Arch Orthop Trauma Surg (1998) 117:110-113

© Springer-Verlag 1998

S. S a i t o h • S. M a t s u d a

Aneurysm of the major vessels in neurofibromatosis

Received: 14 June 1994

A b s t r a c t The case of a patient who presented with a ruptured a n e u r y s m of the brachial artery and type I neurofibromatosis is presented. A n g i o g r a p h y revealed a ruptured a n e u r y s m of the brachial artery in the middle of the upper arm. Repair of the artery with autogenous vein grafting was impossible due to the extremely brittle brachial artery and a c c o m p a n y i n g veins. The blood supply distal to the a n e u r y s m was secured by collaterals, and the aneurysm, including a relatively long portion of the brachial artery and veins adjacent to the aneurysm, was resected. The patient died of massive hemorrhage from the subclavian artery of the i n v o l v e d side 9 days postoperatively. Histological and i m m u n o h i s t o l o g i c a l e x a m i n a t i o n s of the tissues i n v o l v e d in the ruptured a n e u r y s m were conducted. The resected brachial artery and veins were surrounded by hypertrophied tissue which tested positive for S-100 protein and negative for d e s m i n and action. These findings suggest that the origin of the proliferating tissue was not m e s o d e r m a l dysplasia, but n e u r o f i b r o m a occurring near or in the vessels. A ruptured a n e u r y s m in a patient with neurofibromatosis should not be treated with reconstruction of the vessels. The treatment of choice is surgical or e n d o v a s c u l a r occlusion of the vessels involved.

Introduction Neurofibromatosis or von Recklinghausen disease exhibits a wide spectrum of complications i n v o l v i n g long bones, vertebrae, skin, and soft tissue. Occlusive or a n e u r y s m a l vascular i n v o l v e m e n t m a y occur, and cases of renovascular hypertension and intra- and extracranial aneurysms have been reported to date. Extracranial aneurysms m a y occur in the carotid, vertebral, coronary, and mesenteric arteries, and occasionally in the p a r e n c h y m a of the kid-

S. Saitoh (5:~) - S. Matsuda Department of Orthopaedics, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto City, 390 Japan

hey. Cases of aneurysms occurring in patients with neurofibromatosis have not been reported in the orthopedic literature. Recently, a patient with neurofibromatosis type I presented to our clinic with a ruptured a n e u r y s m of the brachial artery. Reconstruction of the brachial artery by vein grafting was attempted, but was complicated by the poor condition of the affected vessels. The blood supply distal to the a n e u r y s m was secured by collaterals, and the aneurysm, including a relatively long portion of the brachial artery and veins adjacent to the aneurysm, was resected. These resected specimens were e x a m i n e d histologically and i m m u n o h i s t o l o g i c a l l y to determine the cause the aneurysm.

Case report A 28-year-old woman with multiple cafe-au-lait spots, freckling on the inguinal region, and multiple subcutaneous tumors on the trunk and extremities including the left upper arm was seen at our clinic. She presented with four of the seven criteria for neurofibromatosis type I, as defined by the National Institute of Health at the consensus develoment conference on neurofibromatosis in 1987 [1]. Her father and sister also exhibited characteristics of neurofibromatosis. The patient had previously undergone an anterior body fusion from the fourth cervical to second thoracic vertebra for scoliosis at the age of 21. At presentation, the patient explained that she fell on April 26, 1993, while walking. Four days after the injury she felt a sudden pain in her left upper arm while turning the driving wheel of her car. She also noted swelling in the region. On preliminary examination, her left upper arm was markedly swollen and tender. Pulsation of the radial artery was palpable at the wrist, and no neurological abnormalities except a slight weakness of elbow flexion were demonstrated. Based on these findings, she was treated as an outpatient for swelling. Three days following our initial examination, the patient presented with the complaint that she had experienced several episodes of extreme pain in the left upper arm. Swelling of the upper arm increased with each episode. Upon examination, it was found that pulsation of the radial artery at the wrist was very weak, and numbness in the median nerve area was present. Angiography revealed a ruptured aneurysm of the brachial artery in the middle of the upper arm. The deep brachial artery as a collateral extended distally while giving off some branches at the elbow which filled

