Treatment
The goal of therapeutic intervention is to maximize the patient's functional outcome while minimizing morbidity. A team approach to treatment is often required. Specialists involved in the diagnosis and treatment of patients with skull base lesions include the following:
- Oncologist/Neuro-oncologist
- Radiation oncologist
- Neurologist
- Neurophysiologist
- Ophthalmologist/Neuro-ophthalmologist
- Oral/maxillofacial surgeon
- Otorhinolaryngologist
- Plastic surgeon
- Neurosurgeon
Treatments may include medical intervention, radiation therapy, surgical intervention, or a combination thereof. A tissue diagnosis is generally required prior to medical or radiation therapy. Chemotherapy can be used as a primary or adjunctive treatment of many skull base tumors. Radiation therapy or stereotactic radiosurgery can also be used to primarily treat a skull base tumor or can be used as adjuvant therapy after surgical resection.
- Osteoma: Typically, complete surgical extirpation of these lesions is curative; if the mass is large, skull reconstruction may be necessary.
- Chondroma:Symptomatic lesions are treated with radical resection that extends back to normal bone margins to prevent recurrence.
- Hemangioma: Complete surgical resection is curative. Radiation therapy is sometimes recommended for incompletely resected or multiple tumors (particularly in the spine), but it is of uncertain efficacy. Incidentally found hemangiomas should be managed conservatively.
- Dermoid and epidermoid tumors of the skull:Surgical treatment is usually indicated for symptomatic or progressive lesions. These lesions often involve a communication between the skin and the intracranial cavity through a tract that should be visualized in any surgical resection.
- Plasmacytoma plasma cell tumors:Because of the high rate of progression to multiple myeloma, a conservative surgical approach with aggressive radiotherapy may achieve the greatest response with the lowest morbidity. In easily accessible lesions, optimal treatment includes complete surgical resection followed by radiation therapy. Systemic evaluation to rule out systemic disease should continue until for at least one year after the initial diagnosis.
- Paragangliomas:Catecholamine secretion can be diagnosed with urine or serum studies. In functional tumors, secretion must be blocked prior to surgical intervention to prevent a hypertensive crisis. Surgery offers the best chance of cure or extended control of the disease. Despite being histologically benign, local invasiveness often leads to recurrence after partial resection, even when followed by radiotherapy. Radiosurgery can be used to decrease tumor volume and provide local disease control.
- Chondrosarcoma:Surgical resection followed by fractionated conformal radiation therapy (Rosenberg, 1999) and surgery with further therapy, when indicated (Wanebo, 2006), have both been associated with 5-year survival rates of more than 90%.
- Osteogenic sarcoma and fibrous sarcoma:Malignant tumors are treated with radical surgical resection with extensive margins, although complete excision is often impossible for lesions at the skull base. Radiotherapy is usually given postoperatively. Charged-particle irradiation, such as proton beam or helium, is particularly effective for chordoma or chondrosarcoma of the skull base and, if available, is the technique of choice. Despite aggressive therapy, recurrence is common.
- Nerve sheath tumors
- Vestibular schwannoma: Treatment aims to cure the tumor and preserve neurological function. Surgery using current microsurgical techniques is highly effective. Facial nerve function can be preserved in more than 95% of patients with small tumors (<2 cm) but in less than 50% of patients with tumors larger than 3 cm. Complete resection cures these tumors, and the slow growth rate allows subtotal resection or conservative treatment in some older patients with minimal symptoms. Radiosurgery is an excellent alternative to surgical resection in tumors less than 3 cm in diameter. Local control is achieved in more than 90% of patients, and hearing has been preserved in a greater proportion of patients than after other forms of surgery. However, delayed hearing loss, delayed facial weakness, and delayed trigeminal sensory loss have been reported in some patients 2-3 years after radiosurgery. Radiosurgery prevents surgical morbidity, and, for well-selected patients at an experienced center, it can be the treatment of choice.
- Trigeminal schwannoma: Surgical resection is highly successful in providing a cure or long-term control of the tumor. Radiosurgery may also control the disease in some patients.
