2.4.3 Perisellar tumours including cysts, hamartomas, and vascular tumours

Approximately 80% of symptomatic tumours in the pituitary region are pituitary adenomas and further 10% are craniopharyngiomas. Among the remaining 10%, a considerable number of rare tumour entities have to be considered (Box 2.4.3.1) which makes the differential diagnosis sometimes difficult. Endocrinological, neuroradiological, and ophthalmological evaluation is the indispensable diagnostic triad to identify typical features in nonadenomatous perisellar tumours, and to provide diagnostic accuracy. This chapter presents typical clinical aspects of various nonadenomatous sellar tumours and the differential diagnostic value of specific symptoms. The current therapeutic strategies are also described.

It is assumed that Rathke’s cleft cysts are related to embryonal pituitary development and consist of remnants of Rathke’s pouch. Microscopic Rathke’s cysts are found during autopsies in 30% of normal pituitary glands. However, it is relatively uncommon for Rathke’s cysts to enlarge considerably in size and become clinically symptomatic. Rathke’s cysts can become symptomatic in childhood or in adulthood.

Essentially, Rathke’s cysts cause three symptoms. In order of frequency these are: hormonal impairments (Fig. 2.4.3.1 and Fig. 2.4.3.2), headache, and impaired vision (1). In the largest published series on 28 symptomatic Rathke’s cleft cysts, endocrine symptoms at presentation were amenorrhea (37.5%), hypopituitarism (14.3%), retarded growth (7.1%), decreased libido and impotence (8.3%) and diabetes insipidus (3.6%) (1). Perception of amenorrhea may explain the more common finding of Rathke’s cysts in women.

MRI is the best technique for evaluation of perisellar cysts. Usually, Rathke’s cleft cysts are rounded lesions. The hyperintense appearance of the protein-rich cyst contents on T₁-weighted images is characteristic but not obligatory. There are two typical locations:

Figure 2.4.3.3 shows a typical suprasellar Rathke’s cleft cyst above the pituitary body and rostral to the hypophyseal stalk. After contrast administration, the thin wall of the cyst may show a moderate enhancement.

Surgery is indicated for these benign cysts only when there is evidence of hormonal or opthalmological deficits or a large space-occupying cyst is present. The vast majority of Rathke’s cysts can be removed by transsphenoidal surgery. Purely suprasellar cysts around the pituitary stalk can be excised using the transsphenoidal, transtuberculum sellae approach. The objective of surgery is drainage of the cyst and biopsy or partial excision of the cyst wall. Radical resection of the often adherent and thin capsule is usually not performed due to the increased morbidity, e.g. nasal cerebrospinal fluid (CSF) fistula, pituitary deficiency. Histologically, the wall of the cyst is mainly lined by columnar ciliated and globlet cells and occasionally with pituitary hormone-producing cells (2). Cases with secondary inflammatory reaction, possibly as a result of a ruptured capsule, have been described.

Hypopituitarism and visual impairment often improve postoperatively. As in the case of pituitary adenomas, however, it is observed that the chances of recovery are limited in cases with serious preoperative deficits (1). The recurrence rate is also relatively low, even in incomplete resection of the cyst wall.

Sellar colloid cysts are often misinterpreted as pituitary adenomas.

Usually, sellar colloid cysts are a chance finding and there are no endocrinological impairments. Surgical treatment is only indicated in cases of symptomatic colloid cysts. In neurosurgical series, the patients are mostly women with menstrual period disruption, galactorrhoea, and headache as the main presenting symptoms. Endocrine deficits are usually mild. In one study, formal endocrinological examination revealed hyperprolactinaemia and hypogonadism in 72% of the symptomatic cases (3). Panhypopituitarism is an exceptional finding.

The oval configuration (like a rugby ball) and localization between the anterior lobe and the posterior lobe of the pituitary are characteristic and reliable features to consider in the differential diagnosis (Fig. 2.4.3.4). Larger cysts may extend into the suprasellar region. In T₁-weighted images, colloid cysts appear hypointense and there is no contrast accumulation at the cyst boundaries.

Surgical draining of symptomatic colloid cysts is performed by transsphenoidal approach. Colloid material is removed. Sellar colloid cysts do not exhibit an epithelial lining but normal pituitary tissue is usually found in specimens of the adjacent tissue (3). Therefore, sellar colloid cysts must be regarded as ‘pseudocysts’. This is probably the reason why they do not appear in current histopathological classifications of sellar tumours and cysts. However, they are relatively frequent sellar lesions and represent a clearly distinct clinical entity. The pathogenesis has not yet been completely elucidated. It has been suggested that sellar colloid cysts are a result of cellular degeneration (3). They must not be confused with colloid cysts of the third ventricle, which are a totally different entity.

