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WSC 14-15 Conf 25 Layout Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2014-2015 Conference 25 13 May 2015 CASE I: EV-UFMG 08/1116 (JPC 3136273). old. At the end of the experimental protocol, prior to release into the field, the calf was subjected to Signalment: 4-month-old male Holstein calf, premunition with Babesia bigemina and B. bovis, Bos Taurus. after which it developed apathy and quickly progressed to death. History: This was an experimental calf. Soon after birth it was placed in an arthropod-free Gross Pathologic Findings: The calf was containment facility. The calf was inoculated with emaciated with moderate anemia and mild icterus. Anaplasma marginale when it was two months There was mild hydrothorax and 1-1. Liver, calf: The liver is markedly enlarged and yellowish with 1-2. Liver, calf: There are coalescing areas of coagulative necrosis focally extensive dark-red areas. Upon close inspection, there are within the submitted section of liver (arrows). (HE 5X) numerous military white nodules within the parenchyma. (Photo courtesy of: Departamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. http://www.vet.ufmg.br) 1 WSC 2014-2015 hydroperitoneum. In the lung there were thickening of the alveolar wall with interstitial multifocal mildly consolidated areas ranging from infiltration of macrophages, lymphocytes and a 0.3 to 0.5 cm in diameter distributed in all few neutrophils. There was multifocal intra- pulmonary lobes. The liver was markedly alveolar accumulation of fibrin and a few enlarged yellowish with focally extensive dark- neutrophils. red areas. There were multiple miliary white nodules in the parenchyma. There was also small Contributor’s Morphologic Diagnosis: Liver: amount of purulent exudate draining on the cut Hepatitis, necrotizing, histiocytic and surface, and small thrombi were grossly observed. neutrophilic, multifocal, random, acute, The spleen was moderately enlarged. Gross associated with thrombosis and intralesional findings did not support babesiosis as a cause of bacterial colonies. death. Contributor’s Comment: Salmonella enterica Laboratory Results: Microbiology: Salmonella comprises more than 2,000 serotypes, including sp. was isolated from the liver. serotypes Dublin and Typhimurium that are often isolated from cattle. The most common clinical Histopathologic Description: In the liver there manifestation of Salmonella infection in cattle is was multifocal random degeneration and necrosis an enteric disease characterized by diarrhea that is associated with an intense neutrophilic infiltrate usually associated with acute fibrino-necrotizing with some lymphocytes and macrophages. There enteritis.9-11 However, systemic salmonellosis in were several intralesional bacterial colonies. A cattle may occur in the absence of enteric disease,5 lymphoplasmacytic and histiocytic infiltrate as observed in the present case. predominates in portal areas. Several blood vessels had fibrinoid necrosis in the vascular wall Salmonella is highly invasive, crossing the associated with thrombosis, particularly in intestinal epithelial barrier inducing ruffling of the centrilobular veins. Some veins are completely apical surface of the epithelial layer, which results obliterated by thrombosis. in internalization of the organism within a cytosolic membrane bound vacuole. This process In the spleen (section not submitted) there were is dependent on the expression of several effector numerous hemosiderin-laden macrophages and bacterial proteins that are translocated into the increased erythrophagocytosis, associated with host cells through a type III secretion system moderate lymphoid depletion. encoded by the Salmonella pathogenicity island 1 (SPI-1).9-12 Once the organism crosses the In the lungs (sections not submitted), there was an epithelial layer, it quickly localizes in the lamina interstitial pneumonia characterized by marked propria, where it is found mostly within 1-3. Liver, calf: Numerous portal veins contain fibrinocellular thrombi 1-5. Liver, calf: Areas of lytic necrosis are infiltrated by moderate and necrotic debris within the vascular wall (vasculitis). (HE 256X) numbers of neutrophils and histiocytes (“paratyphoid nodules”). There are aggregates of post-mortem bacilli throughout the section. (HE 256X) 2 WSC 2014-2015 characteristic for the typhoidal form of salmonellosis.3 P a r a t y p h o i d n o d u l e s o r granulomas may also be found in the kidney, spleen, lymph nodes and bone marrow in cases of septicemic salmonellosis.1 These contribute to the gross miliary pattern in affected organs, most often in the liver and spleen.1 It is unclear whether these nodules are the result of a