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Pineal
Region Tumour Management - A
Stereotactic Perspective
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INTRODUCTION
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Only those conditions which are the rarest evoke our greatest passion.'
Is it "Much Ado about Nothing" or a paradigm of a timely debate among
neurosurgeons about the best treatment of a particular brain lesion?
In the past overestimation of surgical skill with an underestimation
of the patients fragility has too often resulted in a poor outcome.
Both aggressive attitudes of resection and conservative, non-surgical
approaches have been used in the past and are still advocated today.
This wide range includes the recommendation of explorative craniotomies
for each and every case, ventriculoperitoneal/ventriculocardial shunts,
ventriculostomy, endoscopic techniques, stereotactic techniques, radiotherapy,
radiosurgery and various forms of chemotherapy. Radiotherapy trials
without histological diagnosis have been recommended and applied.(2,3)
The neurosurgical discussion in the past has been centered on approaches
to the pineal region, on microsurgical techniques of resection and on
the aspect of "cytoreduction", an assumption which is widely regarded
as self-evident. The tremendous biologic variability of tumours in the
pineal region, however, makes resections or even exploratory craniotomies
futile in the majority of cases.
Tumours of the pineal region vary greatly in their resectability and
their response to radiation and chemotherapy. Clinical parameters, radiographic
findings and Cerebro Spinal Fluid (CSF) markers are unreliable in discriminating
specific tumour types. The beginning first logical step is an accurate
histological diagnosis. Appropriate treatment for the benefit of the
patient has to be based on the specific type of lesion. Some of the
goals and questions to be discussed in this review are:
| 1. | How best to diagnose a pineal tumour? | |
| 2. | How to avoid unnecessary craniotomies? | |
| 3. | How to avoid unnecessary shunts? | |
| 4. | Which is the best primary/adjuvant treatment for a given tumour type? | |
| 5. | What are the rational steps to perform? |
This review is conceived as no more than a suggestion of the way how
to approach this problem of pineal tumours with a stereotactic perspective.
The pineal region. The pineal gland, the tiny cone protruding
from the posterior third ventricle, has a poorly understood function.
Due to its fibre connections with the suprachiasmatic nucleus ( "accessory
optic tract") it is considered the "third eye" of the brain.(4) Pineocytes
have a neurosecretory function (melatonin). Other tissue components
are filial and mesenchymal cells. The pineal region is defined as the
area bordered by the splenium of the corpus callosum and the velum interpositum
dorsally, the roof of the third ventricle anteriorly, the tectum ventrally,
and the vermis of the cerebellum caudally. Tumours of the pineal compress
and obstruct the cerebral aquaeduct resulting in hydrocephalus. They
locally compress the tectal plate and the midbrain which characteristically
leads to paralysis of upward gaze and convergence known a Parinaud syndrome.
Compression of the fasciculus longitudinalis causes nystagmus (Fig.1):
The wide variety of tumours and lesions of the pineal can be subdivided
into four groups: Germ cell tumours, the pineal parenchymal tumours,
filial tumours and a mixed group containing such divergent entities
like meningiomas, metastases to the pineal and pineal cysts (Table 1).
The pineal region is a preferred site for the growth of germ cell tumours
which are the most common type in the pineal region.(27-31) The neoplasms
range from completely benign (mature) teratomas, dermoids, epidermoids
to highly malignant tumours such as choriocarcinomas, embryonal cell
carcinomas and endodermal sinus tumours (yolk sac tumours). The most
common type, i.e. the germinoma, is an intermediate WHO Grade 3 neoplasm.
