Skull Base Tumors 

Updated: Feb 27, 2015
Author: Todd C Hankinson, MD, MBA; Chief Editor: Brian H Kopell, MD 

Overview

Background

This article offers an overview of tumors that develop at the skull base and their surgical management. Although skull base surgical approaches are also used for vascular disease, congenital anomalies, and some nonneoplastic bony disorders, this section focuses on neoplastic disease. Basic surgical approaches to the skull base are outlined. Several illustrative case examples are presented.

The skull base can be divided into the anterior, middle, and posterior compartments or fossae. Tumors and surgical approaches are classified based on the involved area.

The image below depicts a CT scan revealing a skull base tumor.

Osteoma. CT scan with axial bone windows and coron Osteoma. CT scan with axial bone windows and coronal plane reconstruction that demonstrates a fibrous osteoma that involves the right orbit and the floor of the anterior cranial fossa.

Tumor types

Osteoma

Osteomas are the most common primary tumor of the bone of the calvaria.[1] They are benign growths of dense cortical bone. These tumors often arise from the paranasal sinuses but may develop in the frontal bone (arising from the area of the frontal sinus), cranial vault, mastoid sinus, or mandible. These tumors grow slowly and rarely expand internally to compress the brain; therefore, they are usually asymptomatic. Osteomas have been associated with Gardner syndrome, an autosomal-dominant variant of familial adenomatous polyposis, which consists of multiple cranial osteomas, colonic polyposis, and soft-tissue tumors.

Chondroma

Chondromas are rare slowly growing tumors that arise from the cartilaginous portion of bones formed by enchondral ossification. In the cranial region, this includes the bones of the skull base and paranasal sinuses. Progression to a malignant chondrosarcoma (see Chondrosarcoma below) is rare.

Hemangioma

Hemangiomas of the skull are benign vascular bone tumors composed of cavernous or capillary vascular channels. Skull hemangiomas vary from small to very large and may be solitary or multiple. They make up approximately 7% of skull tumors. There are 2 types, the more common cavernous hemangioma and the more rare capillary hemangioma.[1]

Dermoid and epidermoid tumors of the skull

Dermoid and epidermoid tumors are benign lesions of the skull that develop in the cranial vault, paranasal sinuses, orbit, and petrous bone. They are among the most common benign skull lesions in children. These tumors usually arise in the midline, in the diploe of the bone, where they expand both the inner and outer tables of the skull.

Plasmacytoma plasma cell tumors

These tumors are monoclonal expansions of immunoglobulin-secreting plasma cells and may present as solitary benign bone tumors called plasmacytomas (see the image below). Intracranial plasmacytoma is rare; the largest reported series consisted of 9 patients.[2] Disseminated disease is known as multiple myeloma and carries a much less favorable prognosis than solitary plasmacytoma. Solitary intracranial plasmacytoma of the skull base carries a dissemination rate of up to 100%, which is considerably higher than the rate associated with intracranial plasmacytoma of the dura or convexities.

Intracranial plasmacytoma. Sagittal and axial T1-w Intracranial plasmacytoma. Sagittal and axial T1-weighted MRI with contrast enhancement demonstrate a right-sided plasmacytoma of the petrous bone. This tumor was treated through a far lateral approach and suboccipital craniotomy following a superselective embolization of feeding arteries.

Paragangliomas

Paragangliomas, such as glomus jugulare tumors, are benign neuroendocrine tumors that arise from chromaffin cells in the bony canals of temporal bone. These tumors are rare and represent 0.6% of all head and neck tumors; they present with a female-to-male ratio of 6:1.[3] Paragangliomas are locally invasive, and approximately 40% expand into the posterior cranial fossa, where they are identified as lesions of the cerebellopontine angle.[4] They rarely spread distally or involve the lymph nodes.[1]

Larger tumors may cause symptoms related to cerebellar and brain stem compression. Functional tumors represent the 1-3% of paragangliomas that produce catecholamines; the remainder are considered nonfunctional. (See the Lab Studies section.) Those that secrete catecholamines may cause a life-threatening cardiac arrhythmia or hypertensive emergency.[1]

Other benign skull tumors

Other benign lesions that affect bone and sometimes involve the skull include aneurysmal bone cysts, osteoid osteoma, ossifying and nonossifying fibromas, and some variants of giant cell tumors. Bony involvement is best demonstrated on CT scan with bone windows. MRI can demonstrate intracranial extension.

Chondrosarcoma

Chondrosarcoma is a malignant cartilage tumor that originates from enchondral bones. It is composed of cartilage-producing cells. It makes up 0.15% of intracranial tumors and 6% of skull base tumors.[5] When it develops in the skull base, it usually arises in the parasellar area, cerebellopontine angle, or paranasal sinuses. It may also arise in the clivus (see the image below). It is most common in men in the fourth decade of life. Skull base lesions are thought to arise from the persistent islands of embryonal cartilage that occur near the cranial base synchondroses.[5]

Clival chondrosarcoma. Contrast-enhanced T1-weight Clival chondrosarcoma. Contrast-enhanced T1-weighted MRI in the coronal plane. This tumor involved the clivus and posterior clinoid and encroached on the optic chiasm in the suprasellar region. It was subtotally resected through a frontotemporal craniotomy with a zygomatic osteotomy.

Chondrosarcomas can be divided into conventional, clear cell, mesenchymal, and dedifferentiated variants. When located in the skull base, the conventional pattern is most common. Conventional chondrosarcomas have been further subdivided into histologic grades I-III. The lower-grade tumors are less aggressive and have minimal malignant potential. These tumors do not stain for epithelial markers or oncofetal antigens, distinguishing them from chordomas (see below). Low-grade classic chondrosarcomas generally carry a good prognosis. They commonly present with cranial nerve palsies such as diplopia, hoarseness, dysphagia, facial dysesthesia, hearing loss, headache, and gait disturbance. They are overall slow growing, but locally aggressive.[5]

Chordoma

Chordoma is a low-grade malignancy that arises from tissue of the primitive notochord (in normal development becomes the nucleus pulposus of the intervertebral disk).[1] Approximately 40% of these tumors arise in the clivus (see the image below), with the remainder developing along the vertebral axis, most commonly in the sacrococcygeal region. Chordomas may develop in persons of any age, but they manifest most commonly in persons aged 20-40 years. A slight male predominance exists.

Chordoma. T1-weighted MRI with contrast that demon Chordoma. T1-weighted MRI with contrast that demonstrates an enhancing mass that replaced the clivus and invaded the right cavernous sinus. This lesion was subtotally resected using a sublabial approach. The patient was then treated with gamma knife radiosurgery (GKRS).

