize cells in vitro and induce neoplasms in experimentally inoculated hamsters.  More recently, adenoviruses are under investigation as vectors for gene therapy.  Several schemes have been proposed for the classification of adenoviruses, although classification based on hemagglutination profiles is most commonly used. 

          In immunocompetent rhesus macaques, infection with adenovirus rarely results in clinical disease, and reports of adenoviral pancreatitis in nonhuman primates are few.  Infected macaques may develop transient upper respiratory disease, pneumonia, conjunctivitis, or gastroenteritis.  Simian adenoviruses are uncommon, yet significant potential opportunistic pathogens in immunocompromised monkeys.  Simian adenovirus types 20, 23, and 31 have been associated with the development of necrotizing pancreatitis.  More commonly, segmental enteritis involving the ileum is observed with adenovirus infection of immunocompromised macaques.  Adenoviral pneumonia occurs even less frequently, and adenoviral nephritis is rare. 

          At necropsy, an enlarged, discolored, friable, and nodular pancreas with multiple adhesions between the pancreas and nearby organs, most often the left kidney and duodenum, is suggestive of pancreatitis.  Particularly in immunocompromised animals, adenoviral infection should be considered as a differential diagnosis.  Other causes of pancreatitis in rhesus macaques include several protozoa (Cryptosporidium spp., Trichomonas spp., or Enterocytozoon bieneusi), cytomegalovirus infection, descending bacterial infection from primary hepatitis, or complications secondary to diabetes mellitus, pancreatic islet cell amyloidosis, fatal fasting syndrome of obese macaques, or pancreatic duct obstruction.  Significant peritonitis or necrosis of mesenteric fat is uncommon with adenovirus infection.

Histopathologic lesions with adenoviral pancreatitis include multifocal to diffuse interstitial infiltrates of mixed inflammatory cells, with degeneration and necrosis of exocrine pancreatic cells.  Significant interstitial fibrosis may also be present.  Islet cells are not affected.  Characteristic intraepithelial intranuclear inclusion bodies may be seen at the margins of degenerative and necrotic foci, allowing for a presumptive diagnosis of adenoviral pancreatitis.  Definitive diagnosis may be made by virus isolation, immunohistochemistry or immunofluorescence, electron microscopy, or serological neutralizing antibody profile.

 


AFIP Diagnoses: 1.  Pancreas: Pancreatitis, necrotizing, chronic-active, multifocal, severe, with ductular hyperplasia, and eosinophilic and basophilic intranuclear inclusion bodies, etiology consistent with adenovirus, rhesus macaque (Macaca mulatta), nonhuman primate.

2.  Lymph node: Sinus histiocytosis, subcapsular, multifocal, mild, with few multinucleated cells.

 

Conference Comment: The contributor has provided a concise review of adenoviral pancreatitis and SIV infection in rhesus monkeys.  Conference attendees largely agreed with the contributor’s diagnoses; however, proliferative enteritis was not observed in the sections of intestine examined in conference.

 

Contributor: New England Regional Primate Research Center at Harvard Medical School, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772-9102

 

References: 1.  Baskin GB, Murphey-Corb M, Watson EA, Martin LN: Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/Delta. Vet Pathol 25: 456-467, 1988

2.  Chandler FW, McClure HM: Adenoviral pancreatitis in rhesus monkeys: current knowledge. Vet Pathol 19(7):171-180, 1982

3.  Gliatto JM, Bronson RT: Fatal fasting syndrome of obese macaques. In:  Nonhuman Primates I: Monographs of Pathology of Laboratory Animals. ed. Jones TC, Mohr U, Hunt RD, pp. 198-202. Springer-Verlag, New York, NY, 1993

 

 

 


CASE III – DD00644 (AFIP 2741450)

 

Signalment: 77-day-old, male FVB/N mouse, (Mus spp.)

 

History: These negative-control FVB/N mice were on a 28-day repeated-dose dermal toxicity study.  There were no adverse clinical observations and they were necropsied at the scheduled termination of the study.

 

Gross Pathology: None.

 

Laboratory Results: Normal.

 

Contributor’s Diagnosis and Comment: Retinal atrophy, bilateral, diffuse.

 

The retinal atrophy (degeneration) that was observed in these mice was considered to represent a hereditary retinal lesion since all control mice were uniformly affected.  This lesion has been described previously in FVB mice and is considered to be related to the presence of the rd1 gene.