Germ cell tumours localised in the pineal region vary considerably in
their geographic incidence. In North America and Europe they constitute
only 0.3% to 1%. They are more prevalent in Asia where they account
for at least 2% of all primary brain tumours with 9% to 15% of brain
tumours in children in Japan, Korea and Taiwan. (32-35)
| Figure 1 — Pineal Region Anatomy and Syndromes | ||
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| Table 1 — Pineal Region Tumours | ||||||||||
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Pineocytomas and pineoblastomas are the semibenign and the malignant variants (50/50%) of pineal parenchyma) neoplasms. The diagnostic criteria, however, used to differentiate pineocytomas from malignant pineoblastomas are not always clear, i.e. the finding of a pineocytoma in a child should raise doubts.(36) Other tumour entities may be encountered such as low-and high-grade gliomas, ependymomas, papillomas, meningiomas, cavernomas, tuberculoma, metastases and other. In our series these account for 30%. (20) Small, asymptomatic cysts in the pineal are common autopsy findings (25-40%). Pineal cysts rarely become clinically symptomatic with episodic or chronic headache, episodic mental clouding, nausea and gaze paresis. (4,16,24-26,37-43)
How best to diagnose a pineal tumour?
The term "pinealoma" nowadays is used to describe any tumour in the pineal region. It is not a histological tumour entity. Neuroradiological findings (CT, MR, SPECT, PET) are nonspecific. (4-17,24,26,39,40,42-46) All patients with apparently solid tumours undergo serum and CSF analysis for tumour markers. These markers such as Alphafetoprotein (AFP), beta-Human Choriogonadotropin (HCG) and Placental alkaline Phosphatase (PLAP) can be useful in particular with the aim to exclude malignant germ cell tumours (Table 2). They are, however, unreliable in discriminating specific tumour types. (10,11,46-53)
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Table
2
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A tumour tissue diagnosis is mandatory. (30,32,54,56) A positive or negative response to probatory radiation "radiation test" does not result in a histological diagnosis. It is considered clinically unsatisfactory.(7,9,17,47,54,55,57,64) Probatory radiation is legally of questionable value, in terms of science such treatment reports have little value.
How to avoid unnecessary craniotomies?
Craniotomies are routine exercises for neurosurgeons. In case of a pineal tumour, however, a labourious craniotomy and whatever type of resection (biopsy, subtotal, cross total, etc.) can be a rather fruitless undertaking. Germinomas, pineoblastomas and immature teratomas constitute 2/3 of all pineal tumours. Appropriate treatment is non-surgical. The advantage of reduced tumour burden "cytoreduction" has been advocated for patients with pineoblastoma and malignant nongerminoma germ-cell tumours. However, in the light of functional risks this is generally not a feasible goal in this area. The incidence of radical surgery is extremely low for all infiltrative, semibenign or malignant lesions of the pineal region. (7,17,65,66) Biopsy via craniotomy is the next best method when stereotactic techniques are not available. Image guided stereotactic biopsy is the method of choice as it is easier, safer, less expensive and less labour intensive. (15,20,57,67-76)
At my institution stereotactic surgery as a first diagnostic step of the treatment planning is routinely performed using frontal paramedian or lateral parieto-temporal approaches depending on the position of the internal veins in relation to the tumour.20 The site of the burrhole, the passage of the probe through the brain and the tumour diameter are carefully planned and optimised using a workstation or powerful PC. With this type of treatment planning an intraoperative angiography is not a necessity. To accurately localise a tumour image fusion of high resolution MR data with the linear CT data under stereotactic conditions is the method of choice. Operations are performed under local anaesthesia in adults. Children are operated on under general anaesthesia. The attending surgical neuropathologist who has a microscope within the operating theatre is confronted with the patients clinical and imaging data. The neuropathologist prepares intraoperative smear stainings (Methylene Blue) which are instantaneously examined under the microscope. Alternative samples are preserved for standard and immunohistochemical staining procedures. Tumour grading is performed according to the WHO classification. The final diagnosis is made from both the findings of the paraffin embedded tissue specimens and the smear preparations. Immunohistochemistry was carried out with the immunoperoxidase technique using polyclonal antisera to Glial Fibrillary Acidic Protein (GFAP) and monoclonal antibodies to Synaptophysin (SYN), Neurofilament (NF), Neuron Specific Enolase (NSE), Cytokeratin (CK), Vimentin (VIM), Epithelial Membranous Antigen (EMA), Placental Alkaline Phosphatase (FLAP), CarcinoEmbryonic-Antigen (CEA), AFP, and b-HCG. Having an unequivocal intraoperative diagnosis from the attending neuropathologist, including information about the transitional zone between tumour and the normal brain, the biopsy site designated as target, usually the center of the lesion, is then marked with a small titanium ball (diameter 0.5 mm) for radiographic documentation.