Headaches often subside postoperatively. The endocrinological deficits mostly regress and normal prolactin levels are restored. No recurrence is usually expected.

Arachnoid cysts constitute a nonproliferative anomaly of the arachnoidea. An expansile, ‘tumour-like’ cyst can arise due to a loculated collection of cerebrospinal fluid (CSF) within the duplication of the arachnoidal membrane. The pathophysiological mechanism behind the development of intrasellar arachnoid cysts is not fully understood and they are relatively uncommon. In 2007, Dubuisson et al. (4) reported on 14 published series and case reports which included a total of 42 operated intrasellar arachnoid cysts since 1980.

Visual impairment and headache are the main presenting symptoms in sellar arachnoid cysts (4). Visual compromise is explained by suprasellar bulging of the cyst. In a recent publication on intrasellar arachnoid cysts (4), hypogonadism and growth hormone deficiency were described in four of eight (50%) previously untreated cases (see Fig. 2.4.3.1). Hyperprolactinaemia is another frequent finding. However, panhypopituitarism is rarely observed. Diabetes insipidus is not mentioned in the relevant literature as a symptom of sellar arachnoid cysts (see Fig. 2.4.3.2).

MRI shows the typical findings of a cystic space-occupying lesion. Arachnoid cysts may be localized in the suprasellar region or intrasellar with secondary suprasellar arching. The signal of the cyst contents corresponds to the CSF signal (Fig. 2.4.3.5). Due to the thin arachnoidal capsule, no peripheral contrast enhancement is found. The space-occupying character manifests as displacement and compression of the neighbouring anatomical structures, such as the optic chiasm and the pituitary stalk. This also enables diagnostic differentiation from a communicating CSF-filled defect, such as the empty sella.

Surgical treatment of sellar arachnoid cysts is challenging. Most neurosurgeons prefer transsphenoidal surgery despite the high risk of postoperative rhinorrhoea. Wide fenestration of the cyst wall toward the suprasellar CSF spaces has been recommended for communicating arachnoid cysts that refill with CSF after cyst evacuation (4). In noncommunicating arachnoid cysts, only cyst evacuation is performed, leaving the suprasellar capsule in place. For closure, meticulous sellar floor reconstruction is paramount and additional sellar packing (e.g. with a fat graft) is often carried out (4, 5).

Dermoid and epidermoid cysts arise from scattered remnants of embryonal epithelial cells. In both, the cyst wall is lined by benign keratinizing squamous epithelium. Cutaneous adnexa (e.g. hair follicles, sudoriferous or sebaceous glands) are present in dermoid cysts and their presence excludes the diagnosis of an epidermoid cyst. Intracranial dermoid and epidermoid cysts are typically found in the area of the cerebellopontine angle. Very rarely, however, sellar dermoid and epidermoid cysts are observed. Only a few cases of sellar dermoid and epidermoid cysts are described in the literature. Therefore definitive statements cannot be made about the probability of endocrinological impairments. Chemical meningitis may be elicited by rupture of the cyst capsule. Analysis of the signal behaviour on MRI enables neuroradiological differentiation from other sellar masses. Dermoid cysts usually contain fat, which is hyperintense on both T₁- and T₂-weighted images. Epidermoid cysts typically reveal a hyperintense signal on diffusion-weighted MRI due to restricted diffusion within the cyst. Surgical therapy in intrasellar cysts is via the transsphenoidal approach. Care must be taken during the operation that the cyst contents are not spilled into the subarachnoid space. If capsule remnants are not removed, there is danger of recurrence.

Meningiomas are by far the most frequent nonpituitary tumours with secondary spread into the pituitary fossa and encroachment on the pituitary gland or stalk. Consequently, endocrine dysfunction may follow. Meningiomas arise from arachnoid cover cells of the meninges. In the WHO classification of tumours of the central nervous system, the more frequently occurring benign grade I tumours are differentiated from atypical meningiomas (grade II) and anaplastic meningiomas (grade III). The higher-grade meningiomas (grades II and III) are more aggressive and have a greater tendency to recur.

