Skull base chordomas are rare midline malignancies of clival origin that represent one of the most challenging skull base tumors to treat, given their location, invasiveness, potential extension around vital neurovascular structures, and high recurrence rate. Total tumor resection is the mainstay of treatment. The combination of surgery and postoperative irradiation appears to provide the best outcome.
| EBM Question | Level of Evidence | Grade of Recommendation |
|---|---|---|
| Is gross total resection of skull base chordomas better facilitated with a midline endoscopic endonasal approach? | 4 | C |
The aim of this article is to present the epidemiologic and pathophysiologic characteristics of skull base chordomas, outline their anatomic localization and possible extension, describe their clinical features and imaging characteristics, discuss management options, and determine the optimal treatment for these rare but aggressive tumors.
Epidemiology
Chordomas are extra-axial tumors that originate from the remnants of notochord. Approximately 50% develop in the sacrococcygeal region, 35% in the spheno-occipital region, and 15% in vertebrae. Skull base chordomas account for less than 0.2% of all intracranial neoplasms. The overall incidence of chordomas is 0.08 to 0.5 cases per 100,000 individuals per year, and their incidence at the skull base location is 1 case per 2,000,000 individuals per year. The incidence of skull base chordomas is higher in younger-age patients, often appearing in the second to fifth decades.
Histopathology
Chordomas are generally whitish soft multilobulated masses with a fibrous pseudocapsule occasionally filled by a mucoid substance (secondary to hemorrhage) or with hemorrhage, necrosis, calcifications, and fragments of bone. Microscopically they are characterized by physaliphorous cells, which are translucent cells of different sizes rich in mucin and glycogen.
Chordomas are low-grade malignancies with low metastatic potential, divided into 3 overlapping and sometimes coexisting histopathologic types: conventional (typical), chondroid, and dedifferentiated (atypical). Typical chordomas are the most common; chondroid chordomas appear to confer a better prognosis, although many pathologists believe this variant is actually a low-grade chondrosarcoma. The aggressive “dedifferentiated” variety accounts for only 5% of cases and is considered a high-grade neoplasm.
Evident in the immunoprofile of chordoma cells is reactivity for low-molecular-weight cytokeratins 7, 8, 18, and 19 (simple epithelium), as well as high-molecular-weight cytokeratins 4, 5, and 6 (mucosal epithelia), S-100 protein, vimentin, and epithelial membrane antigen. Loss of heterozygosity (LOH) of chromosomes 1p, 9p, 10q, and 17p was reported in chordomas. Although chordomas are usually sporadic, a few familiar cases have been described and the deletion of 1p36 was found to be the most frequent genetic abnormality, occurring in 85% of both sporadic and familiar chordomas. LOH at 10q, 17p, and 9p was identified in 57%, 52%, and 21% of skull base chordomas, respectively, with LOH at 9p being associated with a shorter overall survival.
Histopathology
Chordomas are generally whitish soft multilobulated masses with a fibrous pseudocapsule occasionally filled by a mucoid substance (secondary to hemorrhage) or with hemorrhage, necrosis, calcifications, and fragments of bone. Microscopically they are characterized by physaliphorous cells, which are translucent cells of different sizes rich in mucin and glycogen.
Chordomas are low-grade malignancies with low metastatic potential, divided into 3 overlapping and sometimes coexisting histopathologic types: conventional (typical), chondroid, and dedifferentiated (atypical). Typical chordomas are the most common; chondroid chordomas appear to confer a better prognosis, although many pathologists believe this variant is actually a low-grade chondrosarcoma. The aggressive “dedifferentiated” variety accounts for only 5% of cases and is considered a high-grade neoplasm.