Clival chordoma is locally invasive and may extend into the middle fossa or brainstem. It recurs despite surgical resection and radiotherapy and may destroy surrounding tissues, but it rarely metastasizes. Chordomas are usually extradural in origin. Dural invasion is possible but usually develops late in the course of aggressive tumors or with recurrent tumors if a dural defect was left after the initial operation.

Microscopically, chordomas have a lobular arrangement of physaliferous cells, containing large vacuoles and mucus. These cells are surrounded by abundant extracellular mucoid tissue. Approximately 10% of chordomas show more malignant histologic features, which are sometimes related to previous irradiation.

Osteogenic sarcoma and fibrous sarcoma

Osteogenic sarcoma (osteosarcoma) is the most common malignant primary tumor of bone. It develops most frequently in the second decade of life and may be associated with prior radiation, Paget disease, fibrous dysplasia (see the image below), or chronic osteomyelitis.

Fibrous dysplasia. Coronal reconstruction of nonen Fibrous dysplasia. Coronal reconstruction of nonenhanced CT scan that demonstrates fibrous dysplasia of the right orbit with extension into the floor of the anterior fossa. This lesion was completely resected using a multidisciplinary team and a craniofacial approach that included a bifrontal craniotomy

Nerve sheath tumors

Intracranial nerve sheath tumors grow at the skull base, where cranial nerves exit the brain stem and approach the bony foramina. These lesions develop sporadically or as part of the genetic syndromes neurofibromatosis-1 (NF-1) and neurofibromatosis-2 (NF-2). Sporadic cases generally manifest as a single lesion, whereas multiple tumors present as part of a hereditary syndrome.

The most common intracranial nerve sheath tumors are schwannomas. These lesions arise almost exclusively from sensory nerves. The most common is the vestibular schwannoma (sometimes called acoustic neuroma; see the images below). Much less common are the trigeminal schwannoma and hypoglossal schwannoma (see the images below). Schwannomas and neurofibromas are well encapsulated and can usually be completely resected, although the involved nerve must often be sacrificed. The malignant peripheral nerve sheath tumor is infiltrating and highly aggressive and therefore cannot be cured with excision.

Vestibular schwannoma. T1-weighted MRI scan that d Vestibular schwannoma. T1-weighted MRI scan that demonstrates a large left-sided vestibular schwannoma in a 19-year-old woman with neurofibromatosis type II. Also present on the left is a vagal (tenth nerve) schwannoma. A residual tumor from a right-sided vestibular schwannoma, which was previously operated on, is visible. These lesions were resected through a retrosigmoid approach and suboccipital craniectomy.
Hypoglossal schwannoma. Precontrast (left) and Pos Hypoglossal schwannoma. Precontrast (left) and Postcontrast (right) T1-weighted MRI scans that demonstrate a right-sided schwannoma of the hypoglossal (XII) nerve. This tumor was completely resected using an extreme lateral approach and suboccipital craniectomy.

Vestibular schwannoma (acoustic neuroma, acoustic neurofibroma) is a benign tumor that arises from Schwann cells of the vestibular branch of the VIII nerve in more than 90% of cases; less than 10% arise from the cochlear branch of VIII. Vestibular schwannoma accounts for 5-10% of all intracranial tumors and is the most common tumor of the cerebellopontine angle. The peak age for tumor occurrence is between age 40 and 60 years, and they are twice as common in women as in men. Bilateral tumors occur in less than 5% of patients and, when present, are diagnostic for NF-2 (see the image below).

Vestibular schwannoma. T1-weighted MRI scan that d Vestibular schwannoma. T1-weighted MRI scan that demonstrates a large left-sided vestibular schwannoma in a 19-year-old woman with neurofibromatosis type II. Also present on the left is a vagal (tenth nerve) schwannoma. A residual tumor from a right-sided vestibular schwannoma, which was previously operated on, is visible. These lesions were resected through a retrosigmoid approach and suboccipital craniectomy.

Vestibular schwannomas grow slowly into the internal auditory meatus and the cerebellopontine angle, displacing the adjacent cerebellum, pons, or cranial nerves (usually V and VII). Because they grow slowly, many tumors are large and even cystic before they become symptomatic. The growth rate may increase during pregnancy.

Trigeminal schwannomas account for less than 8% of intracranial schwannomas and less than 0.4% of all intracranial tumors.[6] They originate within the ganglion, nerve root, or 1 of the 3 divisions of the trigeminal nerve. About 50% of these tumors are limited to the middle fossa, while 30% extend into the posterior fossa and 20% are dumbbell-shaped and extend into both fossae. Diagnosis is best established with MRI. The differential diagnosis includes meningioma, vestibular schwannoma, epidermoid lesions, and primary bone tumors of the skull base.

Malignant peripheral nerve sheath tumors are a rare and aggressive type of spindle cell tumor. They affect patients primarily aged 20-50 years. They originate from perineural or Schwann cells of the peripheral nerve sheath. They can present as a painless, progressively enlarging, subcutaneous mass.[7]

Meningioma

Meningiomas arise from meningothelial cells, which are most common in the arachnoid villi, and they comprise 22% of all intracranial tumors. They account for 3-12% of cerebellopontine angle tumors. Most meningiomas are diagnosed in the sixth or seventh decades of life. They are more common in women, with a female-to-male ratio of 3-2:1. Five to fifteen percent of patients with meningiomas have multiple meningiomas (see the images below), especially those with NF-2. More than 90% of tumors are intracranial and 10% intraspinal.

Foramen magnum meningioma. Contrast-enhanced T1-we Foramen magnum meningioma. Contrast-enhanced T1-weighted MRI scans that demonstrate a ventral, left-sided meningioma at the foramen magnum. This tumor was completely resected using a far lateral approach and suboccipital craniotomy with C1 laminectomy.
Multiple skull base meningiomas. Contrast-enhanced Multiple skull base meningiomas. Contrast-enhanced T1-weighted MRI in the coronal (above) and sagittal (below) planes demonstrates a large left-sided petroclival meningioma and a right-sided meningioma at the foramen magnum. After shunt placement to treat hydrocephalus, the petroclival tumor was resected using a presigmoid approach. The foramen magnum tumor was subsequently resected.

The only proven nongenetic risk factor for meningioma formation is radiation exposure. Radiation-induced meningiomas tend to develop over the cerebral convexities rather than at the skull base. Trauma has been suggested as a risk factor for meningioma formation and may be involved in the formation of intraosseous meningiomas, which can present at the skull base.

