Hypertension Due to an Aneurysm of the Left Renal Artery in a Patient with Neurofibromatosis Gian L u c a Faggioli, MD, Mauro Gargiulo, MD, F. Bertoni, MD* Salvatore Tarantini, MD, Andrea Stella, MD, Bologna, Italy
Arterial lesions in patients with neurofibromatosis are rarely described and in most cases are stenotic. The aneurysmal changes reported in the literature are usually characterized by multiple microaneurysms due to the dysplastic lesions of the artery. We report a case of a single aneurysm of the inferior hilar branch of the left renal artery of a young female with neurofibromatosis° The patient showed hypoperfusion of the renal pole fed by this branch and was hypertensive° The aneurysm had a diameter of 4 cm and showed the histological findings typical of dysplastic lesions of neurofibromatosis. The hypertension and the renal pole hypoperfusion recovered after surgical excision of the aneurysm and end-to-end anastomosis of the hilar branch stumps. (Ann Vasc Surg 1992;6:000-000), KEY WORDS:
Renal artery aneurysm; neurofibromatosis; arterial dysplasia,
N e u r o f i b r o m a t o s i s is a c o m m o n hereditary disease with a f r e q u e n c y of 1:3,000, p r o b a b l y due to a hereditary deficit of the neural crest [I]. According to the organs involved, it is divided in two different forms, classic and central, and can present a variety of clinical aspects. Very rarely does it lead to vascular complications; less than 1% of cases are associated with n e p h r o v a s c u l a r hypertension. E v e n rarer is the p r e s e n c e of an associated dysplasia of the renal and vertebral arteries and of the aorta. L e s s than 100 cases o f renal artery lesions secondary to neurofibromatosis are reported in the literature, m o s t of which are represented by stenotic lesions [2]. The aim of this p a p e r is the report of a case o f a saccular a n e u r y s m of a branch o f the left renal artery in a young female with neurofibroma-
From: Servizio e Cattedra di Chirugia Vascotare, Universitd di Bologna, and the lnstituto di Anatomia e Istologia Patotogica, Ospedate Matpighi*, Bologna, Italy. Reprint requests: Dott. Gian Luca Faggioli, Cattedra di Chirurgia Vascolare, Universit~ Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.
tosis and the discussion of its clinical and therapeutic implications.
CASE REPORT PMG, female, 32 years old. The patient, healthy at birth, does not present inhereditability for neurofibromatosis. The disease was diagnosed at the age of 20, due to the appearance on the skin of various "caf6 au lait" spots and multiple neurofibromas. Height at the end of puberty was 152 cm, weight 45 Kg. These two findings are probably not determined by the disease, but are frequently associated with neurofibromatosis [t]. There were no optical or otological neurofibromas. A mild theta anomaly was revealed by EEG in the right temporal region. The patient was admitted to our department for hypertension (170/110 mmHg), with normal renal function. A bilateral renal scintigraphy showed normal kidneys with hypoperfusion of the inferior left pole with elongation of the transit time. Arteriography showed a saccular aneurysm of the inferior hilum branch of the left renal artery (Fig. 1). This aneurysm appeared to be 4 cm in diameter by computed tomography (Fig. 2). The patient underwent surgery through a left retroperitoneal approach. The renal artery was exposed in its proximal
456
VOLUME 6 N o 5 - 1992
HYPERTENSION
457
Fig. 3. Intraoperative aspect of the aneurysm after surgical dissections. Vessel loops are placed around afferent and efferent branches of the aneurysm,
Fig. 1. Digital subtraction arteriography of the left renal artery: view of the inferior hilar branch aneurysm.
