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REVIEWEndocrine-Related Cancer (2008) 15 885–903
The diagnosis and management ofparasellar tumours of the pituitary
Gregory A Kaltsas, Jane Evanson1, Alexandra Chrisoulidou 2
and Ashley B Grossman3
Endocrine Unit, Department of Pathophysiology, National University of Athens, Athens, Greece1Department of Academic Radiology, St Bartholomew’s Hospital, London, UK2Department of Endocrinology, Theagenion Hospital, Thessaloniki, Greece3Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK
(Correspondence should be addressed to A B Grossman; Email: [email protected])
Abstract
The sellar and parasellar region is an anatomically complex area where a number of neoplastic,inflammatory, infectious, developmental and vascular diseases can develop. Although most sellarlesions are due to pituitary adenomas, a number of other pathologies involving the parasellarregion can present in a similar manner. The diagnosis of such lesions involves a multidisciplinaryapproach, and detailed endocrinological, ophthalmological, neuroimaging, neurological and finallyhistological studies are required. Correct diagnosis prior to any intervention is essential as thetreatment of choice will be different for each disorder, particularly in the case of primary malignantparasellar tumours. The complexity of structures that define the parasellar region can produce avariety of neoplastic processes, the malignant potential of which relies on histological grading. Inthe majority of parasellar tumours, a multimodal therapeutic approach is frequently necessaryincluding surgery, radiotherapy, primary or adjuvant medical treatment and replacement ofapparent endocrine deficits. Disease-specific medical therapies are mandatory in order to preventrecurrence or further tumour growth. This is particularly important as neoplastic lesions of theparasellar region tend to recur after prolonged follow-up, even when optimally treated. Apart fromthe type of treatment, identification of clinical and radiological features that could predict patientswith different prognosis seems necessary in order to identify high-risk patients. Due to their rarity,central registration of parasellar tumours is required in order to be able to provide evidence-baseddiagnostic and mainly therapeutic approaches.
Endocrine-Related Cancer (2008) 15 885–903
Introduction
The area immediately around the pituitary, the sellar
and parasellar region, is an anatomically complex area
that represents a crucial crossroads for important
adjacent structures (Ruscalleda 2005). While the sellar
region has specific anatomical landmarks, the para-
sellar region is not clearly delineated and includes all
the structures that surround the sella turcica (Rennert &
Doerfler 2007). Vital structures such as the brain
parenchyma, meninges, visual pathways and other
cranial nerves, major blood vessels, hypothalamo-
pituitary system (HPS) and bony compartments may be
involved. A diversity of clinical symptoms and signs
can develop from a number of neoplastic, inflam-
matory, infectious, developmental and vascular
Endocrine-Related Cancer (2008) 15 885–903
1351–0088/08/015–885 q 2008 Society for Endocrinology Printed in Great
diseases that occupy the parasellar area secondary to
the location, size and growth potential of the lesions,
and the subsequent damage to specific adjacent vital
structures (Freda & Post 1999).
Pituitary adenomas are the most common cause of a
sellar mass extending to the parasellar region (Freda &
Post 1999). However, in w9% of cases, an aetiology
other than a pituitary adenoma is encountered, para-
sellar tumours being the second commonest cause after
non-tumorous cystic lesions (Freda et al. 1996). The
malignant potential of these tumours may be defined
according to the World Health Organization (WHO)
classification of tumours of the central nervous system
(CNS), which relies on histological criteria: WHO
grade I (tumours with low proliferative potential and
the possibility of cure following surgical resection),
Britain
DOI: 10.1677/ERC-08-0170
Online version via http://www.endocrinology-journals.org
G A Kaltsas et al.: Parasellar tumours
WHO grade II (infiltrative tumours with low mitotic
activity that can recur and progress to higher grades of
malignancy),WHO grade III (tumours with histological
evidence ofmalignancy) andWHOgrade IV (mitotically
active tumours with rapid evolution of disease; Kleihues
et al. 1993). The latest version of theWHOclassification,
including somenewhistologically identified variants that
may have some clinical relevance, has recently been
published (Louis et al. 2007). A number of other non-
neoplastic lesions, such as inflammatory, granulomatous,
infectious and/or vascular pathologies can also involve
the parasellar region (Table 1).
In this paper, we primarily attempt an overview of
the clinical, endocrine and radiological features of
Table 1 Classification of parasellar tumours according to
malignant potential and other parasellar lesions
Malignant parasellar tumours
Gliomas
Germ cell tumours
Primary lymphomas
Metastases
Supratentorial primitive neuroectodermal tumours (PNET)
Ependymoblastomas
Potentially malignant parasellar tumours (low-grade
malignant tumours)
Craniopharyngiomas
Chordomas/chondrosarcomas
Haemangiopericytomas
Langerhans’ cell histiocytosis (LCH)
Benign parasellar tumours
Meningiomas (except rare atypical and anaplastic
meningiomas)
Rathke’s cyst
Epidermoids/dermoids
Hamartomas
Paragangliomas
Lipomas
Neurinomas/Schwannomas
Parasellar granular cell tumours
Ganglion cell tumours
Non-neoplastic pathologies of the parasellar region
Granulomatous, infectious and inflammatory lesions
Pituitary abscess, bacterial and fungal
Tuberculosis
Sarcoidosis
Wegener’s granulomatosis
Mucocele (sphenoid)
Hypophysitis (lymphocytic, granulomatous, xanthomatous)
Tolosa–Hunt syndrome
Vascular lesions
Aneurysms
Cavernous sinus thrombosis
Pituitary apoplexy
Miscallaneous (CSF related)
Empty sella syndrome
Arachnoid cyst
Suprasellar-chiasmatic arachnoiditis
886
neoplastic parasellar tumours, taking into consider-
ation their malignant potential (Table 1). In addition,
currently available therapeutic schemes and the long-
term prognosis of these tumours will also be discussed.
Non-neoplastic parasellar lesions will also be briefly
mentioned but not discussed into detail.
Anatomical considerations
The parasellar region includes, laterally, the dural
walls of the cavernous sinus, a multi-lobulated venous
structure containing the intracavernous portion of the
internal carotid artery, cranial nerves III, IV, VI and the
V1 and V2 branches of the trigeminal nerve (Smith
2005; Fig. 1). The relationships of the cavernous sinus
are: inferiorly with the basisphenoid and sphenoid
sinus; superiorly, the diaphragma sella, with the
suprasellar subarachnoid spaces containing the optic
nerves and chiasm, hypothalamus, tuber cinereum and
anterior third ventricle (Ruscalleda 2005). The naso-
pharynx and the medial aspects of the temporal lobes
are also closely related to the parasellar region; in
addition, embryonal remnants can also be found
contributing further to the diversity of the processes
that are involved in delineating the anatomy of this
region (Smith 2005).
Clinical presentation
Non-pituitary adenomatous parasellar lesions do not
present with hypersecretory syndromes but rather with
hypopituitarism or symptoms of mass effect due to
compression of nearby vital surrounding structures, the
Figure 1 Sagittal enhanced T1-weighted image of a hypo-thalamic glioma. This is partially cystic, partially solid andinvolves the chiasm and the hypothalamus.
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Endocrine-Related Cancer (2008) 15 885–903
severity of which depends on the location, size and
growth potential of the tumours (Glezer et al. 2008).
Visual loss is a common presenting complaint due to
the proximity of tumours to the optic nerves, chiasm
and optic tracts. Headache develops either as a
consequence of increased intracranial pressure (IP),
distortion of the diaphragma or irritation of the
parasellar dura (Freda & Post 1999). As parasellar
tumours commonly originate or infiltrate structures
within close proximity to the cranial nerves traversing
through the cavernous sinus, cranial nerve abnormal-
ities develop in w25% of cases (Jagannathan et al.