Almost all familial meningiomas develop within the context of NF-2, and patients with NF-2 are at increased risk for meningiomas as well as vestibular schwannomas. These patients often have multiple tumors of both varieties. Deletion of the c-sis protooncogene (a polypeptide homologous with platelet-derived growth factor [PDGF] receptor) on chromosome 22 has been linked to meningioma formation. Abnormalities in other chromosomes suggest that several oncogenes or tumor suppressor genes are involved in meningioma formation.

Most meningiomas are nodular and compress adjacent structures. Occasionally, they are distributed in sheathlike formations (meningioma en plaque). This pattern is especially common in skull base meningiomas of the sphenoid ridge (see the images below). All meningiomas are encapsulated and attach to the dura, from which they derive their blood supply. Hyperostosis of the underlying bone is common and can be appreciated radiographically.

Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted sagittal MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis, which is best seen on the axial image.
Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted axial MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right side. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis.

The World Health Organization grading system classifies meningiomas as typical (or benign), atypical, or malignant based on cellularity, cytologic atypia, mitosis, and necrosis. Malignant meningiomas are rare but aggressive, and about half metastasize systemically, usually in bone, liver, or lung. Benign meningiomas recur in about 7-20% of patients, atypical variants recur in 29-40% of patients, and anaplastic tumors recur in 50-78% of patients. Brain invasion may develop with all 3 histological grades of meningioma. Brain invasion connotes a greater likelihood of recurrence but does not indicate a truly malignant histologic pattern. Nevertheless, an elevated proliferation index (>5%) does predict a poor outcome.

The most common histologic subtypes of meningioma include meningotheliomatous (syncytial), fibrous, transitional, and psammomatous. Clinically, these subtypes are of little value, but select subtypes have prognostic relevance. Clear-cell meningiomas make up 0.2-0.81% of all meningiomas and are often more aggressive than more common varieties, with frequent recurrence and CNS metastasis.[8] Secretory meningiomas secrete vascular endothelial growth factor (VEGF) and are associated with extensive edema.[9] Papillary or rhabdoid meningioma variants must be treated as malignant tumors.

Hemangiopericytoma

Hemangiopericytoma is a rare lesion that comprises 0.4% of primary CNS tumors. It is a richly vascular and highly cellular tumor that is almost invariably associated with the meninges. They are a type of sarcoma that derives from pericytes that surround blood vessels. They often appear much like meningiomas on imaging.[1] A hemangiopericytoma is also more likely to recur than typical meningioma and systemic metastasis is possible.

Specific tumor locations

Tumors of the skull base may also be described based on their most common presenting location. Tumor location often dictates the presenting signs and symptoms. The skull base can be divided into the anterior, middle and posterior fossae. This distinction helps the surgeon choose which surgical approach offers the greatest opportunity for complete tumor removal with minimal potential for neurological injury.

Tumors of the anterior cranial fossa

The tumors of the anterior cranial fossa may be malignant or benign. The malignant tumors in this group include tumors that arise in the nasal cavity and paranasal sinuses (eg, juvenile angiofibroma, esthesioneuroblastoma [see the image below], inverted papilloma, lymphoma, nasopharyngeal carcinoma). Other malignant tumors that develop in this region include orbital gliomas and other orbital tumors, rhabdomyosarcomas, and osteogenic sarcomas. The benign tumors that develop specifically in the anterior skull base include ossifying fibromas.

Esthesioneuroblastoma. A 39-year-old man presented Esthesioneuroblastoma. A 39-year-old man presented with 1 month of decreased vision, left facial numbness, and swelling. Physical examination demonstrated left-sided exophthalmos and blindness. He was also unable to smell. Contrast-enhanced T1-weighted MRI demonstrated a large lesion that originated in the paranasal sinuses and extended through the cribriform plate into the anterior cranial fossa. He underwent a bifrontal craniotomy for resection of this tumor.

Several of the malignant tumors unique to the anterior skull base are rare entities. Esthesioneuroblastoma, also termed olfactory neuroblastoma, is a very rare tumor. Nasopharyngeal carcinoma is the most common skull base lesion that requires multidisciplinary surgical management. These tumors may enter the intracranial space by extension through the cribriform plate. Histologic variants of nasopharyngeal carcinoma include squamous cell carcinoma and adenoid cystic carcinoma (see the images below).

Adenoid cystic carcinoma. A T1-weighted image from Adenoid cystic carcinoma. A T1-weighted image from an MRI scan that demonstrates a tumor (red arrow) that involves the ethmoid sinuses and cribriform plate.
Adenoid cystic carcinoma. Extension of the tumor i Adenoid cystic carcinoma. Extension of the tumor into the middle fossa anterior to the temporal lobe (blue arrow).

Tumors of the middle cranial fossa

Tumors unique to the middle cranial base are usually benign. These tumors include pituitary adenomas, craniopharyngiomas, cavernous sinus meningiomas, temporal bone tumors, cholesteatomas, and enchondromas. Malignant tumors in this area may arise primarily (chondrosarcoma [see the image below] and osteogenic sarcoma) or secondarily through local invasion or hematologic spread from distant sites.

Clival chondrosarcoma. Contrast-enhanced T1-weight Clival chondrosarcoma. Contrast-enhanced T1-weighted MRI in the coronal plane. This tumor involved the clivus and posterior clinoid and encroached on the optic chiasm in the suprasellar region. It was subtotally resected through a frontotemporal craniotomy with a zygomatic osteotomy.

Meningiomas of the cavernous sinus present a unique challenge because resection is likely to damage multiple cranial nerves. In young patients with no ocular muscle palsy, some authors recommend subtotal resection and radiotherapy.

Tumors of the posterior cranial fossa

Tumors unique to the posterior cranial fossa include both benign and malignant lesions. Malignant tumors are discussed further below (see Malignancy and Metastasis, below). Benign tumors that specifically involve the posterior skull base include meningiomas of the foramen magnum, clivus and cerebellopontine angle, epidermoids, dermoids, chondromas, and chordomas (see the images below).

