Medhat Mustafa, MD,
Department of Neurosurgery
Suez Canal University, Ismailia, Egypt

Hemangioblastomas

INTRODUCTION

The tumor usually grows inside the parenchyma
of the cerebellum, brain stem, or spinal cord; it
is attached to the pia mater and gets its rich
vascular supply from the pial vessels.
However, extramedullary and extradural
hemangioblastomas have also been described.

Upon gross examination, hemangioblastomas
are usually cherry red in color. They may include
a cyst that contains a clear fluid, but solid
tumors are as common as cystic ones.

Epidemology
Hemangioblastomas are relatively uncommon,
accounting for 2% of all brain tumors and 2% to
10% of spinal cord tumors.
Recurrent hemangioblastomas may signal that a
patient has von Hippel-Lindau disease (VHL).
VHL is a hereditary gene mutation that causes
hemangioblastomas, cysts, and other tumors to
grow

Most hemangioblastomas are located in the
posterior cranial fossa; in that region,
hemangioblastomas comprise 8-12% of
neoplasms.
Hemangioblastoma is the most common
primary adult intraaxial posterior fossa tumor

The second most common location of
hemangioblastomas is the spinal cord, where
the frequency ranges from 2-3% of primary
spinal cord neoplasms to 7-11% of spinal cord
tumors.
This tumor's occurrence in other locations, such
as the supratentorial compartment, the optic
nerve, the peripheral nerves, or the soft tissues
of extremities is extremely rare.

Sex and age distribution
Hemangioblastomas are more common in men
than in women. In most clinical series, the male-
to-female ratio is approximately 2:1.
Although hemangioblastomas may develop at
any age, they rarely affect children; the usual
age at diagnosis is between the third and fifth
decades.

The peak age of incidence has been noted to be
between 20 and 50 years.
Hemangioblastomas are uncommon but not
rare in patients older than 65 years.

Von Hippel-Lindau disease
Most hemangioblastomas arise sporadically.
However, in approximately one quarter of all
cases, they are associated with von Hippel-
Lindau (VHL) disease, an autosomal dominant
hereditary syndrome that includes
retinal angiomatosis, central nervous system
hemangioblastomas, and various visceral tumors
most commonly involving the kidneys and
adrenal glands.

This syndrome is classified as a phakomatosis,
although it does not include any cutaneous
manifestations.
The syndrome has variable penetrance, but its
dominant mode of transmission compels
performing at least a screening of family members
of patients diagnosed with VHL disease.
In some patients with VHL disease,
hemangioblastomas may produce erythropoietin-
like substances, resulting in polycythemia at the
time of diagnosis.

Types of Hemangioblastomas
Hemangioblastomas are classified based on the
type of fluid they contain and the size of the
vascular channels inside the tumor.
They are typically defined as cystic or solid, and
are further broken down into four types:

Type 1: A simple cyst without a nodule (the
rarest, at 5% of tumors)
Type 2: A cyst with a mural nodule (60% of
tumors)
Type 3: A solid tumor (26% of tumors)
Type 4: A solid tumor containing small internal
cysts (9% of tumors)

Etiology
Etiology of the hemangioblastoma is obscure,
but its presence in various clinical syndromes
may suggest an underlying genetic abnormality.

However, in 25% of cases, an inherited disorder
called von Hippel-Lindau disease (VHL) causes
the growth of hemangioblastomas and other
types of tumors and cysts in the body. VHL
disease is hereditary and occurs in 1 out of
36,000 people

Hemangioblastoma
Symptoms
The clinical presentation of hemangioblastomas
usually depends on the anatomic location and
growth patterns.
Cerebellar lesions may present with signs of
cerebellar dysfunction, such as ataxia and
discoordination, or with symptoms of increased
intracranial pressure due to associated
hydrocephalus.

In general, intracranial hemangioblastomas
present with a long history of minor neurologic
symptoms that, in most cases, are followed
by a sudden exacerbation, which may
necessitate immediate neurosurgical
intervention.

Patients with spinal cord lesions most frequently
present with pain, followed by signs of
segmental and long tract dysfunction due to
progressive compression of the spinal cord.
Patients with VHL disease may present
with ocular or systemic symptoms due to
involvement of other organs and systems.

Spontaneous hemorrhage is possible in both
intraspinal and intracranial
hemangioblastomas,but this risk is low, and
tumors smaller than 1.5 cm carry virtually no
risk of spontaneous hemorrhage.

