YSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
October 2021
D-V01

Signalment (JPC #1801669):  A young cat

HISTORY:  None

HISTOPATHOLOGIC DESCRIPTION:  Small intestine:  Diffusely there is marked blunting, fusion, and loss of villi and multifocal loss and replacement of crypts by small amounts of karyorrhectic and cellular debris (necrosis), edema, hemorrhage, fibrin, and moderate numbers of lymphocytes, plasma cells, and neutrophils.  Remaining crypts are ectatic, lined by attenuated epithelium, and crypt lumens contain degenerate neutrophils, necrotic debris, and sloughed necrotic epithelial cells (crypt abscesses). There is multifocal crypt regeneration with crypts lined by hypertrophied and piled up, hyperplastic epithelium with coarse nuclear chromatin. Multifocally, within the surrounding lamina propria, there are increased numbers of neutrophils and few vessels contain fibrin thrombi.  The submucosa is moderately expanded by hemorrhage, fibrin, clear space with ectatic lymphatics (edema), few perivascular lymphocytes and plasma cells, and macrophages with intracytoplasmic erythrocytes (erythrophagocytosis).  Multifocally in the tunica muscularis, there is mild perivascular edema with few lymphocytes and plasma cells.

Lymph node, mesenteric:  Multifocally, there is moderate lymphoid depletion characterized by follicular germinal centers often replaced by macrophages as well as a generalized decrease in numbers of lymphocytes resulting in accentuation of the stromal and sinusoidal architecture.  Diffusely, the subcapsular and medullary sinuses are expanded by numerous erythrocytes admixed with low numbers of foamy macrophages with phagocytized erythrocytes (erythrophagocytosis), lymphocytes, plasma cells, neutrophils, small amounts of fibrin, edema, and karyorrhectic debris.   

MORPHOLOGIC DIAGNOSIS: 

1. Small intestine:  Enteritis, necrohemorrhagic, acute, diffuse, marked, with marked villus atrophy and crypt necrosis and loss, breed unspecified, feline.
2. Lymph node, mesenteric: Lymphoid depletion, multifocal, moderate.
3. Lymph node, mesenteric: Draining hemorrhage, acute, diffuse, moderate, with mild sinus histiocytosis and erythrophagocytosis.

ETIOLOGIC DIAGNOSIS:  Parvoviral enteritis

CAUSE:  Feline parvovirus; Feline panleukopenia virus

CONDITION:  Feline panleukopenia; feline enteritis; feline distemper

GENERAL DISCUSSION:

• Feline parvovirus is a ubiquitous, extremely stable, highly infectious virus that produces serious and often fatal disease in young and/or naive animals
• Family Parvoviridae, genus Parvovirus; 25nm, icosahedral, non-enveloped, single stranded DNA virus
• Intranuclear replication with intranuclear inclusions (large basophilic or amphophilic Feulgen-positive) early in the course of disease
• All parvoviruses lack polymerase enzymes and are dependent on host cell DNA polymerase II (produced during S and early G2 phases) for replication; so effects of parvovirus infection are greatest in tissues with a high mitotic rate
• Cause disease in swine, cats, dogs, mink, mice, rats, hamsters, geese, and ducks, rabbits
• Specificity of parvoviruses determined by receptor binding to transferrin receptor TfR in cats and dogs and neuraminic acid in cats

PATHOGENESIS: 

• Fecal-oral route; virus enters and replicates in the oropharynx (mucosal epithelial cells, lymphocytes, dendritic cells and/or macrophages > leukocyte trafficking > viruses attach via capsid to cell neuraminic acid or transferrin receptor > primary cell free or cell associated viremia > infection of rapidly dividing/mitotically active cells in S or early G2 phase of cell cycle (radiomimetic tropism; lymphoid, bone, GI) > cells die (lyse with viral release) or arrest mitosis in the pre-mitotic phase > viral shedding for 3-5 days
• Although the pathogenesis remains the same, disease presentation varies based on the type of cells that are dividing at the time of infection
  • Early in utero infection: Fetal death > abortion/resorption or sometimes no effect
  • Perinatal infection (2 wks prenatal - 2 wks after birth): Arrest of external granular layer in the cerebellum > lack of migration and formation of inner granular and Purkinje layers > cerebellar hypoplasia and permanent ataxia
  • Between 2 and 4 mos.: Infection of bone marrow, thymus, and lymphoid tissue > lymphocytolysis, lymphoid and thymic atrophy, leukopenia and enteritis > loss of villi by attrition (not destruction); virus targets crypt epithelium > malabsorption > diarrhea
  • Between 4 and 12 mos.: Enteritis from necrosis of crypt enterocytes