- Meningioma
- Many skull base meningiomas are asymptomatic or minimally symptomatic. Given the frequency with which vital structures such as cranial nerves and cerebral vessels are involved, observation is sometimes a prudent strategy. When a skull base meningioma requires treatment, surgical intervention is generally the first line because a complete resection is often curative. Partial resection is the surgical objective for tumors in which complete removal would require an unacceptable risk of neurological injury.
- The experience of the individual surgeon and comfort level of the patient are intimately involved in planning the operative goals. Preoperative embolization decreases tumor vascularity and, therefore, intraoperative blood loss. In smaller tumors, embolization may not be required. Advanced imaging techniques such as 3-dimensional reconstruction and intraoperative MRI can greatly assist the surgeon during tumor removal.
- Although tumor removal can lead to improvement in some preoperative neurological deficits, cranial neuropathies are frequently irreversible. Skull base locations such as the medial sphenoid wing, the clivus, the cerebellopontine angle, and especially the cavernous sinus often allow only subtotal resection because of the high risk of injury to adjacent structures such as the internal carotid artery or cranial nerves. Operative morbidity rates associated with skull base meningiomas can be as high as 14% and is significantly riskier than the treatment of convexity lesions.
- Radiotherapy of skull base meningiomas is indicated in some cases of postoperative residual tumors, tumor recurrence, and in some tumors with malignant histology results. Under circumstances of medical instability or anatomic contraindication for surgery, radiotherapy has been used as primary treatment. In meningiomas throughout the intracranial space, tumor regression or stability at 5 and 10 years has been achieved in 95% and 92% of patients, respectively. Radiation has been shown to be very effective as an adjunct in the treatment of tumors that require subtotal resection.
- Proton beam radiotherapy delivers heavily charged particles that may be effective in the treatment of deep tumors, while minimizing damage to normal tissue. Radiosurgery delivers focused radiation in one large dose in an attempt to minimize damage to adjacent structures. Radiosurgery is performed with a linear accelerator or gamma rays (gamma knife) as the energy sources and is limited to tumors smaller than 3 cm in diameter. Radiosurgery is particularly useful in older or infirm patients who cannot undergo surgery. Gamma knife radiosurgery alone can provide excellent control.
- Another approach is stereotactic radiotherapy, in which radiation is given in multiple small fractions for meningiomas of the cavernous sinus or tumors close to the brainstem. Radiosurgery has become the preferred method for delivering radiotherapy to most patients with meningiomas.
- Currently, medical treatment of skull base meningiomas is largely limited to steroid therapy for the short-term treatment of peritumoral edema. Hormone and chemotherapeutics have not met with significant clinical success.
- Tumors of the anterior cranial fossa: Nasopharyngeal carcinoma is the most common skull base lesion that requires multidisciplinary surgical management. Complete surgical resection and tumor cure is the operative objective.
Medical Therapy
The following case is an example of a lesion managed nonsurgically. The patient is a 68-year-old man with squamous cell carcinoma with invasion of his right temporal bone and involvement of his right sigmoid sinus. Surgical excision would require resection of the right sigmoid sinus. Therefore, cerebral angiography (see Image 22) was performed, demonstrating no filling in the left transverse sinus. Because the patient had venous drainage that appeared to pass exclusively through the right transverse sinus, balloon test occlusion (BTO) of the sinus was performed.
The balloon catheter was passed from the femoral vein into the right transverse sinus. The balloon was inflated to occlude the sinus (see Image 23). A concurrent angiogram demonstrated no flow in the right or left transverse sinus (see Image 24). The patient was carefully monitored for neurologic changes and experienced headaches that improved upon deflation of the balloon. The BTO demonstrated that surgical resection of the tumor posed a high risk of venous infarct due to impaired sinus drainage, and the patient received palliative radiation therapy.
Surgical Therapy
Malignant Tumors of the Skull Base
As stated above, malignant neoplasms of the skull base require a unique approach to surgical intervention. In 2002, Pieper et al described an algorithm for choosing the proper operative approach to these tumors5 . The authors divide the lesions into those that involve the anterior skull base, the clivus, or the lateral skull base. Origitano et al added a further contribution regarding the management of malignant lesions of the anterior skull base.6
The goal of surgery for malignant cranial base masses differs from that of benign lesions in that an oncologic resection, including a margin of normal tissue, is optimal. Adjacent vital normal tissue often limits resection margins. This emphasizes the need for multidisciplinary management of these lesions, taking advantage of recent advances in radiotherapy and chemotherapeutics.