111 The tissue at the aneurysm exhibited massive bleeding, numerous small vessels, and proliferating tumor cells. The proliferating tissue was morphologically compatible with neurofibroma (Fig.2). It tested positive for S-100 protein (Fig. 3) but negative for desmin or actin. The brachial artery immediately proximal to the aneurysm was surrounded by tissue with the same morphological characteristics as those of the tissue found at the aneurysm (Fig.4a). This proliferating tissue substituted the adventitia of the artery and was positive for S100 protein (Fig.4b), but negative for actin (Fig. 4c) and desmin (not shown). These findings identified the tissue around the brachial artery as immunohistologically identical to the tumorous tissue at the site of aneurysm. This same tissue also surrounded the brachial vein (Fig. 5).

Discussion

Fig. 1 Angiography of the left brachial artery showing a large aneurysm in the middle of the upper arm the brachial artery distal to the aneurysm in retrograde fashion. An irregularity was seen on the column of contrast medium in the brachial artery proximal to the aneurysm (Fig. 1). The patient was admitted for reconstruction of the brachial artery with autogenous vein grafting. At surgery, we found that the subcutaneous and subfascial space of the upper arm was filled with clot, and both the brachial artery and its accompanying veins were extremely brittle proximal and distal to the aneurysm. Massive oozing occurred with each stroke of dissection. Reconstruction of the brachial artery by vein grafting was abandoned, and the aneurysm together with the brachial artery and veins was resected after ligating the vessels proximal and distal to the aneurysm. The postoperative course was uneventful for the first 8 days. Suddenly, on the ninth day postoperatively, the patient convulsed and lost consciousness. Her blood pressure was unmeasurably low, and a hard mass was noted in her left supraclavicular fossa. Bleeding from the left subclavian artery proximal to the ligation of the brachial artery appeared to be the cause of the hypotension. The patient did not recover.

Results Hematoxylin and eosin staining and immunohistological studies using antibodies for desmin (Bio-Science Products, Switzerland), actin (HHF35, DAKO, Ca., USA), and S-100 protein (DAKO, Denmark) were done to determine the characteristics of the proliferating tissue at the aneurysm and around the vessels. The studies were carried out on the vessels obtained at the time of surgery since an autopsy was not performed.

The association of aneurysms with type I neurofibromatosis has been documented. However, the difficulty in obtaining specimens of the aneurysm and affected vessels has limited the determination of the pathomechanism of aneurysm formation. Some reports have stated that tumorous tissue could not be found around the aneurysm [3, 4, 8]. Also, in cases where tumorous cells were found at the aneurysm, controversy exists as to the origin of the ceils. While some authors proposed that the cause of the aneurysm was mesodermal dysplasia [5], others claimed that neurofibroma involvement adjacent to the vessel was responsible for the aneurysm formation. Tumorous tissue was found in our case of a ruptured aneurysm at both the aneurysm and the adjacent brachial artery and veins. This finding is similar to that reported by Tapp and Hickling [9] in 1969 in a neurofibromatosis patient with a ruptured renal artery. The proliferating tissue at the aneurysm and around the brachial artery and veins proximal to the aneurysm demonstrated characteristics compatible with neurofibroma in our histological and immunohistological examinations. The tissue tested positive for S-100 protein and negative for desmin or actin, which are smooth muscle markers. The results of these studies suggest that the origin of the hypertrophied tissue is neurofibroma near the involved vessels rather than mesodermal dysplasia as suggested by Malecha and Rubin [5] in 1992. Although it has been considered that vascular integrity in neurofibromatosis is not severely affected compared with Ehlers-Danlos syndrome type IV, both the brachial artery and veins bled easily in our patient. Reasons for the excessive bleeding are twofold: the vessels were extremely brittle as a result of tumor invasion, and the hypertrophied tissue was rich in small vessels. Based on these findings, we have concluded that the treatment of an aneurysm associated with neurofibromatosis should not be resection and reconstruction of the affected vessel by autogenous vein grafting. Surgical occlusion of aneurysms by direct ligation or clipping may be