2007). Hypothalamic tumours in children may produce
the diencephalic syndrome manifest as wasting, poor
development and sexual immaturity, whereas in adults
it may lead to disruption of the control of appetite and
cause severe obesity or starvation (Freda & Post 1999).
Involvement of the hypothalamus and pituitary leads to
complete or partial pituitary hormonal deficiencies;
hyperprolactinaemia may also develop secondary to
stalk compression (Glezer et al. 2008). Diabetes
insipidus (DI) is a common finding in parasellar
tumours and indicates that the lesion is unlikely to be
a pituitary adenoma; however, it cannot reliably
distinguish among the various parasellar tumours
(Freda & Post 1999).
Imaging
Radiological imaging of the parasellar region is
challenging since the sella is a small volume region
in close proximity to many complex structures
(Ruscalleda 2005). Both thin-section computerised
tomography (CT) and magnetic resonance imaging
(MRI) play an important role in the anatomical
delineation of lesions in this area (Boardman et al.
2008). MRI is the modality of choice providing
multiplanar high-contrast images, whereas CT has a
complementary role in delineating bony destruction
and the visualisation of calcification (Rennert &
Doerfler 2007). Conventional radiology is no longer
in use, whereas digital subtraction angiography has
been largely replaced by the continuous improvement
in MR and CT angiographies (Rennert & Doerfler
2007). Although the radiological features of parasellar
tumours have many similarities, some may have
distinctive findings (Chong & Newton 1993, Freda &
Post 1999, Ruscalleda 2005, Smith 2005; Table 2).
However, the differential diagnosis among the various
types of tumours remains difficult using currently
available methods of morphological imaging.
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Diagnosis
In formulating a management plan, histological
confirmation is usually required unless there are
lesion-specific clinical, endocrine and/or radiological
features. Existing methods of skull base biopsy in the
anatomically critical parasellar region include either
open skull base approaches or image-guided needle
biopsy (Day 2003, Samandouras et al. 2005). Image-
guided techniques may help in diagnosis, but can be
time-consuming and cannot reliably avoid surrounding
critical neurovascular structures; in selected patients
endoscopic transnasal biopsy can be applied (Frighetto
et al. 2003, Samandouras et al. 2005). However, the
use of such methods should be weighed along with the
potential morbidity and mortality of the procedures
when the risk of inducing damage to a vital structure is
high, while the expected benefit from obtaining the
correct diagnosis may be questionable.
Therapy
Surgery remains the treatment of choice for benign
tumours and malignant tumours that are not responsive
to other forms of treatment, and/or when surgical
debulking is essential (Day 2003, Glezer et al. 2008).
Surgical therapy
Parasellar tumours usually have irregular margins and
adhere to vital neurovascular structures, and thus do
not allow a complete resection without the danger of
affecting critical brain areas (Couldwell et al. 2004).
Resection is attempted by craniotomy and/or trans-
sphenoidally (TSS), particularly for smaller tumours
approachable through the sella (Baskin & Wilson
1986, Honegger et al. 1992). For massive lesions, a
two-stage removal procedure may be necessary;
initially TSS debulking followed by craniotomy later.
This approach may allow residual tumour to descend
inferiorly, facilitating further resection (Maira et al.
1995). Recently, the development of advanced cranial
base TSS approaches has facilitated the exposure of
basal lesions by the removal of osseous structures,
minimising brain retraction and providing safe alterna-
tives when assessing lesions involving the tuberculum
sella, suprasellar region, cavernous sinus or clivus
(Couldwell et al. 2004). The TSS route can also be
used for midline lesions without significant lateral
extension (Day 2003). In cases of hydrocephalus,
resection may be achieved following decompression of
the ventricles and stabilisation of the clinical status of
the patient. In the presence of large cystic lesions, as
with craniopharyngiomas, fluid aspiration can be
887
Table 2 Imaging characteristics of parasellar tumours
Diagnosis CT and/or MRI characteristics
Malignant tumours
Gliomas (hypothalamic or optic pathway) On CT hypo/isodense pre-contrast mass. Variable enhancement on post-contrast
images Rarely calcifications, haemorrhages solid lesions. Occasionally small
cystic or necrotic components in large legions. On MRI hypointense on
T1-weighted images and hyperintense on T2 images. Variable enhancement
following contrast administration
Germ cell tumours On CT, well-delineated masses, usually hyperdense lesions. Most cases show
strong homogenous enhancement. On MRI, isointense on T1-weighted images
and iso- to hyperintense on T2-weighted images
Metastases On MRI, signal intensity varies depending on the primary tumour. Generally
hypointense on T1-weighted images and hyperintense on T2-weighted images
Lymphoma On MRI, slight hypointensity on both T1- and T2-weighted images
Plasmatocytoma On MRI, slight hypointensity on both T1- and T2-weighted images
Potentially malignant tumours
Craniopharyngiomas Calcifications occur in up to 80%, best depicted by CT. Cysts are present in the
majority of craniopharyngiomas that tend to predominate in children containing
highly proteinaceous fluid. The fluid is usually very bright on pre-contrast
T1-weighted MRI. In adults the solid components are larger and the cysts tend
to be small or multiloculated. The solid portions and cyst walls enhance usually
heterogeneously
Chordomas chondrosarcomas On CT, bone destroying mass, centred on the spheno-occipital synchondrosis
with occasional intratumoural calcifications. MR images show a heterogeneous
mass with internal septations and heterogeneous enhancement. Chordomas
are typically midline lesions
Haemangiopericytomas On MRI, hypointense lesions on T1-weighted images and heterogeneously
hyperintense on T2-weighted images
Langerhans’ cell histiocytosis On MRI uniform thickening of the pituitary stalk with homogenous enhancement
of the hypothalamic stalk. Occasionally, solitary nodules may develop in the
HP region
Mostly benign tumours
Meningioma On CT, isodense to slightly hyperdense with dense homogenous enhancement.
Calcification is seen in 20–50%. On MRI appear isointense in both T1- and
T2-weighted images although T2 signal intensity may be more variable. Differ
from pituitary adenomas due to differential uniform enhancing pattern. Majority
exhibit broad dural attachment and show a dural tail on post-contrast imaging
accompanied by bony hyperostosis and normal sellar dimension
Epidermoid cyst On CT lobulated mass with areas of calcification and attenuation values similar to
CSF. On MRI, similar characteristics to CSF without post-contrast enhance-
ment but bright on diffusion scans
Dermoid cyst On CT, round or lobulated with negative density values and foci of calcification.
There is no contrast enhancement or surrounding oedema. On T1-weighted
images, high signal due to lipid content
Hamartoma Pedunculated hypothalamic mass, isodense on CT and MRI, relatively to grey
matter. It does not calcify or enhance following contrast administration
Schwannoma On CT they appear as contrast enhancing masses that follow the course of
involved nerves. On MRI they appear as well-defined masses isointense on
T1-weighted images with strong contrast enhancement; on T2-weighted images
appear isointense to hyperintense
Rathke’s cyst On MRI appear as discrete cystic lesions with variable signal intensity. They
appear to have the density of CSF, with low intensity on T1 and high intensity on
T2-weighted images. Calcification of the cyst is usually absent and this may
help differentiate them from craniopharyngiomas. Contrast enhancement is
rare and when occurs it is confined to the cyst wall
Data derived from the following references: FitzPatrick et al. (1999), Freda & Post (1999), Zee et al. (2003), Ruscalleda (2005), Smith(2005), Karavitaki et al. (2006), Rennert & Doerfler (2007), Glezer et al. (2008) and Jalali et al. (2008).