Anterior skull base
When possible, a tissue diagnosis is established via a minimally invasive biopsy. Extensive resection of malignant lesions of the anterior skull base is performed through an intracranial, extracranial, or combined approach. The 2 most common intracranial approaches are the orbitozygomatic craniotomy and the bifrontal craniotomy, which may be extended to include superior orbital rim osteotomy and nasion resection, as indicated.
Bifrontal craniotomy provides access to the undersurface of the frontal lobe, allowing an extradural subfrontal approach to the floor of the anterior fossa. Extracranial approaches are designed to access a malignant lesion that originated in the nasal or paranasal tissues. Incisions for extracranial approaches may be transfacial or sublabial, the latter of which allows the surgeon to access lesions near the sella turcica or those that involve the clivus. Without the addition of an intracranial component, these approaches may be limited at the superior border of the required resection.
Clivus
Minimally invasive methods to obtain a tissue diagnosis may be appropriate for malignant tumors that involve the clivus, as aggressive resection is not indicated for certain lesions (eg, plasmacytoma, poorly controlled systemic malignancy). Endoscopic biopsy has become a favored approach to achieve this goal.
When aggressive surgical resection is indicated, a subfrontal or transfacial approach, as described above, is commonly used. In addition, lesions confined to the sella turcica or upper third of the clivus may be adequately exposed using a sublabial transsphenoidal approach. Lesions that involve the inferior two thirds of the clivus are more likely to require a sublabial incision and maxillotomy.
Lateral skull base
In their series, the authors note that malignant lesions of the lateral skull base usually originate in the extracranial infratemporal fossa. Neurofibrosarcomas associated with NF-1 or tumors that originate in the parotid gland or paranasal sinuses (via perineural spread) were the most common. Also notable were histologically aggressive meningiomas that had invaded the infratemporal fossa or temporal bone. In a series of 95 patients with lateral skull base malignancies, McGrew et al (2002) reported 35 patients with epithelial tumors (eg, squamous cell carcinoma), 28 patients with salivary malignancies (eg, adenocarcinomas), and 32 patients with tumors of mesenchymal origin (eg, chondrosarcoma).7
The optimal surgical approach to lateral skull base lesions confined to the infratemporal fossa (and possibly the floor of the middle fossa) depends on the anatomy of the region, specifically the relationship of the lesion to the internal carotid artery. For lesions lateral to the internal carotid artery (ICA), a preauricular approach with zygomatic osteotomy may be used. Lesions of the infratemporal fossa lying medial to the ICA are best exposed via mandibulotomy. For all lesions in the infratemporal fossa, proximal and distal exposure and control of the internal carotid artery is prudent.
Lateral skull base malignancies near the jugular foramen or temporal bone may be approached through a postauricular incision and transjugular approach and/or petrosectomy.
Extensive tumors that involve the lateral skull base may require complex reconstructive plans, including free tissue transfers. Optimally, all reconstructive flaps should be planned in the preoperative and perioperative setting. Additionally, the authors emphasize the importance of dural competency in regard to the prognosis of patients with malignant skull base lesions and in regard to the meticulous reconstruction following complex skull base tumor resection. Meticulous dural closure and cranial reconstruction are the surgeon's best tools in the prevention of the most common complications, which include cerebrospinal fluid (CSF) leak and infection (8 ).
Radiosurgery
As described above for meningioma, radiation therapy has been successfully applied as both a primary and adjunctive modality in the treatment of benign and malignant skull base neoplasms. Among radiosurgical modalities, gamma knife radiosurgery (GKRS) technology is the most thoroughly described (see Image 25).
Meningioma
GKRS has been well established in the treatment of meningiomas smaller than 3 cm in diameter. Pollock reviewed 303 patients treated with GKRS between 1990 and 2002. Seventy percent of these lesions were located at the skull base, with an average tumor volume of 7.3 cm3. Following GKRS, 94% of tumors remained stable or decreased in size. Treatment-related complications occurred in 8% of the patients (9 ).
