JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-P05

 

Signalment (JPC #4068027-00): Three-year-old, stray, male, domestic shorthair cat.

 

HISTORY: Within 48 hours of being neutered, this cat became lethargic, bradycardic, and hypothermic, and then died. 

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally throughout the section, approximately 60% of septal capillaries and 80% of larger blood vessels (arterioles, arteries, veins, and venules) contain and are frequently occluded and/or distended by many enlarged macrophages that are often oriented along the endothelium. Macrophages are distended up to 40 µm by intracytoplasmic, developing schizonts that contain many 1-3 µm, basophilic merozoites. There are few, partially occlusive fibrin thrombi. Affected blood vessels are lined by mildly hypertrophic endothelial cells with enlarged nuclei. There is multifocal, mild expansion of the tunica media and tunica adventitia by edema and small amounts of fibrin. There is prominent perivascular edema with small amounts of hemorrhage and fibrin. The peribronchiolar interstitium is mildly expanded by edema. Multifocally alveolar septa contain a mild increase in histiocytes and lymphocytes. There is mild sub-pleural edema. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Histiocytosis, intravascular, multifocal, acute, severe, with mild lymphohistiocytic interstitial pneumonia, few fibrin thrombi, and multifocal vascular occlusion by numerous schizont-laden macrophages, breed unspecified, feline.

 

ETIOLOGIC DIAGNOSIS: Pulmonary cytauxzoonosis

 

CAUSE: Cytauxzoon felis

 

GENERAL DISCUSSION: 

• Cytauxzoonosis is a rapidly progressive, systemic, generally fatal disease affecting domestic and some wild felids in North America (and other locations) 
• Protozoal hemoparasite
• Transmitted by ixodid ticks
• Two phases: Early tissue mononuclear phagocyte phase and late erythrocytic phase
• A less pathogenic form may be emerging

 

PATHOGENESIS:

• Tissue phase: Macrophages/monocytes enlarged by intracytoplasmic schizonts accumulate in vessels or subendothelially causing vascular occlusion, often in the lung, liver, spleen, and lymph nodes (but can occur in any organ including CNS); sequelae include edema, ischemia, and petechial and ecchymotic hemorrhages
• Erythrocytic phase: Late phase, usually innocuous; may lead to intravascular and extravascular hemolysis; piroplasms present in 1-4% of blood erythrocytes
• Parasite by‑products that are liberated upon the release of merozoites from macrophages are toxic, pyrogenic, and vasoactive causing endothelial damage
• Disseminated intravascular coagulation has been reported in natural infection

 

LIFE CYCLE:  

• Transmission by Ixodid ticks (Dermacentor variabilis, Amblyomma americanum) or ingestion or inoculation of infected blood or tissue
• The bobcat is the natural reservoir and has mild disease 
• An ixodid tick ingests RBCs containing merozoites/piroplasm (infected cat, bobcat) à sexual reproduction in the tick à sporozoite inoculated into cat à sporozoites infect monocytes à schizont formation and merozoite development à merozoites enter erythrocytes à develop into piroplasms

 

TYPICAL CLINICAL FINDINGS:

• Marked fever, pallor, icterus, depression, dark urine, occasionally dyspnea
• Non-regenerative anemia (likely “pre-regenerative”), and often neutropenia (inflammation) and thrombocytopenia (hemorrhage, DIC), hyperbilirubinemia, hypoalbuminemia, reduced or low normal serum ALP activity, and hyponatremia.