and distal portions and the aneurysm dissected free and excised (Fig. 3). Macroscopically the aneurysm showed a typical saccular aspect with two orifices (afferent and efferent), both with a caliber much smaller than the generating arterial
branch. The excised aneurysm was histologically examined after fixation with t0% formalin. The intima was thickened by a conspicuous hyaline deposition, protruding into the arterial lumen, with no detectable presence of atherosclerotic clefts. The internal elastic lamina was virtually absent, while the remaining media appeared very thin in various areas, with loss of smooth muscle cells, disruption and disappearance of elastic fibers and collagen disorganization. In other areas the structure of the media appeared to be better preserved, with almost normal thickness and regular arrangement of smooth muscle cells and of collagen fibers. The elastic fibers were however fragmented also in these areas. The adventitia was normal (Figs. 4,5). The artery continuity was reestablished by end-to-end anastomosis of the two arterial stumps. The postoperative course was uneventful with improvement of hypertension to 120/90 mmHg without medications. Scintigraphic and arteriographic follow-up at one month showed the renal pole perfusion and patency of the inferior left hilar renal artery.
DISCUSSION
Fig. 2. Abdominal CT scan. Large aneurysm is visualized close to the left renal hilus.
Renal arteries are probably the most frequently diseased vessels in neurofibromatosis according to the data from the literature; their involvement is however very rare. The etiology is probably linked to a congenital defect of chromosome 17 which determines a kind of dysplasia on the arteries very similar to that of the idiopathic forms [2]. Because of these data, the hypothesis that all the dysplastic forms were the result of a genetic defect was formulated. It remains however to be demonstrated. H y p e r t e n s i o n is present in less than 1% o f patients with neurofibromatosis; it could be determined either by an i n v o l v e m e n t of the renal vessels or by a c o n c o m i t a n t p h e o c h r o m o c y t o m a [1--4]. Macroscopically the arterial i n v o l v e m e n t is usually
458
HYPERTENSION
A
ANNALS OF VASCULAR SURGERY
B
Fig. 4 and 5 Histology of the aneurysm wall. intima (I) is diffusely affected by ialine tissue without atherosclerotic signs. Media (M) is thinned and characterized by collagen fibers and smooth muscle cells disorganization, Elastic fibers are disrupted and absent in some points. Adventitia (A) appears to be normal, (Hematoxilin Eosin and Van Gieson stain 25 X and 40 X).
represented by an occlusive lesion. The aneurysmatic lesions are reported as being present more rarely; most of time they are the result of poststenotic dilatation; sometimes they are the distal manifestation of the fibrodysplastic lesion which involves the arterial orifice, with the aspect of multiple microaneurysms [2-11]. The morphological aspect of our case is peculiar and does not allow one to completely define the cause of the hypertension. The renal scintigraphy showed hypoperfusion of the renal pole fed by the aneurysmal branch. It is however unclear what is the precise hemodynamic mechanism which determines the hypoperfusion and the mechanism by which a renal artery aneurysm can cause hypertension. Different hypotheses have been formulated; microembolization from the aneurysm wall, the compression of neighboring arteries, the presence of unrecognized stenoses and the flow redistribution [12,13]. In our case it is possible that the hypoperfusion would have been determined by the particular morphology of the aneurysm in which the
afferent and efferent orifices were extremely reduced in diameter, probably because of the dysplasia. This was the only detectable possible cause of the hypoperfusion of the inferior renal pole seen at scintigraphy. The histological characteristics of the vessels involved by the neurofibromatosis are well described. The most widely reported classification is the one from Reubi with the addition of the Feyrter modification in which 4 classes are identified. The more recent one from Orcel and Chomette is only slightly different (Table I). According to this classification one can assign our case to the intimal aneurysmal form described by Reubi [8]. In fact the hyaline intimal thickening and particularly the loss of media organization with thinning and disappearance of some areas are typical. The diameter of the involved renal artery branch is in the range measure described for this lesion [8,11]. Therefore its peculiarity is not in the histological aspect, but in the macroscopical finding of a single big saccular aneurysm. In these forms, as well as in the pure dysplas-
