Fibro-Osseous Lesions of the Skull Base in the Pediatric Population

Abstract

Fibro-osseous lesions of the skull base include a variety of lesions with different biologic behavior. The most common lesions include fibrous dysplasia, osteoma, aneurysmal bone cyst, and juvenile ossifying fibroma. The diagnosis can usually be established with radiographic imaging. In the absence of symptoms, slow-growing lesions can often be observed. When surgery is indicated for relief of symptoms, endoscopic endonasal techniques are well suited for all age groups.

Introduction

Fibro-osseous lesions are characterized by the replacement of normal bone with variable amounts of fibroblasts. Both neoplastic and non-neoplastic proliferative lesions fall into this classification including fibrous dysplasia, osteomas, aneurysmal bone cysts (ABCs), and juvenile ossifying fibromas (JOFs). When involving the skull base, these lesions can be challenging to manage due to complex skull base anatomy and proximity to neurovascular structures.

Fibro-osseous lesions can be classified into bone dysplasias and neoplastic tumors. In children, the most common bone dysplasia is fibrous dysplasia. JOFs are benign neoplastic lesions characterized by aggressive growth. Numerous other fibro-osseous lesions exist, including osteomas, ABCs, solitary bone cysts, and metabolic bone disease such as “brown tumors” in hyperparathyroidism.

Fibrous Dysplasia

It is important to note whether fibrous dysplasia is monostotic (single bone), polyostotic (multiple bones), or part of McCune–Albright syndrome. McCune–Albright syndrome is characterized by polyostotic fibrous dysplasia, endocrine hyperfunction disorders (precocious puberty, hyperthyroidism and others), and café-au-lait skin macules. Growth and recurrence of symptoms have been reported to be higher in polyostotic and McCune–Albright syndrome patients versus monostotic fibrous dysplasia. ¹

In fibrous dysplasia, normal bone marrow and cortical bone are replaced with immature fibro-osseous tissue intermixed with woven bone. It was previously thought that growth stops after puberty; however, reports of numerous adults with continued growth contradict this assertion and slow growth may continue. ² Fibrous dysplasia is thought to be related to the mutation of the gene GNAS 1 which causes persistent activation of adenyl cyclase, leading to hyperfunction of the skeletal progenitor cells and abnormal osteoblasts. ³ Craniofacial involvement of fibrous dysplasia is common, with 10% to 27% of monostotic patients and up to 50% of polyostotic patients having involvement or one or more craniofacial bones. ¹

The lesions often present during adolescent years due to rapid bone growth during this period. The most common presentation is painless swelling and facial asymmetry. ¹ Often, symptoms such as nasal obstruction and visual changes may occur slowly, not noticed until they become severe. Many tumors are discovered incidentally when imaging is performed for other reasons (e.g., head trauma). Most commonly, these lesions grow slowly and are more of a cosmetic problem than a functional one. However, sudden symptoms can occur with rapid growth and need to be promptly investigated. Very rarely, malignant change has been reported. ⁴ Salmasi et al ⁵ reported an ABC (see below) developing in the background of fibrous dysplasia leading to rapid vision loss in a 16-year-old boy with McCune–Albright syndrome. An endoscopic endonasal approach in two stages was performed to first decompress and then resect the ABC, and vision recovered.

Medical treatment with bisphosphonates has been considered but never clearly shown to have benefit in skull base disease. Often medical treatment is reserved for patients with diffuse polyostotic disease. Bisphosphonate injections decreased pain and reduced bone resorption on imaging in 50% of cases in a study by Chapurlat in 2006. ⁶ However, studies of Edgerton et al ⁷ and Béquignon et al ² found this treatment to be ineffective. Radiation therapy should never be used as the risk of malignancy elevates 400-fold. ⁷

Example

A 16-year-old male presented with mild right facial asymmetry. Cranial nerve function was intact. Computed tomography (CT) confirmed polyostotic fibrous dysplasia ( Fig. 1 ). In the absence of cranial nerve dysfunction and progressive cosmetic deformity, observation was recommended.

Fig. 1.

Coronal computed tomography demonstrating typical ground glass appearance of fibrous dysplasia. Although there is extensive involvement of bone, the neural foramina (arrow—foramen rotundum) are typically preserved.

At age 5, this male patient was diagnosed with polyostotic fibrous dysplasia. He developed progressive visual loss in the right eye and underwent six transcranial procedures over the next 10 years. Tests were negative for McCune-Albright syndrome or neurofibromatosis. He presented with deterioration of vision in the left eye. CT demonstrated extensive polyostotic disease with marked compression of both optic canals ( Fig. 2 ). An endoscopic decompression of the left orbital apex and optic canal was performed with little improvement in vision.