Foramen magnum meningioma. Contrast-enhanced T1-we Foramen magnum meningioma. Contrast-enhanced T1-weighted MRI scans that demonstrate a ventral, left-sided meningioma at the foramen magnum. This tumor was completely resected using a far lateral approach and suboccipital craniotomy with C1 laminectomy.
Multiple skull base meningiomas. Contrast-enhanced Multiple skull base meningiomas. Contrast-enhanced T1-weighted MRI in the coronal (above) and sagittal (below) planes demonstrates a large left-sided petroclival meningioma and a right-sided meningioma at the foramen magnum. After shunt placement to treat hydrocephalus, the petroclival tumor was resected using a presigmoid approach. The foramen magnum tumor was subsequently resected.
Petroclival meningioma. Contrast-enhanced T1-weigh Petroclival meningioma. Contrast-enhanced T1-weighted and a T2-weighted (upper right) MRI scan that demonstrates a large left-sided petroclival meningioma. This tumor was near totally resected using a presigmoid approach. The patient subsequently underwent gamma knife radiosurgery (GKRS) for the treatment of the residual tumor.
Skull base tumors. Sagittal enhanced T1-weighted i Skull base tumors. Sagittal enhanced T1-weighted image from an MRI scan that shows a hypointense mass (blue arrow) anterior to the brainstem.
Skull base tumors. Axial T2-weighted image from an Skull base tumors. Axial T2-weighted image from an MRI scan that demonstrates a hyperintense mass (blue arrow) anterior to and compressing the brainstem.
Chordoma. T1-weighted MRI with contrast that demon Chordoma. T1-weighted MRI with contrast that demonstrates an enhancing mass that replaced the clivus and invaded the right cavernous sinus. This lesion was subtotally resected using a sublabial approach. The patient was then treated with gamma knife radiosurgery (GKRS).

Clivus meningiomas arise anterior to the brainstem. Lateral extension into the petrous bone may complicate surgery because of cranial nerve involvement. Clear-cell meningiomas are also most commonly found in the posterior fossa.[8]

Foramen magnum meningiomas cause pain, gait difficulties, and wasting of the hand muscles. They are intimately entwined with the cranial nerves, complicating complete resection.

Malignancy and metastasis

Metastasis to the skull base

Malignant tumors that involve the skull base are less common than their benign counterparts. Their aggressive nature and tissue of origin, often adjacent to the intracranial vault, merit a unique approach to their surgical management. As the cranial nerves exit the bony foramina of the skull, they are vulnerable to entrapment and compression by osseous metastasis. Skull base metastases usually arise from a prostate, breast, lung, or head and neck primary lesion or from lymphoma. The cardinal sign of metastatic skull base invasion is cranial neuropathy, which is typically sudden in onset. Although skull base metastases are often painless, localized cranial or facial pain at the site of tumor invasion may be a symptom.

MRI scans can reveal even small skull base metastases. Almost all tumors can be visualized, especially if they lie within the cavernous sinus. Empiric treatment without histologic documentation may be indicated when symptoms are progressive, the clinical picture is clear, and biopsy is difficult or hazardous.

Direct extension of malignant tumors to the skull base

Several malignant tumors involve the base of the skull by direct extension. These include squamous cell carcinoma (of the nasal sinuses and temporal bone), adenoid cystic carcinoma (of the salivary glands; see the images below), esthesioneuroblastoma (of the olfactory mucosa; see the image below), and nasopharyngeal carcinoma.

Adenoid cystic carcinoma. A T1-weighted image from Adenoid cystic carcinoma. A T1-weighted image from an MRI scan that demonstrates a tumor (red arrow) that involves the ethmoid sinuses and cribriform plate.
Adenoid cystic carcinoma. Extension of the tumor i Adenoid cystic carcinoma. Extension of the tumor into the middle fossa anterior to the temporal lobe (blue arrow).
Esthesioneuroblastoma. A 39-year-old man presented Esthesioneuroblastoma. A 39-year-old man presented with 1 month of decreased vision, left facial numbness, and swelling. Physical examination demonstrated left-sided exophthalmos and blindness. He was also unable to smell. Contrast-enhanced T1-weighted MRI demonstrated a large lesion that originated in the paranasal sinuses and extended through the cribriform plate into the anterior cranial fossa. He underwent a bifrontal craniotomy for resection of this tumor.

These tumors affect cranial nerve function, but, unlike metastases, they often also cause pain. Imaging demonstrates erosion of the skull base and the presence of a soft tissue mass; biopsy is diagnostic. Small tumors can sometimes be cured with wide surgical excision before they invade sensitive neural structures. However, most tumors are more extensive when detected, and, despite treatment with radical excision and radiation therapy, the prognosis is often poor.

History of the Procedure

Over recent years, the field of skull base surgery has been revolutionized by multidisciplinary improvements in anesthetic and surgical techniques. The development of brain exposing osteotomies, endoscopic surgery, infection prevention methods (eg, galeal, frontalis, and myofascial flaps), and improved techniques for reconstruction allow surgeons to perform biopsies and resections on most skull base masses. In addition, radiosurgery has become a highly useful tool in treating pathologic conditions at the skull base. As expertise with surgical approaches to the skull base has grown, the optimal application of these methods in combination with adjuvant therapies has become the focus of skull base neurosurgery.

Problem

Many histologic tumor types present in the skull base. Primary tumors may derive from the bone, paranasal sinuses, nasopharynx, inner ear, dura, cranial nerves, and brain. These lesions cause symptoms through mass effect or through the invasion of local structures. Metastatic tumors also present in the skull base and may produce mass effect or invade adjacent tissue.

The anatomical location of a lesion often presents a significant challenge for safe surgical access because of the proximity or involvement of critical neural and vascular structures and the need to preserve the barrier between the cerebrospinal fluid (CSF) and the external environment.

Epidemiology

Frequency

Skull base tumors are relatively rare. The reported frequency of the more commonly encountered tumors is listed below.

Excluding autopsy data, meningiomas comprise approximately 22% of primary intracranial tumors. If autopsy data are included, the overall incidence of meningiomas is 2.3-5.5 cases per 100,000 persons. As with meningiomas in other regions, skull base meningiomas demonstrate a female predominance, with a female-to-male ratio as high as 3:1.[10] Approximately 15% of meningiomas grow along the sphenoid ridge, with 10% developing in the posterior cranial fossa and 5% in the olfactory groove.[11] Meningiomas of the floor of the middle fossa are uncommon and tend to grow quite large before diagnosis.[12]

Schwannomas comprise less than 10% of all primary intracranial tumors. Schwannomas of the vestibular nerve are the most common neoplasms that involve the temporal bone and represent 75% of tumors that occupy the cerebellopontine angle cistern.[13]

Chondrosarcomas comprise approximately 0.1% of all intracranial tumors. Half of these develop at the cranial base.

Chordomas also comprise approximately 0.1% of all intracranial tumors. Forty percent of chordomas develop at the skull base.

Skull base metastases, not including direct extension, occur in 4% of cancer patients.[14]

Etiology

Skull base tumors can be classified based on their tissue of origin, histological characteristics, and common anatomical locations. Unfortunately, even benign lesions may cause progressive and unrelenting deficits if located in an area where complete resection is not allowed and growth cannot be controlled with medical or radiation therapy. The Introduction section reviews some of the more common skull base neoplasms based on the tissue of origin and malignant potential.