TYPICAL CLINICAL FINDINGS:

• Pyrexia, depression, inapptence, vomiting, diarrhea, dehydration, anemia, sudden death; most are subclinical
  • Enteric signs correlate to the severity of intestinal crypt epithelial damage
  • Diarrhea results from reduced functional absorptive surface of the intestine and effusion of tissue fluids and hemorrhage into the lumen
  • Dehydration and electrolyte depletion result from enteric malabsorption, effusion of tissue fluids, vomition, and reduced fluid intake
  • Hypoproteinemia is common and may lead to hydrothorax and ascites
  • Intestinal hemorrhage can lead to anemia

TYPICAL GROSS FINDINGS:

• Flaccid, segmentally reddened, and diffusely dilated intestine; intestinal lesions may be minimal to mild; serositis; grossly observable hemorrhage may be absent, in contrast to dogs
• Cerebellar hypoplasia
• Thymic atrophy/involution; lymph node edema and possibly hemorrhage
• Bone marrow is pale and may have a semi-fluid consistency

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Small intestinal lesions:
  • Crypt epithelial attenuation / necrosis with crypt ectasia, loss, crypt abscesses, and villous atrophy and collapse with epithelial erosion or ulceration with progressive exudation of fibrin and hemorrhage
  • Rare, light basophilic, intranuclear inclusions in enterocytes and lymphocytes (late incubation or early clinical stages)
  • Crypt regeneration in late/healing stage
  • Variable inflammatory cells; neutrophils and eosinophils within the lamina propria
  • Most severe lesions near Peyers patches
  • Peyers patches may be severely depleted or regenerative depending on stage of disease
  • Invasive fungal hyphae may be seen
• Lymph nodes/thymus/splenic white pulp: lymphocytolysis, follicular hyalinosis, and prominent histiocytes; specific areas affected:
• Thymus: cortex; collapsed lobules that are flattened and triangular, prominent Hassall’s corpuscle, absence of small lymphocytes and cortical cells and few lymphoblasts
• Lymph node: follicles and paracortex
• Spleen: white pulp
• Large intestine: Similar lesions to small intestine but less severe
• Cerebellum: Cerebellar hypoplasia with thinning of layers and loss of granular cells and Purkinje cells
• Bone marrow: depletion of all proliferating elements in severely affected animals; followed by marked stem cell hyperplasia
• Retina: Retinal dysplasia (retinal folds and rosettes), multifocal necrosis and scarring
• Others:
• Liver: hepatocyte dissociation; centrilobular atrophy and congestion
• Pancreas: acinar atrophy
• Lung: congestion and edema
• Central nervous system: neuronal vacuolization and necrosis, and lymphoplasmacytic meningoencephalitis are reported (Kokosinska, Vet Pathol. 2019)
• Heart: NOT associated with myocarditis or endomyocardial restrictive cardiomyopathy (McEndaffer, Vet Pathol. 2017)

ADDITIONAL DIAGNOSTIC TESTS:

• PCR
• Virus isolation
• IFA to antigen in tissues

DIFFERENTIAL DIAGNOSIS: 

For feline enteritis:

• Feline leukemia virus (feline retrovirus):
  • Older cats, crypt necrosis is reported
  • Panleukopenia-like syndrome with persistent unresponsive leukopenia and anemia and enteric lesions similar to FPV
  • Bone marrow depletion does not occur, and lymphoid tissue is normal to hyperplastic
• Feline enteric coronavirus affects the villous tips
• Feline infectious peritonitis (mutated feline enteric coronavirus) causes granulomatous vasculitis in many sites, including the small intestine
• Rotavirus affects the upper two-thirds of the villi in the proximal small intestine
• Toxoplasma gondii systemic infection causes leukopenia; iritis and terminal bronchopneumonia are common

COMPARATIVE PATHOLOGY:

FPV in other species:

• FPV infects all Felidae, mink, raccoons, and some other procyonidae

Other selected Parvoviridae:

