JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-B06

 

Signalment: (JPC # 1819609): Sheep

 

HISTORY: Tissue from a sheep.

 

HISTOPATHOLOGIC DESCRIPTION: Slide A (H&E): Lymph node: Diffusely, nodal architecture is effaced and replaced by an abscess characterized by a large central area of lytic necrosis composed of abundant eosinophilic cellular and karyorrhectic debris admixed with necrotic and viable neutrophils and multifocal aggregates of a deeply basophilic, granular mineral, acicular cholesterol clefts, and occasional large colonies of 1x3 µm coccobacilli. This area of necrosis is surrounded by a thin rim of epithelioid macrophages, which are further surrounded by a layer of lymphocytes and plasma cells.  Lastly, surrounding the periphery is a thick 1.5 mm capsule of dense fibrous connective tissue. Multifocally, capsular vessels are surrounded by aggregates of lymphocytes.

 

Slide B: B&B Tissue (Gram stain): Multifocally scattered throughout areas of necrosis and extending into the peripheral zone of lymphocytes, plasma cells and neutrophils are numerous gram positive, up to 1x3 µm coccobacilli.

 

MORPHOLOGIC DIAGNOSIS: Lymph node: Lymphadenitis, necrosuppurative and caseating, focally extensive, chronic, diffuse, severe, with large colonies of gram positive coccobacilli, breed unspecified, ovine.

 

ETIOLOGIC DIAGNOSIS: Corynebacterial lymphadenitis

 

CAUSE: Corynebacterium pseudotuberculosis (ovis)

 

CONDITION: Caseous Lymphadenitis (CLA)

 

GENERAL DISCUSSION:  

• Worldwide chronic disease of sheep and goats that causes abscesses within lymph nodes and visceral organs  
• Severe economic impact on the sheep and goat industry, from decreased milk production and condemnation of carcasses because of internal abscesses
• Gram-positive, non-motile, facultative intracellular bacterial rods that can survive for long periods in the soil (even in direct sunlight)    
• Member of the higher bacteria of the order Actinomycetales; which includes Arcanobacter, Actinomyces sp, Nocardia sp , Rhodococcus sp, Dermatophilus sp, Streptomyces sp, and Mycobacteria sp
• Visceral form of CLA is one of the causal factors of the “thin ewe syndrome”
• Horses, cattle, camels, deer and mules may also be affected

 

PATHOGENESIS:  

• Transmission is via indirect contact, skin wounds (tail docking, castration, shearing) or direct contact from infected discharges or inhalation > local lymph node persistent infection > suppuration > lymphogenous and hematogenous dissemination (older animals) > organ abscesses
• Two serotypes:

• Type 1à affects ovine, caprine, and occasionally bovine
• Type 2à affects buffalo and cattle

• Pathogenicity due to production of a heat labile toxin
• Bacteria have at least two virulence factors:

-Leukotoxic surface lipid: Mycolic acid (R. equi) induces inflammation, is leukotoxic, and prevents phagolysosome formation

-Exotoxin (phospholipase D): Increases vascular permeability to favor leukocyte trafficking and systemic spread; injures cell membranes

• Bacteria are carried via the lymphatics (as free bacteria or within macrophages) to regional lymph nodes
• Non-phagocytic cells may act as a suitable environment for C. pseudotuberculosis survival and play a role in the spread of infection and/or maintenance of a carrier state
• Bacterial proliferation is both extracellular and intracellular

 

TYPICAL CLINICAL FINDINGS:  

• Enlargement of one or more superficial lymph nodes (prescapular, inguinal, mandibular, parotid)
• Progression to visceral disease is usually slow and typically occurs in older animals; often there are no specific clinical signs in sheep affected with the visceral form of CLA
• Mastitis occasionally occurs in sheep and is often observed in goats

 

TYPICAL GROSS FINDINGS:  

