Conference 14 - 2009 Case: 01 20100203

Signalment:

11-year-old, male owl monkey (Aotus nancymaae).This monkey was euthanized due to cardiac and renal failure. Echocardiogram showed dilated cardiomyopathy with left ventricular hypertrophy, pericardial effusion, ascites, and abnormal kidneys.

Gross Description:

At necropsy, the pericardial sac was filled with serosanguineous fluid; the heart was enlarged with multiple white streaks (degeneration/fibrosis) in the ventricular walls. The ascending aorta was doublebarreled, having apparently two lumina; the latter tracked into the abdominal aorta near the kidneys. Several linear yellow streaks (plaques) were observed in the thoracic and abdominal aorta. The kidneys were light brown with black and red speckling (nephropathy); the liver was enlarged (hepatomegaly).

Histopathologic Description:

The aorta is oval-shaped and measures 4-5 mm in diameter; associated with the tunica media of the aorta is a second oval-shaped channel of slightly larger diameter that partially encircles the aorta. The wall of the aorta is approximately 300 μm thick versus approximately 500 μm for the second channel; the wall of the latter has an irregular endothelial lining and contains fibromuscular proliferation, degeneration/necrosis, and granulation tissue.

Morphologic Diagnosis:

Aorta: dissection, tunica media with fibromuscular proliferation, degeneration/necrosis, and granulation tissue.

Lab Results:

Hematocrit 19.6% ↓; RBC 2.66 x 106/μl ↓; BUN 45 mg/dl ↑; creatinine 1.4 mg/dl ↑

Condition:

Aortic dissection

Contributor Comment:

The aortic dissection in this owl monkey started in the ascending aorta and extended to the level of the kidneys. The dissection presented as a double-barreled aorta with a false channel. The false channel was partially endothelialized, suggesting it was a chronic change. Mention should be made of terminology in reference to aortic dissections. That is, while aortic aneurysm is used as a general term by many, a distinction is made by others between an aneurysm and a dissection.(3) A true aneurysm is considered an abnormal dilatation of a blood vessel wall that is bounded by arterial wall components. A false aneurysm involves an interruption in the vessel wall and the development of an extravascular hematoma that communicates with the vessel lumen. On the other hand, a dissection develops when blood enters the wall of an artery (e.g. via intimal tear), dissecting between layers, as in the aorta of this monkey. Other terms used to describe aortic dissections include dissecting hematoma and dissecting aortic aneurysm.

In general, the incidence rates for aortic aneurysms in nonhuman primates appear to be low; however, spontaneous lesions have been reported in the gorilla and squirrel, howler, capuchin, patas, spider, and owl monkeys.(1) In contrast, aortic aneurysms are not uncommon in the owl monkey, with an incidence rate of 8.6% (N=257) in one report. The majority of the aneurysms in this report were classified as dissecting with only three others termed saccular aneurysms. Aortic plaques were seen in some of these animals, as was chronic nephropathy, cardiomegaly, left ventricular hypertrophy, pericardial effusion, pleural effusion, pulmonary edema, hemothorax, hemoperitoneum, hepatomegaly, and cholelithiasis. More females than males were affected.

Hypertension is a major risk factor for aortic dissection in human males aged 40-60 years. Degenerative changes in the tunica media of the aorta may also be important. Inherited connective tissue disorders that lead to abnormal vascular structure (e.g. Marfan syndrome) fall into the latter category. Complications following arterial cannulation and pregnancy have also been associated with aortic dissection in humans. Interestingly, atherosclerosis and medial scarring due to diseases such as syphilis are not usually associated with dissections. Following the particular predisposing factor(s), an intimal tear develops with hemorrhage into the wall of the aorta.(3) Conversely, the initiating event may be a ruptured vasa vasorum with bleeding into media.(5) The pathogenesis of the aortic dissection in this monkey was not determined.

JPC Diagnosis:

Fibroelastic artery, aorta: Aortic dissection lined by endothelium, fibromuscular proliferation, cystic medial degeneration, and mucinosis.