G A Kaltsas et al.: Parasellar tumours
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Endocrine-Related Cancer (2008) 15 885–903
applied first as may provide relief of the obstruction
and facilitate further tumour removal (Karavitaki
et al. 2006).
Radiotherapy (RT)
Conventional RT has traditionally been used either as
primary treatment or as a way to prevent further
tumour growth or recurrence (Brada & Cruickshank
1999, Perks et al. 1999). More sophisticated radio-
therapeutic techniques have recently been introduced.
Stereotactic radiosurgery delivers a single fraction of
high-dose ionising radiation on mapped targets,
keeping the exposure of adjuvant tissues to a minimum
and allowing for the delivery of maximum tolerated
dose of between 10 and 15 Gy (Giller & Berger 2005).
Stereotactic RT combines the accurate focal delivery
of stereotactic radiosurgery with the radiobiological
advances of fractionation; compared with conventional
RT, it minimises long-term toxicities by offering
optimal sparing to surrounding tissue (Tarbell et al.
1994). Robotically controlled frameless radiosurgery
has also been developed and studies assessing its
efficacy are awaited (Giller et al. 2005). In general, RT
seems to be a valuable asset in the treatment of these
tumours, albeit with potential adverse effects to nearby
tissue and the HPS (Brada & Cruickshank 1999).
Medical therapy
Chemotherapy remains the primary therapy for
responsive malignant tumours in either a neoadjuvant
or adjuvant setting following surgery and/or RT.
Patients with infrequently curable or unresectable
tumours should be considered candidates for clinical
trials that evaluate interstitial brachytherapy, radio-
sensitisers, hyperthermia, or intraoperative radiation
therapy in conjunction with external RT to improve
local tumour control. Such patients are also candidates
for studies that evaluate new drugs and biological
response modifiers following RT. Therapy of
established or evolving specific pituitary and hypo-
thalamic hormonal deficits should be detected and
adequately treated (Lamberts et al. 1998). Optimum
hormonal replacement therapy should be aimed for,
although even with replacement therapy parasellar
tumours, particularly craniopharyngiomas, have a
worse prognosis compared with pituitary adenomas
(Tomlinson et al. 2001).
Follow-up
Prognosis is dependent on patient status, comorbid
conditions, tumour size and extension, and the precise
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histopathology. Children and adolescents should have
careful monitoring of height, weight and pubertal
status, while a dedicated neuroendocrine team should
screen patients for endocrine and neuropsychological
deficits at regular intervals. Post-operative imaging
should be performed within 3 months of treatment and
generally at 6 and 12 months to evaluate tumour
recurrence or presence of residual tumour.
Malignant tumours of the parasellar region
Gliomas
Gliomas may arise in the hypothalamus, optic chiasm,
nerve or tract (Zee et al. 2003; Fig. 1). The main
histopathological subtype is the pilocytic astrocytoma
(WHO grade I), which is a low-grade malignant lesion
associated occasionally with neurofibromatosis type 1
(NF1; Zee et al. 2003). In this instance, lesions can be
multiple including optic nerve gliomas, low-grade
brain stem gliomas and basal ganglia non-neoplastic
hamartomas (Zee et al. 2003). The remainder of
hypothalamic/optic chiasm lesions are diffuse astro-
cytomas (WHO grade II), representing 35% of all
astrocytic brain tumours (Smith 2005). This type of
tumour typically affects young adults and has a
tendency for malignant progression to anaplastic
astrocytoma and, very rarely, glioblastoma (WHO
grades III–VI). Hypothalamic/chiasmatic astrocytomas
are primarily seen in adulthood presenting with
impaired vision and retro orbital pain (Black & Pikul
1999). In children, they may present with visual loss,
headache, proptosis and the diencephalic syndrome
(Glezer et al. 2008). On imaging, hypothalamic/
chiasmal gliomas are usually large suprasellar masses,
infiltrating the brain and third ventricle, which enhance
homogeneously; rarely, there is necrosis, haemorrhage
or calcification (FitzPatrick et al. 1999). There is
uncertainty as to the optimum therapy, and many can
be simply observed; obviously, visual loss will
determine the need for surgery. The mean survival
time after surgical intervention is between 6 and 8
years, with considerable individual variation (Kitange
et al. 2003). Optic pathway gliomas generally behave
benignly, with very slow growth; however, tumours
around the chiasm/hypothalamus can be more
aggressive, exhibiting a 50% 5-year survival (Kitange
et al. 2003).
Gliomas can also develop in the brainstem and
extend into the parasellar region (Packer 2000,
Guillamo et al. 2001). Diffuse intrinsic low-grade
glioma (WHO grade II) is the most prominent type,
whereas purely malignant brainstem glioma (WHO
grades III–VI) occurs in 31% of cases (Guillamo et al.
889
G A Kaltsas et al.: Parasellar tumours
2001). The median survival of low-grade gliomas is 7.3
years whereas that of high-grade gliomas was 11.2
months (Guillamo et al. 2001). Stereotactic biopsy has
been reported to provide the diagnosis with minimal
morbidity (Packer 2000). Although glucocorticoids
and irradiation may temporarily improve symptoms,
there seems to be no long-term benefit (Recinos et al.
2007). Occasionally, mixed gliomas may occur, for
which temozolomide, an oral derivative of dacarba-
zine, may be useful therapy. Clinical improvement has
been noted in 51% of patients, with a radiological
response rate of 31% (Hoang-Xuan et al. 2004).
Germ cell tumours (GCTs)
Primary intracranial GCTs are neoplasms most
commonly present in the first two decades of life
(Janmohamed et al. 2002; Fig. 2). Like other
extragonadal GCTs, CNS variants develop around the
midline, with 80% arising around the third ventricle,
mostly in the region of the pineal gland, followed by the
suprasellar compartment and anterior hypothalamic
regions (Jennings et al. 1985). Synchronous GCTs at
both these sites are found at w5–10% (Jennings et al.
1985). Germinomatous GCT (GGCT) are the most
exquisitely radiosensitive, whereas non-GGCT
(NGGCT), comprising choriocarcinoma, teratoma,
embryonal sinus (yolk sac) tumour and embryonal
carcinoma, have a poorer overall response to treatment
and aworse prognosis (Allen et al. 1987,Balmaceda et al.
1996). Non-GCT can also contain germinomatous
elements (Calaminus et al. 2005). Pineal GCT classically
give rise to raised IP, hydrocephalus and Parinaud’s
syndrome, whereas suprasellar GCT typically present
with cranial DI, hypopituitarism and visual disturbance,
and may lead to dissemination via the CSF (Legido et al.
Figure 2 Sagittal enhanced T1-weighted image of a germinomawith both a suprasellar and pineal enhancing mass lesions.
890
1989, Janmohamed et al. 2002). Diagnosis is established
by histology but a subgroup can be diagnosed on the basis
of elevation of specific tumour markers (Calaminus et al.
2005), or typical clinical and radiological features. Yolk
sac tumours secrete a-fetoprotein and choriocarcinomas
b-human chorionic gonadotrophin (b-hCG) that can be
detected in the serumand/orCSF (Calaminus et al. 2005).
Approximately 10% of germinomas may contain
syncytiotrophoblastic elements and secrete b-hCG(Matsutani et al. 1997). Germinomas appear as large
lesions typically slight hyperdense on CT that enhance
after contrast medium administration (FitzPatrick et al.