In addition to the histological classification, meningiomas are also subdivided according to their location. The most important and common meningiomas which may cause hypopituitarism are the so-called suprasellar meningiomas. Dependent on the precise tumour origin, these can be further subdivided into:

The ratio of occurrence in females and males is 5:1.

The main symptom of suprasellar meningiomas is visual impairment, which can be unilateral because of a prechiasmatic lesion or bilateral due to a chiasmal syndrome.

Pituitary failure is rare in planum sphenoidale and tuberculum sellae meningiomas despite their often considerable size. In some cases, hypogonadism is observed or hyperprolactinaemia, due to displacement of the pituitary stalk (6). Serious hypopituitarism or diabetes insipidus are only very rarely present at the time of diagnosis. Hypopituitarism and diabetes insipidus are more likely in diaphragma sellae meningiomas that originate immediately anterior or posterior to the pituitary stalk (7). However, diaphragma sellae meningiomas represent an infrequent subtype of suprasellar meningiomas.

A frequent error in differential diagnostics is misdiagnosing a suprasellar meningioma as a pituitary adenoma. The patients then attend the neurosurgical appointment with the false hope that the tumour can be removed through the nose. Therefore, precise inspection of sagittal MR images is paramount, which will show the meningioma resting with a broad base above the sella turcica, but not growing into the pituitary fossa. The pituitary is located underneath and can be delineated from the tumour (Fig. 2.4.3.6). Meningiomas often show dural enhancement (so-called dural tail or dural sign). The dural tail is explained by tumour spread and also by the increased vascularization of the neighbouring meninges. If the presence of a meningioma is suspected, CT, in addition to MRI, is appropriate to identify tumour calcifications and the hyperostosis that is typically found around the tumour attachment area.

The treatment of first choice is microsurgical resection of suprasellar meningiomas via a pterional or subfrontal craniotomy. In the majority of cases, suprasellar meningiomas can be completely resected. The mortality rate is low in modern microsurgical series.

The chance of postoperative improvement in vision is up to 80% (6). Hyperprolactinaemia and hypogonadism may regress postoperatively. The risk of recurrence is less than 5%.

Meningiomas are also frequently found in the cavernous sinus.

The main symptom of such cavernous sinus meningiomas are ocular motor nerve palsies. Facial numbness due to involvement of branches of the trigeminal nerve is a typical finding. Retro-orbital pain is often reported due to dural involvement and distension of the cavernous sinus.

Hormone deficits occur when the direction of growth is medial. The most frequent endocrine abnormality is hyperprolactinaemia (8).

Neuroradiologically, the expansile tumour within the cavernous sinus shows strong contrast enhancement. The marked dural tail, which extends to the tentorium, is characteristic of cavernous sinus meningiomas.

Whereas suprasellar meningiomas can be removed surgically with low morbidity, radical resection of meningiomas of the cavernous sinus is problematical. The radical cavernous sinus surgery performed in the 1980s has been abandoned due to the high morbidity and tendency to recurrence. Surgical debulking is done in cases of exophytic tumour expansion and in compression of the optic pathways or growth into the optic canal. Thanks to modern MRI techniques, there is usually adequate diagnostic certainty so that histological confirmation of diagnosis is not necessary in typical cavernous sinus meningiomas (9). Symptomatic tumours or growing meningiomas of the cavernosus sinus are currently treated primarily with radiosurgery with a gamma knife or linear accelerator, or with fractionated stereotactic radiation (9, 10).

Tumour control rates of more than 90% can be achieved with the above-mentioned radiation modalities.

In light of the close proximity to the hypothalamo-pituitary system, radiation of perisellar meningiomas requires close attention to radiation-related endocrinological deficits, which may manifest several years after treatment. Endocrinological postprocedural follow-up is required.

Purely intrasellar meningiomas are rare. It is assumed that this entity arises from the lower side of the diaphragma sellae. Thus, it is a special variant of diaphragma sellae meningiomas.

Kinjo et al. (7) reported on a total of 14 published cases. The most frequent symptoms were visual impairment, hormone impairment, and headache. Diagnostic differentiation from pituitary adenomas is difficult.

Hypopituitarism and hyperprolactinaemia are present in more than 40% of patients with intrasellar meningiomas (8). Thus, hormonal deficits are much more frequent than in meningiomas of suprasellar or parasellar origin.

The stronger contrast enhancement compared with pituitary adenomas may help in the differential diagnosis of an intrasellar meningioma.

