Noninflammatory Thoracic Aortic Aneurysms and Dissections
Allen P. Burke, M.D.
Joseph J. Maleszewski, M.D.
Terminology
The term aneurysm refers to a dilatation of a structure beyond its expected borders. Thus, the term is applied somewhat subjectively depending on the observer and modality used for observation. Aneurysms are broadly dichotomized into fusiform or saccular varieties by circumferential extent and shape. Saccular aortic aneurysms are a noncircumferential outpouching of the vessel wall and are typically seen outside the ascending aorta. Fusiform aortic aneurysms are circumferential and typically seen in the ascending aorta.
In addition to shape, aneurysms may also be classified based on the constituency of the aneurysm wall, as evidenced by histopathology. True aneurysms contain portions of all three layers of the vessel wall: intima, media, and adventitia. Dissections (so-called dissecting aneurysms) represent an intramedial channel of blood usually resulting from an intimal tear. False aneurysms (also called “contained ruptures”) represent disruption of the vessel wall to the level of the adventitia, but not beyond. As such, the aneurysm wall of the latter will usually contain adventitia, intima (from reendothelialization), and occasionally mural thrombus (but without media).
Epidemiology
The incidence of thoracic aortic aneurysms is difficult to determine, as most patients are asymptomatic. The incidence is believed to be increasing and has been estimated at about 0.3% of the population, as defined by an aorta >5 cm in diameter.1 There is an approximate 2:1 male predilection.1
The normal ascending aortic diameter as measured echocardiographically increases with age, from a mean of 3 cm at age 30 to 3.5 at age 80, and is related to body mass index.2
Location
Thoracic aortic aneurysms may involve the ascending aorta, aortic arch, descending aorta, or a combination of these locations. Proximal thoracic aortic aneurysms are usually fusiform dilatations of the ascending aorta that typically do not extend into the arch and are associated with systemic hypertension, inherited syndromes, and congenitally bicuspid aortic valves. Descending aneurysms may be fusiform or saccular and often extend into the abdominal aorta. Descending aneurysms are typically atherosclerotic. Other causes of descending thoracic aneurysms include postinfectious or mycotic aneurysms (see Chapter 189) and posttraumatic pseudoaneurysms. Posttraumatic pseudoaneurysms are typically located in the proximal descending thoracic aorta.
TABLE 190.1 Noninflammatory Thoracic Aneurysms: Characteristics by Associations | |||||||||||||||||||||||||
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Etiology
Systemic hypertension is believed to be responsible for most ascending aortic aneurysms, but the exact mechanism is unknown.
Another major cause of noninflammatory thoracic aneurysms is the inherited connective tissue disease syndromes, specifically Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and familial thoracic aortic aneurysm and dissection.3 The major associations are bicuspid aortic valve and systemic hypertension. Approximately 25% of patients with thoracic aortic aneurysms have no known cause or association.
From a series of resected thoracic aneurysms at a referral center, 13% of noninflammatory aneurysms were associated with an inherited connective tissue disease, mostly MFS; 25% of patients had bicuspid aortic valves; and 51% had no association other than hypertension.4
Thoracic aortic aneurysms can be divided in four main categories regarding their association with genetic diseases (Table 190.1):
Sporadic cases often associated with hypertension, with onset in mid or late adulthood. Approximately 20% of these patients have a family history, and the apparent inheritance is usually autosomal dominant and likely owing to multiple genetic and epigenetic factors.
Cases associated with bicuspid aortic valve disease with familial aggregation; these constitute ˜10% of patients and present in the 50s to 60s, with a strong male predominance.
MFS; these constitute 3% to 15% of patients, depending on population.
Other genetic conditions, including type IV Ehlers-Danlos syndrome and LDS (<1% of cases).