In our series with pineal lesion (20) the perioperative mortality was 1.9% and the morbidity was 8.5% (transient and mild: 4/106, transient, serious: 5/106). The rate of complications was thus slightly higher in the pineal region than in our general patient population ( mortality of 0.7% and an overall morbidity of 4.1% ). Regis and co-workers's have analysed a multiinstitutional study and reported an overall perioperative mortality of 1.3% (5/370 Pts.) and an overall morbidity of 8% (30/370 Pts.), with a 0.8% (3/370 Pts.) severe morbidity after stereotactic biopsy in the pineal area. After open surgery a mortality of 4% appears to be realistic for surgeons experienced with pineal lesions. 17,16,77 The morbidity reported varies between 3% and 12%, (66) however many authors did not analyse perioperative morbidity. Complications are pronounced for malignant lesions which are the preferred cases for the stereotactic diagnostic approach. The data suggest that the risk of the stereotactic approach, with an average hospital stay of four days, is less when compared with the invasiveness and the risk of open surgery. The argument that there is an increased risk of seeding through biopsy has never been substantiated although singular cases have been described. 76 There is a natural risk of seeding of germinomas in the range of 13% which is independent of surgical intervention .78 Local pressure from symptomatic pineal cysts can be easily relieved by stereotactic aspiration of the cyst contents. While some authors favour exposure and resection (25) it was obvious in our series that no patient required further therapy nor did a cyst recur .(20)
How to avoid unnecessary shunts?
Obstructive hydrocephalus is a common clinical problem in patients harbouring a pineal tumour. With the patient vomiting, CT/MR demonstrating a hydrocephalus, usually without much consideration a vetriculoperitoneal/cardial shunt is instituted. The patient is out of acute peril. Subacute danger may follow with possible extracranial seeding after shunt placement which is a well-known fact. (30,79,86) Whenever the placement of a foreign body can be avoided it should be avoided. Treatment of an obstructive hydrocephalus follows the stereotactic diagnosis: In case of a malignant germ cell tumour a ventricular drainage is left in place and radiotherapy is started immediately. The drainage is left in place until tumour regression is achieved. In case of a benign tumor or equivocal histological diagnosis a third ventriculostomy is the method of choice. For ventriculostomy endoscopic techniques are very useful. (87)
Which is the best primary/adjuvant treatment for a given tumour type?
Craniospinal radiation is the treatment of choice for patients with germinomas. The low risk of stereotactic biopsy and the impressive results of radiation therapy emphasize that there is no rational basis for cytoreductive surgery for patients with germinoma. (5,7,33,53,57,59,63,70,77,88-91) The role of various chemotherapy protocols as adjuvant treatment using substances such as cisplatin, bleomycin, etoposid, ifosfamid etc. is debated. (58,63,90,92-96) Critics have been inclined to find fault with the additional morbidity. As already mentioned a concomitant hydrocephalus is best treated with an external drainage at the time of the stereotactic biopsy and craniospinal irradiation is started as early as possible in order to prevent extracranial metastases. The concept of craniospinal radiation remains controversial with respect to the inclusion of the spinal canal.(5,30,56,90,93,95) A high proportion of patients with pineal germinomas can be cured with radiation therapy alone. Reported five-year survival rates are up to 95 %. (5,9,28,33,53,59,60,62,63,70,89,91,97,98)
Treatment of non-germinoma germ cell tumours is successful for those patients with benign (mature) teratomas which can be resected totally.(5,7,46) Whether microsurgical techniques have improved the outcome for patients harbouring malignant teratomas and other malignant germ cell tumours with a positive marker profile remains a matter of debate. (17,47,54,65,66) Treatment consists in a combined radio- and chemotherapy which is carried out on an individual basis.(7,9,10,13,30,34,49,50,52,53, 58,62,80,88,90,94, 95,99-102) The prognosis remains poor with less than 10%, .surviving 2 years. Likewise pineobla.stomas, particularly in child age, are prone to craniospinal seeding and occasionally, to extracranial metastases. The prognosis is dismal. 100 Extent of disease at the time of diagnosis strongly affects the survival.(103) Mainstay of treatment is radiotherapy combined, in various protocols, with chemotherapy. (5,30,54,104-106) Reduced tumour burden by partial resection has been advocated for patients with pineoblastomas and other malignant nongerminoma germ cell tumours. (17,47,65,66) However, given the functional risks alone, it is not considered a feasible goal. Radical surgical intervention is not possible.