1999). On MRI, they appear isointense to brain on
T1-weighted images and isointense-slightly hyperintense
on T2-weighted images (Rennert & Doerfler 2007).
Although histological confirmation remains the
‘gold standard’ diagnostic method, the combination
of tumour marker estimation and imaging modalities
can be used in secretory GCT (Packer et al. 2000,
Calaminus et al. 2005). This diagnostic tool is
underscored by the fact that several patients with
parasellar GCT have developed surgical procedure-
related complications (Calaminus et al. 2005). It is
therefore important to avoid aggressive surgical
intervention and develop treatment planning on non-
invasive modalities, and only if in doubt to proceed to a
biopsy (Janmohamed et al. 2002, Calaminus et al.
2005). In cases of non-secretory GCT histological
diagnosis is helpful, but again this may be associated
with considerable morbidity (Packer et al. 2000).
A biopsy can usually be obtained with using
stereotactic neurosurgery or neuroendoscopy;
occasionally, the small tissue fragments obtained can
result in histological specimens that are not represen-
tative of the entire lesion (Packer et al. 2000).
Treatment of GCT involves irradiation to the tumour
bed to obtain local control, craniospinal irradiation to
cover leptomeningeal tumour spread, and chemotherapy
to eliminate leptomeningeal and systemic tumour
dissemination (Gobel et al. 2001). When a pre-operative
diagnosis of a GCT has been obtained, then surgical
exploration is not necessary as these tumours are highly
sensitive to chemotherapy and RT (Gobel et al. 2001,
Janmohamed et al. 2002). Platinum-based chemotherapy
has proven to be highly effective in non-seminomatous
GCT (Allen 1987, Balmaceda et al. 1996) A cumulative
dose of cis-platin of over 300 mg/m2 and tumour
bed irradiation dose of w50–54 Gy, together with
craniospinal irradiation, has a synergistic effect and
achieves a long-term relapse-free survival between 60
and 70% (Janmohamed et al. 2002, Calaminus et al.
2005). Neoadjuvant chemotherapy and delayed
residual tumour resection may be more appropriate
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Endocrine-Related Cancer (2008) 15 885–903
than primary tumour resection followed by the same
chemotherapy (Janmohamed et al. 2002). The presence
of CNS dissemination warrants more aggressive
treatment, such as high-dose chemotherapy with
stem-cell transplantation (Guillamo et al. 2001), or
intraventicular treatment (Osuka et al. 2007). Two recent
studies in children and adults have evaluated long-term
treatment sequelae, revealing mainly impairment of
endocrine function, and rare visual, hearing and
neurological deficits (Legido et al. 1989). In general,
our own approach has been to initiate treatment with
chemotherapy in lesions that appear to be characteristic
of germinomas, even in the absence of positive
tumour markers, and then to re-image several weeks
after initial chemotherapy; rapid shrinkage of the tumour
will usually be confirmatory of the diagnosis, and the
treatment completed.
Primary parasellar lymphomas
Primary CNS lymphomas account for less than 2% of all
intracranial lesions (Fine & Mayer 1993; Fig. 3). By
definition, these tumours are extranodal and arise
primarily in the craniospinal axis, and are distinct from
systemic lymphomas that secondarily metastasise to the
CNS (Megan Ogilvie et al. 2005, Liu et al. 2007).
Although initially described in immunocompromised
patients, a significant increase in the incidence of such
lesions has recently been documented in immunocom-
petent patients (Corn et al. 2000). Lymphomas involving
the sellar/parasellar region are even rarer, representing
less than 1% of all cases in a large cohort of patients who
Figure 3 Coronal enhanced T1-weighted image of lymphoma.There is abnormal dural enhancement of both cavernoussinuses extending to involve the pituitary gland itself and withslight thickening of the stalk.
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underwent TSS (Freda & Post 1999). Recently, the
number of primary parasellar lymphomas has substan-
tially increased, the majority being of B-cell origin and
only a minority of T-cell origin; a case of a NK/T-cell
lymphoma has also been reported (Liu et al. 2007).
Approximately 18 patients with sellar/parasellar lym-
phomas have been described with a mean age at
presentation of 55.5 years and male/female ratio of
13:5 (Fine & Mayer 1993, Liu et al. 2007). Endocrine
abnormalities are relatively common, with 72% of
patients exhibiting anterior, and 39% posterior, pituitary
deficiencies respectively (MeganOgilvie et al. 2005, Liu
et al. 2007). In a recent review systemic symptoms, such
as fever of unknown origin, were the presenting
symptoms in 22% of patients, whereas the commonest
presenting compressive symptoms were headache
(56%), diplopia (39%) and visual field defects (28%)
respectively (Liu et al. 2007). MRI may demonstrate
enhancing parasellar masses with diffuse enlargement of
the pituitary (94%), suprasellar extension (44%),
cavernous sinus extension (39%) and stalk thickening
(22%; Liu et al. 2007). Lymphomas usually appear iso-
or hyperdense on CT scanning and isointense on T1-
weighted and slightly hypointense on T2-weighted
images and enhance homogeneously after gadolinium
administration (Buhring et al. 2001). The diagnosis of
primary lymphomas is established histologically and
their treatment includes surgery, chemotherapy and RT
according to established protocols (Megan Ogilvie et al.
2005, Glezer et al. 2008).
Metastases to the parasellar region
Metastases to the parasellar region are relatively rare,
found in less than 1% of patients undergoing TSS for
sellar/parasellar lesions (Komninos et al. 2004).
However, autopsy series have revealed that metastases
to the region comprise between 0.14 and 28.1% of brain
metastases, the most common primaries being breast
and lung cancer in women and men respectively;
however, virtually any neoplasm can metastasise to the
pituitary (Chiang et al. 1990, Sioutos et al. 1996, Megan
Ogilvie et al. 2005). In a significant number of patients,
the parasellar area and the pituitary gland may appear
macroscopically normal besides the presence of metas-
tases that remain clinically non-significant (Ito et al.
2001). Most cases are found in the sixth–seventh decade
of life as part of a generalised metastatic spread,
commonly associatedwithmultiple, particularly osseous
metastases (Chiang et al. 1990, Sioutos et al. 1996).
However, they can occur in young patients, and very
occasionally are the first manifestation of an occult
cancer or the only site of metastasis (Sioutos et al. 1996).
891
Figure 4 Sagittal unenhanced T1-weighted image of acraniopharyngioma. The mass is inseparable from the chiasmand hypothalamus and is predominantly of low T1 signalsuggesting a cystic mass, although without a high lipid content.
G A Kaltsas et al.: Parasellar tumours
Symptomsofmass effect and cranial nerve palsies are the
most frequent symptoms; when metastatic lesions
involve the pituitary gland, hormonal deficiencies,
particularly DI, develop (Sioutos et al. 1996, Komninos
et al. 2004). Although clinically indistinguishable from
other lesions involving the area, specific clinical settings
may point to the diagnosis (Komninos et al. 2004). The
rapidity of development of symptoms of mass effect,
particularly ophthalmoplegia secondary to VI nerve
involvement, in association with the sudden onset of DI
in patients over 50 years, strongly suggests the presence
of metastases irrespective of a history of malignancy
(Ruelle et al. 1992, Sioutos et al. 1996, Morita et al.
1998). Although not specific, radiology can help identify
parasellar metastases in the presence of other brain
metastases and/or rapidly growing lesions; involvement
of the infundibular recess favours a metastatic lesion
(Morita et al. 1998,Komninos et al. 2004). In the absence
of a primary and/or othermetastatic lesions, confirmation
of the diagnosis relies on histology (Chiang et al. 1990).