 


AFIP Diagnosis: Eye, retina: Atrophy, outer segment, diffuse, severe, FVB/N mouse, rodent.

 

Conference Comment: There are a variety of possible causes for this condition that were discussed in conference, to include heredity, age, and light-induced degeneration.

The FVB/N mouse is homozygous for the rd1 allele, inherited as an autosomal recessive gene and seen in over 50 mouse strains.  The gene is most common in C3H and FVB mice in which there is maldevelopment or maturation failure of the rods, with subsequent degeneration of the entire photoreceptor cell layer.  Elevated levels of cGMP, with a reduction in cGMP phosphodiesterase activity, have been found in these mice.  Normally differentiated photoreceptors are present at birth, but apoptosis of rod and cone photoreceptors is evident beginning in the second week of life.  The FVB/N mouse is useful for the production of transgenic mouse strains because of their large litters and presence of large pronuclei within fertilized eggs that facilitates micromanipulation of DNA.

An autosomal dominant retinal degeneration, called Rd4, has been induced in the DBA/2J mouse.  Heterozygotes develop retinal degeneration in the outer nuclear and plexiform layers beginning at 10 days of age.

Photoreceptor cell and ganglion cell loss is an age-related lesion seen in the senescence-accelerated mouse (SAM) and other mouse strains.  Light-induced retinal degeneration, or so-called “top cage syndrome”, can produce similar lesions in older mice exposed to intense light for extended periods of time.

 

Contributor: Sanofi-Synthelab, 9 Great Valley Parkway, P.O. Box 3026, Malvern, PA 19355

 

References: 1.  Geiss V, Yoshitomi K: Eyes. In: Pathology of the Mouse, ed. Maronpot RR, pp. 479-480. Cache River Press, Vienna, IL, 1999

2.  Tansley K: An inherited retinal degeneration in the mouse. J Heredity 45:123-127, 1954

3.  Tansley K: Hereditary degeneration of the mouse retina. Brit J Ophthal 35:573-583, 1951

4.  Ward J: What’s Your Diagnosis? Society of Toxicologic Pathologists website, http://www.toxpath.org/, July 2000

 

 

 


CASE IV – X3026 (AFIP 2739617)

 

Signalment: 8-year-old, intact, male cougar, Felis concolor.

 

History: This cougar had been found as an orphan in British Columbia, Canada, and had spent almost its whole life in captivity at a zoo in New Brunswick, Canada.  It was fed a standard diet consisting of whole animals (road-killed deer and moose, and chicken) and portions of red meat to which was added a multi-mineral and multi-vitamin supplement.  In February 2000, it was immobilized with xylazine and ketamine because of lameness in its right front leg.  The nails of the right front paw were excessively long and had penetrated the flesh above the pads.  The nails were trimmed, and the animal recovered within 4-5 hours.  The following day, the animal was less active than usual and had no appetite.  Three days after immobilization, its condition had not improved.  It was alert, but in lateral recumbency.  With the help of a protective shield, and without immobilizing drugs, two liters of electrolytes were administered intraperitoneally, and gentamycin, vitamin B and dexamethasone were given intramuscularly.  The cougar died two days later, a total of five days after immobilization.

 

Gross Pathology: The animal had abundant fat reserves.  Lesions were confined to the urinary tract.  The urinary bladder was very distended with urine, and its serosal surface was moderately hemorrhagic.  The urine was brown, but only slightly opaque.  The bladder mucosa contained numerous polypoid growths, each approximately 7 mm in diameter and grouped in clusters; areas of the mucosa that were not covered by these polyps had extensive ecchymotic hemorrhages.  Several small, hard, yellowish uroliths, up to 3 mm in diameter, could be found on the mucosal surface.  One urolith had lodged within the urethra, approximately 10 cm from the bladder.  Another urolith had lodged approximately 3 cm from the tip of the penis; the urethral mucosa at this level was necrotic.

 

Laboratory Results: The vesical uroliths were composed of 50% oxalate, 40% calcium, 5% ammonium, 3% phosphate, and 2% magnesium.  The urine was not cultured.  Escherichia coli and Proteus mirabilis were isolated in very small numbers from the kidneys.

 

Contributor’s Diagnosis and Comment: Cystitis, polypoid, diffuse, chronic, severe.

