8-month-old female domestic shorthair cat (Felis catus).Patient presented for lethargy, depression, and inappetence. Rectal temperature was 105.1F. Initial treatment consisted of antibiotics, anti-inflammatory drugs, and subcutaneous fluids. Five days later, icterus with hypoglycemia, hypo- albuminemia, and leucopenia were noted. Rectal temperature was 103F. The patient died the following day.

Gross Description:  

The spleen was enlarged with a roughened serosal surface. Multiple white pinpoint foci were observed on the serosal surface. The cut surface bulged and had a granular appearance. No other gross lesions were indicated by the submitting veterinarian.

Histopathologic Description:

In sections of spleen, there is disseminated and coalescing necrosis of germinal centers which extends into adjacent red pulp. Foci of necrosis are accompanied by an inflammatory response comprised of neutrophils and macrophages. By use of special technique, numerous small gram-negative coccobacilli are seen within necrotic foci and the cytoplasm of individual inflammatory cells.

Morphologic Diagnosis:  

Severe, subacute, multifocal, coalescing, necrotic, and pyogranulomatous splenitis

Lab Results:  

Francisella tularensis was isolated from the spleen and from a lymph node sample.


Pyogranulomatous splenitis/Francisella tularensis

Contributor Comment:  

Francisella tularensis is a gram-negative, facultative intracellular pathogen.5 F. tularensis is subdivided into two subtypes. Type A is F. tularensis subsp. tularensis and has and infectious dose in humans of <10 CFUs, whereas type B is F. tularensis subsp. holarctica which as an infectious dose of <103 CFU and a milder form of tularemia in humans.5 The organism is abundant in nature and infects many mammalian and arthropod species.7 F. tularensis type A has been isolated from cats on numerous occasions and can be transmitted from cats and other animals (deer, personal experience) to humans.1,3,7

Diagnosis, in some cases, may be difficult, but culture appears to be more sensitive than immunohistochemistry.7 Gross lesions consist of multiple pinpoint white foci on the spleen, liver, and lymph nodes. As a facultative intracellular parasite, it may persist for years as a latent infection.7 The genes for several virulence factors have been identified and shown to share some features with the intracellular parasite, Listeria monocytogenes. 4 Tularemia in other mammalian species such as horses and sheep are often associated with heavy infestation by ticks such as Dermacentor andersoni and Amblyomma americanum. 7 One serologic survey indicated 12  24 percent of cats had antibodies to F. tularensis due to natural exposure.6 Those serologically positive animals were negative for F. tularensis DNA, indicating infection may be may have been cleared naturally. Tularemia should be considered in a differential diagnosis of unexplained febrile illness in cats.

JPC Diagnosis:  

Spleen: Splenitis, necrotizing, multifocal to coalescing, severe, with mild lymphoid depletion and fibrin deposition, domestic shorthair cat, Felis catus.

Conference Comment:  

The contributor provides a great example of typical lesions of Francisella tularensis. In cats, there often is severe systemic disease and pathological manifestations are dependent on the dissemination of the pathogen.1,8,9 As mentioned by the contributor, classic gross lesions for tularemia are miliary white foci 2mm or more in diameter in the liver, spleen, and lymph nodes. Histologically, the lesions are characterized by focal areas of severe necrosis, as seen in this case.8 This gram-negative, intracellular bacillus can infect humans, wild rabbits, rodents, and over 100 species of wild and domestic mammals, birds, fish, and reptiles.3,9 In the North America, the wild rabbit is the reservoir for the biovar tularensis (type A). Biovar holarctica (type B) is more common in aquatic species such as beavers and muskrats. F. tularensis biovar mediasiatica and F. novicida are restricted to central Asia.7,8 Sporadic outbreaks of tularemia are known to occur in sheep and foals in association with heavy infestation with Dermacentor andersoni and Amblyomma americanum ticks. Typically, enlargement of the liver, spleen, and kidneys with miliary foci of necrosis are seen on post-mortem examination.8 Dogs are generally highly resistant to natural infection, but there have been rare reports of mild disease in canines.8 The most common route of infection for humans originates from cleaning and skinning infected rabbits as well as arthropod bites. Humans can also be infected via contaminated water supplies and consumption of undercooked meat.6 In addition to natural infection, F. tularensis is considered to be a serious potential bioterrorism agent, because it is one of the most infectious pathogenic bacteria known. As mentioned by the contributor, inhalation of as few as 10 organisms can cause severe pneumonic tularemia disease leading to serious illness and death.1,6

Experimentally-induced lesions from inhalation in African green monkeys included necrotizing pyogranulomatous lesions which targeted the lung and lymphoid tissue in addition to disseminated miliary necrotic foci on multiple organs and moderate to marked lymphoid depletion of the splenic white pulp and mediastinal lymph nodes.6 Conference participants agreed that in this case, both red and white pulp of the spleen are affected by necrosis; however, lesions generally centered on the white pulp and extended into the red pulp in conjunction with severe lymphoid depletion and lymphocytolysis. There are currently no vaccines available to prevent disease.6 As a result, conference participants discussed that extreme care needs to be taken when dealing with and shipping suspect tularemia cases.

These facultative intracellular organisms are most commonly located within macrophages, but may also be present extracellularly in exudates and necrotic debris. The organisms can also infect and survive in dendritic cells, neutrophils, hepatocytes, and lung epithelial cells. The ability of F. tularensis to infect macrophages, evade the immune system by preventing phagolysosome fusion, rapidly replicate within macrophages, and disseminate widely throughout the body is the key to its pathogenesis.1,7,8


1. Brotcke A, Weiss DS, Kim CC, et al. Identification of Mg1A-regulated genes reveals novel virulence factors in Francisella tularensis. Infect immune. 2006; 74:6642-6655.

2. Gyuranecz M, Szeredi L, Makrai L et al. Tularemia of European Brown Hare (Lepus europaeus): A pathological, histopathological, and immunohistochemical study. Vet Pathol. 2010; 47(5):958-63.

3. Inzana TJ, Glindemann GE, Snider G, et al. Characterization of a wildtype strain of Francisella tularensis isolated from a cat. J Vet Diagn Invest. 2004; 16:374-381.

4. Magnarelli L, Levy S, Koski R. Detection of antibodies to Francisella tularensis in cats. Res Vet Sci. 2007; 82:22-26.

5. Pechous RD, MCCarthy TR, Zahrt TC. Working toward the future: Insights into Francisella tularensis pathogenesis and vaccine 16 development. Microbiol Mol Biol Rev. 2009; 73:684-711.

6. Twenhafel NA, Alves DA, Purcell BK. Pathology of inhalational Francisella tularensis spp. tularensis SCHU S4 infection in African green monkeys (Chlorocebus aethiops). Vet Pathol. 2009; 46:698- 706.

7. Valentine BA, DeBey BM, Sonn RJ, Stauffer LR, Pielstick LG. Localized cutaneous infection with Francisella tularensis resembling ulceroglandular tularemia in a cat. J Vet Diagn Invest. 2004; 16:83-85.

8. Valli VEO. Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA:Elsevier; 2016:184-186.

9. Weinberg AN, Branda JA. Case 31- 2010: A 29-year-old woman with fever after a cat bite. N Engl J Med. 2010; 363:1560-1568.

Click the slide to view.

3-1. Spleen, cat.

3-2. Spleen, cat.

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