Vestibular schwannoma (acoustic neuroma)
In a review of treatment options and follow-up of 162 patients treated for vestibular schwannoma, Kondziolka et al described a 70% tumor reduction rate and a 94% tumor control rate using GKRS. They emphasize the use of radiosurgery as a primary treatment modality but recommend open surgical resection for patients with vestibular schwannomas that require brain stem decompression or patients with greater than 3 cm of extracanalicular extension (10 ).
Pituitary adenoma
In a 2003 review of radiosurgical treatment of pituitary adenomas, Witt discussed the dual therapeutic goals of tumor growth control and endocrine cure. His review demonstrated a control of tumor growth in 92-100% of tumors. The goal of endocrine cure was more difficult to assess because consistent definitions of cure have not been established. Based on the criteria defined in each particular study, endocrine cure rates of 0-96% were reported in cases of growth hormone–secreting adenomas and 0-84% in prolactinomas. Witt recommends GKRS as the best option in the treatment of small, medically refractory lesions in surgically inaccessible locations (11 ).
One significant complication related to radiotherapy or radiosurgery is radiation-induced necrosis. Radiation necrosis may mimic tumor recurrence and can produce significant mass effect through edema (see Image 26). Positron emission tomography (PET) can be used to help distinguish radiation necrosis from recurrent tumor (12 ;2 ).
Endoscopic Surgery
The role of endoscopy in accessing and resecting tumors of the skull base is evolving. Endoscopy offers a minimally invasive route to regions that are difficult to access and is increasingly being implemented as a tool for biopsy of skull base lesions. Expanded endonasal approaches provide direct access to the entire anterior midline skull base without traversing neurovascular structures and with minimal brain retraction (13 ). Current endoscopic techniques are limited by the small working space provided and challenges in the repair of (sometimes large) dural openings.
Surgical Approaches
Safe and complete surgical excision of skull base lesions often requires the combined efforts of a team of specialists that may include an oral/maxillofacial surgeon, otorhinolaryngologist, ophthalmologist (eg, orbital surgeon), plastic surgeon, and neurosurgeon. If operative intervention is planned, an interventional neuroradiologist or endovascular neurosurgeon can help define the vascular anatomy and may be able to embolize vessels feeding the tumor particularly meningiomas, angiofibromas, paragangliomas, and, occasionally, schwannomas).
The goals of surgery are to minimize morbidity and to maximize the extent of tumor removal. When malignant lesions are resected, en bloc resection, including the surrounding margin of tissue, is the goal. With benign lesions, the most complete resection possible with the maximum preservation of function is the goal.
Many surgical approaches to skull base lesions have been described. These approaches are broadly categorized according to the location within the skull base and include anterior, middle, and posterior fossa approaches.
Anterior approaches
As described above, approaches to the anterior skull base can be divided into intracranial, extracranial, and combined approaches. Intracranial approaches often include a bifrontal craniotomy, which may be expanded to include superior orbital osteotomies and removal of the nasion (5 ). Extracranial routes to the anterior skull base may involve transfacial incisions or sublabial incisions for facial degloving procedures. Operative corridors through the oral cavity may also be achieved. Descriptions of common open surgical approaches with case examples are below.
Orbital approaches
The anterior cranial base, which is located behind and above the orbit, can be approached through a pterional craniotomy with orbitozygomatic osteotomy. This exposure also offers access to lesions of the middle cranial fossa, including tumors of the gasserian ganglion and tumors that involve the cavernous sinus. It can also be used to approach selected lesions in the posterior fossa, such as basilar artery aneurysms.
A case example is a 66-year-old man who presented with slowly progressive right eye proptosis and unilateral loss of visual acuity (see Images 13 and 14). This en plaque meningioma of the sphenoid wing also invaded the orbit and involved the periorbita. It was completely resected using a frontotemporal craniotomy with orbitozygomatic osteotomies.
Nasal cavity (transsphenoidal) approach
Tumors in the sella turcica, including those with limited extension above the diaphragma sella, can be approached through the nasal cavity by a transsphenoidal approach. This is the most commonly used approach to pituitary adenomas. Very large tumors of the sellar and suprasellar region may require a combined surgical approach, including a transsphenoidal approach and pterional craniotomy (see Image 27).