Many patients with aortic aneurysm and dissection do not fit any syndrome of collagen vascular disease, such as MFS, yet as many as 20% of those will have at least one first-degree family member with a known aneurysm in the arterial tree, usually with autosomal dominant inheritance.5 In a series of patients with nonfamilial aortic aneurysms, only 3% carried mutations associated with aortic dissections, including ACTA2 (α-actin2) or FBN1 (fibrillin1). A higher rate (17%) of mutations, including FBN1 and TGFβR2, was found in familial non-Marfan aneurysm patients.3
Bicuspid aortic valve disease is a common congenital cardiac defect that affects ˜1% to 2% of the general population. There is a greater than fivefold risk for the development of proximal aortic aneurysms and
dissections.6 Unicuspid aortic valve is associated with thoracic aortic aneurysm at an even higher rate.6
dissections.6 Unicuspid aortic valve is associated with thoracic aortic aneurysm at an even higher rate.6
The cardiac manifestations of bicuspid aortic valve disease, which becomes manifest in most patients during the course of their lifetimes, are isolated aortic regurgitation (see Chapter 36), isolated ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm, isolated aortic stenosis (see Chapter 35), and aortic stenosis with aneurysm.7 One-third of patients with bicuspid aortic valve and aortic aneurysms have aortic valve stenosis, and the other two-thirds valve insufficiency, with a small number having normal valve function.8,9
The genetic basis for bicuspid aortic valve syndrome, which is inherited as autosomal dominant disease in a minority of patients, is still unknown, although several cohorts with mutations in GATA5, NKX2.5, and NOTCH1 have been reported.10,11,12
MFS is a disorder characterized by abnormalities of the eyes, skeleton, and cardiovascular system. MFS is an autosomal dominant disease, with 25% of patients having no family history (presumed de novo mutations). Cardiovascular manifestations of MFS include aortic root dilatation, ascending aortic dilatation, aortic dissections, other sites of aortic aneurysm, and mitral valve prolapse.3 The histologic feature of aortic aneurysms in MFS is loss of elastic laminae with pooling of proteoglycans, so-called medial degeneration. The histologic findings are also seen to lesser degrees in familial non-Marfan aortic dissection and those associated with bicuspid aortic valve.
In the absence of surgical treatment, patients with MFS have a 50% risk of developing aortic dissection during their lifetime. The aortic dilatation observed in MFS is the result of defects in a specific component of the elastic fiber, fibrillin-1,13 which is encoded by the FBN1 gene on chromosome 15. An online database (http://omim.org/entry/134797) contains more than 250 mutations with variations of clinical expression. In a series of unrelated patients with suspected MFS and aortic aneurysms, a mutation could be found in 31%, mostly FBN1, and one mutation in TGFβR1, using sequencing and multiplex polymerase chain reaction techniques.3
LDS is an autosomal dominant Marfan-like connective tissue disorder that is an increasingly recognized cause of thoracic aortic aneurysm (http://omim.org/entry/6091912). It results from genetic mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized by hypertelorism, bifid uvula, cleft palate, and arterial tortuosity with aneurysms and dissections. LDS has an earlier onset than does MFS, with recommendations for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Histologically, there is diffuse medial degeneration, which may be subtle.14 In a series of unrelated patients with suspected MFS and aortic aneurysms, a mutation could be found in 17%, mostly TGFβR23
Type IV Ehlers-Danlos syndrome (EDS) (vascular type) is due to defects in the type III procollagen (COL3A1) (http://omim.org/entry/130050). It causes vascular fragility with aneurysm formation, rupture, and dissections. The aorta is involved in a small percentage, since this disease affects most often smaller arteries. Usually, there are multiple rupture sites in the aorta. Patients with type IV EDS may also have thoracic aortic aneurysms; however, the typical complication is rupture in normal-caliber artery. Coronary artery dissections, aortic rupture, iliac and femoral rupture, and coronary and other muscular arterial aneurysms are among the different complications seen in these patients. Generally, fewer than 1% of patients in series of thoracic aneurysm have EDS.
Osteogenesis imperfecta shares some clinical features with EDS. Type I osteogenesis imperfecta, the result of mutations in COL1A1, is weakly associated with aortic root dilatation, aortic insufficiency, and mitral valve prolapse (http://omim.org/entry/166200).
Ninety percent of descending thoracic aortic aneurysms are atherosclerotic. They are less frequently resected than ascending aortic aneurysms and are frequently treated medically or by endovascular repair.15
Clinical Features
A large percentage of patients with thoracic aortic aneurysms are asymptomatic. Thoracic aneurysms are usually found incidentally by imaging studies; the pathologist may encounter them at autopsy, sometimes after unexpected rupture (Figs. 190.1 and 190.2; Table 190.2). Symptoms develop in the setting of aortic insufficiency (aneurysms involving the aortic root or ascending aorta), dissection, or rupture.