Most intrasellar meningiomas have been treated by the transsphenoidal approach (8), but resection of these often highly vascular tumours is more difficult than resection of pituitary adenomas. Additional transcranial operation may possibly be necessary. If the correct diagnosis has been made preoperatively, a primary transcranial operation can also be taken into consideration (7).

Meningiomas of the anterior clinoid process (so-called clinoidal meningiomas) or medial sphenoid wing meningiomas can also spread to hypothalamo-pituitary structures. In such cases, examination of the pituitary hormone status is required.

Metastases are reported in published autopsy series of patients with malignant disease with a frequency of 1% to 11.8%. By contrast, metastases in the pituitary and hypothalamus are relatively rare in surgical series. It is assumed that metastasis to the bone, in particular into the clivus, usually occurs with secondary spread to the pituitary. Other sites of predilection for metastasis are also the pituitary itself and the pituitary stalk. Breast and lung cancer are predominant among the cancers that metastasize to the pituitary region (11).

It is important to differentiate these tumours from pituitary adenomas because the diagnosis often impacts on the treatment offered: metastases require early therapy, while slow-growing pituitary adenomas can often simply be kept under observation. Preoperatively, there are usually certain factors that point to metastasis and against the presence of pituitary adenoma. Among these are:

Other frequent complaints are retro-orbital pain and visual impairment. MRI usually shows strong, homogeneous contrast enhancement. Fig. 2.4.3.7 shows a malignant tumour of the clivus encroaching on the pituitary gland.

Diabetes insipidus is clinically found in 40–60% of patients presenting with pituitary metastases (11, 12). This might be explained by the destructive nature of malignant tumours, or by direct haematogenic metastasis to the posterior pituitary lobe. Anterior pituitary insufficiency is encountered with almost equal frequency and panhypopituitarism is fairly common (11, 12). Mild hyperprolactinaemia is often found (11).

Indication for surgery depends on the clinical context. The main arguments for surgery are relief of visual deficits and pain, confirmation of diagnosis, and removal of the tumour mass if considered beneficial for the overall outcome. The transsphenoidal approach is most often used (12). Usually, the indication is given for adjuvant radiation therapy after surgical treatment and confirmation of diagnosis (11, 12). Administration of chemotherapy depends on the underlying malignant disease.

While ophthalmological symptoms are likely to improve after surgical decompression, endocrinological deficits are usually not reversible. In two large series, the mean survival time has been reported to be 6 and 17 months, respectively (11, 12). The prognosis strongly depends on the origin and type of malignant tumour.

Chondrosarcomas and chordomas are often reported together in the literature since they show similar clinical and imaging characteristics and the same therapeutic modalities are used.

Chordomas arise from persisting remnants of the notochord and consist of typical so-called physaliphorous tumour cells (Fig.c 2.4.3.8). They can occur everywhere along the neuraxis although the sites of predilection are the sacrum and the clivus. Chordomas of the clivus may expand toward the pituitary fossa as well as in a suprasellar direction toward the pituitary stalk and hypothalamus, and thus cause hormonal impairments.

The main symptom of chordoma in the upper clivus area is a one- or two-sided abducens nerve palsy, since the abducens nerve enters the clivus via the Dorello canal. Visual impairments occur with suprasellar expansion. Depending on the direction of growth, other cranial nerves may also be affected (13). Hypothalamo-hypophyseal endocrinological deficits are relatively rare (see Fig. 2.4.3.1). Hyper‑prolactinaemia can occur.

MRI shows a tumour which is typically hyperintense on T₂-weighted images and enhances nonhomogeneously after contrast administration. In chordomas, too, in addition to MRI, CT is appropriate as it will reveal the typical osteodestructive growth. Expansive growth with convex arching of the clivus dura toward the brain stem and pons cerebri is typical. Suprasellar expansion may occur starting from involvement of the dorsum sellae. The pituitary gland which is displaced in large tumours, can usually still be identified.

Chordomas are characterized by their local, relatively slow but aggressive and destructive growth, and by a high tendency to recurrence. Metastasis is rarely observed. The primary treatment is surgical. In chordomas near the midline in the upper and middle third of the clivus, resection is initially transsphenoidal. Gross total or near-total tumour removal is accomplished using the transsphenoidal approach in 67–89% of patients with clival chordoma (13).

In such procedures, which go well beyond the operative corridor of classical pituitary surgery, we refer to extended transsphenoidal surgery. The entire area of the clivus and also the parasellar area can be reached via such extended approaches. Depending on experience and preference of the individual surgeon, microsurgical or endoscopic techniques, or both techniques in a complementary fashion, are used.