Presentation

The clinical presentation of skull base tumors varies greatly and relates directly to the location of the lesion and the growth rate.

  • Osteoma: These tumors grow slowly and rarely expand internally to compress the brain; therefore, they are usually asymptomatic. When symptoms manifest, they may include local pain, headache, or recurrent sinusitis. Dural erosion and CSF rhinorrhea are rare.

  • Chondroma: Chondromas of the parasellar region or cerebellopontine angle often manifest as cranial nerve palsies. Other manifestations may include nasal obstruction, shortness of breath, and hoarseness.

  • Hemangioma: These tumors receive blood supply from the scalp or meningeal vessels, and periosteal involvement may produce headaches.

  • Dermoid and epidermoid tumors of the skull: These tumors usually arise in the midline, in the diploe of the bone, where they expand both the inner and outer tables of the skull.

  • Paragangliomas: They are slowly growing hypervascular lesions that usually present with gradual hearing loss, unilateral pulsatile tinnitus, and lower cranial nerve palsies. Larger tumors may cause symptoms related to cerebellar and brain stem compression. Functional tumors represent the 1-3% of paragangliomas that produce catecholamines; the remainder are considered nonfunctional. The functional tumors may cause hypertensive emergency or cardiac arrhythmias due to catecholamine release.

  • Metastasis to the skull base: The cardinal sign of metastatic skull base invasion is cranial neuropathy, which is typically sudden in onset. Although skull base metastases are often painless, localized cranial or facial pain at the site of tumor invasion may be a symptom.

  • Direct extension of malignant tumors to the skull base: These tumors affect cranial nerve function, but, unlike metastases, they often also cause pain.

  • Chondrosarcoma and chordoma: Chordomas and chondrosarcomas of the skull base may present with similar symptoms. Headache and diplopia (due to cranial nerve palsies) are the most common, occurring in approximately 60-65% of patients.[15] Accurate diagnosis is critical, however, because chondrosarcoma has a more favorable prognosis than chordoma.

  • Vestibular schwannoma: Increased clinical awareness and MRI have allowed earlier detection of these lesions, improving clinical outcomes. When these tumors go untreated, progressive unilateral hearing loss develops in nearly all patients. Hearing loss is often preceded by difficulty with speech discrimination, especially when the patient is talking on the telephone. Tinnitus (70%) and unsteady gait (70%) are also common. Further tumor growth can cause facial numbness (30%) or, less often, facial weakness, loss of taste, and otalgia due to encroachment on the trigeminal and facial nerves. Larger tumors grow into the cerebellopontine angle, causing headache, nausea, vomiting, diplopia, and ataxia or increased intracranial pressure and hydrocephalus. Other signs include nystagmus and cerebellar ataxia. The constellation of late symptoms can develop with any mass in the cerebellopontine angle; however, only vestibular schwannomas present with initial symptoms oftinnitusorhearing dysfunction.[16]

  • Trigeminal schwannoma: Nearly all patients develop numbness and pain in the trigeminal distribution, and about 40% have some weakness in the muscles of mastication. True trigeminal neuralgia is exceptional. Extension of the tumor into the posterior fossa is associated with seventh and eighth nerve dysfunction and cerebellar and pyramidal tract signs.

  • Meningioma: The clinical presentation of meningiomas is based on the structures adjacent to the lesion. Lesions at the skull base present with cranial neuropathies. Slow tumor growth may allow the lesion to grow large before coming to clinical attention.

  • Tumors of the anterior cranial fossa: Benign tumors of the anterior cranial fossa include meningiomas of the planum sphenoidale. These tumors, by virtue of their slow growth rate, often come to clinical attention only after they are very large and have caused significant mass effect on the frontal lobes. Neural injury may result in personality changes.

  • Tumors of the posterior cranial fossa: Cerebellopontine angle meningiomas often present with hearing loss and facial pain or numbness. They often have a characteristic en plaque shape. By the time eighth nerve dysfunction is evident, the tumor is usually large. Foramen magnum meningiomas cause pain, gait difficulties, and wasting of the hand muscles. They may present with a typical rotating paralysis, with sequential weakness beginning in the ipsilateral upper extremity and progressing to involve the ipsilateral lower extremity, contralateral lower extremity, and ipsilateral upper extremity, in that order.

The clinical presentation of a series of case examples is presented below (see the Surgical Therapy section).

Indications

The indications for resecting a skull base mass are evolving. The symptoms and life expectancy of the patient, natural history of the disease, and structures involved by the tumor all must be considered before recommending treatment. In many cases, biopsy helps determine the diagnosis. A larger craniotomy for extensive resection may then be recommended. In patients who harbor aggressive malignant lesions, which often preclude surgical cure, biopsy can prevent the need for an extensive craniotomy. When craniotomy is undertaken, the goals of surgery are to minimize morbidity and to maximize the extent of tumor removal.

Relevant Anatomy

The skull base is a highly complex region that includes multiple bones. Eleven pairs of cranial nerves and the olfactory nerves (CN I) pass through the inner table of the skull via 7 pairs of bony foramina and the cribriform plate (CN I). The skull base also has multiple foramina that provide passage for vascular and other neural elements. The anatomy relevant to surgery greatly varies and depends on the location of the tumor and adjacent skull base structures.

Contraindications

Contraindications to surgical correction of skull base tumors are based on the patient’s comorbidities and his or her ability to tolerate surgery. The poor long-term prognosis for patients with malignancy often overshadows the use of a large skull base resection in favor of a less-invasive palliative approach. For a case example of a patient with a skull base tumor that was not amenable to surgical correction, see the Medical therapy section.

 

Workup

Laboratory Studies

Preoperative laboratory studies include a complete blood cell count, electrolyte evaluation, and bleeding and coagulation parameters.

Masses located in or around the sella turcica merit serum endocrine studies.

Paragangliomas: Catecholamine secretion can be diagnosed with urine or serum studies.

Imaging Studies

General imaging studies for assessment of skull base tumors include the following:

  • CT scan of the brain with thin cuts and sagittal and coronal reconstructions can reveal abnormalities of the bone (eg, erosion, hyperostosis) and calcification in the tumor.

  • Brain MRI with and without gadolinium is the best study to evaluate soft tissue masses and structures.

  • Cerebral angiography is beneficial if the tumor encroaches on the carotid or other major intracranial arteries or a major venous sinus. It is used to assess whether arteries and venous sinuses are patent. In the case of meningioma and other vascular tumors, angiographic embolization of appropriate feeding vessels can decrease blood loss during operative resection and contribute to the ease of tumor removal.