 

TYPICAL GROSS FINDINGS:

• Pulmonary congestion and edema (non-collapsing lung); splenomegaly; hepatomegaly; icterus
• Enlarged red lymph nodes
• Serosal petechiae and ecchymoses
• Pleural, pericardial, abdominal effusions

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Tissue monocyte/macrophage phase:

• Macrophages are enlarged with intracytoplasmic merozoite-containing schizonts and often partially or completely occlude vessels
• Ischemic necrosis; lung, spleen, and liver are usually the most severely affected with numerous infected monocytes; 
• CNS lesions include occlusion of leptomeningeal and parenchymal arterioles in the brain as well as small capillaries in the gray and white matter and choroid plexus, accompanied by variable numbers of lymphocytes and plasma cells surrounding vessels; variable ischemic changes such as neuronal degeneration and necrosis and swollen axons
• Interstitial pneumonia and intravascular macrophages containing schizonts

• Erythrocytic phase
• Piroplasms are 1-3 µm comma-shaped, elongated “safety-pin”, linear, or signet-ring forms

 

ADDITIONAL DIAGNOSTIC TESTS:

• Wright's/Giemsa stain on blood smears and impression smears (performed at necropsy) especially of lung, spleen, but also of liver, lymph nodes, and bone marrow
• Cytologic findings: Erythrocytic (piroplasm) and tissue (schizont) forms

• Piroplasms: Small, 1- to 1.5-μm, signet ring–shaped structures in red blood cells
• Schizonts: Macrophages may contain developing merozoites that are small, dark blue–to-purple bodies or larger ill-defined to lobulated light blue–to-purple globules 

• PCR if parasitemia is low

 

DIFFERENTIAL DIAGNOSIS:

• Intraerythrocytic piroplasms: Cytauxzoon, Babesia, and Theileria are closely related non-pigment-forming piroplasms that infect erythrocytes
  • Theileria also forms schizonts in lymphocytes. 
• Other cause of piroplasmosis in cats:

• A differential for piroplasmosis in cats is Babesia felis (mainly found in South Africa), but Babesia typically does not cause a leukopenia

 

COMPARATIVE PATHOLOGY:

• North American Bobcat: Reservoir host; usually mild illness or clinically healthy carrier state
• Non-domestic felids: Both subclinical and fatal disease reported
• Cytauxzoon spp. infect African wild ungulates (e.g., kudu, eland, giraffe)

• Theileria has been shown to infect lymphocytes AND macrophages in African wild ungulates, thus some researchers consider Cytauxzoon to be a synonym of Theileria (Clift, Vet Pathol. 2020)

 

REFERENCES:

1. Aschenbroich SA, Rech RR, Sousa RS, Carmicheal KP, Sakamoto K.  Pathology in Practice. J Am Vet Med Assoc. 2012; 240(2): 159-161.
2. Durham AC, Boes KM.  Bone marrow, blood cells and the lymphoid/lymphatic system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:724.
3. Cerreta AJ, Yang TS, Ramsay EC, et al. Detection of vector-borne infections in lions and Tigers at two zoos in Tennessee and Oklahoma, USA. J Zoo Wildl Med. 2022;53(1). doi:10.1638/2020-0199 
4. Clarke LL, Rissi DR.  Neuropathology of Natural Cytauxzoon felis infection in domestic cats. Vet Pathol. 2015: 52(6): 1167-1171.  
5. Clarke LL, Krimer PM, Rissi DR.  Glial changes and evidence for apoptosis in the brain of cats infected by Cytauxzoon felis. J Comp Pathol. 2017; 156: 147-151.
6. Clift SJ, et al.  The Pathology of Pathogenic Theileriosis in African Wild Artiodactyls. Vet Pathol. 2020: 57(1): 24-48. 
7. Kastl BC, Springer NL. Serum biochemical changes in cats with naturally acquired Feline Cytauxzoonosis. J Am Vet Med Assoc. Published online 2023:1-9. doi:10.2460/javma.22.05.0207 
8. Lane, LV, Yang, PJ, Cowell, RL. Selected Infectious Agents. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier; 2020:56. 
9. Raskin RE. Hemolymphatic System. In: Raskin RE, Meyer DM, Boes, KM. Canine and Feline Cytology, 4^th Ed. St. Louis, MO:Elsevier. 2023:158-161.
10. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 139, 162, 177, 185, 234, 684, 692.
11. Valli VEO, Kiupel M, Bienzle D, Wood RD. Hematopoetic system. In: Maxie MG, ed. Jubb, Kennedy, Palmer's Pathology of Domestic Animals.  6th ed. St. Louis, MO. Elsevier; 2016:(3):120.

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