Depending on the expansion, other skull base approaches or combined procedures may be necessary. Complete cure by means of surgery is usually not possible. Usually the patients undergo radiotherapy after surgical treatment, preferably with heavy particles, such as proton radiation. Radiosurgery may also be considered in the case of small tumours or discrete recurrences (14).

Due to the tendency to recur, repeated surgical procedures and radiotherapy are often necessary.

Chondrosarcomas arise from primitive mesenchymal cells of the chondral matrix. At the skull base, chondrosarcomas usually arise in the clivus or in close vicinity. The tumour control rate after surgery and radiation is more favourable for chondrosarcomas than for chordomas. In a large series of skull base chondrosarcomas treated by surgery and consecutive fractionated radiation therapy, the 5- and 10-year local control rates were 99% and 98%, respectively (15).

Optic pathway gliomas account for approximately 5% of all brain tumours in children and are frequently associated with neurofibromatosis 1. The majority of optico-hypothalamic gliomas occur during the first decade of life (16), but they are, however, also observed in later childhood and in adults (17).

Clinically, visual impairments are in the foreground. Deficits in field of vision are often unsystematic due to growth within the optic nerve, optic chiasma, or optic tract. Headache and nausea are the second most-common, caused in cases of large tumours by an occlusive hydrocephalus secondary to foramen of Monro occlusion (Fig. 2.4.3.9).

Preoperative differentiation from craniopharyngiomas may be difficult. Contrary to craniopharyngiomas, hypopituitarism is relatively rarely seen preoperatively (see Fig. 2.4.3.1). In a series of 38 cases, only seven patients (18.4%) showed endocrine deficiency (17). More than one hormonal axis is rarely affected. Diabetes insipidus is relatively rare (see Fig. 2.4.3.2). Hyperprolactinaemia is the most frequent endocrinological abnormality. However, in cases of optico-hypothalamic gliomas, attention must be paid to hypothalamic syndrome, which occurs in about 20% of the patients (17). Among hypothalamic disorders, cachexia prevails. However, hypothalamic obesity or precocious puberty may also occur (17).

Typical distension of the optic pathways by optico-hypothalamic gliomas should be watched for on MRI while compression and displacement are found in craniopharyngiomas. Sometimes the tumour has already attained a gigantic size at the time of diagnosis. The numerically dominant pilocytic astrocytomas show both cystic and solid portions with areas of high contrast uptake (see Fig. 2.4.3.9).

Pilocytic astrocytomas (WHO grade I) of the optic pathways and hypothalamus region present a very heterogeneous growth tendency. Spontaneous remissions have been described. The unpredictable growth pattern has led to divergence of opinion about management (16). The approach can be conservative and therapy withheld if tumour size and vision are stable. This policy has particularly been recommended for patients with optico-hypothalamic gliomas associated with neurofibromatosis 1, who have a much better prognosis (16).

Surgery is generally indicated in patients with progressive tumours and with visual deterioration or severe visual compromise. Initial surgical treatment ranges from biopsy to large-scale resection (17). Due to the intrinsic growth in the area of the visual pathways and the hypothalamus, radical operation is often not possible. If the tumour is very large, tumour debulking should be attempted. Radiotherapy and chemotherapy are effective and established treatment modalities and can often result in tumour control (16). In very young patients, radiotherapy is avoided where possible due to the adverse long-term sequelae on the developing brain, and chemotherapy is performed instead. An overall 5-year survival rate of 40–88% in patients with optico-hypothalamic gliomas has been reported (16).

In addition to low-grade pilocytic astrocytomas, higher-grade optico-hypothalamic astrocytomas are also seen. As in other locations, radiotherapy or radiochemotherapy is required in addition to surgical therapy in anaplastic astrocytomas (WHO grade III) or glioblastomas (WHO grade IV).

Suprasellar germinomas (also called ectopic pinealomas) are extragonadal germ cell tumours, which are primarily observed in children. They are corresponding tumours to seminomas in the testis and to dysgerminomas in the ovary. The incidence is especially high in Japan.

The triad of anterior pituitary insufficiency, diabetes insipidus, and visual compromise is found in practically all those affected. Often, panhypopituitarism is present. Diabetes insipidus with no imaging evidence of a lesion may be a nascent germinoma and requires close monitoring.