Treatment is mainly palliative and depends on the
symptoms and the extent of systemic disease (Morita
et al. 1998). Due to the invasive, vascular and
haemorrhagic nature of the lesions, surgical excision is
not usually possible (Sioutos et al. 1996). However,
surgical debulking may offer improvement of symptoms
ofmass effect; this should be followed by local radiation,
systemic chemotherapy and adequate hormonal sub-
stitution. Radiosurgery is sometimes a useful alternative,
particularly for previously irradiated regions, and for
smaller lesions (diameter !30 mm). The overall
prognosis is poor, with a median survival of less than 2
years (Laigle-Donadey et al. 2005).
Supratentorial primitive neuroectodermal tumour is
an embryonal tumour (WHO grade IV) of the cerebrum
or suprasellar region composed of undifferentiated or
poorly differentiated neuroepithelial cells, which have
the capacity for differentiation along neuronal, astro-
cytic, ependymal, muscular or melanocytic lines (Ohba
et al. 2008). Synonyms include cerebral medulloblas-
toma, cerebral neuroblastoma, cerebral ganglioneuro-
blastoma and ‘blue tumour’. This rare tumour occurs
mainly in children with an overall 5-year survival rate
of 34% (Ohba et al. 2008).
Ependymoblastoma is a rare, malignant, embryonal
brain tumour (WHO grade IV) that occurs in neonates
and young children. Ependymoblastomas are often
large and supratentorial and generally relate to the
ventricles, though they can occur in the parasellar
region (Matthay et al. 2003). These types of tumours
grow rapidly, with craniospinal dissemination, and
have a fatal outcome within 6–12 months of diagnosis
(Matthay et al. 2003).
892
Potentially malignant parasellar lesions
Craniopharyngiomas
Craniopharyngiomas are rare epithelial tumours that
arise along the pathway of the craniopharyngeal duct
(Bunin et al. 1998; Figs 4 and 5). They account for
2–5% of all primary intracranial neoplasms and follow
a bimodal age distribution with a peak incidence rate in
children and adults between the ages of 5 and 14 and 50
and 74 years respectively (Bunin et al. 1998). The
majority show a suprasellar component (94–95%), and
may extend into the anterior, middle or posterior fossa
(Petito et al. 1976). Tumours can be solid (1–16%), but
most are cystic or mixed (84–99%); cysts may be
multiloculated and contain liquid that has high content
of membrane lipids and cytokeratins (Karavitaki et al.
2006). Despite their benign histological appearance
(WHO grade I), their infiltrative tendency into critical
parasellar structures and aggressive behaviour, even
after apparently successful treatment, heralds a
significant morbidity and mortality (Karavitaki et al.
2006). Cases of malignant transformation have also
been described, for which the role of previous RT has
not been discounted (Nelson et al. 1988). There are two
primary histological subtypes: the adamantinous and
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Figure 5 Sagittal enhanced T1-weighted image of a solidlyenhancing craniopharyngioma. This mass is inseparable fromthe hypothalamus and chiasm. There is an area of low signalwithin the mass representing calcification (confirmed on CT).
Endocrine-Related Cancer (2008) 15 885–903
the papillary, but transitional or mixed forms have also
been recognised (Zhang et al. 2002). The adamanti-
nous subtype is the most common and bears some
similarity to the adamantinoma of the jaw (Karavitaki
et al. 2006), accounting for the calcification and the
development of teeth encountered particularly in
children (Petito et al. 1976). Adamantinous cranio-
pharyngiomas tend to adhere to the surrounding brain
tissue, often making complete surgical resection
impossible (Petito et al. 1976). The papillary variety,
mostly found in adults, is well circumscribed and
shows less infiltration to adjacent tissues (Karavitaki
et al. 2006). Although, headaches, nausea/vomiting,
papillo-oedema, cranial nerve palsies and hydro-
cephalus are more frequent in children, a large series
found no differences when compared the presenting
manifestations among children and adults (Karavitaki
et al. 2006). Spontaneous rupture of cystic craniophar-
yngioma is rare, but when it occurs can cause chemical
ventriculitis and meningitis (Zee et al. 2003).
Endocrine dysfunction in children manifests as growth
failure in 93% or delayed sexual development in
w20% (Freda & Post 1999). Many adults present with
a variety of anterior pituitary hormone deficiencies and
23% develop DI (Freda & Post 1999). CT is the ideal
modality for the evaluation of the bony anatomy,
identification of calcification and in distinguishing the
solid and cystic components of the tumour (Pusey et al.
1987). Pre- and post-contrast enhanced images identify
the cystic lesions as a non-enhancing areas of low
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attenuation; the solid component and the cystic capsule
appear as contrast-enhancing areas (Pusey et al. 1987).
MRI following contrast enhancement offers valuable
topographic and structural analysis (Karavitaki et al.
2006; Table 2). Radical surgery may be successful in
selected tumours; however, when surgical removal was
substantiated with radiological confirmation, complete
removal was accomplished in 18–84% of cases, clearly
a wide range (Hald et al. 1994). Post-operative RT
following either complete or incomplete tumour
removal is associated with significantly decreased
recurrence rate; RT alone provides 10-year recurrence
rates between 0 and 23% (Rajan et al. 1997). Although
the optimum total dose or fractionated protocols have
not been established, it seems that recurrences are
fewer with total doses above 54 Gy (Karavitaki et al.
2006). Recurrent tumours develop at a mean interval
between 1 and 4.3 years, but recurrences as late as 26
years have been described (Coke et al. 1998); such
tumours exhibit higher microvessel density values
(Vidal et al. 2002), and chromosomal aberrations
(Lefranc et al. 2003). Stereotactic radiosurgery is used
for well-defined residual tumour tissue after surgery or
for the treatment of small solid recurrent tumours,
especially after failure of conventional RT (Suh &
Gupta 2006). In large cystic portions, multimodality
approaches with installation of radioisotopes or
bleomycin may provide further benefits (Karavitaki
et al. 2006). Recurring tumours and those that have
undergone malignant transformation have been treated
with systemic chemotherapy and interferon-a, albeitwith short-lived results (Karavitaki et al. 2006).
However, the treatment for aggressive tumours
remains to be assessed by trials including large number
of patients with adequate follow-up. In general, our
own approach has been to attempt surgical removal,
TSS where possible, but not to be radical where this
may in any way compromise the hypothalamus;
this would generally be followed by standard
fractionated RT.
Chordomas and chondrosarcomas
Approximately 10% of non-pituitary parasellar lesions
are cartilaginous, originating from the primitive
notochord in the skull base, chordomas being more
frequent than chondrosarcomas (Allan et al. 2001;
Fig. 6). These are slowly growing tumours presenting
with visual complaints, mainly diplopia, whereas a
third of patients complain of headache (Korten et al.
1998). Less common presentations include dizziness,
tinnitus, facial sensory deficits, ataxia and hemiparesis.
Both tumours are associated with extensive bone
893
Figure 6 Coronal enhanced T1-weighted image of a chon-drosarcoma. This is an enhancing mass involving the left side ofthe sella and the cavernous sinus, but arising from the skullbase just off midline.
G A Kaltsas et al.: Parasellar tumours
destruction (Meyers et al. 1992) but significant
endocrinopathy is unusual, although anterior pituitary
deficiencies may be encountered, particularly with
chordomas (Allan et al. 2001). Following the establish-
ment of clearly defined histopathological criteria, a
distinction can be made as both tumours are positive
for S-100 protein but, unlike chordomas, chondrosar-
comas are negative for cytokeratin markers (CAM 5–2)
and epithelial membrane antigens (Salisbury &
Isaacson 1986). Intracranial chordomas are most
frequently seen around the third decade and in
w10–15% can be intradural (Allan et al. 2001).
