Case 4 -

Arterial Aneurysms Associated with α-1-antitrypsin Deficiency Metastatic Lymphoma in Aneurysm Alan G. Rose

Clinical History The patient was a 48-year-old male with α-1-antitrypsin deficiency (AATD) who underwent a right single lung transplant for emphysema in 1991. Cholecystectomy was performed in 1997, but RUQ pain continued postoperatively. Radiology showed a 4 cm diameter right intercostal artery aneurysm and a 2.5 cm diameter left intercostal aneurysm. Embolization of the right-sided aneurysm was performed in 1997. Family history: his brother had undergone a lung transplant for AATD and his son had AATD. In November 1999, he developed a pleural effusion and a drop in hemoglobin due to bleeding from an intercostal aneurysm. The main aneurysm was found on the 9th intercostal artery. Microcoils were placed in the T6-10 intercostal arteries with good hemostasis for 2 days, followed by hemoptysis due to rupture into the left lung by one of multiple intercostal arterial aneurysms. A drop in blood pressure accompanied the enlarging pleural effusion, which was consistent with hemorrhage. A cardiovascular radiologist embolized the T8-10 intercostal arteries and achieved good hemostasis. Patient underwent emergency thoracotomy for evacuation of the hematoma, left pneumonectomy and resection of T7-10 intercostal aneurysms. An Aspergillus flavus pneumonia plus a Mycobacterium avium intracellulare infection in the transplanted right lung complicated his postoperative course. He subsequently developed a gastrointestinal bleed. Laparotomy revealed a post-transplant, jejunal, high-grade large cell B-cell lymphoma, which had spread to the liver. He received one treatment with Rituximab (monoclonal antibody, usually used to treat low grade lymphoma, but patient could not tolerate more aggressive therapy). Death was due to severe sepsis syndrome with lactic acidosis and multiorgan failure. The aneurysm in the section used in this seminar was found at autopsy in the right thoracic paravertebral region and measured 2 X 2 X 1.5 cm. The appearance is that of a fibrous walled, thrombus lined false aneurysm with compression of adjacent veins and arteries. A muscular artery opens into the aneurysm obliquely at one level. Dystrophic calcification is noted in the fibrous wall of the false aneurysm in areas. There are no specific histologic features that allow one to recognize the aneurysm as being related to an AATD. Not present in the original slides, but evident in the seminar slides was a small focus of metastatic lymphoma in the aneurysm. Comment: The balance between proteinases and their inhibitors is important in maintaining structural integrity of connective tissues, including the arterial wall. Elevated serum elastase level is a possible marker serum marker of patients with a high risk of aneurysm formation. Possibly, the heterozygous and the homozygous AAT deficiency states are genetic risk factors that could predispose to aneurysm formation. [1] Coronary arterial [2]and intracranial [3] arterial dissections have been described in association with AATD. Fibromuscular dysplasia of the internal carotid artery has been associated with a heterozygous alpha-1-antitrypsin deficiency. [4] A patient with AATD who had a carotid artery dissection associated with multiple aneurysmal dilatations has been reported. [5] It has been suggested that high plasma elastase levels may play a role in the systemic arterial elastin degradation seen in patients with intracranial aneurysms. [6] AATD has also been associated with both intracranial aneurysms and cervical artery dissections. [7] Schievink et al. [8] reported a ruptured giant intracranial aneurysm in a girl with AATD. AATD has been associated with the development of aneurysms of the mesenteric and the splenic arteries. [9, 10, 11] and with iliac artery dissection. [12] The association between AATD and abdominal atherosclerotic aneurysms (AAA) is less clear. A number of reports have been equivocal or negative in this regard. [13, 14, 15, 16] However, others have suggested a possible link between AATD and AAA development. [17, 18, 19, 20] Cohen et al. [21] point out that the elastase in the aorta of patients with AAA has the exact properties of the serine elastase found in the smooth muscle cells of the aorta in rats. AAT plays a critical role in determining functional elastase activity. Smooth muscle cell regulation of elastin metabolism may be important in determining why some patients have AAA and others develop occlusive arterial disease. Whilst the above reports have all attributed aneurysm development to alterations in serum elastase activity due to AATD or other causes, Mazodier et al. [22] have attributed systemic necrotizing vasculitides to severe AATD. Of the 8 patients in this Swedish series, 6 had systemic vasculitis of the microscopic polyangiitis form, one had Wegener's granulomatosis and another had Henoch-Schonlein purpura. They also reviewed 6 additional cases in the literature. A lot is still not known about the range of vascular disease attributable to AATD. Other Causes of Intercostal Arterial Aneurysms A. Coarctation of the aorta Aneurysms of the intercostal arteries are very rare and are most often associated with congenital coarctation of the aorta. Aneurysms of the aorta may also occur in coarctation of the aorta and are situated immediately distal or proximal to the coarctation in patients as young as 5 years of age. B. Polyarteritis nodosa Any form of arteritis may affect the intercostal arteries. Such involvement is often overlooked since the intercostal arteries are not routinely examined at autopsy. Table 1: List of Arterial Aneurysms [23] Aneurysms of Medium-sized and Peripheral Arteries Berry aneurysm Mycotic aneurysm Atherosclerotic aneurysm Polyarteritis nodosa Fibromuscular dysplasia Neurofibromatosis Traumatic aneurysms (true / false) Other Arterial Aneurysms Large arteries Complete dissecting aneurysm Incomplete dissecting aneurysm yielding saccular aneurysm Syphilis Congenital aneurysm (sinus of Valsalva) Idiopathic aortitis (Takayasu's, ? other) Microaneurysms Charcot-Bouchard aneurysm (? kinked artery) Diabetes mellitus Cerebral amyloid angiopathy Table 2: Causes of Coronary Arterial Aneurysms (Adapted From [24]) Congenital Atherosclerotic Infectious Mycotic Infective endocarditis Trauma, including percutaneous transluminal coronary angioplasty Connective tissue disorders Marfan syndrome Ehlers-Danlos syndrome Vasculitides Kawasaki syndrome Takayasu arteritis Polyarteritis nodosa Systemic lupus erythematosus Miscellaneous Osler-Rendu-Weber disease Metastatic tumor Aneurysms of the Splenic Artery While arterial aneurysms in general (Table 1) are more common in males (by a ratio of 5 to 1), splenic artery aneurysms are more frequent in females (3 to 1). The female patients tend to be young. The etiology of 50% of the splenic artery aneurysms is attributed to atherosclerosis, while 10 to 30% are regarded as congenital in origin. Mycotic or dissecting aneurysms are each present in 5% of patients. The aneurysms tend to rupture during pregnancy for some unknown reason. The arterial media in such cases shows reticulin fiber fragmentation, decreased acid mucopolysaccharides, and hypertrophy plus hyperplasia of smooth muscle cells. References Lisowska-Myjak B. Elastase imbalance alpha-1-antitrypsin in aneurysm. Neurol Neurochir Pol 1999; 33:143-149. Martin D M, Delgado PM, Garcia RM, Gonzalez GJ, Puig RAM, Lopez PR, Carbajo VM. Coronary artery dissection in alpha-1-antitrypsin deficiency. Histopathology 1999; 34: 376-378. Schievink WI, Katzmann JA, Piepgras DG. Alpha-1-antitrypsin deficiency in spontaneous intracranial arterial dissections. Cerebrovasc Dis 1998; 8: 42-44. Schievink WI, Meyer FB, Parisi JE, Wijdicks EF. 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