Neoplasms of the anterior skull base (ASB) continue to challenge skull base surgeons, despite tremendous advances in multidisciplinary management. These lesions represent a diverse group of tumor types located within a surgically treacherous region. Historically, these tumors were considered unresectable. If surgery was attempted, it generally consisted of a lateral rhinotomy which inevitably resulted in incomplete tumor resection and dismal survival outcomes. The first combined neurosurgical and transfacial resections were reported in the mid-1950s, and the craniofacial resection was popularized by Ketcham and colleagues in 1963. Since this time, advances in diagnostic technology, interventional radiology, endoscopic endonasal surgery, and minimally invasive neurosurgery have facilitated the emergence of the young subspecialty of skull base surgery. Contemporary ASB surgical techniques have significantly expanded the limits of technical resectability while consolidating the gains that have been made in reducing morbidity and mortality.

The ASB is located at the interface of the central nervous system and the upper aerodigestive tract. ASB lesions may therefore arise from the bones of the skull base, “from above” (intracranially), or “from below” (the sinonasal cavity and orbits).

Anatomy of the skull base is covered is detail in Chapter 1 and will only be briefly addressed in this section. The ASB is separated from the central or middle skull base by a line running through the chiasmatic sulcus, the anterior clinoid processes, along the posterior margin of the lesser sphenoid wings, and the superior rims of the greater sphenoid wings. The ASB borders the posterior wall of the frontal sinus anteriorly, the frontal bones laterally, and the planum sphenoidale, or roof of the sphenoid sinus, posteriorly. The major components of the ASB are the orbital plates of the frontal bone, the fovea ethmoidalis, and the cribriform plate. The cribriform plate, situated more inferiorly than the ethmoid roof, is composed of thin bone that is traversed by olfactory nerve fibers, and is easily invaded by tumors. The dura mater attaches anteriorly at the frontal crest and crista galli to form the falx cerebri. The anterior cranial fossa contains the frontal lobes, the olfactory bulb, and the olfactory tract.

It is important to clarify that the ASB is distinct from neighboring structures that are often surgically approached with similar techniques. The sella turcica and pituitary gland are constituents of the middle or central skull base, and the clivus is a component of the posterior skull base, not the ASB. The ASB overlaps partially with the anterolateral skull base, which is the region between the mid-orbit and the petrous internal carotid artery, and includes the lateral orbit, infratemporal fossa, and portions of the frontal, sphenoid and temporal bones. This chapter will focus on lesions of the ASB.

Tumors from below

The most common lesions of the ASB arise from the sinonasal cavity. Further details of sinonasal malignancy can be found in Chapter 17. Nasal and paranasal sinus cancers are rare, comprising 3% of head and neck cancers. In the United States, the most common histology is squamous cell carcinoma, followed by adenocarcinoma and minor salivary gland neoplasms. The remainders of sinonasal tumors are those arising from olfactory neuroepithelium (esthesioneuroblastoma), lymphoma, melanoma, sarcomas, and undifferentiated carcinomas.

Squamous cell carcinomas comprise 50% of sinonasal cancers, with the maxillary antrum the most common epicenter. Tobacco exposure is a major risk factor. Metastases are uncommon, with fewer than 10% of patients presenting with cervical metastases, and approximately 5% of patients developing distant metastases. However, the rate of cervical recurrence is as high as 20–30% when the neck is not electively treated with neck dissection or radiation. These tumors are staged using the AJCC staging system (see Chapter 17). Tumors involving the cribriform plate, sphenoid or frontal sinus, are staged T4a. Tumors involving the dura, brain, orbital apex, or clivus are staged T4b.

Adenocarcinomas comprise 30% of sinonasal cancers in the United States although they are the most common histologic subtype in most European series. Risk factors for sinonasal adenocarcinoma are exposure to leather dust, wood dust, nickel, and asbestos. Survival outcomes are slightly better than for squamous cell carcinoma.

Adenoid cystic carcinoma arising from minor salivary glands accounts for approximately 10% of sinonasal cancers. These tumors are generally slow growing with a low rate of cervical metastasis, but exhibit a high rate of perineural invasion, which contributes to a 30% rate of local recurrence. Metastases at presentation are rare, but ultimately, the incidence of distant metastasis is approximately 40%, most commonly to the lungs and bone.