Chordomas can reach considerable size at the time of
diagnosis and patients may develop neck pain and
nasopharyngeal obstruction, and some tumours may
progress to malignant transformation (Rennert &
Doerfler 2007). These tumours can extend along the
entire skull base causing destruction of the sella instead
of the ballooning often seen in pituitary adenomas
(Glezer et al. 2008). Bone destruction and calcification
occur in 50% of cases and are better seen on CT; on
MRI they appear heterogeneously hyperintense on T2-
weighted images and show marked contrast enhance-
ment (Rennert & Doerfler 2007).
Less than 200 cases of intracranial chondrosarcomas
have been described (Korten et al. 1998). These
malignant tumours (WHO grades II–III) occur more
commonly in the axial part of the skeleton, represent-
ing less than 5% of skull base tumours with w75%
arising in the parasellar region (Kunanandam &
Gooding 1995). Chondrosarcomas arise off the midline
at the suture line, unlike chordomas that arise from the
894
clivus in the midline. Radiological examination almost
always reveals bone destruction and variable degrees
of calcification on CT, involvement of the neural and
vascular structures on MRI, and mostly hypovascular-
ity on angiography (Korten et al. 1998). Occasionally,
cyst-like hypodense centres secondary to necrosis can
be found (Cohen-Gadol et al. 2003). Although
chondrosarcomas rarely metastasise outside the skull
they tend to have a better 5-year survival rate compared
with chordomas, they expand locally and compress
adjacent structures (Rosenberg et al. 1994). Surgery is
the treatment of choice for both tumours; however, due
to bone invasiveness, total excision is generally not
possible (Glezer et al. 2008). Given the importance of
residual tumour volume as a prognostic indicator,
adjacent therapy is frequently employed (Allan et al.
2001). Standard external RT has been disappointing in
achieving local control although most of the reported
cases refer to chordomas, but radiosurgery may be
more effective (Allan et al. 2001). Although a
sustained response to the combination of ifosfamide
and doxorubicin in a case of recurrent chondrosarcoma
has been described, in most cases chemotherapy fails
(La Rocca et al. 1999).
Haemangiopericytomas
Haemangiopericytomas are rare tumours accounting
for less than 1% of all intracranial tumours (Glezer
et al. 2008, Jalali et al. 2008). Although the majority
are supratentorial, parasagittal or falcine, they can
rarely arise in the sellar/parasellar region with less than
ten cases reported (Jalali et al. 2008). These tumours
are aggressive and highly vascular with numerous
penetrating vessels; although previously considered as
a subtype of angioblastic meningioma, they represent
distinctive mesenchymal neoplasms arising from
pericytes (Stout & Murray 1942). Besides the absence
of firmly established histological criteria for grading
haemangiopericytomas, they appear to correspond to
WHO grades II–III (Kleihues et al. 1993). Most
patients present in middle aged with visual field
defects, headaches and rarely symptoms of endocrine
dysfunction; a case of acromegaly due to a GHRH-
secreting haemangiopericytoma has been described
(Yokota et al. 1985). Surgery followed by RT is the
standard treatment; however, as haemapericytomas are
highly vascular and tend to bleed profusely, it is critical
that the neurosurgeon bases his approach on a
reasonable pre-operative diagnosis (Mena et al. 1991,
Suh & Gupta 2006). Local tumour recurrence
following treatment is common, and late widespread
metastasis can occur (Jalali et al. 2008). In two large
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Endocrine-Related Cancer (2008) 15 885–903
series haemangiopericytomas recurred in 91 and 85%
after 15 years (Mena et al. 1991, Jalali et al. 2008).
Cystic and necrotic areas, haemorrhage and prominent
vascular channels contribute to the heterogeneity in
signal intensity (Zee et al. 2003).
Langerhans’ cell histiocytosis (LCH)
LCH is a rare disease characterised by the clonal
accumulation and/or proliferation of specific dendritic
cells and in this manner represents a neoplastic
disorder (Arceci 1999; Fig. 7). LCH shows a particular
predilection for involvement of the HPS leading to DI
and/or anterior pituitary dysfunction (Arceci 1999,
Makras et al. 2007), but can virtually involve any
organ such as bone, lung, skin, liver, spleen, lymph
nodes and bone marrow (Makras et al. 2007). Making
an early and accurate diagnosis is important as
multisystem LCH is associated with a 20% mortality
rate, and 50% of those who survive develop at least one
permanent consequence (Makras et al. 2007).
Although there is no specific MRI appearance of
HPS–LCH, almost all patients with LCH-induced DI
demonstrate loss of the physiologic intense signal
‘bright spot’ of the posterior pituitary; other common
MRI findings are infundibular enlargement, and/or
the presence of hypothalamic mass lesions (Kaltsas
et al. 2000). In cases where a precise diagnosis cannot
be obtained histological diagnosis from the parasellar
pathology may be required (Kaltsas et al. 2000).
Figure 7 Coronal enhanced T1-weighted image of Langerhans’cell histiocytosis. There is diffuse enlargement and enhance-ment of both cavernous sinuses. The pituitary gland is bulky,although the stalk is not thickened.
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The combination of vinblastine with steroids is the
most frequently used initial therapy of LCH involving
the CNS and for multisystem disease (Arico et al.
2003). Although etoposide was initially extensively
used, it is not used any long due to its associated high
risk for the development of leukaemia (Arico et al.
2003). The purine analogue cladribine (2--
chlorodeoxyadenosine, 2-CdA) has been shown to be
effective for patients with recurrent and/or dissemi-
nated disease (Makras et al. 2007). RT, at doses up to
25 Gy, has been used in patients with endocrine
deficiencies and radiological involvement of the
parasellar region with partial or temporary radiological
improvement (Arico et al. 2003).
Mainly benign lesions
Meningiomas
Meningiomas (WHO grade I) are the most common
non-glial primary brain tumour comprising 15% of
primary brain tumours with a peak incidence between
40 and 70 years (Zee et al. 2003; Figs 8 and 9).
Tumours arise from the diaphragma sella, tuberculum
sella, medial lesser wing of sphenoid, anterior clinoid,
clivus cavernous sinus or optic nerve sheath (Smith
2005). In w10–15% of cases, meningiomas arise from
the parasellar region and represent the commonest
tumour of that region after pituitary adenomas; rarely,
they occur entirely within the sella mimicking a
pituitary adenoma (FitzPatrick et al. 1999). There is
a strong association between meningiomas, NF
(multiple tumours) and ionising radiation, depending
on the dose applied (Hartmann et al. 2006). The
clinical presentation is usually with visual disturbance
and occasionally endocrine dysfunction with mildly
raised prolactin levels (Freda & Post 1999). The visual
field defects vary and depend on the location of the
tumour; meningiomas may increase in size during
pregnancy and then become symptomatic (Freda &
Post 1999). Atypical (WHO grade II) meningiomas
may develop in 4–7%, whereas anaplastic tumours
(WHO grade III) are seen in 1–2.8% of cases
(Hartmann et al. 2006). However, malignant
behaviour, although very rare, may occur with any
grade of meningioma (Bruna et al. 2007, Ko et al.
