Signalment:  

Adult, male, Wistar Hannover rat (Rattus norvegicus)An approximately 2 year old male sentinel rat was found dead with no premonitory clinical signs.


Gross Description:  

Gross findings included prominent, dark-red mesenteric vasculature. Additional findings included approximately 3 ml of hemorrhagic fluid in the abdomen, a deformed spleen that was constricted in the middle, an 2.0 cm diameter, thin walled cyst filled with clear fluid and extending from the pancreatic region, and a 1.0 cm diameter clear cyst protruding from the right kidney.


Histopathologic Description:

Large and medium sized muscular mesenteric and pancreatic arteries are primarily affected. Some arteries have acute lesions of intimal and medial fibrinoid necrosis with thrombosis and luminal dilatation, destruction of the elastic laminae, mural hemorrhage, and segmental to global transmural infiltration of neutrophils, eosinophils, and mononuclear cells. Inflammatory infiltrates multifocally extend from the adventitia into the periarterial tissues. Other arteries have chronic lesions of irregular mural thickening due to fibrosis (sometimes causing narrowing of the lumen), mononuclear cell infiltrates, and organizing / recanalizing thrombi. Mural mineralization is also multifocally present within the medial layers of some arteries.

Other lesions on the slide include a dilated cystic structure adjacent to the pancreas interpreted to be a dilated lymph vessel as well as mesenteric lymph nodes with sinuosidal erythrocytosis and phagocyte hemosiderosis. 


Morphologic Diagnosis:  

1. Mesenteric and pancreatic arteries; Polyarteritis, necrotizing, multifocal, with mixed cell inflammation, fibroplasia, mural hemorrhage, and occlusive thrombi, rat

2. Mesenteric arteries, media; Mineralization, moderate, multifocal

3. Lymph nodes (multiple); Erythrocytosis, sinusoidal, moderate, multifocal, with phagocyte hemosiderosis

4. Abdomen, peripancreatic; Dilated lymph vessel, focal


Condition:  

Polyarteritis nodosa


Contributor Comment:  

The signalment, anatomical locations, gross appearance, and histologic characteristics of this case are consistent with those of polyarteritis nodosa (PAN). PAN is a progressive degenerative, inflammatory, and necrotizing disease that most commonly affects small to large arteries of the mesentery, pancreas, kidney, and testis7 . The aorta, arterioles, and smaller caliber vessels are typically spared 7. As observed in this case, the presence of acute, healing, and old lesions within a single animals is highly characteristic of PAN7 . Clinically, polyarteritis nodosa tends to occur in aged rats (reports vary between 500 and 900 days). Although polyarteritis nodosa is most often an incidental finding in aged rats, it can be fatal if, as is likely in this case, severely thrombosed mesenteric arteries rupture leading to fatal hemorrhaging into the abdominal cavity2.

PAN is typically considered to be an immune-mediated disease7,12 , but the disease has also been associated in some studies with corticosteroid adminstration, estrogen treatment, exposure to chemical carcinogens, and hypersensitivity2. PAN has a high incidence in spontaneous hypertensive rat strains as well as in rats with late stage chronic nephropathy (which was present in this case)7,9. The multifocal, moderate mineralization of the arterial media seen in this animals may also be secondary to chronic renal disease7.

Other related lesions observed microscopically in this animal included a focally extensive area of splenic coagulative necrosis with abundant intralesional thrombi, inflammation, hemorrhage, and hemosiderosis. This likely represents an infarct associated with the thrombi initiated by necrotizing polyarteritis. 


JPC Diagnosis:  


1. Pancreas and mesentery: Arteritis and periarteritis, proliferative and necrotizing, chronic, multifocal, severe, with multifocal mineralization and thrombosis, Wistar Hannover rat (Rattus norvegicus), rodent.
2. Pancreas, exocrine: Atrophy, multifocal, mild.
3. Lymph node: Draining hemorrhage, chronic, with sinusoidal ectasia.


Conference Comment:  

The characteristic histologic lesion of polyarteritis nordosa (PAN) is segmental fibrinoid degeneration and thickening of the tunica media of affected arteries with an inflammatory infiltrate composed mainly of mononuclear cells with fewer neutrophils.9 The size of the vessel lumen are markedly variable, with potential thrombosis with or without recanalization.9 Both acute and chronic inflammatory processes may occur within the same individual. 