Fig. 2.

Computed tomography demonstrating marked narrowing of the optic canals (arrows).

Juvenile Ossifying Fibromas

JOFs are aggressive tumors with high recurrence rate if not completely excised. They are a benign neoplasm distinguished from other fibro-osseous lesions by onset (between 5 and 15 years), clinical presentation (rapid growth), and behavior (can result in considerable facial disfigurement).

In 2005, the World Health Organization classified JOF into two categories: psammomatoid and trabecular. ⁸ Trabecular lesions most commonly involve the mandible. Psammomatoid lesions are more common and typically occur in the paranasal sinuses, anterior skull base, and orbits. They are often painless and usually present with signs or symptoms such as nasal obstruction, proptosis, visual loss, or facial deformity.

Example

A 17-year-old male presented with right nasal obstruction with evidence of a large right intranasal mass. CT demonstrated a large expansive cystic and solid mass of the right nasal cavity with erosion of the cribriform plate ( Fig. 3 ). Magnetic resonance imaging (MRI) demonstrated fluid levels consistent with an ABC. An endoscopic extradural resection of the tumor was performed with decompression of the medial orbit. Pathology conformed a JOF with ABC. Postoperative course was uneventful.

Fig. 3.

Coronal computed tomography demonstrating an expansive tumor with erosion of the medial maxilla, medial orbit, and cribriform plate. There are solid and cystic components of the mass.

Aneurysmal Bone Cyst

Very rare in the skull base, ABCs are another fibro-osseous lesion that occurs predominately in children. ABCs are non-neoplastic expansile bone lesions characterized by cystic cavities, usually filled with blood. These lesions can expand rapidly, resulting in cranial nerve palsy, pain or other changes. Aghaghazvini et al ⁹ reported an unusual case of an ABC arising in the central skull base, leading to jugular foramen compression and multiple cranial neuropathies over a 2-year period prior to seeking treatment. Other authors have published case reports of these lesions affecting the anterior skull base. ^{10 11 12}

ABCs have also been noted to develop in the setting of fibrous dysplasia and JOF ( Fig. 3 ). This may be suspected when there is a rapid change in growth or symptoms. Decompression is a temporary solution and resection of these lesions is necessary to prevent further expansion and destruction.

Other Lesions

Most other fibro-osseous skull base lesions such as osteomas and metabolic bone lesions are exceedingly rare in children and therefore not described here.

Evaluation

Complete history and examination are necessary. In the history, important points include timeline of growth as well as careful consideration of any symptoms. As these are slow growing lesions, some symptoms may not be realized without a careful history and examination. Physical examination should include a complete assessment of cranial nerve function. If the lesion involves the temporal bone, audiologic evaluation is an important component of the evaluation. If the lesion involves any orbital bone or the sphenoid bone, referral for complete ophthalmologic evaluation, including testing of visual fields, is essential. Maxillary or mandibular involvement should prompt including a dentist or maxillofacial surgeon in the treatment planning team. A neurosurgeon is an essential member of the team with pathologies of the skull base and should be included in evaluation and treatment discussions.

Photo-documentation of any facial asymmetries is helpful in monitoring changes over time. One of the most important components of the evaluation for benign slow growing lesions, particularly fibrous dysplasia, is assessing the goals of the patient and/or family. With aggressive growth or organ compromise, the need for surgery is clear. With facial asymmetry or subjective symptoms, the goals of surgery need to be clearly defined. Complete resection is often not possible and there may be a need for multiple surgeries. As mentioned, including additional physicians in a multidisciplinary approach can be immensely helpful in both evaluating risks from no treatment and defining reasonable surgical expectations.

Imaging

Both CT and MRI are helpful in evaluation. While CT is better known for showing bony lesions, one must also consider the number of scans needed and radiation exposure. MRI can be useful and avoids radiation. It is important to use consistent imaging techniques with the expertise of an experienced head and neck/neuroradiologist.

Fibrous dysplasia is characterized by a ground glass appearance on CT, with intradiploic lesions that are expansile and blend into normal bone. ¹³ Different patterns may be observed with some being mostly sclerotic and some being predominantly cystic or lytic. Most often there is a combination of both patterns. Despite extensive involvement of the skull base, there is characteristically sparing of the carotid canal and neural foramina without compression of cranial nerves. ¹³ MRI imaging is variable and in the past, was not recommended. However, in light of the harms of ionizing radiation on children, MRI for fibrous dysplasia is more frequently used for monitoring growth. On MRI, T1 sequences show low-to-intermediate signal versus muscle; T2 sequences also show low signal. Fibrous dysplasia lesions also have variable degrees and patterns of enhancement with intravenous contrast. ¹³ Without the characteristic findings of CT, imaging with MRI alone can result in an erroneous interpretation as an aggressive malignant neoplasm.