• Sheep: Lymph nodes are greatly enlarged and consist of a central core of thick creamy necrotic material that is greenish-white and gritty

• Older lesions in sheep are characterized by concentrically lamellated layers of fibrous connective tissue with alternating zones of caseous, friable material (“onion skin”) that is entirely bounded by a thick fibrous capsule; i.e. encapsulated abscess
• Locally extensive bronchopneumonia with abscess formation with inhalation or extension from lymph nodes; uncommon presentation

• Goats: Exudate is moist and is not concentrically laminated or mineralized

• May be more severe than in sheep with different distribution of abscesses; lesions primarily on head and neck – mandibular and parotid lymph nodes and superficial jaw and neck region; resembles melioidosis; rarely involves mediastinum or mesentery

• Horses: Ulcerative lymphangitis or deep pectoral and ventral abdominal wall abscesses (“pigeon fever”)
• Cattle: Ulcerative lymphangitis; rarely get caseous lymphadenitis, generally remains localized to 1-2 regional nodes draining an infected surface wound

   

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Caseous necrosis of lymph nodes is the predominant feature
• The initial lymph node lesion begins as lymphadenitis with the formation of multiple microscopic abscesses in the cortex; eosinophils may predominate initially 
• Microabscesses rapidly coalesce, forming areas of caseation
• Abscesses become rapidly encapsulated by fibrous connective tissue, and the lymph node enlarges

 

DIFFERENTIAL DIAGNOSIS:  

Abscessed lymph nodes:

• Melioidosis/pseudoglanders (Burkholderia pseudomallei): Lymph node abscesses in goats and sheep
• Tularemia (Francisella tularensis): Superficial lymph node abscesses and pneumonia in sheep
• Rhodococcus equi: Uncommon; causes systemic pyogranulomatous infections in goats with macroscopic similarities to caseous lymphadenitis

 

COMPARATIVE PATHOLOGY: (of Corynebacterium and related bacteria)

 

Organism                                                            Principal Disease

Corynebacterium diptheriae	Diphtheria in humans
C.  renale and C. pilosum	Cystitis in cows, NHPs
C. cystitidis	Hemorrhagic cystitis and pyelonephritis in cows
C. bovis	Rare cause of mastitis; dermatitis in nude mice
Actinobaculum suis (Eubacterium suis)	Pyelonephritis and cystitis in swine
C. kutscheri	Pseudotuberculosis in rodents
C. ulcerans	Bite wounds, abscesses, mastitis in macaques and other NHPs
Arcanobacter pyogenes	Suppurative infections in cattle, sheep, goats and swine
Rhodococcus equi	Pyogranulomatous pneumonia, lymphadenitis, osteitis and colitis in foals
C. pseudotuberculosis (ovis)	Ulcerative lymphangitis on fetlocks and pectoral abscesses in horses (pigeon fever or dryland strangles) and rarely cattle Purpura hemorrhagica in horses Interstitial nephritis in a chimpanzee Pneumonia and sepsis in NHPs
C. amycolatum	Necrotizing gastroenteritis, diphtheritic stomatitis in penguins.

 

References:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:68-69.
2. Miller MA, Lyle LT, Zachary JF. Mechanisms and Morphology of Cellular Injury, Adaptation, and Death. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:34-35. 
3. Robinson WF, Robinson NA. Cardiovascular System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:97. 
4. Simmons J, Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012: 110.
5. Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:228-229. 
6. Stidworthy MF, Denk D. Sphenisciformes, Gaviiformes, Podicipediformes, Procellariiformes, and Pelecaniformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018: 670-671, 683
7. Valli VEO, Kiupel M, Bienzle D, Wood RD. The hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, Palmer's Pathology of Domestic Animals, Vol 3. 6th ed. St Louis, MO: Mosby Elsevier; 2016:204-208. 
8. Wunschmann A, Armien AG, et al. Birds of Prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier. 2018: 735.

 

 

 

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