Skull Base Lesions: Extracranial Origins

A number of extracranial anatomical sites, including the nasopharynx, paranasal sinuses, and masticator space, may give rise to lesions involving the skull base. Implicit in the nature of an invasive lesion, the majority of these lesions are malignant. Accordingly, for optimal patient outcomes and treatment planning, it is imperative to include a search pattern for extracranial sites and to assess accurately the character and extent of these diverse lesions. Of particular importance to radiologists are lesions arising from each extracranial site, the search patterns, and relevant information important to convey to the referring clinician.

Introduction

In spite of varied origins, extracranial lesions breaching the skull base create diverse diagnostic challenges while sharing similar characteristics. Contiguous with critical neurovascular structures, extracranial lesions that penetrate beyond traditionally observed anatomical borders to reach the skull base demand critical observation of their site of origin, biological behavior, and imaging characteristics to optimize treatment planning.

Nasopharyngeal malignancies account for most invasive skull base lesions arising from extracranial sites and are most commonly nasopharyngeal carcinomas (NPCs) with lymphoma occurring less commonly.1, 2, 3 To appreciate skull base involvement from nasopharyngeal lesions, it is necessary to understand the anatomical relationship of the nasopharynx to the skull base. The roof of the nasopharynx is formed by the basisphenoid (the floor of the sphenoid sinus), basiocciput (clivus), and the anterior aspect of the vertebral bodies of C1 and C2 (Fig. 1).⁴ Deep to the mucosal layer of the nasopharynx lies the pharyngobasilar fascia, a dense aponeurotic sheet forming the superficial layer of the deep cervical fascia. The middle layer of deep cervical fascia, the buccopharyngeal fascia, bounds the pharyngobasilar fascia posteriorly. The buccopharyngeal fascia is loosely apposed to the subjacent deep layer of deep cervical fascia, the alar fascia, thus creating a space, the retropharyngeal space, whose origin is at the skull base. The alar fascia lies interposed between the retropharyngeal space and another deep layer of deep cervical fascia, the preverterbral fascia, creating the danger space. These fascial layers act as a barrier to spread of infection or neoplasm; transgression indicates the malignant or aggressive nature of the process (Fig. 2).

Tumor penetration through the layers of the deep cervical fascia in the nasopharynx provide the most direct access to the skull base; however, an anatomical avenue in the buccopharyngeal fascia provides an additional means for tumor extension. The sinus of Morgagni is a notch at the posterior superior margin of the buccopharyngeal fascia and the superior aspect of the superior constrictor through which the levator palatini muscle and eustachian tube pass from the skull base to the pharyngeal mucosal space of the nasopharynx (Fig. 3). Note the intimate relationship of the fossa of Rosenmüller to the sinus of Morgagni. This allows NPCs arising from within the fossa of Rosenmüller to access the skull base.

NPCs arise from the squamous epithelium of the nasopharynx in the pharyngeal mucosal space. During infancy and childhood, the epithelium is predominately composed of columnar ciliated respiratory epithelium, which is gradually replaced by stratified squamous epithelium during adolescence and adulthood.⁴ Hence NPCs are typically squamous cell carcinomas, although rarely, minor salivary glands in the mucosa may give rise to adenoid cystic carcinoma or adenocarcinomas.5, 6, 7, 8 The World Health Organization classifies NPC into 3 categories based on histology: type I NPCs are well-to-moderately differentiated keratinizing squamous cell carcinomas, most common in North American (Caucasian) populations; type II NPCs are non-keratinizing, transitional carcinoma or lymphoepileliomas; and type III NPCs are undifferentiated carcinomas. Types II and III are more common in Asian populations and are associated with Epstein-Barr virus.9, 10

Small or early-stage NPC presents as an asymmetric fullness in the pharyngeal mucosal space of the nasopharynx, typically with effacement of the fossa of Rosenmüller (Fig. 4). The normal nasopharyngeal mucosa, even in the presence of adenoid hypertrophy, appears bilaterally symmetric, hence, the presence of asymmetry warrants consideration of a malignant process. In the most recent American Joint Committee on Cancer Staging Manual (seventh edition, 2010), NPCs confined to the pharyngeal mucosal space, even with extension to the oropharynx or nasal cavity, are staged as T1. Extension into the parapharyngeal space, however, upstages NPC to T2. This refinement of the staging reflects the recognition that extension to the parapharyngeal space occurs only with transgression of the pharyngobasilar fascia (Fig. 5). Patients with small, T1 lesions are often asymptomatic, may complain of vague, mild eustachian tube symptoms or hearing loss. Indeed, these patients may be imaged initially for middle ear etiology. Thus, any asymmetric middle ear or mastoid effusion in the absence of otologic etiology should prompt close inspection of the nasopharynx.¹¹

The pattern of spread from larger NPCs breeching the pharyngobasilar fascia is most commonly posterolateral or posterior extension into the sphenoid rostrum, basisphenoid, and or clivus. This is best appreciated on T1-weighted magnetic resonance imaging, which demonstrates loss of the normally bright signal (Fig. 6). As most NPCs arise from off midline, lesions extending into the clivus often extend to, and widen, the petroclival fissure (Fig. 6B).¹² This is an important feature to recognize, as the presence of adenoidal hypertrophy in both pediatric population and adult populations may obscure a nasopharyngeal primary tumor.12, 13

More extensive NPCs may erode through the sphenoid and sphenoid sinus and extend to the cavernous sinus (Fig. 7A). A key feature to examine when there is involvement of the sphenoid is extension of the mass through the sinus of Morgagni and laterally to the ptyergopalatine fossa (Fig. 7B). Extension to the pytergopalatine fossa may occur via the sphenopalatine foramen, or via extension along the vidian or palatovaginal canals.14, 15 Note, however, that in the current American Joint Committee on Cancer Staging Manual staging system, extension to the sphenoid sinus (or any of the paranasal sinuses) and skull base only upstages the lesion to T3. Advanced (T3-T4) lesions often obliterate the bone of the skull base; nevertheless, rapidly advancing NPCs may leave ossified fragments of the skull base, creating an appearance that may mimic the chondroid matrix of chordoma or chondrosarcomas (Fig. 8). NPCs are upstaged to T4 when there is extension into the orbit, intracranial extension or extension along cranial nerves, or extension to the infratemporal fossa (masticator space) (Fig. 9).