 

Histologically, the vesical mucosa showed marked polypoid proliferation.  The polyps were lined by well-differentiated stratified columnar or transitional epithelium that also formed numerous, irregular acinar structures within individual polyps.  The lamina propria of these polyps was infiltrated by moderate to large numbers of lymphocytes and plasma cells, was moderately to very edematous, and contained some areas of hemorrhage and a few mineral deposits.  The serosal surface was moderately congested and hemorrhagic and showed some perivascular fibroplasia and infiltration by neutrophils.  No significant lesions were seen in the kidneys.  There was microscopic evidence of mild to moderate, acute, multifocal, fibrinopurulent pneumonia, possibly a result of prolonged recumbency.

          Despite the remarkable degree of proliferation of the vesical urothelium, its very well differentiated appearance, and the conspicuous inflammation within the vesical mucosa, identified this lesion as inflammatory rather than neoplastic.  Because of the chronicity of this lesion and of the lack of any long-term clinical information on the animal, the cause of this cystitis could not be determined. 

Chronic polypoid cystitis has been described in humans and domestic animals, but we are not aware that it has ever been reported in captive wild felids.  In humans, it has been associated with the presence of indwelling urethral catheters.  In domestic animals, chronic inflammation from a variety of causes, to include infectious agents, presumably could result in such proliferative lesions.  The origin of the uroliths and their potential contribution in causing chronic irritation of the vesical mucosa are difficult to evaluate.  The relatively small number and size of these uroliths would seem insufficient to account for the extent of the mucosal lesions.  Conversely, formation of uroliths composed of calcium oxalate does not appear to be a common manifestation of chronic cystitis.  In domestic cats, other causes such as dietary imbalance or some metabolic diseases have been associated more often with the formation of this type of urolith.  Although the multi-mineral supplement that this cougar received in his diet was not analyzed, it is a standard component of the diet provided to large captive cats in many zoos.

          The occurrence of urinary blockage in this cougar shortly after immobilization is intriguing.  Increased relaxation of the bladder during sedation of the animal may have facilitated the suspension of calculi in the urine and their eventual passage into the urethra.

 


AFIP Diagnoses: 1.  Urinary bladder: Cystitis, polypoid, chronic, diffuse, moderate, cougar (Felis concolor), feline.

2.  Urinary bladder: Edema and hemorrhage, transmural, diffuse, mild, with multifocal fibroplasia, and acute, fibrinous serositis.

 

Conference Comment: Conference attendees essentially agreed with the contributor’s diagnosis and comments.  The hemorrhage and edema present transmurally within the urinary bladder are similar to that seen with cases of lower urinary tract obstruction in domestic species.

 

Contributor: Atlantic Veterinary College, Department of Pathology & Microbiology, University of Prince Edward Island, 550 University Avenue, Charlottetown, Prince Edward Island, C1A 4P3, Canada

 

References: 1.  Ekelund P, Anderström C, Johansson SL, Larsson P: The reversibility of catheter-associated polypoid cystitis. J Urology 130:456-459, 1983

2.  Kirk CA, Ling GV, Franti CE, Scarlett JM: Evaluation of factors associated with development of calcium oxalate urolithiasis in cats. J Am Vet Med Assoc 207:1429-1434, 1995

3.  Lopez A, Lofstedt J, McNichols L: Mixed papillary-polypoid cystitis in a heifer. Can Vet J 31:585-586, 1990

4.  Maxie MG: The urinary system. In: Pathology of Domestic Animals, ed. Jubb KVF, Kennedy PC, Palmer N, 4th ed., vol. 2, pp. 529-534. Academic Press, San Diego, CA, 1993

5.  Osborne CA, Kruger JM, Lulich JP, Polzin DJ, Lekcharoensuk C: Feline lower urinary tract diseases. In: Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat, ed. Ettinger SJ, Feldman EC, 5th ed., pp. 1710-1711, 1725-1728. WB Saunders Co., Philadelphia, PA, 2000

 

 

                                                          Randall L. Rietcheck, DVM

                                                          Major, Veterinary Corps, U.S. Army

                                                          Wednesday Slide Conference Coordinator

                                                          Department of Veterinary Pathology

Armed Forces Institute of Pathology

                                                          Registry of Veterinary Pathology*

 

 

 

*Sponsored by the American Veterinary Medical Association, the American College of Veterinary Pathologists, and the C. L. Davis Foundation