MRI reveals a tumour with marked contrast uptake in the area of the pituitary stalk. In some cases, a second lesion is found in the area of the pineal gland and raises strong suspicion of a germinoma (Fig. 2.4.3.10). If a germinoma is suspected, MRI of the entire cranio-spinal axis is indicated.

The differential diagnosis from other lesions with contrast uptake in the area of the pituitary stalk, such as infundibulo-hypophysitis, Langerhans’ cell histiocytosis (formerly known as histiocytosis X), or metastases is often difficult. A detailed CSF analysis with examination for tumour cells, inflammatory cells, and tumour markers is mandatory in such cases. If an intracranial germ cell tumour is suspected, analysis of the tumour markers α-fetoprotein and b-human chorionic gonadotropin (hCG) in CSF and serum is required. Raised levels of α-fetoprotein and b-hCG indicate the presence of a nongerminomatous germ cell tumour which is, however, extremely rare in the suprasellar location.

If a germinoma is suspected, stereotactic or endoscopic biopsy confirmation of the histopathological diagnosis is obligatory. In small lesions, open biopsy via craniotomy under direct vision is to be preferred due to the vicinity of critical vascular and neural structures. Radical operation is not justified in the light of the radiosensitivity of suprasellar germinomas. Pathological examination of germinomas shows large undifferentiated tumour cells with vesicular nuclei resembling primordial germinal elements and often abundant lymphocytic infiltration (18).

Fractionated radiation is the treatment of choice in suprasellar germinomas (19). In intracranial germinomas, 5-year survival rates of 80–100% are attained (20). Whether local, whole-brain, or cranio-spinal radiotherapy is required for isolated suprasellar germinomas is a matter of controversy. The occurrence of distant recurrences after local radiation of suprasellar germinomas does not appear to be common (19). Some centres first administer chemotherapy and select the dose of subsequent radiotherapy based on the response. This concept is especially appropriate in very young patients to reduce the detrimental sequelae of radiotherapy (20).

Hypothalamic hamartoma is a non-neoplastic, malformed mass, which consists of atypically differentiated glial and neural tissue. The diagnosis can usually be made based on the characteristic clinical symptoms and typical neuroradiological signs.

Clinically, precocious puberty and gelastic (‘laughing’) seizures predominate. Those affected by hypothalamic hamartomas usually become clinically symptomatic in early childhood. Gonadotropin-releasing hormone (GnRH)-positive neurons have been found in some hypothalamic hamartomas, so that a heterotopic GnRH pulse generator is assumed to be the cause of precocious puberty. As an alternative hypothesis, substances such as GnRH or transforming growth factor a (TGFα), which are excreted by hypothalamic hamartomas, may elicit premature activation of the adjoining endogenous GnRH pulse generator (21).

The laughing seizures constitute a specific epileptic disorder (so-called gelastic epilepsy), which is pathognomonic for the presence of a hypothalamic hamartoma. Gelastic epilepsy is pharmaco-resistant and leads to secondary epileptogenesis with additional types of seizures. In addition, cognitive impairment and behavioural disturbances occur varying in severity up to serious psychiatric symptoms. Hypothalamic hamartomas may also elicit further hypothalamic syndromes, such as polyphagia and obesity.

MRI reveals a tumour without contrast uptake in the area of the tuber cinereum or the mamillary bodies, which appears isointense to grey matter on T₁-weighted images. Neuroradiological follow-up does not show progression. Pediculated and small hamartomas lead more often to precocious puberty, while broad-based and large hamartomas with intrahypothalamic expansion and involvement of the third ventricle more often elicit gelastic epilepsy (21).

Precocious puberty is usually treated nowadays with GnRH analogues. A few authors prefer operative resection via a transcranial approach in the case of pedunculated hamartomas, and report a good rate of success in regression of precocious puberty.

Due to the serious pharmaco-refractory course of the gelastic epilepsy, operative or radiotherapeutic treatment is required.

In open surgery, the hamartoma is resected or the attachment disconnected. Hamartomas extending into the third ventricle can be treated via a transcallosal approach, while hamartomas at the floor of the hypothalamus with exophytic expansion into the CSF cisterns are operated via a pterional approach. The surgical results reported in the literature vary widely. The cited rate of freedom from seizure ranges from 15 to 67%. The complication rate is between 0 and 54% and includes endocrinological and neurological deficits. The complication rate of treatment by experienced surgeons appears, however, to be quite low.