• Canine parvovirus: CPV-1 causes a subclinical enteritis and CPV-2 (D-V02) causes severe enteritis, lymphoid depletion, panleukopenia, and myocarditis (in 4-6 week old pups); CPV-2c may also infect cats
• Mink enteritis virus causes lymphoid depletion with secondary infections and resultant enteritis
• Bovine parvovirus is reported to cause enteritis in calves and abortion and birth of weak calves
• Porcine parvovirus: A cause of SMEDI (Stillbirth/Mummification/Embryonic death/Infertility), and vesicular and ulcerative dermatitis and glossitis
  • Porcine circovirus 2 and porcine parvovirus – together can cause postweaning multisystemic wasting syndrome
• Rat parvoviruses include four groups; however, Kilham’s rat virus is the most pathogenic and may be the only one to produce clinical disease
  • Intestinal mucosal lesions do not occur in the rat/mice
  • Adults: Random hemorrhage within the cerebral and cerebellar white and gray matter; coagulation necrosis and hemorrhage within the testes and epididymis; hepatic necrosis; infertility and fetal resorption
• Mouse parvoviruses include minute virus of mice (cerebellar hypoplasia in neonates) and mouse parvovirus (anomalies in immune function in adults)
• Aleutian mink disease parvovirus (U-V05, P-V14)
  • Fatal to mink homozygous for the gene that confers the Aleutian coat color
    • Persistent infection with continuous release of virions > hypergammaglobulinemia > immune complex deposition within vascular system, glomeruli, and other tissues (liver, spleen, etc.) often with a marked plasmacytosis
  • Hamster parvovirus (HaPV)
    • Gross lesions: Discolored or missing incisors; small testes; cerebellar hypoplasia
    • Histologic lesions: Enamel hypoplasia with mineralization and fibrosis of remaining incisor tissue; suppurative periodontitis; atrophy of testicular seminiferous tubular epithelium; multifocal cerebral myelomalacia
  • Small Indian Civets- Fatal hemorrhagic gastroenteritis associated with Carnivore protoparvovirus-1 (CPPV-1) (Chaiyasak, Vet Pathol. 2020)
  • Goose parvovirus (Derzy’s disease virus) causes a highly lethal disease of goslings 8-30 days old with severe hepatitis and degeneration of striated and smooth muscle, including myocardium
  • Rabbit parvovirus causes a mild enteritis

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:17-19,122-124,175-176, 259.
2. Boes KM, Durham AC. Bone marrow, blood cells, and the lymphoid / lymphatic system.  In: Zachary JF, ed. Pathological Basis of Veterinary Disease. 6th ed. Philadelphia, PA: Mosby Elsevier Inc.; 2017:803.
3. Chaiyasak S, Piewbang C, Banlunara W, Techangamsuwan S. Carnivore Protoparvovirus-1 Associated With an Outbreak of Hemorrhagic Gastroenteritis in Small Indian Civets. Vet Pathol. 2020;57: 706-713.
4. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery, and peritoneal cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:406-407,410.
5. Greene, CE, Addie DD. Feline parvovirus infections. In: Greene C, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier; 2012:80-88.
6. Kokosinska A, Maboni G, Kelly KM, et al. Lymphoplasmacytic Meningoencephalitis and Neuronal Necrosis Associated With Parvoviral Infection in Cats. Vet Pathol. 2019;56: 604-608.
7. McEndaffer L, Molesan A, Erb H, Kelly K. Feline Panleukopenia Virus Is Not Associated With Myocarditis or Endomyocardial Restrictive Cardiomyopathy in Cats. Vet Pathol. 2017;54(4):669-675.
8. Pfankuche VM, Jo WK, van der Vries E, et. al. Neuronal Vacuolization in Feline Panleukopenia Virus Infection. Vet Pathol. 2018;55(2):294-297.
9. Shetty BD, Zachariah A, Farver TB, Smith B, Goldstein T, Mazet JAK. Carnivore Protoparvovirus 1 (Parvoviruses) at the Domestic-Wild Carnivore Interface in India. J Zoo Wildl Med. 2020;50: 1016-1020.
10. Terio KA, McAloose D, Mitchell E. Felidae. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 270-271.
11. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:154-158.
12. Valli VEO, Kiupel M, Bienzle D. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:145.

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