 FIGURE 190.1 ▲ Proximal ascending aortic aneurysm, with rupture. The right side of the proximal ascending aorta is shown. There is a discrete area of saccular aneurysm, with a rupture site (arrow). There was no dissection. The histologic findings were those of marked cystic medial necrosis (not shown). Thoracic aneurysms with underlying cystic media necrosis have a variety of possible outcomes: dissection before significant dilatation, dilatation and then rupture without dissection, and dilatation with dissection. (Reproduced with permission from Virmani R, Burke AP, Farb A, et al. Cardiovascular pathology. In: Virmani R, Burke AP, Farb A, et al., eds. Major Problems in Pathology Series. Philadelphia, PA: WB Saunders; 2001;40:489.) |
The growth of aneurysm may be indolent, and there is debate as to the appropriate timing of surgical intervention, which typically occurs when the size reaches 5 cm. Serial imaging studies have shown a slow growth rate (about 1 mm yearly) until the diameter is about 5 cm, at which time it may be more rapid.16,17
Gross Findings
As noted above, uncomplicated thoracic aortic aneurysms can be divided grossly into saccular and fusiform. Fusiform aneurysms are most common and affect the entire circumference of the aorta and have tapered borders. Among the types of thoracic aneurysms, only infectious (mycotic) aneurysms, posttraumatic pseudoaneurysms, and penetrating atheromatous ulcers are typically saccular, all of which have a propensity for the distal thoracic aorta.
Aneurysms of the proximal portion of the aorta may stretch the aortic ring, resulting in aortic insufficiency (annuloaortic ectasia).
Involvement of the aortic root is typical of MFS, syphilitic aneurysms, noninfectious aortitis, and bicuspid aortic valve disease. In noninflammatory aneurysms, the arch is generally spared, but aneurysms caused by aortitis18 and atherosclerotic aneurysms frequently involve to the arch vessels.
Involvement of the aortic root is typical of MFS, syphilitic aneurysms, noninfectious aortitis, and bicuspid aortic valve disease. In noninflammatory aneurysms, the arch is generally spared, but aneurysms caused by aortitis18 and atherosclerotic aneurysms frequently involve to the arch vessels.
 FIGURE 190.2 ▲ The aneurysm involves the ascending aorta with little involvement of the aortic root, explaining why there was no prior aortic valve insufficiency. (Reproduced with permission from Virmani R, Burke AP, Farb A, et al. Cardiovascular pathology. In: Virmani R, Burke AP, Farb A, et al., eds. Major Problems in Pathology Series. Philadelphia, PA: WB Saunders; 2001;40:489.) |
The adventitial appearance of thoracic aneurysm is generally unremarkable, unless there is rupture without dissection, resulting in soft tissue hemorrhage. The intimal surface may exhibit atherosclerosis or occasionally mural thrombus in the region of the aneurysm.
Histologic Findings
Noninflammatory aortic aneurysms in adults are caused by myriad conditions, which may manifest as many histopathologic patterns, some subtle and others overt. No histopathologic patterns have been shown to exhibit disease specificity, and therefore, correlation with the presentation and clinical setting is paramount.
One of the more common histopathologic manifestations of noninflammatory aortic disease is so-called medial degeneration. This term has replaced legacy terminology such as cystic medial necrosis or cystic medial degeneration, which has largely fallen out of favor given that the observed lesions are neither cystic nor necrotic. Medial degeneration is characterized by an accumulation of basophilic ground substance in the media with areas of elastic fiber dropout19 (Fig. 190.3). The pooling of proteoglycans is accompanied by extensive loss of elastic lamellae and smooth muscle cells. These changes result in the medial weakening that progresses to aneurysm, dissection, or both.
TABLE 190.2 Percent Presence of Histologic Findings in Noninflammatory Aortic Aneurysm, Surgically Resected Specimens, Ascending Aorta4 | ||||||||||||||||||||||||||||||
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