HYPERTENSION
VOLUME 6 No 5 - 1992
459
TABLE t.--Histoiogical classification of arterial lesions in patients with neurofibromatosis Classification of Reubi and Feyrter (8) Pure intimal form
Classification of Orcel and Chomette (11) Circumscribed
Intimal-aneurysmal form
Diameter 50-400/~m 500-1000/~m
Periarterial nodular form
Nodular
100-700/zm
Epithelioid form
Diffuse
200-700/~m
tic ones, the characteristic finding is that of multiple microaneurysms in correspondence with the minor resistance loci in the media. Probably in this case the area of weakness was unusually wide and allowed the development of a single large aneurysm. This can be determined by the site of the lesion, since the renal bifurcation appears to be structurally poor in elastic fibers, as reported by Stanley who found that more than 3/4 of renal artery aneurysms involve this area [14]. Surgery is indicated in these cases both for the treatment of hypertension and because of the high rupture risk which is determined by the complete lack of supporting structures in the arterial wall, especially in fertile women in whom pregnancy could be an adjunctive risk of rupture [ 12]. As already suggested by others a retroperitoneal access permits an easier dissection of the lesion compared to the traditional anterior laparotomic access [14]. The dissection of the aneurysmal wall is usually facilitated by the spontaneous separation of surrounding veins due to the slow enlargement of the aneurysm [12]. This allowed us to perform an anatomical reconstruction of the artery with no graft interposition, and good perfusion of the ischemic renal pole. REFERENCES 1. RICCARDI VM. Von recklinghausen neurofibromatosis. N Engl J Med t991 "305:1617-1627. 2. CRADDOCK GR, CHALLA VR, DEAN RH. Neurofibromatosis and renal artery stenosis: a case of familiar incidence. J Vasc Surg 1988;8:489-494.
mmm
Histology of lesion Intimal proliferation, medial thinning, normal adventitia Hyaline intimal thickening, elastic disruption and medial loss, normal adventitia Neurofibromatous nodules of 300/~m between media and adventitia, sometimes protruding into the intima Proliferation of fusiform cells throughout the wall
Morphology Stenosis Small aneurysms
Stenosis
Stenosis
3. FRY WJ, ERNST CB, STANLEY JC, et al. Renovascular hypertension in the pediatric patient. Arch Surg 1973;107: 692~o98. 4. BOURKE E, GOTNBY PBB. Renal artery dysplasia with hypertensin in neurofibromatosis. Br Meal J 1971 3:681--682. 5. SALYER WR, SALYER DC. The vascular lesions of neurofibromatosis. Angiology 1974;25:510-519. 6. HALPERN M, CURRARINO G. Vascular lesions causing hypertension in neurofibromatosis. N Engl J M e d 1965;273: 248-252. 7. BLOOR K, WILLIAMS RT. Neurofibromatosis and coarration of the abdominal aorta with renal artery involvement. Br J Surg 1963;50:811-813. 8. REUBI F. Les vaiseeaux et les glandes endocrines dans la neurofibromatose: le syndrome sympathicotonique dans la maladie de recklinghausen. Schweiz Z Pathol Bakteriol 1944;7:168-236. 9. FEYRTER FR. Uber neurome und neurofibromatose, nach untersuchungen am menschlichen mayen-darmschlauch. Wiem Med Wochemschr 1948;98:287-290. 10. GREEN JF, FITZWATER JE, BURGEES J. Arterial lesions associated with neurofibromatosis. A m J Clin Pathol 1974;62:481-487. 11. ORCEL L, CHOMETTE G. Anatomie pathologique vasculaire. Flammarion Medecine-Scinces, Paris 1978. 12. MARTIN RS, MEACHAM PW, DITESHEIM JA, et al. Renal artery aneurysm: selective treatment for hypertension and prevention of rupture, J Vasc Surg 1989;9:26-34. 13. STANLEY JC, RHODES EL, GEWERTZ BL. Renal artery aneurysms: significance of macroaneurysms exclusive of dissections and fibrodysplastic mural dilatations. Arch Surg 1975;110:1327-1333. 14. STANLEY JC. Discussion of MARTIN RS, MEACHAM PW, DITESHEIM JA, et al. Renal artery aneurysm: selective treatment for hypertension and prevention of rupture. J Vasc Surg 1989;9:34.