112

Fig.3 Proliferating tissue at the aneurysm immunohistologically stained for S-100 protein, showing a positive result. The staining is located mainly at the nuclei. Calibration bar indicates 30 btm

indicate 200 btm. b Left brachial artery stained for S-100 protein. The proliferating tissue around the artery, replacing the adventitia and surrounding the entire media of the brachial artery, is positive for S-100 protein, c Left brachial artery stained immunohistologically for actin. The proliferating tissue surrounding the media is negative for actin. The actin-positive tissue is the original media of the artery. Arrows indicate outer margin of the tissue

Fig.4 a Left brachial artery adjacent to the aneurysm. The adventitia of the artery is substituted by a proliferating tissue which has the same characteristics as those of the tissue seen at the aneurysm as well as around the brachial veins. H&E stain; calibration bars

Fig. 5 Left brachial vein is surrounded by a tissue which is rich in small vessels. The proliferating tissue is morphologically identical to that seen at the aneurysm and around the brachial artery adjacent to the aneurysm. H & E stain

Fig.2 Proliferating tissue at the aneurysm. The proliferating cells have a wavy profile with spindle or star-shaped nuclei. H & E staining; calibration bar indicates 30 g m

113 considered [7]. High rates of morbidity and mortality have, however, b e e n reported with the procedure [2]. Endovascular occlusion by Sponzel and spring coil [10] or detachable balloons [2, 6] m a y be r e c o m m e n d e d if the circulation distal to the a n e u r y s m has been secured by collateral vessels. Acknowledgements Our thanks go to Dr. Touru Ichikawa and his staff in Central Clinical Laboratories, Shinshu University Hospital, for their help in preparing the specimens for histological and immunohistological examination.

References 1. Crawford AH (1990) Neurofibromatosis. In: Morrissy RT (ed) Lovell and Winter's pediatric orthopaedics, 3rd edn. JB Lippincott, Philadelphia, pp 175-201 2. Detwiler K, Godersky JC, Gentry L (1987) Pseudoaneurysm of the extracranial vertebral artery. Case report. J Neurosurg 67: 935-939 3. Hardy DG, Hately W, Newton JR, Dathan JRE, Blandy JP, Eadie DGA, Goodwin FJ (1975) Hypertension and renal artery stenosis with aneurysm formation in a solitary kidney in a patient with neurofibromatosis. Br J Urol 47:137-144

4. Kuo J, Okada Y, Takeuchi H, Yoshida O, Suzuki H, Kim YC (1989) Neurofibromatosis associated with renovascular hypertension due to stenosis and aneurysm of the left renal segmental artery: report of a case. Urol Int 44:177-180 5. Malecha MJ, Rubin R (1992) Aneurysms of the carotid arteries associated with von Recklinghausen's neurofibromatosis. Pathol Res Pract 188:145-147 6. Negoro M, Nakaya T, Terashima K, Sugita K (1990) Extracranial vertebral artery aneurysm with neurofibromatosis. Neuroradiology 31 : 533-536 7. Schubiger O, Yasargil MG (1978) Extracranial vertebral aneurysm with neurofibromatosis. Neuroradiology 15:171-173 8. Sobata E, Ohkuma H, Suzuki S (1988) Cerebrovascular disorders associated with yon Recklinghansen's neurofibroamtosis: a case report. Neurosurgery 22 : 544-549 9. Tapp E, Hickling RS (1969) Renal artery rupture in a pregnant woman with neurofibromatosis. J Pathol 97 : 398-402 10.Tsuha M, Kashiwagi S, Katoh S, Wakuta Y, Aoki H (1988) Traumatic arterio-venous fistula with false aneurysm in neurofibromatosis. Neuroradiology 30 : 88-89