Turkis/i NeuroSllrgery 10: 135 - 141, 2000 KILtln!!: VHLS & ScliwnllllOllln

Sciatic Nerve Schwannoma in a Patient With Von Hippel­Lindau Syndrome: Case Report and Literature Review

hastada Siyatik SinirGözden Geçirilmesi

Von Hippel-Lindau Sendromlu BirSchwannomu: Olgu Sunumu ve Literatürün

MURA T KUTLAY, AHMET ÇOLAK, NUSRET DEMIRCAN, OSMAN N IYAZI AKIN

Gülhane Military Medical Academy, Haydarpasa Training Hospital, Department ofNeurosurgery (MK,AÇ,ND,ONA), Istanbul, Türkiye

Received: 22.10.1998 ~ Accepted: 11.1.1999

Abstract: Radiological examinations of a 21-year-old manwith headache and gait abnormality revealedhemangioblastomas in both cerebellar hemispheres andin the cervical spinal cord. There were also other findingsconsistent with the diagnosis of von Hippel-Lindausyndrome (VHLS), but no retinal hemangioblastomas weredetected. The patient underwent bilateral suboccipitalcraniectomy for removal of the cerebellar tumorso Threemonths after this surgery, a C6 laminectomy wasperformed and the cervical hemangioblastoma was alsototally excised. In the immediate postoperative period, thepatient developed motor weakness and radiating pain inhis right leg. Physical examination and a computerizedtomography sean revealed a well-circumscribed solid massin his right posterior thigh, which was thought to be sciaticnerve tumor. A third operation was done to totally excisethis mass. Histological examination identified theneoplasm as a schwannoma. Although we considered thepres ence of a sciatic nerve schwannoma in this patient tobe coincidental, we believe that maintaining a high indexof suspicion for clinically silent peripheral nerve sheathtumors in individuals with VHLS may reveal that thesemasses are yet another manifestation of this syndrome.Aiready more than 30 lesions characteristic of thiscondition have been described to da te. This is the firstreported case of VHLS accompanied by a pe~ipheral nervesheath tumor.

Özet: Bas agrisi ve yürüme güçlügü olan 21 yasindaki birerkek hastada radyolojik incelemeler sonucu her ikiserebellar hemisferde ve servikal spinal korddahemanjioblastomlar saptandi. Retinal hemanjioblastomhariç, von Hippel-Lindau sendromunun (VHLS) digerbulgulari da mevcuttu. Bilateral suboccir.ital kraniotomiyapilarak serebellar tümörler çikarildi. Uç ay sonra, C6laminektomi yapilarak servikal yerlesimlihemanjioblastomda tam olarak çikarildi. Hastadapostoperatif erken dönemde sag bacaga yayilan agri vegüçsüzlük gelisti. Fizik muayene ve bilgisayarlitomografide, sag uyluk arkasinda, siyatik sinir tümörüoldugu düsünülen iyi sinirli bir kitle saptandi. Üçüncübir operasyonla kitle tam olarak çikarildi. Histolojikincelemede kitlenin schwannoma oldugu saptandi. Herne kadar bu hastadaki siyatik sinir schwannom varligininrastlantisaloldugu düsünülse de, VHLS mevcut kisilerde,klinik olarak sessiz periferik sinir kilifi tümörlerininolabileceginin akilda tutulmasinin, bu sendromun yenibir seklini ortaya çikarabilecegini düsünüyoruz. Çünkübugüne kadar, bu sendromun 30' dan fazla farkli klinikdurumu tanimlanmistir. Bu olgu VHLS ile birlikte olanilk periferik sinir tümör olgusudur.

Key words: Hemangioblastoma, peripheral nerveschwannoma, von Hippel-Lindau syndrome

Anahtar kelimeler: Hemanjioblastoma, periferik sinirschwannomu, von Hippel-Lindau sendromu

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INTRODUCTION

Hemangioblastomas are uncommon neoplasmsthat represent only 1.5% to 2.5% of aii intracranialtumors (4,7,19,22,25). AIthough one report hasdocumented subarachnoid spread ofhemangioblastoma in two patients (17), these vascularneoplasms are almost always histologicaiiy benign, andusuaiiy arise in the posterior cranial fossa (7,20,22).Hemangioblastomas typically arise in the third throughfifth decades of life, and there is a slight predominancein males (7,22). There is a strong association betweenhemangioblastoma and von Hippel-lindau syndrome(VHlS), an autosomal dominant disorder with partial

Kutlny: VHLS & SC/iWIlIIIIOllln

penetrance that is characterized by cerebellar, spinalcord and retinal hemangioblastomas.