  • MR arteriography and venography may also be used to assess the patency of arterial and venous structures.

  • If a metastatic tumor has an unknown primary source, a systemic workup should be performed. Imaging tests include posteroanterior and lateral chest radiography; contrast-enhanced CT scan of the chest, abdomen, and pelvis; and a bone scan.

Tumor-specific and site-specific imaging techniques include the following:

  • Osteoma: Diagnosis is based on the radiographic appearance. The most sensitive test is CT scanning, in which the lesion appears as a circumscribed homogeneous bony density (see the image below).

    Osteoma. CT scan with axial bone windows and coron Osteoma. CT scan with axial bone windows and coronal plane reconstruction that demonstrates a fibrous osteoma that involves the right orbit and the floor of the anterior cranial fossa.
  • Chondroma: Radiographically, chondromas are best characterized by CT scanning; these tumors appear as lytic lesions with sharp margins and erosion of surrounding bone. Stippled calcification within the lesion helps distinguish it from a metastasis or chordoma.

  • Hemangioma: Skull radiographs may demonstrate a circular lucency with trabeculations. CT scanning demonstrates a nonenhancing hypodense lesion. Flow voids may be visualized on MRI.

  • Dermoid and epidermoid tumors of the skull: Radiographs demonstrate rounded or ovoid lytic lesions with sharp sclerotic margins. On CT scans, these lesions are nonenhancing and hypodense and involve all 3 bone layers. MRI demonstrates a low-intensity lesion on T1 and a high-intensity lesion on T2.

  • Paragangliomas: MRI and magnetic resonance (MR) angiography best characterize paragangliomas because these modalities usually reveal their extensive vascularity, meriting preoperative embolization in many cases (see the images below).

    Paraganglioma. Contrast-enhanced MRI scan of the a Paraganglioma. Contrast-enhanced MRI scan of the axial (left) and coronal (right) planes that demonstrates a paraganglioma (glomus jugulare) at the right cerebellopontine angle. Extension out of the jugular foramen into the extracranial soft tissue is visible (right).
    Paraganglioma. Arterial phase external carotid art Paraganglioma. Arterial phase external carotid artery angiograms. Pre-embolization imaging (left) demonstrates the rich vascularity of the tumor. Postembolization imaging (right) demonstrates that the arterial feeding vessels have been significantly reduced.
  • Metastasis to the skull base: MRI scans can reveal even small skull base metastases. Almost all tumors can be visualized, especially if they lie within the cavernous sinus.

  • Direct extension of malignant tumors to the skull base: Imaging demonstrates erosion of the skull base and the presence of a soft tissue mass.

  • Osteogenic sarcoma and fibrous sarcoma: Fibrous sarcoma is a soft tissue tumor that arises from bone, periosteum, scalp, or dura. It is often accompanied by bony destruction, showing a regular but discrete lytic radiographic picture.

  • Vestibular schwannoma: MRI is the best modality for the diagnosis of a vestibular schwannoma. The tumor enhances vigorously, and its origin in the internal auditory canal distinguishes it from a meningioma. CT scanning with contrast demonstrates most tumors larger than 1.5 cm.

  • Trigeminal schwannoma: Diagnosis is best established with MRI.

  • Meningioma

    • Imaging of skull base meningiomas includes CT scanning, MRI, and sometimes angiography, which can be obtained in conjunction with embolization of feeding arteries. On nonenhanced CT scans, the tumor is isodense or slightly hyperdense compared with the brain. The mass is generally smooth and sometimes lobulated, and calcifications are often appreciated. Contrast enhancement is strong and homogeneous; margins are distinct, and the tumor’s dural base can usually be appreciated, as in the first image below. Hyperostosis of the underlying bone is common and can be appreciated radiographically. Hyperostosis of the immediately adjacent bone is seen in 25% of patients, as in the second and third images below.

      Meningioma of the tuberculum sella. Contrast-enhan Meningioma of the tuberculum sella. Contrast-enhanced T1-weighted MRI scan that demonstrates a meningioma in a patient who presented with headaches and slowly progressive visual loss. Note the broad dural base, best appreciated on the sagittal image (right). This lesion was completely removed using a frontotemporal craniotomy with orbital osteotomy.
      Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted sagittal MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis, which is best seen on the axial image.
      Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted axial MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right side. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis.
    • On MRI, the tumor is isointense (65%) or hypointense (35%) when compared with normal brain on both T1-weighted and T2-weighted imaging. Intense and homogeneous gadolinium enhancement is visible, and the dural tail is often evident. MRI is the best modality to define the relationship between the tumor and surrounding structures.

    • Atypical radiographic features such as cysts, hemorrhage, and central necrosis, which can mimic features of glioma, are visible in about 15% of meningiomas. Malignant meningiomas commonly demonstrate bone destruction, necrosis, irregular enhancement, and extensive edema. MRI demonstrates the rare cases of direct brain invasion by tumor. The differential diagnosis of radiographically atypical meningiomas includes dural metastasis, other primary meningeal tumors (eg, sarcoma), granuloma, or aneurysm. Metastases are commonly associated with abundant surrounding edema and bone destruction; in contrast, hyperostosis and moderate edema suggest meningioma.

    • On angiograms, skull base meningiomas are hypervascular, generally with feeding vessels from the external carotid artery. Encased or compromised arteries and venous sinus involvement can be assessed using MR or CT angiography, which greatly contributes to operative planning. Catheter angiography is reserved for cases in which balloon test occlusion (BTO) or arterial embolization is planned.

  • Hemangiopericytoma: Gadolinium-enhanced MRI best characterizes these lesions (see the image below). CT scanning may help differentiate hemangiopericytoma from a meningioma by demonstrating local osteolysis, rather than the hyperostosis that may be seen with meningioma. Angiography can demonstrate the tumor’s vascularity, and embolization can be a helpful adjunct prior to surgical intervention.

    Hemangiopericytoma. Contrast enhanced T1-weighted Hemangiopericytoma. Contrast enhanced T1-weighted MRI scans that demonstrates a large hemangiopericytoma originating from the floor of the anterior fossa in a young man with progressive headaches, blurred vision, and papilledema. This tumor was subtotally resected through a frontotemporal craniotomy with orbital osteotomy.
  • Tumors of the posterior cranial fossa: MRI usually differentiates a meningioma from a vestibular schwannoma because the latter begins within the internal auditory canal.

Other Tests

In the appropriate clinical setting, additional tests are used to formally evaluate cranial nerve function. Tests may include a formal visual field evaluation, audiography, or swallowing study.