Diagnosis
MRI of hemangioblastomas usually
shows an enhancing mass clearly delineated
from the surrounding brain or spinal cord tissue.
The tumor tissue may be hypointense or
isointense on precontrast T1-weighted images
and hyperintense on T2-weighted
images.

Cerebral and spinal angiography reveals a highly
vascular tumor blush, and this diagnostic
modality may be extremely useful for assessing
the vascular supply to the tumor.
This information may help the surgeon during
tumor resection.

In patients with hemangioblastomas, complete
neural axis imaging usually is recommended to
rule out multiple lesions, especially in those
cases in which VHL syndrome is either
diagnosed or clinically suspected.

Histologic Findings
Histologically, hemangioblastomas are vascular
neoplasms.
In addition to relatively normal-appearing
endothelial cells that line capillary spaces,
hemangioblastomas have 2 distinct cellular
components that may occur in the same tumor
in different proportions.

The first type is small, perivascular, endothelial
cells that have dark, compact nuclei and sparse
cytoplasm.
Cells of the second type contain multiple
vacuoles and granular eosinophilic cytoplasm
rich in lipids.
These stromal cells may show some nuclear
pleomorphism, but mitotic figures are rarely
seen..

The exact histogenetic origin of stromal cells is
unknown, but studies indicate that they
may represent a heterogeneous population of
abnormally differentiating mesenchymal cells of
angiogeni lineage, with some morphologic
features of endothelium, pericytes, and smooth-
muscle cells

Two histologic subtypes (cellular and reticular)
have been described in primary
hemangioblastomas of the central nervous
system and have been found to correlate with
the probability of tumor recurrence.
The reticular subtype is more commonly
encountered;
the cellular subtype is associated with higher
probability of recurrence.

Treatment
Because hemangioblastomas are benign tumors
and generally are not invasive in nature they
may be cured by surgical excision.
Therefore, surgical resection is considered a
standard of treatment and should be offered to
the patient unless the risk of operation
outweighs its potential benefits.

The tumors usually are well demarcated from
the surrounding brain or spinal cord, but this
border of separation does not contain any
particular membrane or capsule.

Thorough evaluation of preoperative imaging
studies is the key to the safest possible exposure
of the tumor.
In addition to MRI and CT scans, review the
angiography findings to identify the principal
blood supply to the tumor mass.

Other therapeutic modalities include
endovascular embolization of the solid
component of the tumor, which may decrease
the vascularity of the tumor and lower blood
loss during its resection,
and stereotactic radiosurgery of the tumor using
either a linear accelerator or a gamma knife.

Regarding general surgical management, having
blood products available for transfusion is very
important because the vascular character of
hemangioblastomas may result in serious
intraoperative blood loss.
Additionally, anesthesia for patients with VHL
disease may be quite challenging because of
associated renal and endocrine dysfunction.

The surface of the tumor may be coagulated with
wide bipolar forceps; however, avoid penetration of
the tumor
itself because of its extreme vascularity and
difficulties with hemostasis.
Try to dissect the tumor circumferentially by
careful coagulation and cutting the small feeding
vessels and adhesions between the tumor and the
surrounding brain or spinal cord and by putting
cottonoid strips into the developing plane to avoid
direct pressure on the brain or spinal cord tissue.

If an associated hydrocephalus exists, it must be
addressed separately, usually by means of external
ventricular drainage (EVD) prior to tumor resection.
After the tumor is removed, the need for
permanent shunt placement may be determined by
the patient's response to EVD clamping.
In most cases, an intramedullary syrinx does not
require a separate drainage procedure because it
usually resolves after tumor removal.

Outcome and Prognosis
Long-term results of hemangioblastoma
management are generally favorable.
Advancement of neuroimaging
methods, improvements in microsurgical
technique, and the addition of preoperative
embolization have significantly lowered
morbidity and mortality associated with
hemangioblastoma surgery.

Subarachnoid dissemination of
hemangioblastomas is extremely rare,
and local recurrences after complete tumor
resection seem to be more frequent in patients
with von Hippel-Lindau (VHL) disease,
in patients diagnosed at a young age,
and in patients with multiple
hemangioblastomas.

The recurrence rates vary in different surgical
series but generally remain less than 25%.
Histologic subtype has been found to correlate
with a probability of hemangioblastoma
recurrence, with a 25% recurrence
rate in cellular subtype and an 8% recurrence
rate in reticular subtype.