耳 鼻 49 (補2): S81～S85, 2003

Headache, vomiting, and nystagmus : a case of

cerebellar hemangioblastomas

Hai-Bo SHI(1), Meiho NAKAYAMA(2), Lei CHENG, Min YIN(1),

Ryuichi KoNDA(3), Takeyuki SAMBE(4), Tomoya YAMAMOTO,

Sohtaro Ko-YAMA(5)and Akira MIYOSHI(6),(7)

Hemangioblastoma (HBL) is highly vascularized tumor of not well-defined histological origin. Cerebellar HBL may manifest as a sporadic tumor or act as

one of the manifestations of the von Hippel-Lindau syndrome (VHLS). Here we report a 36-year-old female patient with left cerebellar HBL. The patient

presented with back headache, nausea, vomiting, and clouding of consciousness. The symptoms were gotten serious in the morning and then relieved from

noon. Nystagmus was detected through spontaneous nystagmus test and

positional nystagmus test, both showing parallel or rotative nystagmus with leftward quick component operative resection of the lesion was performed via

osteoplastic craniotomy. The mural nodule was a reddish mass about 7 mm in diameter and about 10 ml self-transparent oil-liked liquid was elicited from the cyst. The tumor specimen showed typical histological features of hemangio-blastoma. Post - operative MRI scanning of the abdominal and spinal canal failed to reveal any stigmata of VHLS.

Key words : hemangioblastoma, von Hippel-Lindau syndrome, central

neural system, headache, nystagmus

Introduction

Hemangioblastoma (HBL) is highly vascu-

larized tumor of not well-defined histological

origin that is frequently associated with

cysts.1) HBL arises preferentially in cerebel-

lum, medulla and spinal cord and is his-

tologically indistinguishable from vascular

lesions in the retina. Cerebellar HBL is one

of the most frequent manifestations of the

autosomal dominantly inherited von Hippel-

Lindau syndrome (VHLS) and also may

manifest as a sporadic tumor.2) Although

the tumor is histological benign, its multi-

plicity and eloquent location still make it one of the major causes of death of the pa-

tients.3) Here we report a case of HBL in

the left cerebellar hemisphere.

Case report

A 36- year- old female patient was seen in

Miyoshi ENT Clinic, who presented with

back headache, nausea, vomiting, and cloud-

ing of consciousness. These symptoms were

gotten serious in the morning and then re-lieved from the noon. No hearing loss,

tinnitus or vertigo was complained. She had

no hereditary disease family history. There

were no positive findings about her nose,

pharynx, and larynx. Pure tone audiometry

showed a normal hearing curve between 15

dB and 30 dB. Neurological examination

showed normal findings. Nystagmus was

detected through spontaneous nystagmus

Corresponding author : Akira Miyoshi. Miyoshi ENT Clinic, Izumichuo 1-34-1, Izumi-ku, Sendai 981-3133, Japan

S 82 耳 鼻 と 臨 床 49 巻 補 2 号

test and positional nystagmus test, both

showing parallel or rotative nystagmus with

leftward quick component (Fig. 1). Consi-

dering the headache, spraying vomiting, and

the rotative nystagmus, central neural sys-

tem (CNS) disease was strongly suggested.

Then, computed tomography (CT) scan-

ning of the brain revealed a cystic lesion

with a mural nodule in the cerebellar left

hemisphere and showed mild hydrocephalus

with the IV th ventricular deformity due to

Figure 1 Spontaneous nystagmus test and

positional nystagmus test de-

tected parallel or rotative nys-

tagmus with leftward quick com-

ponent.

Figure 2 Axial plain computed tomography scanning

of the brain revealed a cystic lesion with a

mural nodule in the cerehellar left hemi-

sphere and showed mild hydrocephalus with the IV th ventricular deformity due to

dilated cyst at the left cerehellar hemi-

sphere.

dilated cyst at the left cerebellar hemisphere

(Fig. 2). The cystic components were hyper-

intense on T2 - weighted images (Fig. 3) .

The tumor was about 5 cm in diameter. No

other intracranial lesions were identified.

Retinal image showed mild retinal telang-

iectasia, but no reticuloblastoma was found

(Fig. 4). Cerebral angiography demonstrated

tumor staining in the capillary phase images,

fed by the posterior inferior cerebellar artery

(PICA) (Fig. 5).