cell- mediated immune r e s p o n s e o r accumulate due to bacterial replication within macrophages.1,7 1-5. Liver, calf: Areas of lytic necrosis are infiltrated by moderate numbers of neutrophils and histiocytes (“paratyphoid nodules”). There are aggregates of post-mortem bacilli throughout the section. (HE 256X) Typhoidal s e r o t y p e s o f macrophages. Salmonella processes another type Salmonella spp. III secretion system encoded by SPI-2 that is are less common than the nontyphoidal forms in activated as soon as the bacteria localizes in the most species, including humans with the phagosome. This SPI-2-encoded type III secretion exception being in mice. Mice regularly develop system is essential for intracellular survival of the septicemia with oral inoculation of Salmonella organism in macrophages and, therefore, systemic isolates, often without exhibiting gross and dissemination of the infection.8 microscopic changes in the alimentary tract.2,7 In our empirical experience, Salmonella is usually The nontyphoidal or enteric form of not observed in HE-stained section, both in salmonellosis, characterized by self-limiting enteric and systemic sites of infection. enterocolitis or diarrhea in the absence of Interestingly, in the present case there were systemic disease, is a major cause of morbidity abundant intralesional bacterial colonies, which and mortality in calves and often over one billion likely represent postmortem overgrowth of the human cases per year. While both are organism. incriminated in cattle, Salmonella enterica serovar Typhimurium infects all species and is the JPC Diagnosis: Liver: Hepatitis, necrotizing, most common isolate in people, while S. enterica multifocal, random, with vasculitis, thrombosis, serovar Dublin is more specific to cattle.1,6 The and rare paratyphoid nodules. similarity in enteric disease manifestation between cattle and humans and has led to their Conference Comment: The accumulations of use as an experimental model for human mixed mononuclear inflammatory cells infections.6,11 Characteristic histopathology of multifocally scattered throughout the liver in this nontyphoidal salmonellosis is the massive influx case are called “paratyphoid nodules” and are of neutrophils, which is also suggested as the 3 WSC 2014-2015 major triggering event of gastrointestinal necrosis 7. Percy DH, Barthold SW. Pathology of and diarrhea.6 Vasculitis and thrombosis is also Laboratory Rodents and Rabbits 3rd ed. Ames, IA: prominent, and in severe cases can lead to rectal Blackwell Publishing; 2007:61-63. strictures in pigs who have poor collateral 8. Santos RL, Bäumler AJ. Cell tropism of circulation.4 Fibrinous cholecystitis is Salmonella enterica. Int J Med Microbiol. pathognomonic for acute enteric salmonellosis in 2004;294:225-233. calves.4 Chronic enteric salmonellosis is 9. Santos RL, Tsolis RM, Bäumler AJ, Adams characterized by discrete foci of necrosis and LG. Pathogenesis of Salmonella-induced enteritis: ulceration called “button ulcers” and seen most a review. Braz J Med Biol Sci. 2003;36:3-12. often in pigs but also cattle and horses.4 10. Santos RL, Zhang S, Tsolis RM, Kingsley RA, Adams LG, Baumler AJ. Animal models of The colonies of coccobacilli and large numbers of Salmonella infections: gastroenteritis vs. typhoid rods found in some areas of the slide are both fever. Microbes Infect. 2001;3:1335-1344. gram-positive, leading conference participants to 11. Santos RL, Zhang S, Tsolis RM, Bäumler AJ, conclude these are postmortem bacterial Adams LG. Morphologic and molecular overgrowth not related to the Salmonella infection characterization of Salmonella typhimurium in this case. infection in neonatal calves. Vet Pathol. 2002;39:200-215. Contributing Institution: Departamento de 12. Zhang S, Santos RL, Tsolis RM, Stender S, Clínica e Cirurgia Veterinárias, Escola de Hardt WD, Bäumler AJ, et al. The Salmonella Veterinária, Universidade Federal de Minas enterica serotype Typhimurium effector proteins Gerais, Belo Horizonte, MG, Brazil. http:// SipA, SopA, SopB, SopD and SopE2 act in www.vet.ufmg.br concert to induce diarrhea in calves. Infect Immun. 2002;70:3843-3855. References 1. Brown CC, Baker DC, Barker IK. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 5th ed. Vol 2. Philadelphia, PA: Elsevier Saunders; 2007:200-202. 2. Brown DE, Libby SJ, Moreland SM, et al. Salmonella enterica causes more severe inflammatory disease in C57/BL6 NrampIG169 mice than SV129S6 mice. Vet Pathol. 2013;50(5): 867-876. 3. Cullen, JM, Brown DL. Hepatobiliary system and exocrine pancreas. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier Mosby; 2012:433. 4. Gelberg HB. Alimentary system and the peritoneum,
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