Approximately 20% of aii hemangioblastomasoccur in association with VHlS (7,20,25). Individuals

with this syndrome are at risk of developing a varietyof lesions, including cysts or tumors of the kidney,pancreas, liver, adrenal gland and epididymis, inaddition to pheochromocytoma (2,4,5,7,9,10,12,13,20­23,24). In this report, we present the case of a VHLSpatientwho had hemangioblastomas in thecerebeiiumand spinal cord, cysts in both kidneys and in thepancreas, erythrocytosis and schwannoma. Ourliteratlire search indicated that this is the first report ofa peripheral nerve sheath tumor in a patient withVHlS.

CASE REPORT

A 21-year-old man was admitted to our centerwith severe headache and gait distlirbance of 2 weeks'duration. Physical examination revealed bilateralpapilledema, mild disorientation, ataxia, dysmetria,intention tremor and stance-dysequilibrium. Thepatient's white blood ceii count, platelet count andplasma volume were normal, but his packed ceiivolume and blood hemoglobin concentration wereboth markedly elevated. These findings indicatedsignificant erythrocytosis. Urinalysis and renal function

Figure 1:Radiologic results prior to the first operation: A gadolinium-enhanced Tl- weighted MR image (axial image) (A)and right vertebral angiography (lateral view) (B), reveal findings typical of cerebellar hemangioblastoma. Inaddition, a I-I weighted MR image (sagittal plane) shows syringobulbia and a multilocular syrinx (C). Ihere wasno communication between the syringobulbia and the fourth ventricle.

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were normaL. Contrast-enhanced computerizedtomography (CT) scans demonstrated two cysticlesions with hyperdense mural nodules in thecerebellum, as well as a separate, noncystic,hyperdense nodule. There was no enhancement at thecyst margins. Magnetic resonance imaging (MR!)demonstrated smooth and sharply defined cystborders. The mural nodules were isointense on T1­

weighted images, and were hyperintense on T2­weighted images. Intravenous administration ofgadolinium 100 to intense enhancement of the muralnodules. We alsa noted longitudinal syringobulbia andsyringomyelia. Vertebral angiography showOOthat twoof the nodules were highly vascular (Figure I-A,B,C).

When the patient developed depressed mentalstatus, we immediately performed bilateralsuboccipital craniedomy. At surgery, we noted thatthe cyst fluid was xanthochromic. We removed bothmural nodules. Duraplasty involved the use of asurgical membrane constructed of expandedpolytetrafluoroethylene (Gore-Tex, W.L. Gore &Associates, Arizona, USA).The patient' s postoperative

Kiiliay: VHLS & ScJiwallllOllia

course was uneventfuI. Histological analysis of theremoved tissue was consistent withhemangioblastoma, as indicated by numerousendothelium-lined vascular channels and stromal cells

that appeared foamy because of their lipid contents.The finding of this tumor type in association with eysticlesions, erythrocytosis and the family history ofVHLSled to a presumptive diagnosis of VHLS. The patient' smother and brother had both undergone surgery forhemangioblastoma 10 years and 2 years earlier,respedively.

Two months after his first surgery, the patientwas readmitted for iurther evaIuation. CenTical MRI

revealed another contrast-enhanced, globular, sharplydemarcated mass in the spinal cord at the level of C6.There was no sign of the previously notedsyringobulbia, but the syringomyelic cavity that hadbeen found during the initial work-up was still present.Vertebral angiography revealed well-definedvascularization of the lesi on at C6 (Figure 2-A,B).Testing indicated that the erythrocytosis hadresolved. Abdominal ultrasonography and CT

Figure 2: Preoperative radiologic findings pertaining to the cervical tumor: A gadolinium-enhanced Tl-weighted MR image(midsagittal plane) (A) and spinal cord angiography (lateral view) (B) demonstrate an intensely enhanced lesionat the level of C6. The tumor was fed by the thyrocervical trunk.