Just after the cerebral angiography exami-

nation, the patient suffered from a serious

convulsion. At the same day, operative re-

section of the lesion was performed via

osteoplastic craniotomy. From the cyst , about 10 milliliter self - transparent oil- liked

Figure 3 The cystic components were hyperintense

on T2 - weighted images. The tumor was

about 5 cm in diameter.

Figure 4 Retinal image showed mild retinal telangi-

ectasia but no reticuloblastoma was found.

H-B Stu et al = Headache, vomiting, and nystagmus S83

Figure 5 Cerebral angiography demonstrated tumor

staining in the capillary phase images, fed

by the posterior inferior cerebellar artery.

liquid was elicited. The mural nodule was a

reddish mass about 7 mm in diameter, with

the appearance of a cluster of blood vessels.

A total resection was subsequently accom-

plished. The tumor specimen was stained

with hematoxylin and eosin, and showed

typical histological features of HBL. Post-

operative magnetic resonance imaging (MRI)

scanning of the abdominal and spinal canal

failed to reveal any stigmata of VHLS. The

patient recovered after operation and kept

follow-up.

Discussion

Intracranial HBL is benign neoplasm of

vascular origin occurring in the cerebellum,

brain stem, and spinal cord. They account

for about 2% - 3% of all intracranial tu-

mors.4) They may arise either as sporadic

lesions or in the setting of VHL disease, an

autosomal dominantly inherited disease, pre-

disposing to HBL of the CNS and retina,

clear cell renal carcinomas, pheochromocy-

tomas, endolymphatic sac tumors, and cysts

in different organs. While the cerebellum

(83%-95%) is the most frequent site of these

tumors, followed by spinal cord (3.2%-13%),

and medulla oblongata (2.1%).5)

Intracranial HBL is known to have three

morphologic patterns : a cyst with a small

mural nodule, a solid mass with a central

cystic component, and solid tumor without a

cystic component.6) The cyst occurring with-

in a solid tumor is usually thought to be di-

lated vascular spaces or degenerative regions.

On the other hand, the cystic fluid around

a mural nodule is considered as diffusion

from the vascular component of the mural

nodule. In the present patient, about 10 ml

yellowish, transparent cystic fluid was elic-

ited during operation. The cyst was found

surrounding the mural nodule. The left

PICA was the feeding artery and two main

veins were the drainers for the mural nodule.

The color of the veins was redder than

that of other vein and turned into normal

when the feeding artery was obstructed. It

might suggest that there was a higher blood

press in the capillary of the nodule and this

could contribute to the diffusion of vascular

components.

The diagnosis of cerebellar HBL is getting

easy by introduce of CT or MRI examina-

tion. The cerebellum is the most frequent

site of HBL, but these tumors also arise in

the medulla and spinal cord. A general ex-

amination is necessary for those patients

who had been detected HBL, especially in

cases of VHLS.

Cerebellar HBL is one of the most frequent

manifestations of the inherited VHLS. The

diagnosis of HBL is often connected with the

detection of the VHLS, but the present case

failed to reveal any stigmata of VHLS ac-

cording to the physical examination. Since

Latif et al successfully isolated the VHL gene

in 1993, genetic diagnosis of VHLS has be-

come available.7 Tse et al (1997) studied

the alterations of the VHL gene in HBL.8)

Allelic losses on chromosome 3p were ob-

served from two patients with VHLS in one

family and in one of two sporadic HBL. No

hypermethylations of the VHL gene was

S 84 耳 鼻 と 臨 床 49 巻 補 2 号

detected in any of the tumors that were ex-

amined. The results suggested that the

VHL tumor suppressor gene was the target

for inactivation in the tumor and was in-

volved in the pathogenesis of familial and

sporadic HBL. Recently, Lemeta et al (2002)9)

studied the cytogenetic changes in HBL. 22

cases were studied through comparative

genomic hybridization to screen for DNA copy number changes in both sporadic and

VHL - associated HBL. They found that 6 of

22 samples (27%) contained DNA copy num-

ber losses, whereas no gains were observed.

The loss of chromosomal arm 6q, 3, and 8

was observed in five, two, and one cases, re-

spectively. No differences were noted be-

tween VHL - associated and sporadic tumors,

nor did the cytogenetic aberrations correlate

with the clinical outcome. The authors con-

sidered that the chromosome area might con-

tain tumor suppressor genes involved in the

early steps of tumorigenesis.