Esthesioneuroblastomas are also called olfactory neuroblastomas, and comprise 3–6% of sinonasal tumors. These tumors are believed to arise from the basal cells of the olfactory neuroepithelium, which is primarily located on the cribriform plate. Histologically, these tumors are defined by small, round, blue cells and a fibrous background. Homer-Wright pseudorosettes are commonly present, and Flexner-Wintersteiner rosettes are rarely present in high-grade tumors. Radiographically, CT images will demonstrate a solid, enhancing mass with bone erosion. Intralesional calcifications are pathognomonic for esthesioneuroblastoma. On MR, tumors homogeneously enhance with intermediate intensity on T1-weighted images, and ARE hyperintense on T2 on T2-weighed images. At the border of cerebral invasion, the tumor will be hypointense to brain on T1, and are hyperintense to brain on T2. These tumors may be staged using the traditional Kadish system, which is sometimes modified with the addition of Stage D for distant disease (Table 60–1). The modified Kadish system has been shown to effectively stratify tumors by survival outcome. A TNM staging system has also been developed (Table 60–2).

Less common cancers include melanoma, undifferentiated carcinoma, sarcoma and lymphoma. Mucosal melanomas are rare, comprising 1–3% of all melanomas, but occur most commonly in the nasal cavity. Sinonasal undifferentiated carcinomas (SNUC) are highly aggressive sinonasal tumors that commonly involve the orbital or intracranial compartments. Common sinonasal sarcomas include rhabdomyosarcoma and chondrosarcoma. The nasal cavity is a location of extranodal lymphoma, most commonly T-cell lymphoma. Previously called lethal midline granuloma, this tumor is now appreciated to be an angiocentric T-cell lymphoma that is associated with Epstein-Barr virus, and presents as a midline destructive lesion.

Less commonly, orbital tumors may involve the ASB. The most common histologies are lacrimal gland neoplasms, neurogenic tumors, lymphomas, rhabdomyosarcomas, and chloromas (extramedullary myeloblastomas). The thick orbital roof serves as a more effective barrier to intracranial extension than does the cribriform plate.

The most common benign neoplasms involving the ASB are inverted papillomas and juvenile angiofibromas. Inverted papillomas arise most commonly from the lateral nasal wall. These tumors exhibit a 5–15% rate of conversion to invasive squamous cell carcinoma. Juvenile angiofibromas occur in adolescent boys and arise from the junction of the nasopharynx and the posterior lateral nasal wall. Both tumors generally present with symptoms of nasal obstruction or epistaxis and usually remain extracranial.

Tumors from above

Central nervous system tumors involving the ASB are nearly all meningiomas, which are intradural, extra-axial lesions. It is rare for primary brain tumors to involve the ASB, unless there is a pre-existing surgical defect. Olfactory groove meningiomas may involve the cribriform plate, and sometimes extend through it into the ethmoid sinuses. Less commonly, the planum sphenoidale, tuberculum sellae, or anterior clinoid processes may be involved. Superiorly, the frontal lobes may undergo subpial invasion and venous engorgement, and ASB meningiomas may render the optic apparatus vulnerable to compression and ischemia. On MRI, these tumors are isointense to brain on both T1 and T2 weighted images, and enhance intensely. A dural tail is common. Adjacent ASB bone may show evidence of remodeling or sclerosis. Far less common are subfrontal schwannomas, rare neoplasms believed to originate from the olfactory nerve. Although slow-growing, extension through the cribriform plate is common.

Chordomas are rare tumors arising from remnants of the notochord. Along the skull base, most chordomas arise from within the bone of the clivus, but they have been described in extra-axial locations such as the nasopharynx or sphenoid sinus. Although the clivus is technically part of the posterior skull base, these tumors may expand to involve the ASB.

Neural Invasion

A particular challenge in malignant lesions of the ASB (particularly sinonasal cancers) is the presence of neural invasion, either perineural invasion or intraneural invasion. Overall, 20% of nonneurogenic sinonasal cancers demonstrate evidence of neural invasion, which is most common in sinonasal undifferentiated carcinomas (60%) and adenoid cystic carcinomas (55%). Neural invasion is present in a smaller percentage of paranasal sinus squamous cell carcinomas and adenocarcinomas (15–20%), and is rare in sarcomas and melanomas. The presence of neural invasion significantly increases the likelihood of positive margins and local recurrence in skull base surgery.

Symptoms

Common presenting symptoms include nasal obstruction, epistaxis, rhinorrhea, anosmia, facial pain, and facial swelling. Many of these symptoms are nonspecific and mimic chronic sinus disease. Certain symptoms, however, are more suggestive of neoplasm, such as unilateral nasal obstruction, significant bleeding, diplopia, epiphora, and numbness (especially of cranial nerve V2).