Vestibular schwannoma: Hearing function can be evaluated using brainstem auditory evoked potentials, caloric stimulation with electronystagmography, and audiometry.

Tumors of the posterior cranial fossa: Abnormalities found on electronystagmography, audiography, and brainstem auditory evoked potentials testing are less common than with vestibular schwannomas, but these tests are rarely needed with current imaging techniques.

Diagnostic Procedures

Balloon test occlusion (BTO): Large vessel compromise due to tumor involvement can be documented preoperatively with angiography to allow for adequate presurgical planning. If a large vessel requires ligation during the operative approach or tumor resection, a BTO gives the surgeon an indication of whether the patient might tolerate vessel sacrifice or if a bypass procedure is required.

 

Treatment

Approach Considerations

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.

Of 42 patients who underwent image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma or chondrosarcoma, 5-year overall survival rates and local control rates were 85.6% and 65.3% for chordoma patients and 87.8% and 88.1% for chondrosarcoma patients. Ten patients progressed locally, 8 of whom were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3), and none of the 8 patients with grade 1 chondrosarcoma failed. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively.[17]

  • 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 and surgery with further therapy, when indicated, have both been associated with 5-year survival rates of more than 90%.[18, 19]

  • 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. Gross total surgical resection correlates with lower recurrence rates and is the strongest factor in patient survival.[20]

  • 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.[21]

      • 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.[22]

    • 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 the image below) 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.

Squamous cell carcinoma. Venous phase of a cerebra Squamous cell carcinoma. Venous phase of a cerebral angiogram that demonstrates filling of the right transverse sinus (red arrow) but no filling of the left transverse sinus (blue arrow).

The balloon catheter was passed from the femoral vein into the right transverse sinus. The balloon was inflated to occlude the sinus (see the first image below). A concurrent angiogram demonstrated no flow in the right or left transverse sinus (see the second image below). 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.

Squamous cell carcinoma. Balloon test occlusion wi Squamous cell carcinoma. Balloon test occlusion with the balloon inflated in the right transverse sinus (red arrow).
Squamous cell carcinoma. Venous phase of a cerebra Squamous cell carcinoma. Venous phase of a cerebral angiogram with the balloon occluding the right transverse sinus (red arrow).

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 tumors.[23] 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.[24]

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).[25]

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.[26]

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 the image below).

Gamma knife radiosurgery plan. This patient presen Gamma knife radiosurgery plan. This patient presented with adenoid cystic carcinoma of the right lacrimal gland. The tumor metastasized to the right middle fossa and cavernous sinus.

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.[27]

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.[28]

Subtotal resection followed by GKRS has proven to be a viable treatment option for large vestibular schwannomas, owing to good tumor growth control and facial nerve function preservation, plus the possibility of preserving serviceable hearing and the low number of complications.[29]

Between 1998 and 2009, 383 patients were treated for an acoustic neuroma by a single surgeon using a facial nerve–sparing paradigm. Larger tumors were treated with initial microsurgical resection, focusing on facial nerve preservation and leaving residual tumor if the facial nerve was determined to be at risk, while smaller tumors and postmicrosurgical tumor regrowth were treated with GKRS. The results from the 151 patients treated with microsurgery showed that facial nerve–sparing microsurgery provided good tumor control (13.2% of patients required radiosurgery for tumor regrowth after microsurgery) with excellent facial nerve preservation rates (97% of patients initially treated with microsurgery had House-Brackmann grade I or II function at last follow-up), showing the efficacy of this facial nerve–sparing paradigm for acoustic neuromas.[30]

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.[31]

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 the image below). Positron emission tomography (PET) can be used to help distinguish radiation necrosis from recurrent tumor.[32, 3]

Radiation necrosis. This patient presented with ad Radiation necrosis. This patient presented with adenoid cystic carcinoma of the right lacrimal gland. The tumor metastasized to the right middle fossa and cavernous sinus. The patient subsequently developed tumor recurrence and underwent right orbital exenteration and further gamma knife radiosurgery (GKRS). He presented 18 months later with new headaches and seizures. Contrast-enhanced T1-weighted and T2 FLAIR (center) MRI demonstrate radiation necrosis at the site of previous radiation therapy.

Endoscopic surgery

Endoscopic neurosurgery offers a minimally invasive route to specific lesions and is increasingly being implemented as a tool for the biopsy and removal of these lesions. The role of endoscopy in accessing and resecting tumors of the skull base has been evolving since it was first used for the intranasal removal of pituitary tumors in the late 1980s.[33] Expanding upon the original transnasal approach, many centers have developed different approaches that increase the applicability of endoscopic surgery.

Although prior work in this field has depended on cadaveric studies, case reports, and small case series, larger center experiences are now emerging in the literature. As the field develops, indications continue to expand and outcomes after endoscopic surgery improve. The most common endoscopic skull base procedures currently include the transsphenoidal approach to sellar lesions, but this may changes as other approaches gain popularity.

Advantages of endoscopic skull base surgery include its ability to access areas that the conventional microscope can not and that the view of lesions is both easy to access locations and more difficult approaches are better visualized with the panoramic endoscopic view, compared with the narrow view of the microscope. In addition, the endoscope can gain access to many lesions of the skull base with minimal manipulation of neurovascular structures and decreased brain retraction.

Disadvantages of endoscopic surgery compared with more traditional minimally invasive techniques include visualization, difficulty due to the loss of binocular vision, and a moderate risk of CSF leak. In addition, operating in an area where access is limited creates disadvantages in itself, such as limited visualization of the lesion, difficulty inserting and using certain instruments, and difficulty controlling bleeding in the event of a hemorrhagic complication. The multiple advantages of endoscopic surgery, however, combine with rapidly growing interest to indicate that the endoscope will play an increasingly important role in skull base surgery.

Endoscopic approaches

Traditional approaches to anterior skull base lesions involve a craniotomy, such as the frontal, bifrontal, expanded bifrontal, frontotemporal orbitozygomatic, and transbasal approaches. Although effective, these approaches carry risk of morbidity, including dissection of the temporalis muscle, risk to the frontalis branch of the facial nerve, and creation of an epidural space. Specific endoscopic approaches can avoid these complications through minimally invasive access.[34, 33]

Transnasal approaches

Through the transnasal approach, it is possible to perform transcribriform, transclival, and transodontoid approach. These approaches target lesions of the olfactory groove, lower two-thirds of the clivus, and the odontoid-cervico-medullary junction, respectively.[35]

Transsphenoidal approach

This approach is the most commonly used and can be employed in the transsellar, transtuberculum, transplanum, transclival, and transcavernous approaches. These approaches permit access to the sella, supracellar cistern, upper third of the clivus, and the medial cavernous sinus.