Evident in the immunoprofile of chordoma cells is reactivity for low-molecular-weight cytokeratins 7, 8, 18, and 19 (simple epithelium), as well as high-molecular-weight cytokeratins 4, 5, and 6 (mucosal epithelia), S-100 protein, vimentin, and epithelial membrane antigen. Loss of heterozygosity (LOH) of chromosomes 1p, 9p, 10q, and 17p was reported in chordomas. Although chordomas are usually sporadic, a few familiar cases have been described and the deletion of 1p36 was found to be the most frequent genetic abnormality, occurring in 85% of both sporadic and familiar chordomas. LOH at 10q, 17p, and 9p was identified in 57%, 52%, and 21% of skull base chordomas, respectively, with LOH at 9p being associated with a shorter overall survival.
Surgical anatomy
Skull base chordomas arise in bone but may grow to involve multiple areas of the cranial base, and occasionally erode into the intradural space to encompass neurovascular structures and compress the brainstem. The selection of an operative approach depends on the tumor location and the relationship to the internal carotid, vertebral, and basilar arteries, cavernous sinus, and brainstem. In the sagittal plane the clivus, the site of origin of skull base chordomas, can be divided for the purpose of surgical planning into 3 regions :
- •
Upper clivus: above the crossing point of the trigeminal nerve root over the clivus, including the dorsum sellae ( Fig. 1 A)
Fig. 1
( A ) Sagittal T1-weighted magnetic resonance (MR) image with gadolinium (Gd) shows a mass involving the upper clivus/dorsum sellae ( arrow ). The chordoma extends into the pituitary fossa. The anterior stronger enhancement area represents the anteriorly displaced pituitary gland. ( B ) Sagittal T1-weighted MR image without Gd shows a mass in the region of the middle clivus ( arrow ). The tumor appears to emanate from the bone with projection into the prepontine cistern. It is inferiorly elongated and lies very close to the basilar artery. ( C) Sagittal T1-weighted MR image with Gd demonstrates a mass of the lower clivus that extends down to the dens ( arrow ). It is an expansile destructive lesion, bulging and extending into the posterior fossa, where it abuts the cervicomedullary junction.
- •
Mid clivus: from the trigeminal root inferiorly to the level of the glossopharyngeal nerve root (see Fig. 1 B)
- •
Lower clivus: from glossopharyngeal nerve to foramen magnum (see Fig. 1 C).
The real extension of skull base chordomas can exceed the clival anatomy and extend ventrally, to the anterior cranial fossa, or caudally, involving the upper cervical spine ( Fig. 2 ).
Of significant surgical importance is the potential extension of the tumor in the coronal plane to involve the petrosphenoclival junction, petrous apex, occipital condyle, and jugular foramen. For further lateralized tumors, the petrous ridge is divided into two areas:
- •
Medial area: medial to internal auditory canal (IAC) ( Fig. 3 A)
Fig. 3
( A ) Axial T1-weighted MR image shows a large, lobulated mass centered on the right petroclival synchondrosis with heterogeneous signal. There is posterior extension with displacement of the posterior fossa and involvement of the right cerebellopontine angle. ( B ) Axial T1-weighted MR image demonstrates a larger clival chordoma extending more laterally compared with the previous image. The tumor extends into the cerebellopontine angle and beyond the internal auditory canal on the right with distortion of the cerebellum, lower pons, and medulla. ( C ) Axial T1-weighted MR image shows a large skull base chordoma with intradural extension that exerts severe mass effect on the pons and medulla. The fourth ventricle is narrowed, and displayed to the left and posteriorly. The basilar artery appears to be encased by the mass.
- •
Lateral area: lateral or posterior to the IAC (see Fig. 3 B).
Most of the clival chordomas are completely extradural. However, some invade the outer layer of the dura mater, extend into the space between the outer and inner layers of the dura, or invade both layers of the dura and extend into the intradural space, resulting in direct brainstem compression (see Fig. 3 C).
Clinical presentation
Clinical presentation is related to tumor location and direct compression of the surrounding neural structures. Clival chordomas typically present with cranial neuropathies, most commonly visual deterioration (cranial nerve [CN] II) and CN III palsy with tumors confined to the upper clivus; diplopia (CN VI) with tumors of the mid clivus; and lower nerve palsies (CN IX, X, XII) when tumors involve the lower clivus. Direct brainstem compression results in long tract dysfunction, and is accompanied by high morbidity and mortality. Headache due to direct dural invasion, trigeminal nerve compression, or increased intracranial pressure is another common complaint.