A case example is a 69-year-old woman who presented with bilateral deterioration of vision but no other endocrine or cranial nerve symptoms or findings. MRI (see Image 27) demonstrated a very large tumor that arose from the sella turcica, with significant suprasellar extension. This tumor required a combined pterional craniotomy and transnasal transsphenoidal approach in order to achieve a gross total resection.
Midface approach
A transfacial approach can be used to resect tumors that range from the paranasal sinuses to the upper one third of the clivus, which forms the anterior wall of the posterior cranial fossa. When mandibular exposure or resection is necessary, the midface can be degloved.
A case example is a 73-year-old man with adenocystic carcinoma of the ethmoid sinuses. T1-weighted MRI (see Image 17) showed tumor involvement of the ethmoid sinuses and floor of the anterior fossa in the region of the cribriform plate. CT scan (see Image 18) showed extension of the mass into the middle fossa, anterior to the temporal lobe. The patient underwent a combined transfacial and transcranial approach for resection of the tumor, with a pericranial graft reconstruction of the dura.
Transoral approach
Tumors of the upper clivus can be approached using a sublabial, transoral, or transpalatal approach. Transoral and transpalatal approaches require an incision in the posterior pharynx. Clival approaches can be extended via a mandibular osteotomy in order to access lesions that involve the odontoid process.
A case example is an 80-year-old woman who presented with double vision and a right sixth nerve palsy. An MRI one year previously had demonstrated no intracranial lesions. MRI on admission (see Image 7) demonstrated a clival tumor with growth into the right cavernous sinus. This tumor was subtotally resected using a sublabial approach, above the palate. The patient had no new postoperative deficits. She was further treated with GKRS.
Middle fossa approaches
Lateral approaches to the middle cranial fossa go through the temporal bone to access tumors in the temporal bone, middle ear, pterygoid fossa, gasserian ganglion, cavernous sinus, and middle third of the clivus. The petrosal or presigmoid approach is one example in which portions of the petrous portion of the temporal bone are drilled away, allowing access to the middle fossa. These approaches require navigation through a very small corridor adjacent to structures such as the inner ear and the facial nerve. Make all attempts to avoid damaging these structures if they are still functional.
A case example is a 68-year-old man who presented with a seizure after developing slowly progressive double vision and left-sided hearing loss. An MRI (see Image 19) demonstrated a large meningioma that involved the petrous apex and clivus. The lesion caused considerable mass effect on the brain stem. Angiography did not demonstrate vascular supply that was appropriate for embolization. A presigmoid approach was used to achieve a near-total resection. A small amount of residual tumor in the Meckel cave was treated with GKRS.
Posterior approaches
Posterior approaches to the skull base include the extreme or far lateral approach, retromastoid craniotomy, and retrosigmoid/suboccipital craniotomy or craniectomy. An extreme lateral approach exposes the lower third of the clivus, cerebellopontine angle, and petrous surface of the temporal bone. Retromastoid craniotomy and suboccipital craniotomy are used to approach lesions of the cerebellopontine angle and the petrous surface of the temporal bone.
A 23-year-old woman presented with headache and bilateral abducens palsies. T1-weighted MRI (see Image 20) showed a hypointense mass within the posterior cranial fossa that compressed the pons and medulla posteriorly. T2-weighted MRI (see Image 21) demonstrated a hyperintense mass consistent with an epidermoid. The patient underwent suboccipital craniectomy for complete resection of the mass.
A 38-year-old woman presented with chronic headaches and tingling in the fingers of her left hand. MRI scan (see Image 11) demonstrated a contrast-enhancing lesion at the foramen magnum, consistent with a meningioma. This tumor was completely resected using a far lateral approach and suboccipital craniotomy with C1 laminectomy.
Complications
Complications of surgery at the skull base can be classified into neurologic, wound related, cosmetic, and perioperative.