In rats, lesions occur most commonly in medium-sized arteries of the mesentery, pancreas, pancreatic-duodenal arteries, and testis of male, Sprague-Dawley and spontaneous hypertensive rat (SHR) strains.9 Microscopic lesions may occur in most organs except for the lungs.9 In mice, most lesions occur within small and medium-sized arteries of the tongue, pancreas, heart, kidneys, mesentery, urinary bladder, uterus, testes, and gastrointestinal tract of MRL and NZB mice.9

Changes within the vessel walls can be highlighted with special stains. The modified Movats pentachrome method stains elastic laminae black, collagen and reticular fibers yellow, ground substance and mucin blue, fibrin intense red, and muscle fibers red.11 With the Movats pentachrome method, the quantity of intimal proliferation is readily apparent as are disruptions of the elastic laminae. Other stains such as Massons trichrome and smooth muscle actin aid in differentiating increased amounts of intimal connective tissue from smooth muscle hyperplasia.11

In dogs, lesions similar to polyarteritis nodosa occur as a syndrome of unknown etiology termed juvenile polyarteritis syndrome or beagle pain syndrome.13 An immune-mediated etiology is suspected. 


References:

1. Bishop SP: Animal models of vasculitis. Toxicol Pathol 17:109-117, 1989
2. Carlton WW, Engelhardt JA: Polyarteritis, rat. In: Monographs on Pathology of Laboratory Animals, eds. Jones TC, Mohr U, Hunt RD, vol. 9, pp. 71-76. Springer-Verlag, Berlin, 1991
3. Chamanza R, Parry NMA, Rogerson P, Nicol JR, Bradley AE: Spontaneous lesions of the cardiovascular system in purpose-bred laboratory nonhuman primates. Toxicol Pathol 34:357-363, 2006
4. Cohen JK, Cai LQ, Zhu YS, La Perle KM: Pancreaticoduodenal arterial rupture and hemoabdomen in ACI/SegHsd rats with polyarteritis nodosa. Comp Med 57:370-376, 2007
5. Kempner W, Peschel E, Black-Schaffer B: Effect of diet on experimental hypertension and on the development of polyarteritis nodosa in rats. Circ Res 3:73-78, 1955
6. Maxie MG, Robinson WF: Cardiovascular system. In: Jubb, Kennedy, and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., vol. 3, pp. 69-73. Elsevier Limited, St. Louis, MO, 2007
7. Mohr U, Dungworth DL, Capen CC: Cardiovascular system. In: Pathobiology of the Aging Rat, vol. 1, pp. 306-309. ILSI press, Washington, D.C, 1996
8. Percy DH, Barthold SW: Mouse. In: Pathology of Laboratory Rodents and Rabbits, 3rd ed., p. 105. Blackwell Publishing, Ames, IA, 2007
9. Percy DH, Barthold SW: Rat. In: Pathology of Laboratory Rodents and Rabbits, 3rd ed., p. 164. Blackwell Publishing, Ames, IA, 2007
10. Porter, BF, Frost P, Hubbard GB: Polyarteritis nodosa in a Cynomolgus macaque (Macaca fascicularis). Vet Pathol 40:570-573, 2003
11. Prophet EB, Mills B, Arrington JB, Sobin LH: Laboratory Methods in Histotechnology, pp 128-130. American Registry of Pathology, Washington DC, 1994
12. Schoen FJ: Blood vessels. In: Robbins and Cotran Pathologic Basis of Disease, eds. Kumar V, Abbas, AK, Fausto N, 7th ed., pp. 539-540. Elsevier Saunders, Philadelphia, PA, 1999
13. Son WC: Idiopathic canine polyarteritis in control beagle dogs from toxicity studies. J Vet Sci 5:147-150, 2004
14. Van Vleet JF, Ferrans VJ: Cardiovascular system. In: Pathologic Basis of Veterinary Disease, eds. McGavin MD, Zachary JF, 4th ed., pp. 606-607. Elsevier, St. Louis, MO, 2007


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