2007). Imaging features of meningiomas frequently
allow pre-operative diagnosis, distinguishing them
from other parasellar tumours (Smith 2005). Lesions
arise from the dura and have a broad attachment to the
dura or fill and expand the cavernous sinus. There may
be a linear, enhancing dural tail extending along the
dura away from the lesion. Bone reaction, with bone
thickening and sclerosis, or expansion of the sphenoid
895
Figure 8 Sagittal enhanced T1-weighted image of a suprasellarmeningioma. The mass lies above the pituitary (which isnormal), involves the chiasm and extends anteriorly along theplanum sphenoidale.
G A Kaltsas et al.: Parasellar tumours
sinus air space, may also be seen (Smith 2005).
Meningiomas typically are similar to grey matter in CT
density and T1- and T2-weighted MR image signal
intensity, enhancing homogeneously and brightly with
occasional areas of diffuse calcification (Smith 2005).
In contrast to other parasellar tumours, meningiomas
encase blood vessels and tend to narrow the lumen
(Young et al. 1988). Surgical excision, particularly in
the presence of symptomatic or growing lesions,
remains the treatment of choice (WHO I). Following
Figure 9 Coronal enhanced T1-weighted image of a menin-gioma in the left cavernous sinus. The meningioma enhancesavidly, expands the cavernous sinus and is causing somenarrowing of the left cavernous carotid artery, which is ofsmaller calibre than the right carotid.
896
surgical excision, grade I tumours recur in 7–20%,
whereas atypical and anaplastic recur in 39–40% and
50–78% respectively (Bruna et al. 2007, Ko et al.
2007, Nakane et al. 2007). Surgery and RT is used in
selected cases, such as for patients with known or
suspected residual disease or with recurrence after
previous surgery, whereas radiation alone is used in
patients with unresectable tumours (Freda & Post
1999, Aghi & Barker 2006). The prognosis is worse for
patients with WHO grades II and III tumours as
complete resection is less common and the prolifera-
tive capacity is greater (Bruna et al. 2007, Ko et al.
2007, Nakane et al. 2007). Malignant histology is
generally associated with a poor prognosis with a
survival less than 2 years (Hartmann et al. 2006, Bruna
et al. 2007, Nakane et al. 2007).
Rathke’s cysts
Rathke’s cleft cysts arise from remnants of squamous
epithelium of Rathke’s pouch and consist of a single
layer of epithelial cells with mucoid, cellular or serous
components in the cyst fluid (Freda & Post 1999;
Fig. 10). Although the majority has a major intrasellar
component, about a third can extend into the parasellar
region; occasionally they can be entirely suprasellar
(Mukherjee et al. 1997, Freda & Post 1999). Many of
these are small and asymptomatic, but they may
become symptomatic due to compressive symptoms
and pituitary hormonal deficiencies, when DI may
develop in up to 20% (Mukherjee et al. 1997). Atypical
presentations include haemorrhages into the cyst and
Figure 10 Sagittal enhanced T1-weighted image of a Rathke’scleft cyst. The cyst is seen to be non-enhancing and lying on thesuperior aspect of the pituitary gland that appears flattened. It iscausing elevation of the optic chiasm.
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Figure 11 Sagittal enhanced T1-weighted image of a hypo-thalamic hamartoma. This is seen as a pedunculated masshanging from the undersurface of the hypothalamus. It does notenhance and has the same signal as the grey matter of the brainparenchyma.
Endocrine-Related Cancer (2008) 15 885–903
abscess formation rarely can coexist with pituitary
adenomas (Mukherjee et al. 1997). They are distin-
guished from craniopharyngiomas histologically by
having walls composed of columnar or cuboidal
epithelium (FitzPatrick et al. 1999). Although no
specific radiological features have been identified,
Rathke’s cysts appear as discrete cystic and non-
enhancing lesions on MRI with variable signal
intensity on either T1- or T2-weighted images; these
lesions need to be differentiated from craniopharyn-
giomas and arachnoid cysts (Mukherjee et al. 1997,
Freda & Post 1999). Treatment involves drainage of
the fluid with or without resection of the cystic wall
(Mukherjee et al. 1997, Freda & Post 1999). Although
these lesions tend not to recur, repeated resections may
be required in as many as a third of patients; it has been
suggested that many relapsing lesions may contain
overlapping histological features with craniopharyn-
giomas (Mukherjee et al. 1997, Freda & Post 1999).
The role of RT for recurrent lesions has not been
clearly defined (Mukherjee et al. 1997).
Epidermoids/dermoids
These benign tumours (WHO grade I) comprise less
than 2% of all intracranial tumours and arise as a result
of incomplete separation of the neuroectoderm from
cutaneous ectoderm (FitzPatrick et al. 1999). Epider-
moids/dermoids occur in the cerebellopontine angle,
pineal region, middle cranial fossa as well as in the
suprasellar region, and consist of tissue of purely
epidermal origin; dermoids also contain tissue of
mesodermal origin (hair follicles, fat, sebaceous
glands). Tumours are cystic structures lined by
keratinised squamous epithelium and the clinical
presentation may be due to local mass effect such as
hydrocephalus, visual disturbance, hypopituitarism, DI
and/or cranial nerve abnormalities (Freda & Post
1999). On CT scan, the cyst contents are very similar
to CSF; both lesions are often hypointense on T1- and
hyperintense on T2-weighted MR images and do not
enhance with contrast. Depending upon fat and
calcium content, dermoid tumours can show a
hyperintense signal in T1 images (Rennert & Doerfler
2007). Diffusion-weighted images can be helpful in
epidermoids, typically showing a markedly increased
signal (Rennert & Doerfler 2007).
Hypothalamic hamartomas
Hypothalamic hamartomas are of neuronal origin and
represent congenital heterotopias usually located
within the tuber cinereum and mostly affecting
children causing precocious puberty and epileptic
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seizures (Judge et al. 1977; Fig. 11). As they are
usually less than 2 cm in diameter, they produce few
symptoms of mass effect (Freeman et al. 2004).
Typically, they appear as non-enhancing lesions and
demonstrate rounded expansion of the tuber cinereum,
best seen in coronal and sagittal images; they are
isointense to the cerebral cortex in both T1- and
T2-weighted MR images (Rennert & Doerfler 2007).
Thehamartomas associatedwithprecociouspubertymay
contain GNRH1 neurons, and have been classically
associated with ‘gelastic’ (laughing) seizures.
Paragangliomas
Paragangliomas are rare, usually encapsulated and
benign neoplasms (WHO grade I), that arise in
specialised neural crest cells associated with segmental
or collateral autonomic ganglia (Freeman et al. 2004).
Although the majority develop in the carotid body and
jugular glomus, paraganglionic cells have been demon-
strated in the pituitary gland and adjacent structures
(Steel et al. 1993). Only seven cases of intrasellar, two
cases of suprasellar and four cases of parasellar non-
malignant paragangliomas have been described (Boari
et al. 2006). Tumour location is more relevant than
histology in assessing prognosis; the metastatic rate in
para-aortic paragangliomas ranges between 28 and
42%, whereas only 5% of CNS paragangliomas exhibit
metastatic potential (Boari et al. 2006). Symptoms of
pituitary hormonal deficiency and mass effects are the
897
Figure 13 Coronal enhanced T1-weighted image of a left sidedSchwannoma of the trigeminal nerve. There is an enhancingmass expanding the left cavernous sinus which followed thecourse of the trigeminal nerve on other images.
G A Kaltsas et al.: Parasellar tumours
main presenting symptoms (Steel et al. 1993, Boari
et al. 2006). Surgical excision, when possible, remains
the treatment of choice; there are no data regarding the
prophylactic effect of RT on tumour recurrence.