Arterial lesions in patients with neurofibromatosis are rarely described and in most cases are stenotic. The aneurysmal changes reported in the literature are usually characterized by multiple microaneurysms due to the dysplastic lesions of the artery. We report a case of a single aneurysm of the inferior hilar branch of the left renal artery of a young female with neurofibromatosis° The patient showed hypoperfusion of the renal pole fed by this branch and was hypertensive° The aneurysm had a diameter of 4 cm and showed the histological findings typical of dysplastic lesions of neurofibromatosis. The hypertension and the renal pole hypoperfusion recovered after surgical excision of the aneurysm and end-to-end anastomosis of the hilar branch stumps. (Ann Vasc Surg 1992;6:000-000), KEY WORDS:
Renal artery aneurysm; neurofibromatosis; arterial dysplasia,
N e u r o f i b r o m a t o s i s is a c o m m o n hereditary disease with a f r e q u e n c y of 1:3,000, p r o b a b l y due to a hereditary deficit of the neural crest [I]. According to the organs involved, it is divided in two different forms, classic and central, and can present a variety of clinical aspects. Very rarely does it lead to vascular complications; less than 1% of cases are associated with n e p h r o v a s c u l a r hypertension. E v e n rarer is the p r e s e n c e of an associated dysplasia of the renal and vertebral arteries and of the aorta. L e s s than 100 cases o f renal artery lesions secondary to neurofibromatosis are reported in the literature, m o s t of which are represented by stenotic lesions [2]. The aim of this p a p e r is the report of a case o f a saccular a n e u r y s m of a branch o f the left renal artery in a young female with neurofibroma-
From: Servizio e Cattedra di Chirugia Vascotare, Universitd di Bologna, and the lnstituto di Anatomia e Istologia Patotogica, Ospedate Matpighi*, Bologna, Italy. Reprint requests: Dott. Gian Luca Faggioli, Cattedra di Chirurgia Vascolare, Universit~ Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy.
tosis and the discussion of its clinical and therapeutic implications.
CASE REPORT PMG, female, 32 years old. The patient, healthy at birth, does not present inhereditability for neurofibromatosis. The disease was diagnosed at the age of 20, due to the appearance on the skin of various "caf6 au lait" spots and multiple neurofibromas. Height at the end of puberty was 152 cm, weight 45 Kg. These two findings are probably not determined by the disease, but are frequently associated with neurofibromatosis [t]. There were no optical or otological neurofibromas. A mild theta anomaly was revealed by EEG in the right temporal region. The patient was admitted to our department for hypertension (170/110 mmHg), with normal renal function. A bilateral renal scintigraphy showed normal kidneys with hypoperfusion of the inferior left pole with elongation of the transit time. Arteriography showed a saccular aneurysm of the inferior hilum branch of the left renal artery (Fig. 1). This aneurysm appeared to be 4 cm in diameter by computed tomography (Fig. 2). The patient underwent surgery through a left retroperitoneal approach. The renal artery was exposed in its proximal
456
VOLUME 6 N o 5 - 1992
HYPERTENSION
457
Fig. 3. Intraoperative aspect of the aneurysm after surgical dissections. Vessel loops are placed around afferent and efferent branches of the aneurysm,
Fig. 1. Digital subtraction arteriography of the left renal artery: view of the inferior hilar branch aneurysm.
