Hemangioblastoma
Neoplasm
of uncertain histogenesis
- benign,
slowly growing lesion
- WHO
Grade I
- highly
vascular lesions (usually supplied from pia)
Epidemiology:
- account
for 2% of intracranial neoplasms and 7% of posterior fossa tumors
- most
common primary intraaxial tumor in adult posterior fossa
- may
occur sporadically or 25% in association with the von Hippel-Lindau syndrome
(see
below)
- in VHL
the tumors generally occur at a younger age (3rd-4th decade) vs 5th-6th decade
Presentation:
- slowly
growing mass
-
hydrocephalus due to obstruction of fourth ventricle from mass effect
- rarely
present with secondary polycythemia as tumor can produce erythropoietin
Imaging:
- usually
occurs in cerebellum (85%), less frequently spinal cord (3%) or brainstem
(2-3%); the latter occuring mainly in VHL
-
multiple tumors only in VHL
-
typically cyst with mural nodule
- nodule
is contrast-enhancing while cyst is usually not
- may see
syrinx in brainstem or spinal cord
Pathology (Click HERE to see picture):
Two cell
populations:
1)
Endothelial cells and pericytes (reactive component)
- dense
network of small vascular channels with thin lining
2)
Stromal cells (felt to be the actual neoplastic cells)
- exhibit
some hyperchromasia and pleomorphism
-
classically lipidized with "clear cell" ("foamy") features
- usually
no necrosis or mitotic activity but intratumoral hemorrhage can occur
- may see
reactive changes and even Rosenthal fibres in cyst wall
(major
differential diagnosis is the pilocytic astrocytoma)
-
well-dermacated interface with brain and not infiltrative
Immuno:
stromal cells may label with S100, vimentin or even GFAP (but uncertain
etiology)
- do NOT
stain with EMA or cytokeratins (to differentiate from clear cell renal
carcinoma)
Treatment
- surgery
may be curative in sporadic cases
-
sufficient to remove tumor nodule; cyst wall is non-neoplastic
-
radiotherapy is occasionally used to reduce tumor size preoperatively or retard
growth in non-surgical candidates (multiple lesions or inoperable location)
-
radiation does not prevent regrowth following subtotal resection
Prognosis:
- low
recurrence risk if total resection
- risk of
multiple tumors in VHL and so worse prognosis
- need to
screen for mutation if young person with hemangioblastoma, if family history
positive, any other tumors (esp retinal)
=>
look for pheochromocytoma if VHL positive
von
Hippel-Lindau syndrome:
-
Autosomal dominant inheritance with 90% penetrance
-
mutation in VHL tumor suppressor gene on chromosome 3p25-26
- half of
cases due to spontaneous mutations
- occurs
in 1:36-45,000 population
- leads
to overexpression of VEGF
Associated
with:
-
multiple hemangioblastomas, including CNS and retina
(must
have one of these + one of typical other tumors or a positive family history)
- clear
cell renal cell carcinoma
-
pheochromocytoma (20% of these tumors are associated with VHL)
-
pancreatic islet cell tumors / inner ear tumors (endolymphatic sac tumor)
- renal
& pancreatic cysts
-
polycythemia
Pathophysiology:
-
inactivation of the VHL gene leads to loss of gene product, the protein pVHL
- this is
a major regulator of HIF (hypoxia-inducible factor) and without it HIF is not
removed
-
overproduction of HIF leads to turning on genes for VEGF and other growth
factors, as well as erythropoietin
Median
life expectancy is 49 years
- death
usually related to CNS hemangioblastoma or renal cell carcinoma
References:
George
DJ, Kaelin Jr WG. The von-Hippel Lindau
protein, Vascular Endothelial Growth Factor, and Kidney Cancer. NEJM 2003; 349: 419-421.
Kleinheus
P, Cavenee WK eds. Pathology and
genetics of tumors of the nervous system.
IARC Press: 2000
Greenberg.
Handbook of Neurosurgery
Last
update: February 2004
Reviewed
by: pending review
Neurological
Medicine Pocketbook
© 2003-2004
UWO Neurology Residents
http://www.uwo.ca/cns/resident
All
Rights Reserved