Endoscopic disconnection is used especially for hamartomas with expansion into the third ventricle. Using a navigation system, the endoscope is inserted into the third ventricle via the foramen of Monro. The low rate of complications has been reported for the endoscopic technique.

In a leading centre, freedom from seizures was achieved in 48.5% of the patients using combined open surgical and endoscopic procedures (22).

This technique is especially suited for the treatment of small and medium-sized hamartomas. Régis et al. (23) conducted a prospective study with 60 patients and achieved total freedom from seizures in 37%.

A radioactive source is placed stereotactically in the hamartoma. The success rate appears to be lower than that of the other procedures described above.

Gangliocytomas consist of neural cells. In addition to gangliocytomas in the brain, gangliocytomas are also observed in the hypophysis. Of the sellar gangliocytomas, 65% are associated with adjacent pituitary adenomas which are mostly hormone secreting (Fig. 2.4.3.11). Associated growth hormone-secreting pituitary adenomas, leading to acromegaly, prevail (24). As the hypothalamic-releasing hormone corresponding to the hormonal oversecretion syndrome has been demonstrated in gangliocytomas, the formation of the adenoma as a result of stimulation by the gangliocytoma is assumed (24). The exact histogenesis of sellar gangliocytomas has not, however, been completely elucidated. A common progenitor cell with transformation into two cell types is also discussed. Some investigators propose that adenohypophyseal cells transform into neuronal cells (25, 26). The diagnosis of two distinct tumours (i.e. gangliocytoma and adenoma) is difficult to establish on the basis of preoperative imaging studies. The mainstay of therapy is transsphenoidal surgery, and the double lesion can be removed. A review of the literature found a 63% chance to normalize the associated hypersecretory endocrinopathy by surgery (24).

Granular cell tumours consist of lysosome-rich granular cells and may arise at various sites of the body, most frequently on the tongue.

Granular cell tumours are the most common primary lesions of the neurohypophysis and pituitary stalk. They are classified as WHO grade I tumours. The histogenesis of granular cell tumours at different sites of the body is still unclear. It is assumed that granular cell tumours of the sellar region develop from pituicytes, specialized glial cells in the infundibulum, and the neurohypophysis.

While small granular cell tumours are often observed in autopsy series, large and symptomatic granular cell tumours of the pituitary occur only rarely (27, 28). No reliable clinical features exist to distinguish granular cell tumours from other sellar tumours. Visual compromise prevails among presenting symptoms. Partial pituitary insufficiency and hyperprolactinaemia is present in 33% and 7% of symptomatic cases, respectively (28). Diabetes insipidus is surprisingly rare despite the infundibular or posterior lobe origin (28). Symptomatic granular cell tumours are treated by transsphenoidal surgery. Radiotherapy is beneficial in cases with less than total removal (28).

Pituicytomas are extremely rare neoplasms that arise from pituicytes. The pituicytoma is now accepted as a distinct entity and is included in the new WHO classification of tumours of the nervous system. The pituicytoma is classified as grade I tumour. Histological features are different from granular cell tumours, but pituicytomas and granular cell tumours may be related neoplasms. Wolfe et al. (29) reported on only 28 cases in the literature that met the histological criteria. Pituicytoma have a male to female ratio of approximately 1.6:1 and occur most often during the middle decades of life. Pituicytomas are slow-growing tumours and 39% of the reported patients presented with impaired visual acuity and visual field defects, and 53% with signs of pituitary insufficiency (29). On MRI, these intrasellar or suprasellar tumours are circumscribed with strong and homogeneous contrast enhancement.

As pituicytomas are firm and highly vascular, surgical removal is difficult. Gross total removal can be curative (29). Mostly a transsphenoidal approach has been used, but transcranial and extended procedures have also been reported. Given the low number of reported cases, the role of adjuvant radiotherapy following less than total resection is not well established.

After traversing the skull base, the carotid artery travels in close proximity to the pituitary over a longer distance. Initially it runs extradural in the cavernous sinus and is called the carotid siphon at that point due to its convoluted course. After entering the intradural space, the carotid artery runs into the suprasellar cisterns on both sides and then divides at its bifurcation into the anterior cerebral artery and the middle cerebral artery.

Extradural aneurysms of the carotid artery in a medial direction result in a sellar ‘tumour’ with compression of the pituitary gland and stalk. They can thus also induce hyperprolactinaemia or hypopituitarism. More frequent symptoms, however, are ocular motor nerve palsies. Deficits are not elicited primarily by compression of the structures, but rather by continuous arterial pulsations.