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revealed a clinically silent cyst in the pancreas andcysts in both kidneys (Figure 3-A,B). We detected nohemangiomas of the retinal capillaries on a seconddetailed fundoscopic examination.

A second surgery was needed to address thelesion in the cervical spinal cord. For this procedure,a C6 laminectomy was performed with the patientin the sitting position. The incision in the dura at thislevel exposed a tumor on the dorsal surfaceDof thecord, and we were able to totally excise the mass. Inthe immediate postoperative period, the patientcomplained of radiating pain, motor weakness and

Kiitlay: VHL5 & ScllWl1ll1lOma

dysesthesia in his right leg. Initially, we suspectedan entrapment neuropathy brought on by the lengthof time he was in the sitting pasition during surgery.Physical examination revealed a painful swelling inhis right posterior thigh and hypoalgesia in the righ tLS and 51 dermatomes. His motor power on plantarflexion was scored as 4 on the manual muscle test.CT revealed a solid and well-circumscribed tumor

on the right sciatic nerve, with surroundinghyperdense areas that were thought to represent focalhemorrhage. Contrast injection caused enhancementat the tumor periphery (Figure 4-A,B).

Figure 3: A) Abdominal ultrasonography reveals a cyst in the pancreas. B) CT seans of the abdomen demonstrate cysts inthe pancreas (c) and the left kidney (arrow). The cysts did not enhance with either intravenous or oral contrast.

Figure 4: A CT sean (axial view) of the right thigh without (A) and with contrast (B). Intravenous injection of contrastmaterial caused enhancement at the periphery of the tumor.

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The patient's third surgery revealed a well­demarcated, encapsulated, solid mass. We separatedthe tumor capsule from the surrounding nervefascides, and then severed the fascicles running intothe tumor immediately proximal and distal to themass to acliieve total excision. In the earlypostoperative period, the patient's pain was relievedbut his musde weakness and hypoalgesia persisted.

Grossly, the excised tissue was an encapsulatedtan-yellow mass. Histological examination confimiedit was a schwannoma (Figure 5), a neoplasm that isdistinguished from other nerve sheath tumors by itscomposition of Schwann cells only. There were noperineural cells or fibroblasts, nor were there nervefibers running through the tumor. The Schwann cellswere arranged in alternating hyperceIlularpahsading regions (Antoni A) and hypoceIlularloosely meshed regions (Antoni B).

Figure 5: The light microscopic appearance of theschwannoma shows hypercellular palisadingregions (Antoni A). There are narrow elongatedbipolar cells with small amounts of cytoplasm(hematoxylin and eosin x 200).

DISCUSSION

Hemangioblastomas typically arise eithersporadically or as a component of VHLS (28). Theretinal and cerebellar forms are the most common.

Patients with cerebellar hemangioblastomas tend todevelop symptoms in the third through fifth decadeof life (7,20,21,25). Sporadic cases ofhemangioblastoma tend to be seen in patients whoare in their forties, whereas VHLS cases generallypresent earlier. In familial VHLS, the mean age atonset of symptoms is 30 years, the range being 3 to83 years 0,22). Our patient was 21 years old.

Kutlay: VHLS & Sc/iivalillOlIla

One interesting feature of hemangioblastomais that it is the only central nervous system tumorknown to be associated with erythrocytosis05,16,22,28). This is thought to occur throughsecretion of erythropoietin or an erythropoietin-likesubstance by the neoplastic tissue. Ultrastructuralstudies of some hemangioblastomas have identifieddistinctive granules that are considered to representintracellular erythropoietin (5,7,16,24). it has alsobeen demonstrated that the systemic effects of thistype of activity disappear after tumor excision (15,26).Erythrocytosis has been reported in 9 and 50 cases ofposterior fossa and supratentorialhemangioblastoma, respectively, but has never beenobserved in association with purely spinal lesions(22). Prior to his first operation, our patient exhibitederythrocytosis in the absence of splenomegaly or anyelevation in his white cell or platelet counts. Testingdone before the second operation showedOthat thepatient's erythrocytosis had resolved, even thoughhis other lesions had not been treated. We deduced

that the erythrocytosis in this case was likely causedby the mature hemangioblastomas that wereremoved from the posterior fossa.