The search pattern for NPC begins with identification of the nasopharynx as the source of the skull base lesion. As NPCs may not present with an obvious mucosal mass, the submucosal asymmetry (Fig. 4) and associated findings of eustachian tube obstruction warrant visual inspection and tissue sampling of the nasopharynx. Positron emission tomography-computed tomography (PET/CT) scan has shown to be of limited efficacy in the diagnosis of primary NPC. The wide overlap in 18 F-Fluorodeoxyglucose uptake between carcinoma and adenoidal or palatine lymphoid tissue in response to increased cellular metabolism in the presence of functional demand or inflammation limits the diagnostic efficacy of PET/CT for primary NPC.16, 17 Moreover, other studies have suggested that PET/CT may underestimate the amount of skull base involvement relative to magnetic resonance (MR).18, 19 This is particularly important, given that more recent studies suggest that the degree of hypermetabolism relative to tumor volume may be a better predictor of overall survival and the need for aggressive therapy.²⁰ Accurately delineating the tumor extension and volume is critical for treatment planning, as most lesions are treated with radiation and chemotherapy.¹⁰ Importantly, many advanced stage NPCs are now treated with proton beam radiation21, 22 necessitating accurate volume determination, particularly with regard to skull base, cavernous sinus, orbital, and intracranial extension. Finally, because the dose profile of proton beam allows higher doses to be delivered with reduced treatment volumes,23, 24, 25 the radiation oncologist needs to know whether there is an extension to the brainstem, the optic chiasm or optic nerve, the cavernous sinus, or the carotid.

Nasopharyngeal lymphoma accounts for approximately 20% of nasopharyngeal malignancies3, 26, 27, 28 and most commonly presents as a diffuse but symmetrically exophytic mass confined to the pharyngeal mucosal space, most often with local extension confined to the oropharynx (Fig. 10).27, 28 Nasopharyngeal non-Hodgkin's lymphoma less commonly infiltrates into the skull base, and when it does so, it typically is limited.²⁷ The MR characteristics of lymphoma, specifically the T2 hypointensity and lack of significant enhancement, are key to differentiating these lesions from NPC. Nasopharyngeal lymphoma when it does infiltrate through the skull base may expand rather than destroy bone.²⁸

Minor salivary gland malignancies arising within the nasopharynx are rare but are typically nonspecific in appearance, presenting as an enhancing mass within the pharyngeal mucosal space of the nasopharynx (Fig. 11). Adenocarcinomas more typically extend into the skull base rather than adenoid cystic carcinomas, which have a greater predilection for perineural spread.

Skull base extension from the paranasal sinuses typically occurs from lesions involving the cribiform plate, ethmoid, and sphenoid sinus. Lesions arising in the cribiform plate are most commonly esthesioneuroblastomas. Given their origin at the cribiform plate, the vector of spread for esthesioneuroblastomas is often cranially into the basal frontal lobes; skull base extension for these lesions results from posterior extension through the ethmoid and sphenoid sinuses (Fig. 12). The commonly used Kadish staging system for esthesioneuroblastoma does not differentiate between intracranial and skull base extension; thus any skull base extension with or without intracranial extension is a Kadish stage C. However, if the lesion remains confined to the nasal cavity or paranasal sinuses, these would be staged as Kadish A or B, respectively.29, 30

Although any higher-grade sinonasal malignancy may extend to involve the skull base, this occurs more commonly with sinonasal undifferentiated carcinoma or high-grade squamous cell carcinoma (Fig. 13).

In considering skull base involvement from extracranial sites, the masticator space must be assessed. The masticator space consists of the muscles of mastication and the mandible and is commonly referred to as the infratemporal fossa. Any malignancy involving the masticator space has the potential, given the proximity, to extend to the skull base. Thus, the skull base should be carefully assessed with any sarcoma of the masticator space, but it is prudent as well to look for skull base involvement with more extensive squamous cell carcinomas arising from or involving the masticator space. Squamous cell carcinomas involving the retromolar trigone or buccal space, in particular, may run along or through the mandible, or through the muscles of mastication to the skull base (Fig. 14). These patients often present with significant trismus; cranial nerve deficits should prompt concern for cavernous sinus or Meckel's cave involvement. Extension into Meckel's cave may result in denervation atrophy, which in the acute phase results in enhancement of the muscles of mastication, potentially complicating the interpretation of disease extent (Fig. 14B). Nevertheless, any signs of denervation atrophy warrant thorough inspection of the skull base.

Although malignant disease accounts for most cases of skull base involvement from the masticator space, some benign lesions may expand or erode into the skull base. Schwannomas involving cranial nerve V may not only expand the foramen but also may remodel or focally infiltrate into the greater wing of the sphenoid (Fig. 15). Moreover, juvenile nasopharyngeal angiofibromas although classically associated with widening of the pterygopalatine fissure and anterior displacement of the posterior wall of the maxillary sinus, may occasionally infiltrate into the skull base (Fig. 16). This is more common with recurrent lesions, but may occur with more aggressive lesions on initial presentation. Recognizing extension of these lesions into the sphenoid, cavernous sinus or intracranially, is important as this complicates the surgical management and increases the probability of recurrence.³¹