Imaging

Radiologic evaluation of a skull base tumor generally requires both computed tomography (CT) and magnetic resonance (MR) imaging. CT imaging is critical to evaluating skull base and paranasal sinus bone anatomy, in addition to cranial foramina. Modern multidetector techniques allow thin sections for the evaluation of small landmarks, 3D reconstruction, and CT angiography for the evaluation of vascular structures. MRI is critical for assessment of soft tissue involvement, dural invasion, intracranial extent, and perineural spread. In the paranasal sinuses, MRI can be particularly helpful in differentiating tumor from post-obstructive secretions, which do not enhance and generally show T1- and T2-weighted intensity that is distinct from tumor. MRI may be helpful in narrowing the differential diagnosis of intracranial lesions not easily amenable to biopsy. Because both CT and MRI imaging contribute vital anatomic information, several centers have developed CT/MR fusion technology.

Nuclear medicine imaging can be helpful in a subset of patients. Positron emission tomography, generally combined with CT (PET/CT), is not sufficiently sensitive to definitively rule out regional metastases, but may be helpful in identifying distant metastases, and in identifying recurrent disease after treatment. CT cisternography (with intrathecal contrast agents such as Omnipaque or metrizamide) and MR cisternography (which does not require intrathecal contrast) can both be helpful in the setting of suspected cerebrospinal fluid leak.

Interventional radiology techniques can be indispensable in certain challenging cases. When tumor involvement of the internal carotid artery or other vascular structures is suspected, carotid and cerebral angiography are essential, and the endovascular placement of stents may be considered in certain cases. A balloon occlusion test is mandatory if sacrifice of the internal carotid artery is countenanced. Endovascular embolization of highly vascular tumors such as juvenile angiofibromas can be helpful prior to surgery.

If an endoscopic or endoscopic-assisted surgical approach is being considered for the patient, the surgeon may elect to obtain diagnostic CT or MR images under a protocol for an intraoperative navigation system, some of which utilize a headframe or fiducial markers. Additionally, advances in imaging have now made intraoperative imaging feasible. Cone-beam CT scanners on a mobile C-arm may prove valuable in providing real-time anatomic information during surgery.

When evaluating an ASB mass, it is critical to rule out lesions that do not usually require surgical resection, such as lymphoma or metastases to the skull base. Therefore, an endoscopic or image-guided biopsy should be performed in most cases. Some tumors may be diagnosed based on history, clinical and radiologic findings, such as juvenile angiofibroma, rendering biopsy unnecessary.

Indications for Surgery

Surgery is the preferred treatment for most ASB lesions, with the exception of most cases of lymphoma and metastatic disease. In select lymphoma or metastatic cases, however, the desire to palliate local symptoms such as bleeding, fungating tumor, or CSF leak may necessitate surgery for these tumors. Non-neoplastic conditions such as skull base trauma, encephalocele, mucocele, and CSF leak will not be covered in this chapter although surgical approaches are similar. In most cases of ASB malignant disease, surgery is the index treatment, followed by adjuvant radiation or chemoradiation, depending on tumor type and pathologic findings (see “Non-surgical therapy,” below). The contraindications to surgical resection of ASB disease can be divided into patient and tumor factors. Patients with significant medical comorbidity may not be appropriate for the risks of craniofacial resection (see “Outcomes,” below). Similarly, the patient’s personal preferences and willingness to accept the potential cosmetic, functional, and neurological morbidities of surgery must also be discussed frankly prior to surgery.

The technical limits of tumor resectability have evolved over time and continue to be in flux. Initially, Ketcham argued that tumors were unresectable if they eroded the pterygoid plates, invaded the dura extensively, extended into the brain parenchyma, or demonstrated significant gross perineural spread. Many of these characteristics remain included in stage T4b, traditionally a signifier of nonresectability. Today, however, the limits of resectability are not as strictly defined. Certainly tumors should be considered inoperable if they invade the brain stem, both internal carotid arteries, or both cavernous sinuses. In many cases, invasion of the superior sagittal sinus or vital bridging veins is unresectable, as interruption of cerebral venous flow would be fatal. Most surgeons consider involvement of both optic nerves or both orbital apices to be unresectable. Many surgeons also consider involvement of only one internal carotid artery to be unresectable, and many surgeons consider invasion of the cerebral cortex to be unresectable although opinions differ with respect to the intracranial extent of disease. Some centers will accept minimal brain invasion in selected patients, when the area involved is noneloquent. Many of these locations may be technically resectable but often will represent incurable disease.