The development' of multiple smaIlhemangioblastomas in the cerebellar hemispheresand cervical spinal cord in patients with VHLS canpose problems regarding treatment. Some of theselesions may represent recurrence, whereas others areimmature tumorso Although hemangioblastomas areconsidered benign, they recur in up to 25% of cases,and recurrence is more common in famihal disease(8). Several factors are known to be correlated withtumor recurrence, including younger age (less than30years at time of diagnosis), VHLS, and multicentrichemangioblastomaOof the central nervous system atpresentation (1,8). Patients who undergo repeatedsurgeries often have adhesions that present difficultyfor the surgeon. At the initial operation, since it isknown that the hemangioblastoma recurrence rateis very high, and particularly in multicentric cases, itis best to prepare the patient for the hkelihood ofsubsequent reexploration and to ensure that thesurgical site is approached with this in mind.Reexploration is extremely difficult in cases whereadhesions have formed due to inadequate duraldosure in a previous procedure. In both opera tion s,we used Gore- Tex surgical membrane as opposed toautogenous material because Gore- Tex ten ds toremain inert, and has provenObeneficial in terms ofpreventing adhesions (6,27). We believe that use ofthis synthetic material should always be consideredin patients with immature andi or multifocal

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hemangioblastomas, with a view to preventingneural tissue adhesions at the site of repair.

Hemangioblastomas account for 1.5% to 2.5%of all spinal cord neoplasms, and an estimated 60%of these tumors are intramedullary (4,18,19,22). Theytend to arise in the cervical or thoracic region, andmore than half are accompanied by syringomyelia(4,22). The development of syringomyelia in thesecases is considered similar to the development of acystOwithin a cerebellar hemangioblastoma. In ourcase, the patient's cervical tumor wasextramedullary, and was situated in the dorsal halfof the spinal cord. Initially, the patient's large syrinxextended superiorly from the tumor to the medullawithout communicating with the fourth ventricle,and extended inferiorly to the end of the thoracicsegment of the spinal cord. Prior to the secondoperation, we noted that the extent of the syrinxsuperior to the tumor had markedly diminished, butthat the size of the lower section remained

unchanged. In these cases, syringomyelia occurs asa result of transudation from capillaries, but we alsobelieve that obstruction of the central canal probablyplays an important role, especially in patients withextramedullary tumorso

Patients with VHLS invariably havemulticentric hemangioblastoma (2,28). Although awide variety of lesions have been described in thissyndrome, the vast majority of tumors occur in theretina and the posterior fossa. The literature alsodocuments many visceral lesions associated withVHLS, including renal cell carcinoma (13,19)pheochromocytoma (12), adrenal hemangioblastoma(5), pancreatic carcinoma (10), epididymal tumor (9)and cysts in the pancreas, kidney (2,13) and liver (23).Hemangioblastoma associated with primaryhyperparathyroidism, and optic nervehemangioblastoma have also been observed (11,14).This type of tumor very ra rely affects peripheralnerves (3).

To date, there are no reports in the literature ofVHLS associated with peripheral nerve sheathtumorso We believe that our finding of a sciatic nerveschwannoma in this patient was incidenta!, and thatthis neoplasm was distinct and not a component ofVHLS. However, this case highlights the fact thatclinically silent peripheral nerve sheath tumors doarise as a separate clinical manifestation in patientswith VHLS. Aiready more than 30 lesionscharacteristic of this condition have been described.

We wish to emphasize that the neurosurgeon should

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Kul/ay: VHLS & ScliwaiiilOlIIll

be alert to the possibility of a link with peripheralnerve sheath tumors, as future discoveries of this

nature may expand the broad spectrum of lesionsassociated with VHLS.

Correspondence: Dr. Murat KUTLAYGATA Haydarpasa Egitim HastanesiBeyin Cerrahi Klinigi, Kadiköy 81327Istanbul, TürkiyePhone: 216-3450295

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