JPC SYSTEMIC PATHOLOGY
HEMOLYMPHATIC SYSTEM
April 2024
H-V08

 

Signalment (JPC #1432798): A pheasant

 

HISTORY: Tissue from a pheasant that was found dead. Fifteen to twenty other pheasants were found dead in this flock of 15,000 birds. Gross lesions consisted of enlarged, mottled spleens with multiple areas of necrosis. These birds had very dark red, edematous, and congested lungs. Several birds necropsied had numerous gapeworms (Syngamus trachea) in the trachea.

HISTOPATHOLOGIC DESCRIPTION: Spleen: The white pulp is prominent which diffusely contains a moderate to abundant amount of karyorrhectic and eosinophilic debris (lytic necrosis) within expanded periarteriolar lymphoid sheaths and the centers of adjacent lymphoid follicles. There is mild, diffuse histiocytosis of both the white and red pulp. Macrophages (and possibly lymphocytes) often contain cellular debris and/or a basophilic, smudgy, 10-15 µm, intranuclear viral inclusion body that marginates the chromatin. The red pulp also contains a moderate amount of necrotic cellular debris, fibrin that expands red pulp vascular spaces, and few plasma cells and lymphocytes. 

 

MORPHOLOGIC DIAGNOSIS: Spleen: Lymphoid hyperplasia and necrosis, acute, diffuse, severe, with moderate histiocytosis and numerous intrahistiocytic intranuclear viral inclusion bodies, pheasant, avian.

 

ETIOLOGIC DIAGNOSIS: Adenoviral splenic necrosis

 

CAUSE: Marble spleen disease virus (MSDV)

 

CONDITION: Marble spleen disease (MSD)

 

GENERAL DISCUSSION: 

• MSD is a condition of confinement-reared pheasants that causes peracute to acute death in 3 to 8 month old birds due to respiratory compromise
• Caused by a nonenveloped, 70 to 90nm, double stranded DNA virus in the Siadenovirus genus; closely related (serologically indistinguishable) to hemorrhagic enteritis virus (HEV) of turkeys and avian adenovirus splenomegaly virus (AASV) of chickens; all given one species name, Turkey adenovirus A (turkey adenovirus 3; TadV-3)
• Replicates in the nucleus and produces basophilic intranuclear adenoviral inclusions

PATHOGENESIS:  

• MSDV and HEV are considered lymphotropic and lymphocytopathic; IgM-bearing B lymphocytes are primary target with macrophages also supporting replication
• Noted for HEV, presumed to be similar to MSD: 
  • Transmission is fecal-oral/cloacal (“cloacal drinking”) or possibly via aerosol droplets > virus replicates in B lymphocytes of intestine, bursa of Fabricius, and/or spleen > infects more B lymphocytes and macrophages > influx of CD4+ T lymphocytes and macrophages into white pulp (hyperplasia) > macrophages produce IL-6 and TNF-a > macrophage activation and nitric oxide production (may be antiviral) > continued viral replication and cytokine production induce massive apoptotic event (lymphoid depletion) > immunosuppression > cytokine release initiates systemic shock (pulmonary lesions) and possibly apoptosis of nearby cells (local effect)
  • Pulmonary lesions may reflect anaphylactic changes and other immune reactions 
  • The loss of both B-cells and macrophages decreases antigen presentation and subsequent humoral immunity; decreased macrophages lessens cell-mediated response

TYPICAL CLINICAL FINDINGS:

• Typically acute death with no clinical signs
• Occasionally depression, weakness, and progressive dyspnea and/or nasal discharge
• Flock morbidity usually approaches 100%; mortality may reach 5 to 20% over a course of 10 days to several weeks

TYPICAL GROSS FINDINGS: 

• Spleen: Marked enlargement (2-3X normal size) with a mottled or marbled surface (gray foci of necrosis)
• Lung: Severe congestion and edema
• Intestinal hemorrhage is *not* a feature of MSD (versus HE of turkeys)

TYPICAL LIGHT MICROSCOPY FINDINGS:

• 3 to 4 days post-infection: White pulp hyperplasia
• 4 to 5 days post-infection: Large, irregular, confluent islands of white pulp that begin to undergo necrosis
• 6 to 7 days post-infection: Complete involution of white pulp
• Intranuclear viral inclusion bodies may be present, common between days 3-5 post-infection; inclusions may be found in macrophages and lymphocytes
• Histiocytosis

• Expansion of atria and tertiary bronchi with fibrin, hemorrhage, and edema
• Vascular congestion
• Multiple small necrotic foci of epithelial and endothelial cells

ULTRASTRUCTURAL FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

• Agar gel immunodiffusion
• Antigen-capture ELISA
• PCR (most common)

DIFFERENTIAL DIAGNOSIS (not comprehensive):

