JPC SYSTEMIC PATHOLOGY

HEMOLYMPHATIC SYSTEM

February 2024

H-P04 (NP)

 

Signalment (JPC Accession # 2237036): A 10-year-old domestic shorthair cat.

 

HISTORY: Tissue from a cat that was found in a pasture in a near-comatose state and was submitted to a local veterinarian. Hemorrhage was noted in the sclera of the left eye. The cat was found dead in the cage the next morning.

 

HISTOPATHOLOGIC DESCRIPTION: Lymph node: Multifocally within congested cortical and medullary vessels, and less frequently within sinuses, are numerous large macrophages which often marginate within or fill vessel lumina and sinuses. Macrophages contain either multiple 30 µm irregularly round developing schizonts with many large, vesiculate nuclei, or many mature schizonts with 1-3 µm round lightly basophilic uninucleate merozoites. There are few lymphocytes, plasma cells, and macrophages transmigrating affected vessel walls. The perivascular connective tissue is occasionally loosely arranged with mildly increased clear space (edema).

 

Liver: Multifocally, portal and centrilobular vessels and random sinusoids contain moderate to high numbers of macrophages containing similar protozoal schizonts as described in the lymph node. Periportal connective tissue is multifocally expanded by small aggregates of lymphocytes and plasma cells.

 

Lung: Pulmonary vessels and alveolar capillaries are multifocally expanded by moderate to high numbers of macrophages that often marginate along endothelium and contain similar protozoal schizonts as described in the lymph node. Perivascular connective tissue is multifocally expanded by increased clear space (edema), eosinophilic beaded to fibrillar material (fibrin), and low numbers of lymphocytes, plasma cells and macrophages. Alveoli are variably filled with homogenous eosinophilic fluid (edema).

 

MORPHOLOGIC DIAGNOSIS: Lymph node, liver, lung: Vascular occlusion with numerous schizont-laden macrophages, domestic shorthair, feline.

 

ETIOLOGIC DIAGNOSIS: Lymphatic, hepatic and pulmonary cytauxzoonosis

 

CAUSE: Cytauxzoon felis

 

CONDITION: Cytauxzoonosis

 

GENERAL DISCUSSION: 

• Intraerythrocytic apicomplexan protozoal piroplasm in the family Theileriidae that causes an often fatal disease in domestic and exotic cats in the south-central US
• Has both a non-replicating erythrocytic (piroplasm) phase and replicating tissue phase, where schizonts are present in intravascular macrophages  
• Transmission is tick-borne (via Amblyomma americanum or Dermacentor variabilis); natural reservoir is the North American bobcat (Lynx rufus)

 

PATHOGENESIS:

• Infected tick feeds on host  > schizonts develop in mononuclear phagocytes > phagocytes enlarge and accumulate within vessels > schizonts undergo division by schizogony and binary fission > schizonts develop buds (merozoites) > host cell ruptures > release of merozoites into blood or tissue fluid > merozoites appear first in macrophages, then in erythrocytes
• Vascular obstruction often extensive from schizont-containing macrophages > pulmonary congestions, reddened lymph nodes, petechial and ecchymotic hemorrhages, and pleural, pericardial, and peritoneal effusion.

 

TYPICAL CLINICAL FINDINGS:

• Tissue schizonts are responsible for clinical disease and death; level of parasitemia is typically very low
• Acute hemolytic anemia from erythrocytic phase
• Leukopenia, thrombocytopenia, increased bilirubin
• Depression, anorexia, pyrexia, dehydration, pallor and icterus 
• Most cases are fatal within a few days of onset of clinical signs

 

CLINICAL PATHOLOGY:

• Anemia is normocytic, normochromic and nonregenerative
• Profound leukopenia +/- thrombocytopenia in late stages of disease
• High total bilirubin and bilirubinuria
• APTT (in conjunction with thrombocytopenia) is consistently elevated

 

TYPICAL GROSS FINDINGS:  

• Enlarged, edematous, hemorrhagic lymph nodes
• Petechial and ecchymotic hemorrhages on serosal surfaces of lung and abdominal organs
• Splenomegaly

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Large numbers of schizont-containing phagocytic cells within, and often occluding, the lumina of vessels in the lung, liver, lymph node and spleen
• 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; 
  • 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: 

• Demonstration of erythrocyte phase on peripheral blood smear:  "Signet ring"-shaped or irregularly pear-shaped, often paired, organisms in erythrocytes, 1 to 1.5µm in diameter
• Demonstration of tissue phase in aspirate or impression smear of bone marrow, spleen, lymph node: Schizonts in macrophages

• Mac387; a monoclonal antibody against calprotectin (a superficial adhesion molecule widely expressed in cells of monocyte-macrophage lineage); Infected cells are negative; this suggests down regulation of calprotectin which inhibits macrophages from exiting vessels
• P53; a nuclear transcription factor not expressed in normal monocyt-macrophages; infected cells are positive, having strong, cytoplasmic immunoreactivity
• PCNA; up to 80% of parasitized cells have positive nuclear immunoreactivity; suggests parasitic stimulation of cell replication 

 

DIFFERENTIAL DIAGNOSIS:

• Mycoplasma haemofelis: Rod or ring-shaped organisms at the periphery of erythrocytes; does not have a tissue phase
• Babesia spp: Single or paired piriform bodies in erythrocytes; does not have a tissue phase; no cases of feline babesiosis reported in U.S

 

COMPARATIVE PATHOLOGY:

• Cytauxzoon spp infect wild ungulate species in Africa, including kudu, eland, and giraffe        
• The domestic cat is considered to be a dead-end host

 

REFERENCES:

1. Cohn LA, Birkenheuer AJ. Cytauxzoonosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Saunders;2012:764-771.
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: 845.
3. Frontera-Acevedo K, Balsone NM, Dugan MA, et al. Systemic immune responses in Cytauxzoon felis-infected domestic cats. American Journal of Veterinary Research. 2013;74(6):901-909.
4. 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 Mosby; 2014:56. 
5. Meinkoth J, Kocan AA, Whitworth L, Murphy G, Fox JC, Woods JP.  Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997-1998). J Vet Intern Med. 2000;14:521-525.
6. 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.
7. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013: 139, 162, 177, 185, 234, 684, 692.
8. Valli VEO, Kiupel M, Bienzle D, Wood RD. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 3. Philadelphia, PA: Elsevier Saunders;2016:120-121.

 

 

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