and distal portions and the aneurysm dissected free and excised (Fig. 3). Macroscopically the aneurysm showed a typical saccular aspect with two orifices (afferent and efferent), both with a caliber much smaller than the generating arterial
branch. The excised aneurysm was histologically examined after fixation with t0% formalin. The intima was thickened by a conspicuous hyaline deposition, protruding into the arterial lumen, with no detectable presence of atherosclerotic clefts. The internal elastic lamina was virtually absent, while the remaining media appeared very thin in various areas, with loss of smooth muscle cells, disruption and disappearance of elastic fibers and collagen disorganization. In other areas the structure of the media appeared to be better preserved, with almost normal thickness and regular arrangement of smooth muscle cells and of collagen fibers. The elastic fibers were however fragmented also in these areas. The adventitia was normal (Figs. 4,5). The artery continuity was reestablished by end-to-end anastomosis of the two arterial stumps. The postoperative course was uneventful with improvement of hypertension to 120/90 mmHg without medications. Scintigraphic and arteriographic follow-up at one month showed the renal pole perfusion and patency of the inferior left hilar renal artery.
DISCUSSION
Fig. 2. Abdominal CT scan. Large aneurysm is visualized close to the left renal hilus.
Renal arteries are probably the most frequently diseased vessels in neurofibromatosis according to the data from the literature; their involvement is however very rare. The etiology is probably linked to a congenital defect of chromosome 17 which determines a kind of dysplasia on the arteries very similar to that of the idiopathic forms [2]. Because of these data, the hypothesis that all the dysplastic forms were the result of a genetic defect was formulated. It remains however to be demonstrated. H y p e r t e n s i o n is present in less than 1% o f patients with neurofibromatosis; it could be determined either by an i n v o l v e m e n t of the renal vessels or by a c o n c o m i t a n t p h e o c h r o m o c y t o m a [1--4]. Macroscopically the arterial i n v o l v e m e n t is usually
458
HYPERTENSION
A
ANNALS OF VASCULAR SURGERY
B
Fig. 4 and 5 Histology of the aneurysm wall. intima (I) is diffusely affected by ialine tissue without atherosclerotic signs. Media (M) is thinned and characterized by collagen fibers and smooth muscle cells disorganization, Elastic fibers are disrupted and absent in some points. Adventitia (A) appears to be normal, (Hematoxilin Eosin and Van Gieson stain 25 X and 40 X).
represented by an occlusive lesion. The aneurysmatic lesions are reported as being present more rarely; most of time they are the result of poststenotic dilatation; sometimes they are the distal manifestation of the fibrodysplastic lesion which involves the arterial orifice, with the aspect of multiple microaneurysms [2-11]. The morphological aspect of our case is peculiar and does not allow one to completely define the cause of the hypertension. The renal scintigraphy showed hypoperfusion of the renal pole fed by the aneurysmal branch. It is however unclear what is the precise hemodynamic mechanism which determines the hypoperfusion and the mechanism by which a renal artery aneurysm can cause hypertension. Different hypotheses have been formulated; microembolization from the aneurysm wall, the compression of neighboring arteries, the presence of unrecognized stenoses and the flow redistribution [12,13]. In our case it is possible that the hypoperfusion would have been determined by the particular morphology of the aneurysm in which the
afferent and efferent orifices were extremely reduced in diameter, probably because of the dysplasia. This was the only detectable possible cause of the hypoperfusion of the inferior renal pole seen at scintigraphy. The histological characteristics of the vessels involved by the neurofibromatosis are well described. The most widely reported classification is the one from Reubi with the addition of the Feyrter modification in which 4 classes are identified. The more recent one from Orcel and Chomette is only slightly different (Table I). According to this classification one can assign our case to the intimal aneurysmal form described by Reubi [8]. In fact the hyaline intimal thickening and particularly the loss of media organization with thinning and disappearance of some areas are typical. The diameter of the involved renal artery branch is in the range measure described for this lesion [8,11]. Therefore its peculiarity is not in the histological aspect, but in the macroscopical finding of a single big saccular aneurysm. In these forms, as well as in the pure dysplas-