Complete removal of the mural nodule is

the treatment of choice. On the other hand,

Gamma knife radio-surgery has been proved

as an efficient method to control HBL.

Niemela et al10) found that a solitary small-

or medium - sized HBL usually shrinked or

stopped growing after radio - surgery. The

recommended margin dose was 10 to 15 Gy.

The adjoining cyst often did not respond to

radio-surgery but requires later, sometimes

repeated evacuation.

References

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Schwartz JH (eds), pp381-384, Armed Forces Institute of Pathology, Washing DC, 1994.

2) Neumann HP and Wiestler OD : Clustering of features of von Hippel - Lindau syndrome -

evidence for a complex genetic locus -. Lancet 337 : 1052-1054, 1991.

3) Bohling T et al : von Hippel-Lindau disease and capillary haemangioblastoma. Pathology

and genetics of tumours of the nervous sys- tem. Kleihues P and Cavenee WK, pp223-226,

World Health Organization International Agency for Research on Cancer, Lyon, 2000.

4) Matsumoto K and Kannuki S : Hemangio- blastoma and von Hippel - Lindau disease.

Nippon Rinsho 53 : 2672-2677, 1995. 5) Constans JP et al : Posterior fossa heman-

gioblastomas. Surg Neurol 25 : 269-275, 1986. 6) Elster AD and Arthur DW : Intracranial

hemangioblastomas -CT and MR findings-. J Comput Assist Tomogr 12 : 736-739, 1988.

7) Latif F et al : Identification of the von Hippel - Lindau diaease tumor suppressor gene . Sci-

ence 260 : 1317-1320, 1993. 8) Tse JY et al : Molecular genetic analysis of

the von Hippel - Lindau disease tumor sup-

pressor gene in familial and sporadic cere- bellar hemangioblastomas. Am J Clin Pathol

107 : 459-466, 1997. 9) Lemeta S et al : Recurrent DNA sequence

copy losses on chromosomal arm 6q in capil- lary hemangioblastoma. Cancer Genet Cyto- genet 133 : 174-178, 2002.

10) Niemela M et al : Gamma knife radiosurgery in 11 hemangioblastomas. J Neurosurg 85 :

591-596, 1996.

H-B SHI et al = Headache, vomiting, and nystagmus S 85

頭痛、嘔吐、眼振を伴 った小脳血管芽腫の1例

時 海 波(1)・ 中 山 明 峰(2)・程 雷 ・殷 敏(1)・今 田 隆 一(3)

三 邉 武 幸(4)・ 山 本 智 矢 ・小 宮 山 荘 太 郎(5)・三 好 彰(6),(7)

(1) Department of Otorhinolary.gology)The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

(2) Department of Otorhi.olaryngology Aichi Medical University, Aichi 480-1113, Japan(3) Department Qf Neurosurgery, Miyagi Health Association Izumi Hospital, Sendai 98113212, Japa.

(4) Department of Otorhinolaryngology, Tokyo Metropolitan Ebara General Hospital, Tokyo 145-0065, Japan

(5) Department of Otorhinolaryngology, Kyushu University Hospital, Fukuoka 812-8582, Japan(6) lnternatiQnal Research Centre for Nasal Allergy Nanjing Medical University, Nanjnng 210029, China

& Sendai 981-3133, Japa.(7) Miyoshi ENT CIinic, Sendai 981-3133, Japan

血管芽腫 は、 血管 の豊富 な組織学 的に低分化型 の腫瘍 であ り、時 にVon Hippel-Lindau病 の一部 と して出

現す る ことが ある。今 回われ われ は、36歳 女性の小脳血管芽腫 の症例を経験 した。本症例 は、 朝 ひど く、 日中

になる と軽減す るとい う特徴 を有 した後頭 部痛 、吐 き気、 嘔吐な らびにふ らつ きを訴 え、三好耳鼻咽喉科 ク リ

ニ ックを受診 した。 自発眼振検査 と頭位 眼振検査 にて水平性 眼振 が観察 された。 本症例 は、 脳外科 にて開頭手

術 を施行 され たが、 嚢胞内 の結節 は直径7mm程 で赤 みを帯 びてお り、嚢 胞は約10mlの 半透明な液体 によ って

満 たされていた。摘 出 された腫瘍 には、血 管芽 腫の典型的特徴が認 め られ た。術 後、MRIに て腫瘍 の完全 除去

が確認 できた。