JOFs can also show ground glass appearance, but have identifying features including a circumscribed, often multiloculated mass with a rim or “shell” of irregular thickened bone. ¹³

ABCs are expansile lesions with a “pushing” rim of bone circumscribing a fluid filled cavity that is often multiloculated. Osteomas show a dense sclerotic pattern on CT scan. ¹³

Treatment Planning

In cases of aggressive lesions, specifically JOF, complete surgical resection is essential. Without this, recurrence rate is very high. Therefore, treatment planning is dependent on defining the best surgical approach for treatment. However, slow growing lesions such as fibrous dysplasia have a less defined surgical algorithm. In these lesions, planning starts with identifying the goals of the patient and, for children, the parents. Following this, multidisciplinary evaluation and input will define the best surgical treatment for safe and effective correction of pathology. In many cases of fibrous dysplasia, no surgical treatment is needed at initial presentation.

When considering fibrous dysplasia, surgical intervention is indicated for diplopia, proptosis, optic nerve compression, and other cranial nerve palsies. Headaches associated with fibrous dysplasia may not resolve with surgery, and medical treatment of headaches should be tried instead. More commonly, facial asymmetry and distortion is the primary complaint in fibrous dysplasia. In these cases, the question becomes: when to operate? Unfortunately, there is limited published evidence to guide these decisions. Kusano et al ¹⁴ reported on 11 patients treated from 1984 to 2006, reporting cessation of growth in adolescence in the majority of patients. They could not establish why growth continues in a minority of patients. They found growth lasted longer in polyostotic lesions (mean age 22.3 years) versus monostotic lesions (mean age 18.6 years). Béquignon et al ² presented a case series of three adult patients (mean age 35 years) with continued growth. This is not to say that recontouring surgery cannot be performed prior to adolescence or adulthood. In some children, the deformity, even if only a cosmetic change rather than functional problem, is intolerable. Counseling to patients and families must be robust, explaining the likely return of the deformity as the lesion continues to grow, necessitating further surgery.

The discussion of prophylactic versus therapeutic surgery for fibrous dysplasia continues to generate controversy, especially regarding optic nerve compression. Prior to 2002, many authors recommended prophylactic optic nerve decompression when fibrous dysplasia affected the optic canal, even in the absence of visual disturbance. They predicted this would impede subsequent visual disturbance. ^{15 16 17} In a study by Lee et al ¹⁸ published in the New England Journal of Medicine in 2002, 38 patients (mixed adult and pediatric) with fibrous dysplasia were studied. They underwent CT imaging and ophthalmology evaluation. Of the 38 patients (67 affected optic canals), only 2 had visual disturbances. Tan et al ¹⁹ in a 2007 study looked at 18 patients with 22 optic canals affected by fibrous dysplasia. Twelve of them underwent therapeutic decompressions (i.e., patient had decreased visual acuity or visual field loss) and six underwent prophylactic optic nerve decompression (normal visual acuity and visual fields). In those who underwent therapeutic decompression, ∼50% had no further visual loss. Of those that underwent prophylactic decompression, 33% developed visual loss over subsequent months-years. The authors of both studies, as well as others, therefore, recommend therapeutic but not prophylactic decompression. In those patients without visual loss, regular ophthalmology evaluations should be initiated to identify problems at an early stage.

Once surgical treatment is decided, the next stage of planning is to compare approach options. While many fibro-osseous lesions of the maxillofacial region will require open or combined approaches to access the tumor, fibro-osseous lesions of the skull base can often be approached with endoscopic endonasal surgery (EES) with less morbidity for the patient.

Surgical Technique

Endoscopic skull base surgery is possible, even in young children, and has become more reliable as more surgeons have become facile with skull base surgery in children. Studies have analyzed the morphometric data from radiographs. ^{20 21} In very young children, the pyriform aperture can be limiting, ²¹ but by approximately age 2, most are of sufficient width to accommodate telescopes and instruments necessary for skull base surgery. Another challenge of EES in children is incomplete pneumatization of the sphenoid bone, requiring significant drilling to access the sella, optic nerves, planum, and other structures in this area. This is not a limitation to surgery, but should be performed by surgeons who have experience with this anatomy. The lack of anatomical landmarks is partially offset by the use of image-based navigation. Intraoperative navigation systems allow the surgeon to confirm tumor borders and anatomic landmarks, enabling more complete resection and more reliable preservation of normal structures.