Imaging findings
Both computed tomography (CT) and magnetic resonance (MR) imaging are required for the evaluation of skull base chordomas because of the bone involvement and the tumor proximity to critical soft-tissue structures.
The classic appearance of clival chordoma with high-resolution CT is that of a centrally located, well-circumscribed, expansile soft-tissue mass that arises from the clivus with associated extensive lytic bone destruction. Intratumoral calcifications usually represent bone destruction rather than dystrophic calcifications in the tumor itself ( Fig. 4 ). However, the chondroid variant is more likely to demonstrate real intratumoral calcifications. There is moderate to marked enhancement following administration of iodinated contrast material.
MR imaging is the single best modality for radiologic evaluation of skull base chordomas. On conventional spin-echo T1-weighted MR images, chordoma has intermediate to low signal intensity and is easily recognized within the high signal intensity of the fat of the clivus. On T2-weighted images, chordoma has high signal intensity, a finding that likely reflects the high fluid content. The majority of chordomas demonstrate moderate to marked enhancement following contrast material injection ( Fig. 5 ). The enhancement pattern of the tumor may have a “honeycomb” appearance. Fat suppression is useful for differentiating enhanced tumor margins from adjacent bright fatty bone marrow, and this technique is especially useful in detecting small intraclival chordomas. Chondroid chordomas may not be as bright as typical chordomas on T2-weighted images. Also, T2-weighted imaging is excellent for differentiating tumor from adjacent neural structures.
Even though multiple synchronous tumors or drop metastases from an intracranial chordoma are very rare, screening of the entire spine at the initial evaluation of a skull base chordoma patient should be considered.
Management
The therapeutic approach to skull base chordoma has traditionally relied on surgical resection. However, gross total resection (GTR) is not always possible because of the tumor extension, invasiveness, and proximity to critical structures. Radiation therapy has been demonstrated to be a valuable modality for local control in the postoperative setting, particularly with the advent of charged-particle radiotherapy and specifically with proton beam irradiation. At present, the mainstay of therapy is surgical resection combined with high-dose radiation therapy.
Surgical approaches
In the absence of extenuating medical factors, the surgical goal should be a GTR with minimal morbidity. The surgical approaches used are broadly classified as (1) anterior midline and (2) lateral approaches. Anterior midline approaches consist of extended subfrontal, transmaxillary, transmandibular, transsphenoidal, endoscopic endonasal, transoral, and transcervical approaches. Lateral open skull base approaches include frontotemporal transcavernous orbitozygomatic, anterior transpetrosal, preauricular infratemporal, combined supratentorial and infratentorial transtemporal, and extreme lateral transcondylar approaches. Combined or staged surgeries are often necessary, depending on the size and anatomic distribution of the tumor.
The following 4 transcranial approaches and the endoscopic endonasal approach (EEA) are the most frequently used, alone or in combination, for resection of skull base chordomas. For the purpose of this article the authors briefly outline the advantages and disadvantages of each of them, with emphasis on the advances of EEA, as it represents the most promising approach for total resection of skull base chordomas.
Extended Frontal Transbasal Approach
This approach is useful for midline tumors of the upper to lower clivus with extension into the sphenoethmoidal region, medial cavernous sinus (CS), petrous apex, occipital condyles, or foramen magnum. The dorsum sella cannot be reached directly with this approach. Chordomas with extensive lateral components may not be totally resectable. The lateral limits of resection are the optic nerves, carotid arteries, CN VI, and CN XII. Accordingly, structures at highest risk of injury in this approach are the optic nerves, cavernous carotid artery, and CN VI.