Lipoma
Lipomas are benign fatty tumours, derived from
remnants of maldevelopment of the primitive meninx
(Smith 2005; Fig. 12). In the sellar region, they occur
as lesions adherent to the surface of the infundibulum,
floor of the third ventricle or adjacent cranial nerves
(Smith 2005). They are usually discovered incidentally
but rarely may enlarge and produce symptoms.
Lipomas are all well-circumscribed, homogeneous
lesions that appear identical to fat on CT and all MRI
sequences, do not enhance and usually exhibit rim
calcification (Smith 2005).
Schwannoma/Neurinoma
Nerve sheath tumours (WHO grade I) in the parasellar
region are very rare and usually arise from the
trigeminal nerve (V1/V2) or the III, IV and VI cranial
nerves (Rennert & Doerfler 2007; Fig. 13). Neurinomas
are slowly growing tumours, rarely causing bony
remodelling of the lateral portion of the sella or the
apex of the petrous bone (Rennert & Doerfler 2007).
Schwannomas are slow-growing tumours that may
erode the walls of cavernous sinus, are found in
associationwithNF2 and exhibit inactivatingmutations
of the NF2 gene in 60% (Aghi & Barker 2006).
They usually develop symptoms of trigeminal nerve
Figure 12 Sagittal unenhanced T1-weighted imageof a suprasellar lipoma. The high signal mass containing fat isseen lying on the undersurface of the hypothalamus in theinterpeduncular cistern.
898
involvement and extremely rarely they can undergo
malignant change (Aghi & Barker 2006). On MRI and
CT, they show an intense (usually heterogeneous)
contrast enhancement (Rennert & Doerfler 2007).
Parasellar granular cell tumours
These are rare tumours originating from either the
neurohypophysis or infundibulum and include
myoblastomas, choristomas and infundibulomas (Cone
et al. 1990, Cohen-Gadol et al. 2003; Fig. 14). In 50% of
cases cause anterior pituitary hormone deficiencies and
hyperprolactinaemia, and rarely visual field defects
(Freda & Post 1999). Although choristomas arise from
the infundibulum and/or posterior lobe, only two cases of
Figure 14 Sagittal enhanced T1-weighted image of a granularcell tumour. This enhancing mass lesion involves the pituitarystalk and the median eminence.
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Endocrine-Related Cancer (2008) 15 885–903
DI have been described; a case presenting with
acromegaly secondary to GHRH secretion has also
been described (Cohen-Gadol et al. 2003). These lesions
are typically isointense to brain, and enhance inhomo-
geneously (Freda & Post 1999). Their firm and vascular
nature, alongwith the lack of an obvious dissection plane
between the tumour and normal brain, prohibits gross
total resection (Cohen-Gadol et al. 2003). Although
radiation therapy has been used, the recurrence rate in
those who underwent RT was not different compared
with those who did not, 4.7 and 5.4 years respectively
(Cohen-Gadol et al. 2003).
Ganglion cell tumours (gangliocytoma)
These are rare tumours that consist of purely neuronal
or mixed adenomatous and neuronal tissue, usually
found in association with a hormonally active pituitary
tumour (Freda & Post 1999). Gangliocytoma (WHO
grade I) and ganglioglioma (WHO grades I–II) are
well-differentiated, slow-growing neuroepithelial
tumours comprised of neoplastic, mature ganglion
cells, either alone (gangliocytoma) or in combination
with neoplastic glial cells (ganglioglioma). Anaplastic
gangliogliomas (WHO grade III) are sometimes seen;
rare cases exhibit WHO grade IV (glioblastoma)
changes in the glial component. The correlation of
anaplasia with clinical outcome is inconsistent (Day
2003, Zee et al. 2003).
Rare parasellar tumours
Ependymomas are glial neoplasms that very rarely can
develop in the parasellar region with only four cases
described up to date; surgery with or without RT is the
treatment of choice (Karim et al. 2006). Pituitocytoma
is a primary tumour of the neurohypophysis, also
located at the pituitary stalk, presenting with headache
and hypopituitarism. Although histologically benign,
the location and vascular nature of the tumour makes
surgical resection difficult (Glezer et al. 2008). Other
tumours such as plasmatocytomas, brown cell tumours
and melanocytic tumours have been described as cases
reports (Glezer et al. 2008).
Non-neoplastic pathologies involving the
parasellar region
A number of non-neoplastic processes can also involve
the parasellar region and present in a similar manner to
parasellar neoplasms (Table 1). Their diagnosis is
usually established in the presence of relevant clinical
settings and if necessary histologically. Abscesses in
the region can develop following direct extension from
the sphenoid sinus, cavernous sinus and CSF or
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secondary to bacteraemia; masses of the sella can
become secondarily infected (Freda et al. 1996).
Tuberculosis can produce basilar meningitis and
findings suggestive of a sellar/parasellar mass with
hypopituitarism; there is usually evidence of tubercu-
losis elsewhere (Freda et al. 1996). Fungal, parasitic
and opportunistic infections may also develop particu-
larly in immunocompromised patients (Freda & Post
1999). Sarcoidosis can also present in a similar manner
with varying degrees of hypopituitarism, DI and
cranial neuropathy that in a minority can occur without
evidence of sarcoidosis elsewhere (FitzPatrick et al.
1999). Other granulomatous diseases that can involve
the parasellar region include giant cell granulomatous
hypophysitis, Wegener’s granulomatosis and the
Tolosa–Hunt syndrome (Glezer et al. 2008). Aneur-
ysms originating from the cavernous sinus or circle
of Willis can project into the parasellar region and
their appearance is mostly affected by the amount of
calcification and thrombosis present within the
aneurysms (Zee et al. 2003).
Summary
The parasellar region can be affected by a variety of
tumours. The presentation of these tumours can be
similar to that of large non-functioning pituitary
tumours with extensive extrasellar extension and
other non-neoplastic lesions involving the same region.
Although symptoms of mass effect to adjacent
structures and anterior pituitary endocrine deficits do
not distinguish parasellar tumours from non-function-
ing pituitary tumours, the presence of DI directs
towards a non-pituitary aetiology. Considering the
specific morphological characteristics of MRI and CT,
a presumptive diagnosis is possible in many cases of
parasellar lesions. However, in the majority of cases
their diagnosis involves a multidisciplinary effort
including detailed endocrinological, ophthalmological,
neurological and imaging procedures. In cases of
doubt, a histological diagnosis may still be required to
allow appropriate treatment planning. Treatment
involves a joint effort requiring the collaboration of
different specialties. Although a significant number of
parasellar tumours are slow growing and mostly
benign, it is important to identify those which are
malignant and/or exert a strong malignant potential.
Surgical decompression and/or clearance of the tumour
along with means to prevent recurrence and/or further
tumour growth, such as RT, are usually applied.
Specific hormonal replacement therapy of established
or evolving endocrine deficits is required to maintain
the patient’s quality of life. Primary or adjuvant
899
G A Kaltsas et al.: Parasellar tumours
medical treatment may be necessary for malignant,
recurrent tumours and/or tumours undergoing malig-
nant transformation. Multidisciplinary teams for the
management and support of patients with these
tumours are required for better long-term results.
Tumour-specific therapies are required and need to
be addressed on the basis of tumoral biology. The
central registration of patients seems necessary as it
may provide correlates between forms of treatments
and outcomes and establish prognostic factors at the
pathological or molecular level.
Declaration of interest
These authors declare that there is no conflict of interest that
could be perceived as prejudicing the impartiality of the
research reported.
Funding
This research did not receive any specific grant from any
funding agency in the public, commercial or not-for-profit
sector.
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