Many studies have examined the effectiveness and safety of EES in children. ^{22 23 24 25 26} All have shown this to be an effective technique with acceptable morbidity. Surgical considerations in pediatric patients are different from adults. Children have smaller blood volume and thus are less tolerant of intraoperative blood loss. Fibro-osseous lesions can bleed significantly and blood products should be available. Hemostatic techniques include the use of diamond drill bits, infiltration of hemostatic agents (Floseal [Baxter Healthcare Corp, Deerfield, IL], Surgifoam [Ethicon, Somerville, NJ]), and warm saline irrigation. ²⁷ While open approaches involving brain retraction are not ideal in any age group, they can be particularly morbid in the developing brain, risking encephalomalacia and long-term cognitive change. Craniofacial growth must also be considered in the pediatric population. Disruption of facial growth centers or tooth buds can have a long-term impact on subsequent development. In aggressive lesions in unfavorable locations, preservation of all structures may not be possible. In indolent lesions with minimal symptoms, these factors play a major role in treatment planning.

Fibro-osseous lesions such as fibrous dysplasia and JOF are softer than normal bone and can be drilled or fragmented with dissecting instruments. With fibrous dysplasia, complete excision is frequently not possible. In such cases, the involved bone is recontoured with the drill. Expansion of the bone may make it difficult to remove the diseased bone without combining multiple surgical approaches.

Postoperative Care and Surveillance Needs

In fibrous dysplasia, continued growth and recurrence of symptoms are common, particularly in a remodeling (incomplete) resection. Kruse et al ²⁸ reported a 25% recurrence rate of functional impact. Valentini, ²⁹ in a large series of 95 patients, reported radical resection in 61 of 68 patients with monostotic lesions of the craniomaxillofacial skeleton. There was no recurrence following these radical resections. Similarly, in a study from Fattah et al, ³⁰ 26 children (mean age 13 years) underwent surgery for fibrous dysplasia, again of the craniomaxillofacial skeleton. Recurrence was identified at a mean of 2.5 years later in 1/13 who underwent complete resection and 8/14 who underwent debulking. They found total resection or debulking after skeletal maturity had a lower recurrence rate, and complete resection after surgical maturity has the lowest rate. They found patients with McCune–Albright syndrome have the highest rate of recurrence and the most complex disease; therefore, the authors feel these patients may benefit more from repeated debulking procedures rather than complex resections. In lesions of the skull base, radical complete resection is often not possible.

In 2010, Park et al ³¹ looked at the ability to monitor disease with serum alkaline phosphatase in a small study of 18 patients with fibrous dysplasia. They found that in seven patients who had incomplete resection and subsequent regrowth, the levels of alkaline phosphatase abruptly increased prior to growth. This is a small study, however, and does not suggest following laboratory levels rather than CT scans.

If incompletely excised, JOFs recur at a rate of 30% to 56%. ^{32 33} For example, Appiani et al ³⁴ report that in their early experience with endoscopic resection, they left tumor behind at the skull base. In all three of these cases, the remaining tumor regrew at a rate of 1mm per month, a significant growth rate near vital neurovascular structures. Following complete endoscopic endonasal transbasal resection, the patients remained free of recurrence. Wang et al ³⁵ reported on 11 patients who underwent complete resection by endoscopic endonasal approach, with only 1 recurrence over a mean follow-up of 25.8 months.

Imaging studies are a necessary part of follow-up. Study type (MRI vs CT) is dictated based on quality of preoperative images. If MRI shows the lesion preoperatively, this will be both an effective surveillance tool and avoid ionizing radiation. Timing of first study and frequency depends on lesion type and growth rate preoperatively. At ∼3 months, it is prudent to obtain new imaging to both assess for tumor and also serve as a new baseline. However, in cases of JOF close to important structures, such as the optic nerve, earlier imaging may be warranted.

Summary

Fibro-osseous lesions of the skull base are typically benign and most commonly include fibrous dysplasia, JOF, and ABC. Symptom onset is often gradual, though in some cases, nerve or orbital compression can lead to sudden symptoms. A multidisciplinary approach to evaluation and treatment of these patients is essential. EES is often possible to treat these pathologies at the anterior skull base, though extensive lesions with cranial or maxillofacial skeleton involvement may require a combined approach. Follow-up is of great importance as each of these lesions may recur.