Frontotemporal Transcavernous Approach
Combined with an orbitozygomatic osteotomy for better exposure, this approach provides excellent intradural access to the CS for chordomas extensively involving the CS. In combination with the subtemporal approach, it allows access to the upper clivus and petrous apex. It does not address any associated major bony involvement, so an auxiliary second approach may be needed to facilitate total tumor resection. Structures at highest risk of injury are the frontotemporal branch of CN VII, supraorbital nerves and vessels, and the optic nerves as well as CN III and IV during the resection of the clinoid. Large lacerations of the periorbita may result in muscle entrapment syndromes if not repaired.
Subtemporal and Subtemporal-Infratemporal Approach
The subtemporal approach provides access to the middle fossa, petrous apex, upper clivus, horizontal petrous internal carotid artery (ICA), and posterior CS. The subtemporal-infratemporal approach provides additional exposure of the clivus to the level of the foramen magnum, the CS, sphenoid, maxillary, and ethmoid sinuses, the infratemporal fossa, the retropharyngeal and parapharyngeal space, and the orbit. The latter approach is used when the petroclival bone is involved inferior to the level of the horizontal segment of the petrous ICA. Cerebrospinal fluid (CSF) leak and associated meningitis are the most common complications of this approach. Almost all the CNs can be exposed and injured in the more extensive subtemporal-infratemporal approach. The ICA can also be injured during drilling. Mild trismus and malocclusion of the jaw may occur after distraction or resection of the condyle of mandible.
Extreme Lateral Transcondylar Approach
This approach is useful for chordomas involving the ventral upper cervical spine, lower clivus, foramen magnum, and occipital condyles. For extradural resection of chordomas, the complete transcondylar approach is most commonly employed, which must be combined with an occipitocervical fusion to ensure stability of the occipitocervical junction. Lower CN dysfunction, CSF leak, and vascular injury to the vertebral artery or its branches, leading to brainstem or cerebellar infarction, are the most common complications of this approach.
Endoscopic Endonasal Approach
The binarial, purely endoscopic, 2-surgeon approach to the skull base has been described in detail. For the purpose of a clival chordoma resection, image guidance and neurophysiological monitoring (monitoring of CNs in addition to brainstem-evoked responses and somatosensory evoked potentials) are substantial. The vascularized nasoseptal flap provides reconstruction of the skull base defect for tumors that extend beyond the margins of the clivus when dural penetration can be expected. The limitation of EEA is the extension of the tumor to anatomic areas that cannot be reached. However, the advent of endoscopic technologies and techniques (image guidance, angled endoscopes) has expanded the limits of conventional endoscopic approaches. The EEA allows surgical access to the entire ventral skull base, from the frontal sinus to the second cervical vertebra in the sagittal plane, and from the midline to the roof of the orbit, the floor of the middle cranial fossa, and the jugular foramen in the coronal plane. Lateral extension of the chordoma at the level of the dorsum sella (upper clivus) requires a transposition of the pituitary gland superiorly with preservation of the pituitary stalk. Lateral extension of the chordoma at the level of paraclival and petrous ICA (mid clivus) requires an endoscopic transpterygoid approach with or without transposition of the vidian nerve. Lateral extension of the tumor at the level of the lower clivus (from the foramen magnum across the occipital condyle and hypoglossal canal to the jugular foramen) requires an endoscopic medial maxillectomy with, if needed, a Denker maxillotomy and resection of the Eustachian tube.
All of the CNs, but especially CN VI as it exits the Dorello canal and courses toward the CS, can be injured during EEA. The ICA or its branches can also be injured during drilling. EEAs for extreme lateral extended tumors that require manipulation of the ICA are considered the most difficult EEAs, as they demand incremental experience in managing the ICA endoscopically. The potential complication of postoperative CSF leak can be avoided in most cases with the use of the vascularized nasoseptal flap. Even in young patient populations, despite the smaller nares and nasal cavities, most patients older than 4 years are considered good candidates for EEA. A true limitation of EEA is the extension of tumor lateral to the optic nerves; in such cases, another approach is better considered.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