• Splenic enlargement and marbling without MSDV antigen:
  • Marek’s disease (Gallid herpesvirus 2, alphaherpesvirus)
  • Lymphoid leukosis (Avian leukosis virus, subgroup Avian type C oncovirus, family Retroviridae)
  • Reticuloendotheliosis (Avian type C oncoviruses, family Retroviridae)
• Acute death due to respiratory distress without enlarged, marbled spleen:
  • Newcastle disease (Avian paramyxovirus type 1)
  • Avian influenza (family Orthomyxoviridae)
  • Syngamus trachea infection
  • Infectious laryngotracheitis (Alphaherpesvirus, Gallid herpesvirus 1)
  • Infectious bronchitis (family Coronaviridae):  Highly infectious and contagious respiratory disease of chickens 
• Splenic enlargement and congestion with respiratory signs:
  • Bacterial pathogens:   E. coli, Salmonella spp.Pasteurella multocida, and Erysipelothrix rhusiopathiae
  • Toxins:  Carbon monoxide, carbon dioxide, and natural gas in confinement operations

 

COMPARATIVE PATHOLOGY (not comprehensive):

Adenoviruses, four genera:

• Mastadenovirus 
  • Canine adenovirus type 1 (CAV-1): Infectious canine hepatitis
  • Canine adenovirus type 2 (CAV-2): Bronchointerstitial pneumonia with necrotizing bronchiolitis; clinical disease is usually a consequence of immunosuppression
  • Equine adenovirus types 1 and 2: In SCID Arabian foals, adenoviral infection leads to severe bronchiolitis and atelectasis (equine mastadenovirus A and B)
  • Porcine: Associated with encephalitis and diarrhea (porcine mastadenoviruses A-C; porcine adenoviruses 1-5)
  • Guinea pig: Adenoviral pneumonitis (Guinea pig adenovirus (GPAdV))
  • Non-human primates: Mild to moderately severe respiratory and enteric disease as well as keratitis/conjunctivitis
  • Sheep: Ovine mastadenoviruses A and B (includes ovine adenoviruses 1-5, bovine adenovirus 2, and goat adenovirus 2)
  • Pinnipeds: California sea lion adenovirus-1 (CSLAdV-1); multifocal necrotizing hepatitis with hepatocellular intranuclear inclusions; may cause necrotizing enteritis
  • Mustelids: CAV-2 identified in striped skunks and captive Eurasian river otters; fatal hepatitis 
• Atadenovirus 
  • Wildlife: Cervine adenovirus (Odocoileus hemionus deer adenovirus 1 (OdAdV-1) – proposed to be cervid atadenovirus A; cervid adenovirus 1 causes Adenovirus Hemorrhagic Disease of Deer present in Oregon and California; in deer it produces pulmonary edema and erosions, ulcerations, hemorrhage or abscesses in the oral cavity (similar to Bluetongue virus and Epizootic Hemorrhagic Disease (orbiviruses) with widespread vasculitis and endothelial intranuclear inclusions
  • Chickens, ducks, geese: Egg drop syndrome (duck atadenovirus A; duck adenovirus 1)
  • Bearded dragons: Necrotizing but also occasionally proliferative hepatic lesions (Agamid adenovirus 1)
• Aviadenovirus 
  • Chickens: 
    • Inclusion body hepatitis (fowl aviadenovirus D and E; fowl adenovirus 2 (FAdV2), FAdV8, FAdV11))
    • Hepatitis-hydropericardium syndrome virus (fowl aviadenovirus C; FAdV4)
    • Gizzard erosion (fowl aviadenovirus A; FAdV1)
  • Quail bronchitis virus (fowl aviadenovirus A)
  • Turkey aviadenovirus B (turkey adenovirus 2; TAdV2)
  • Falcon aviadenovirus A (falconid adenovirus-1; FAdV1)
• Siadenovirus        
  • Turkey siadenovirus A (TAdV3)
    • Hemorrhagic enteritis (turkeys)
    • Marble spleen disease (pheasants)
    • Avian adenovirus splenomegaly (broilers) 

 

References: 

1. Abdul-Aziz T, Fletcher OJ, Barnes HJ. Avian Histopathology. 4th Philadelphia, PA: American Association of Avian Pathologists; 2016: 5, 14, 274, 319-320, 357, 426.
2. New Colegrove KM, Burek-Huntington KA, Roe W, Siebert U. Pinnipediae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 577-578.
3. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Columbiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 745-746.
4. Howerth EW, Nemeth NM, Ryser-Deglorgis MP. Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 157-158.
5. Sellers, H, Ojkic D. Viral diseases.  In: Boulianne M, ed. Avian Disease Manual. 8th ed. Jacksonville, FL: American Association of Avian Pathologists; 2019:20-25.
6. Origgi FC. Lacertilia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 875.
7. Rautenschlein S, Mahsoub HM, Fitzgerald SD, Pierson FW. Hemorrhagic enteritis and related infections. In: Swayne DE, ed. Diseases of Poultry Vol 1. 14^th ed. Ames, AI: Wiley Blackwell; 2020: 339-347. 
8. Schmidt RE, Reavill DR, Phalen DN, eds. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, AI: Wiley Blackwell; 2015: 184.
9. Williams BH, Burek-Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 297.
10. Wunschmann A, Armien AG, Hofle U, Kinne J, Lowenstine LJ, Shivaprasad HL. Birds of prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 723.

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