Patients harbouring a pineocytoma either undergo microsurgical resection or are treated locally with interstitial irradiation (5,15,20,83) (Fig. 2). As with low-grade gliomas of the pineal region pineocytomas are characterised by a slow proliferation rate which makes these tumours susceptible to continuous low dose rate radiation of an interstitial implant. (107)
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| Figure 2(a) — Sagittal magnetic resonance image demonstrating a contrast enhancing, partly cystic tumour in the pineal region with consecutive hydrocephalus. Stereotactic biopsy had revealed a pineocyoma in a 35 year old male. After biopsy a temporary (25 days Iodine-125) seed in the tip of a tellon catheter was placed in the centre of the tumour. | Figure 2(b) —Magnetic resonance image four years after interstitial radiosurgery of a pineocytoma [see Fig. 2(a)] Note the complete regression of the tumour and the lasting effect of the stereotactic ventriculostomy. |
The low-activity implant approach can be interpreted as the ultimate
form of fractionation. A complete dosimetric coverage of the target
volume is considered essential for local tumour control. Results today
suggest that treatment of low-grade gliomas, pineocytomas and other
small, delineated tumours with interstitial radiosurgery is feasible
and long term survival can result. (15,20) Standard (fractionated) radiotherapy
is not precluded, and can be postponed. Since the volume of irradiated
tissue in interstitial radiosurgery is very small and surrounding normal
brain is not affected, it will not result in a conflicting situation
with standard radiotherapy. It is our experience that standard radiation
treatment can be delivered without reducing the prescribed dose. Experiences
with external focussed beam radiosurgery are rare. (71,108-110;69) Single
shot radiosurgery may be considered as treatment for solitary metastasis
to the pineal, (23) for meningiomas, arteriovenous malformations (69)
and other small discrete lesions(71)
What are the rational steps to perform?
Extent of disease and histological diagnosis are the most important
predictors for the outcome of patients. Accurate preoperative assessment
of the extent of disease includes craniospinal CT/ MR examination, serum
and CSF marker profiles, an ophthalmologic examination and CSF cell
pathology in the absence of a hydrocephalus. Stereotactic biopsy has
replaced operative exploration via craniotomy in all patients, particularly
those who obviously will not benefit from open surgery (Table 3).
Based on a conclusive neuropathological diagnosis (i.e. conclusive with
radiographic findings, age of the patient, marker profile etc.) the
appropriate subsequent treatment is offered to the patient. Fractionated
radiotherapy is the treatment of choice for all germinomas, pineoblastomas
and malignant nongerminoma germ cell tumours. Whether this is combined
with an established chemotherapy protocol depends on the individual
situation. Delineated low-grade tumours such as astrocytomas, pineocytomas
are candidates for interstitial radiosurgery. Microsurgical removal
is considered for benign tumors such as pineocytomas, meningiomas, mature
mixed teratomas, dermoids, epidermoids. The stereotactic diagnostic
approach is therapeutic at the same time for pineal cysts. Intraoperative
tissue diagnosis directs the method of treatment of an existing hydrocephalus
(external drainage, endoscopic ventriculostomy or ventriculocardial/-peritoneal
shunt).
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Table
3
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