HYPERTENSION
VOLUME 6 No 5 - 1992
459
TABLE t.--Histoiogical classification of arterial lesions in patients with neurofibromatosis Classification of Reubi and Feyrter (8) Pure intimal form
Classification of Orcel and Chomette (11) Circumscribed
Intimal-aneurysmal form
Diameter 50-400/~m 500-1000/~m
Periarterial nodular form
Nodular
100-700/zm
Epithelioid form
Diffuse
200-700/~m
tic ones, the characteristic finding is that of multiple microaneurysms in correspondence with the minor resistance loci in the media. Probably in this case the area of weakness was unusually wide and allowed the development of a single large aneurysm. This can be determined by the site of the lesion, since the renal bifurcation appears to be structurally poor in elastic fibers, as reported by Stanley who found that more than 3/4 of renal artery aneurysms involve this area [14]. Surgery is indicated in these cases both for the treatment of hypertension and because of the high rupture risk which is determined by the complete lack of supporting structures in the arterial wall, especially in fertile women in whom pregnancy could be an adjunctive risk of rupture [ 12]. As already suggested by others a retroperitoneal access permits an easier dissection of the lesion compared to the traditional anterior laparotomic access [14]. The dissection of the aneurysmal wall is usually facilitated by the spontaneous separation of surrounding veins due to the slow enlargement of the aneurysm [12]. This allowed us to perform an anatomical reconstruction of the artery with no graft interposition, and good perfusion of the ischemic renal pole. REFERENCES 1. RICCARDI VM. Von recklinghausen neurofibromatosis. N Engl J Med t991 "305:1617-1627. 2. CRADDOCK GR, CHALLA VR, DEAN RH. Neurofibromatosis and renal artery stenosis: a case of familiar incidence. J Vasc Surg 1988;8:489-494.
mmm
Histology of lesion Intimal proliferation, medial thinning, normal adventitia Hyaline intimal thickening, elastic disruption and medial loss, normal adventitia Neurofibromatous nodules of 300/~m between media and adventitia, sometimes protruding into the intima Proliferation of fusiform cells throughout the wall
Morphology Stenosis Small aneurysms
Stenosis
Stenosis
3. FRY WJ, ERNST CB, STANLEY JC, et al. Renovascular hypertension in the pediatric patient. Arch Surg 1973;107: 692~o98. 4. BOURKE E, GOTNBY PBB. Renal artery dysplasia with hypertensin in neurofibromatosis. Br Meal J 1971 3:681--682. 5. SALYER WR, SALYER DC. The vascular lesions of neurofibromatosis. Angiology 1974;25:510-519. 6. HALPERN M, CURRARINO G. Vascular lesions causing hypertension in neurofibromatosis. N Engl J M e d 1965;273: 248-252. 7. BLOOR K, WILLIAMS RT. Neurofibromatosis and coarration of the abdominal aorta with renal artery involvement. Br J Surg 1963;50:811-813. 8. REUBI F. Les vaiseeaux et les glandes endocrines dans la neurofibromatose: le syndrome sympathicotonique dans la maladie de recklinghausen. Schweiz Z Pathol Bakteriol 1944;7:168-236. 9. FEYRTER FR. Uber neurome und neurofibromatose, nach untersuchungen am menschlichen mayen-darmschlauch. Wiem Med Wochemschr 1948;98:287-290. 10. GREEN JF, FITZWATER JE, BURGEES J. Arterial lesions associated with neurofibromatosis. A m J Clin Pathol 1974;62:481-487. 11. ORCEL L, CHOMETTE G. Anatomie pathologique vasculaire. Flammarion Medecine-Scinces, Paris 1978. 12. MARTIN RS, MEACHAM PW, DITESHEIM JA, et al. Renal artery aneurysm: selective treatment for hypertension and prevention of rupture, J Vasc Surg 1989;9:26-34. 13. STANLEY JC, RHODES EL, GEWERTZ BL. Renal artery aneurysms: significance of macroaneurysms exclusive of dissections and fibrodysplastic mural dilatations. Arch Surg 1975;110:1327-1333. 14. STANLEY JC. Discussion of MARTIN RS, MEACHAM PW, DITESHEIM JA, et al. Renal artery aneurysm: selective treatment for hypertension and prevention of rupture. J Vasc Surg 1989;9:34.