Neurologic
Neurologic complications include cranial nerve injuries and injury that affects the CNS. The location of the tumor determines which cranial nerves are at risk. Stretch or traction injury, thermal injury due to electrocautery, or sharp transection of nerves can occur. Cranial nerves displaced by or under tension from tumor growth are most vulnerable, but any cranial nerve in or near the operative field is at risk.
Concurrent injury to multiple cranial nerves can be devastating. For example, concurrent injury to cranial nerves V and VII may cause the eye to be both insensate and exposed because of an inability to close the eyelid. This puts the patient at risk for corneal ulceration and infection and, ultimately, loss of the eye. A large cerebellopontine angle tumor, such as a vestibular schwannoma, is an example of a tumor that may damage both cranial nerves V and VII.
Injury to the lower cranial nerves (IX, X, XI, XII) can produce swallowing difficulties and can place the patient at risk for aspiration and pneumonia. Foramen magnum meningiomas and chordomas of the lower clivus can grow near these nerves.
Intraoperative cranial nerve monitoring is designed to alert the surgeon when nerves are at risk of damage. Cranial nerves II-XII can be monitored intraoperatively. The facial nerve is frequently monitored using electromyography (EMG), and the auditory nerve can be monitored with brainstem auditory evoked responses (BAERs).
Operative morbidities that affect the CNS include the following:
- Cerebrospinal fluid (CSF) leak
- Pneumocephalus
- Intracranial hemorrhage
- Hydrocephalus
- Cerebral contusion
- Meningitis
- Cerebral edema
- Stroke
- Epidural abscess
- Seizures
- Diabetes insipidus
- Altered mental status
- Anosmia
CSF leaks occur if the dura is violated either intentionally or by tumor invasion. They may also result from hydrocephalus. Many areas of the skull base dura are thin and difficult to repair. Dura that lies over the cribriform plate can be troublesome because the olfactory nerves travel through it into the nasal cavity. The use of pericranial flaps to repair holes in the dura decreases the risk of CSF leaks. Other vascularized flaps (eg, temporalis muscle flaps, trapezius muscle flaps, free radial forearm flaps, free rectus abdominis muscle flaps) are used when appropriate. Complications associated with CSF leakage include poor wound healing and meningitis.
Wound related
Wound complications include the following:
- Cellulitis
- Infected cranial bone flap or osteomyelitis
- Oronasal fistula
- Necrosis of a pericranial flap
- Encephalocele
- Crusting of the nasal cavity
Because the nasal cavity may be included in the wound, chronic sinusitis from infection, loss of sinus mucociliary transport, and stenosis of the sinus ostia can occur. In addition, nasal airway stenosis may occur.
Cosmetic
Cosmetic complications include enophthalmos, facial scar, burr hole–related scalp depression, and ocular dystopia. Cosmetic deformity is more likely with anterior surgical approaches because they may involve the orbit or face. After surgery, the position of the eye and the contour of the facial structures should be maintained. Various reconstructive techniques, including free flaps and bony reconstruction with miniplate fixation, have been developed to address these issues.
Perioperative
Intraoperative blood loss may be significant because of the extensive dissection that is sometimes necessary for approaches to the skull base. The scalp, skull, and dura are highly vascular; therefore, blood loss should be monitored closely and blood products should be replaced aggressively.
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Further Reading
Keywords
skull base tumors, brain tumor, skull base surgery, skull-base tumor, skull-base surgery, brain surgery, skull-base mass, skull base mass, brain mass, meningioma, intracranial tumor, schwannoma, chondrosarcoma, chordoma, metastatic bone lesion, osteoma, en plaque tumor, en masse tumor, neurinoma, neurilemoma, acoustic neuroma, anterior cranial fossa tumor, juvenile angiofibroma, esthesioneuroblastoma, inverted papilloma, lymphomas, nasopharyngeal carcinoma, orbital glioma, orbital tumor, orbital mass, rhabdomyosarcoma, osteogenic sarcoma, ossifying fibroma, esthesioneuroblastoma, olfactory neuroblastoma, nasopharyngeal carcinoma, middle cranial base tumor, pituitary adenoma, craniopharyngioma, temporal bone tumor, cholesteatoma, enchondroma, posterior cranial fossa tumor, epidermoid tumor, dermoid tumor, chondroma, glomus tumor, paraganglioma