Conference Comment:

This interesting case was reviewed in consultation with the AFIP Department of Cardiovascular Pathology. During the conference, participants discussed the nomenclature pertinent to this case, with a focus on the distinction between an aneurysm and a dissection; inappropriate interchangeable use of the terms aneurysm and dissection may be culpable for undue perplexity when reviewing case reports in the literature. A true aneurysm is a localized abnormal dilation of a blood vessel or the heart, and can be further classified by its overall shape and size, with saccular (i.e. focal, bulging, asymmetrical outpouching) and fusiform (i.e. segmental to diffuse, circumferential) types being described. By contrast, a false aneurysm, also referred to as a pseudo-aneurysm, results from a vessel wall defect and extravasation of blood into a hematoma within the extravascular connective tissue that communicates freely with the vascular space (i.e. pulsating hematoma). Like a false aneurysm, a dissection is characterized by the extravasation of blood; however, the blood in a dissection accumulates between layers of the vessel wall, rather than in the extravascular connective tissue as occurs in a false aneurysm. Blood usually extravasates via an intimal tear, as with a false aneurysm, but a dissection may also occur by rupture of vessels of the vasa vasorum within the media. Dissections may be aneurysmal (i.e. present within a vessel that is also abnormally dilated), but are not always so; therefore, use of the term dissecting aneurysm may be inappropriate.(3)

The most important risk factor for aortic dissection in humans is hypertension; less commonly, aortic dissection is associated with abnormal vascular extracellular matrix (ECM) due to inherited or acquired connective tissue disorders.(3) Participants reviewed one such disorder, Marfan syndrome, an inherited defect in the extracellular glycoprotein fibrillin-1 which results from a mutation in the FBN1 gene. Fibrillin-1 is a major component of the ECM microfibrils that provide the scaffolding on which tropoelastin is deposited to form elastic fibers. Fibrillin-1 abnormalities result in defective mechanical properties of the ECM in the cardiovascular system and eyes, resulting in aortic aneurysm, aortic dissection, and lens subluxation or dislocation. Moreover, since normal microfibrils sequester transforming growth factor β (TGF-β) and control its bioavailability, Marfan syndrome is characterized by excessive activation of TGF-β; this not only further contributes to the altered vascular ECM integrity, but likely accounts for other clinical manifestations of the syndrome not attributable to ECM abnormalities (e.g. bone overgrowth).(2) These observations are supported by studies in a mouse model of Marfan syndrome in which Fbn1 +/- mice developed myxomatous mitral valve and aortic lesions that were prevented by the administration of TGF-β antibodies, demonstrating the importance of TGF-β in the pathogenesis of the lesions and indicating that elevated TGF-β may be primarily responsible for the development of mitral valve prolapse in children with Marfan syndrome.(4)

While in most cases of aortic dissection no specific underlying pathology is identified in the aortic wall, the most frequently detected lesion is cystic medial degeneration in the absence of inflammation. In this case, some participants noted areas of cystic medial degeneration and therefore considered, in addition to Marfan syndrome, other causes of vascular ECM abnormalities, including Ehlers-Danlos syndrome, vitamin C deficiency, and defects in copper metabolism.(3) Some participants noted the presence of foam cells and rare cholesterol clefts, reminiscent of atherosclerosis; however, their subadventitial location is not consistent with atherosclerosis, and as mentioned by the contributor, while atherosclerosis is among the most important predisposing factors for aneurysms (along with hypertension), dissections are unusual in the presence of atherosclerosis, presumably because of medial fibrosis precluding propagation of the dissection.(3) Nevertheless, the gross description of yellow plaques within the aorta is consistent with atherosclerosis and participants could not exclude it as a causal or contributory factor in this case. Finally, some participants noted striking microscopic resemblance to a stented vessel, and dissection can occur iatrogenically due to complicating arterial cannulations.(3)

References:

1. Baer JF, Gibson SV, Weller RE, Buschbom RL, Leathers CW: Naturally occurring aortic aneurysms in owl monkeys (Aotus spp). Lab Anim Sci 42:463-466, 1992
2. Kumar V, Abbas AK, Fausto N, Aster JC: Genetic disorders. In: Robbins and Cotran Pathologic Basis of Disease, eds. Kumar V, Abbas AK, Fausto N, Aster JC, 8th ed., pp. 144-145. Saunders Elsevier, Philadelphia, PA, 2010
3. Mitchell RN, Schoen FJ: Blood vessels. In: Robbins and Cotran Pathologic Basis of Disease, eds. Kumar V, Abbas AK, Fausto N, Aster JC, 8th ed., pp. 506-510. Saunders Elsevier, Philadelphia, PA, 2010
4. Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JM, Mecham RP, Judge DP, Dietz HC: TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest 114:1586-1592, 2004
5. Virmani R, Burke AP: Nonatherosclerotic diseases of the aorta and miscellaneous diseases of the main pulmonary arteries and large veins. In: Cardiovascular Pathology, eds. Silver MD, Gotlieb AI, Schoen FJ, 3rd ed., pp. 109-117, Churchill Livingstone, New York, NY, 2001