Transethmoidal approach

This endoscopic approach is used for access through 3 structures: transfovea ethmoidalis, transorbital, and transsphenoidal. Respectively, these approaches permit access to lesions of the anterior fossa, orbital apex, and cavernous sinus.

Transmaxillary approach

Access through the maxilla must be used to perform a transpterygoidal approach, which permits access to the pterygopalatine fossa, infratemporal fossa, Meckel cave, the petrous apex, the lateral sphenoid sinus, and the lateral cavernous sinus.

Endoscopic surgery of the skull base provides a minimally invasive alternative to open surgery for many specific lesions. As a nascent field, it will continue to grow and change significantly in the near future as its popularity and indications broaden.

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.[23] 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 the images below). 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.

Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted sagittal MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis, which is best seen on the axial image.
Right sphenoid wing meningioma with intraorbital i Right sphenoid wing meningioma with intraorbital involvement. Contrast-enhanced T1-weighted axial MRI scan. This tumor manifested as slowly progressive unilateral vision loss and mild proptosis on the right side. It was resected using a frontotemporal craniotomy with orbitozygomatic osteotomy. Note the right sphenoid hyperostosis.

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 the image below).

Giant pituitary adenoma. Contrast-enhanced MRI sca Giant pituitary adenoma. Contrast-enhanced MRI scan that demonstrates a very large pituitary adenoma with significant suprasellar extension. Large tumors of the sellar and suprasellar region may require a combined craniotomy and trans-sphenoidal approach to achieve complete resection.

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 the image above) 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 the first image below) showed tumor involvement of the ethmoid sinuses and floor of the anterior fossa in the region of the cribriform plate. CT scan (see the second image below) 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.

Adenoid cystic carcinoma. A T1-weighted image from Adenoid cystic carcinoma. A T1-weighted image from an MRI scan that demonstrates a tumor (red arrow) that involves the ethmoid sinuses and cribriform plate.
Adenoid cystic carcinoma. Extension of the tumor i Adenoid cystic carcinoma. Extension of the tumor into the middle fossa anterior to the temporal lobe (blue arrow).

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 the image below) 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.

Chordoma. T1-weighted MRI with contrast that demon Chordoma. T1-weighted MRI with contrast that demonstrates an enhancing mass that replaced the clivus and invaded the right cavernous sinus. This lesion was subtotally resected using a sublabial approach. The patient was then treated with gamma knife radiosurgery (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 the image below) 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.

Petroclival meningioma. Contrast-enhanced T1-weigh Petroclival meningioma. Contrast-enhanced T1-weighted and a T2-weighted (upper right) MRI scan that demonstrates a large left-sided petroclival meningioma. This tumor was near totally resected using a presigmoid approach. The patient subsequently underwent gamma knife radiosurgery (GKRS) for the treatment of the residual tumor.

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 the first image below) showed a hypointense mass within the posterior cranial fossa that compressed the pons and medulla posteriorly. T2-weighted MRI (see the second image below) demonstrated a hyperintense mass consistent with an epidermoid. The patient underwent suboccipital craniectomy for complete resection of the mass.

Skull base tumors. Sagittal enhanced T1-weighted i Skull base tumors. Sagittal enhanced T1-weighted image from an MRI scan that shows a hypointense mass (blue arrow) anterior to the brainstem.
Skull base tumors. Axial T2-weighted image from an Skull base tumors. Axial T2-weighted image from an MRI scan that demonstrates a hyperintense mass (blue arrow) anterior to and compressing the brainstem.

A 38-year-old woman presented with chronic headaches and tingling in the fingers of her left hand. MRI scan (see the image below) 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.

Foramen magnum meningioma. Contrast-enhanced T1-we Foramen magnum meningioma. Contrast-enhanced T1-weighted MRI scans that demonstrate a ventral, left-sided meningioma at the foramen magnum. 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).

Hearing loss after surgery for vestibular schwannoma is a concern. In a comparative analysis, Wind et al found that standard audiometry and patient-perceived hearing function evaluation may be helpful in identifying subjective hearing loss after surgery for vestibular schwannoma and could aid in determining further treatment for these patients.[36] Rachinger et al determined that the origin of the tumor is of vital importance to the prognosis for cochlear nerve preservation when performing vestibular schwannoma surgery. Of the patients in their study, hearing was preserved in 42% with superior vestibular nerve origin, versus 16% with inferior vestibular nerve origin.[37]

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.

Outcome and Prognosis

Because skull base tumors can be any one of many unrelated tumors, outcome and prognosis vary.

Benign tumors, such as meningiomas, can be resected with minimal mortality and acceptable morbidity. In a series of skull base meningiomas published in 1994 by Sekhar, the rate of total excision was 60%, the postoperative mortality rate was 15%, and the postoperative major morbidity rate was 16%.[15] Sixty percent of patients developed a new cranial nerve deficit, and 3% of the patients had a recurrence.

Malignant tumors, such as nasopharyngeal carcinoma and esthesioneuroblastoma, can also be controlled with skull base resection. In a 1989 study by Levine et al, a survival rate of 82% was obtained with craniofacial resection of esthesioneuroblastoma, compared with a rate of 37% before the technique of skull base resection.[38] In a study by Van Tuyl and Gussack, dural invasion was a factor associated with prognosis; when this occurs, prognosis is worse.[39]

Forty-one patients with esthesioneuroblastomas treated at UCLA were retrospectively studied to profile clinical presentation and treatment results from 2002 to 2013. The 5-year recurrence-free survival (RFS) and overall survival (OS) were 54% and 82%, respectively. Modified Kadish stage was the only factor that was identified as affecting OS, and tumor grade was the only factor that was shown to have an independent impact on RFS. There was no statistical difference in survival between the surgical approaches chosen, but the endoscopic approach was associated with a decreased length of hospital stay, as well as reduced blood loss, ICU admission, and complications.[40]

Hayhurst et al studied benign and malignant skull base lesions in 23 children ranging from 13 months to 15 years who underwent resection. They concluded that children tolerate these procedures well. They experience minimal surgical morbidity and good long-term success in controlling the tumor and in functional outcomes. Adjuvant treatment was sometimes required.[41]

Future and Controversies

As surgical techniques continue to evolve, the morbidity and mortality rates of surgery to resect skull base lesions should continue to decrease. Additionally, advances in medical therapy, radiosurgery, and endoscopic techniques will contribute to improved outcomes while decreasing the morbidity associated with treatment. The indications and applications of these techniques continue to evolve.