On MRI, aneurysms can be recognized by their position in relation to the vessels and by their flow signal (Fig. 2.4.3.12). It is extremely important to recognize the neuroradiological signs, since aneurysms may imitate pituitary tumours. The transnasal operation of a wrongly-interpreted aneurysm could have fatal consequences. If an aneurysm is suspected, digital subtraction angiography (DSA) is the gold standard to confirm the diagnosis (Figure 2.4.3.12). CT angiography and MR angiography are increasingly used alternative non-invasive methods to investigate vascular lesions.

Surgical access to extradural carotid aneurysms is difficult. Symptomatic or growing aneurysms are usually treated by endovascular means. Since extradural aneurysms often present with a wide neck, endovascular coil embolization of the aneurysm is usually assisted by stenting to reconstruct the vessel wall. Recently, stents with very tight meshes (so-called flow diverters) have been successfully employed to induce thrombosis and shrinkage of the aneurysm by altering the haemodynamics in the parent artery. If cross-flow via the contralateral carotid artery is adequate, endovascular occlusion of the carotid artery can also be considered.

Intradural aneurysms of the carotid artery can lead to visual impairment due to compression of the optic nerves and optic chiasm. Endocrinological deficits are only rarely reported in the case of intradural aneurysms of the carotid artery without subarachnoid haemorrhage (SAH), but they have not yet been subjected to systematic investigation. Intradural aneurysms of the carotid artery can also imitate a pituitary tumour, as can aneurysms of the anterior communicating artery and basilar artery if they project towards the pituitary area.

Intradural aneurysms are classically treated by microsurgical clipping. Endovascular coil embolization has become an alternative.

Increasing attention is being paid to endocrinological deficits after SAH in ruptured intracranial aneurysms. Speculation about the cause is about not only direct damage due to SAH but also secondary vascular events elicited by vasospasms. The exact incidence of endocrinological deficits after SAH, including in dependence on the site of the aneurysm, is currently the subject of intensive research.

Cavernous hemangiomas are vascular malformations composed of closely apposed dilated vascular channels, which appear as discrete tumours. In the perisellar region, there are two rare but well-defined entities of cavernous haemangiomas, namely haemangiomas of the cavernous sinus and haemangiomas of the optic chiasm.

Cavernous haemangiomas of the cavernous sinus are rare lesions that account for 2% of cavernous sinus tumours. They mostly affect females.

Clinically, cranial neuropathies, visual compromise, and headaches are in the foreground (30). Pituitary insufficiency may occur with medial expansion toward the pituitary.

Unlike cavernous haemangiomas of the brain, these lesions rarely manifest by bleeding. MRI is the first choice examination method in these cases, too. Cavenous haemangiomas appear strongly hyperintense on T₂-weighted images (Fig. 2.4.3.13), and show marked contrast uptake. In the differential diagnosis, cavernous haemangiomas must be differentiated from meningiomas of the cavernous sinus and, in cases with medial expansion, from pituitary adenomas as well.

Cavernous sinus haemangiomas are approached by a fronto-temporal or pterional craniotomy. Extensive blood loss must be anticipated in these highly vascular lesions. Total removal has been reported in 44% of the cases (30). Radiotherapy should be considered after subtotal removal. Postoperative improvement and deterioration of cranial neuropathies has been reported with equal frequency (30). Due to the low number of reported cases, there are no valid data on endocrinological outcome.

Cavernous haemangiomas of the optic chiasm are a relatively rare differential diagnosis in suprasellar tumours. Clinically, acute or subacute visual impairment due to acute bleeding occurred in most of the cases described in the literature. MRI may reveal bleeding into the optic chiasm, with a berry-shaped ‘tumour’ arising in the optic chiasm. Therapeutically, evacuation of a haematoma and resection of the lesion is performed via a transcranial approach.

With today’s experience, the differential diagnosis of sellar tumours can often be made with a high degree of certainty even before histological confirmation. In particular, use of modern endocrinological diagnostics and increasing experience with MRI is of paramount importance in differentiating between the various tumours that can be encountered in the perisellar area. In parallel, the histopathological classification has further developed and now allows a more precise distinction and definition of tumour entities.

The differing frequency of endocrinological deficits can be used in the differential diagnosis. The differential diagnosis and classification of pituitary and hypothalamic tumours is important for planning the therapeutic procedures and prognostic evaluation.