Andrew M. Bauer, MD and Mustafa K. Başkaya MD

Department of Neurological Surgery, University of Wisconsin Hospitals and Clinics, Madison, Wisconsin, USA

 

 

Introduction Embryology and Development of the Skull Base Part I.  Tumors of the Skull Part III.  Tumors of the Skull Base Tumors of the Anterior Fossa Olfactory Neuroblastoma (Esthesioneuroblastoma) Table 1: Kadish staging for olfactory neuroblastoma Juvenile Nasal Angiofibroma Rhabdomyosarcoma Table 2: IRS clinical group and TNM staging systems for rhabdomyosarcoma Tumors of the Middle Fossa and Sellar Region Pituitary Adenoma Craniopharyngioma Tumors of the Posterior Fossa Chordoma Meningioma Acoustic Schwannoma Cholesteatoma Part IV.  Skull Base Approaches, Outcomes, and Pediatric Pitfalls Figure 1 Conclusion References Corresponding Author: Number of views

 

 

Introduction

 

 

Skull base tumors comprise some of the most complex and technically difficult pathology faced by the neurosurgeon.  True skull base pathology in the pediatric population is rare and thus, many of the current conventions regarding treatment of these lesions come from the available adult skull base literature.  It is also true that many of these tumors are treated by conservative management and therefore never come to the attention of the pediatric neurosurgeon.  Many of the approaches used in resection of these tumors require extensive tissue dissection and bone resection which may be detrimental in further normal growth and development of the skull.  When transfacial approaches are used in children it is important to consider the location of the undeveloped permanent dentition within the maxilla and the possible need for later reconstruction when these are disrupted.  A large multidisciplinary team is necessary for the adequate treatment of these lesions.   Given the rarity of the tumors, this team may not be as accustomed to working together as that in the adult population.

 

The types of lesions commonly seen in the pediatric population are quite different from those in adults. In pediatric skull base tumors there is a gender predominance favoring males (69%) over females which may be due to the differing tumor types seen in children. In pediatrics it is always necessary to consider pathology in terms of development which places children at higher probability for developmental tumors such as teratomas, choristoma, epidermoid, dermoid, nasal glioma, and lipoma. A number of reports of childhood skull base tumors have been published (8, 24, 25, 37, 78, 94, 103, 112, 169, 189, 193, 203), however true class one evidence is scarce given the rarity with which these tumors occur.  Skull base tumors are still a rare case for the pediatric neurosurgeon, however with the trend toward more specialized centers, these will likely receive more attention for surgical treatment in the future. In this chapter, we will focus on the most common types of tumors seen in the pediatric skull base and discuss the differences faced in the treatment of these tumors in pediatric patients versus adults. 

 

Embryology and Development of the Skull Base

 

Since children are still in a growth phase, no literature on the surgical treatment of the pediatric patient would be complete without a brief review of the development of the anatomy. The development of the skull base begins during the fourth week of development in the occipital somites. Neural crest cells and paraxial mesoderm migrate to a position between the developing brain and foregut (137). These cells migrate laterally to form the chondrocranium.  The basicranium begins to form around the rostral end of the notochord. By the eighth week of gestation, ossification of the chondrocranium has begun (17).  Ossification continues in a multitude of centers throughout the developing cranium and is not complete until the fusion of the spheno-occipital synchondrosis between the age of 12 and 16 years (130). The primary difference between the skull base and the remainder of the skull is the base of the skull develops through both endochondral and intramembranous ossification while the calvaria forms primarily through intramembranous ossification (71). While the growth of the calvaria is essentially driven by the growth of the brain within, the growth of the skull base seems to be regulated by some genetic mechanism (71). The skull base then acts as a template for the growth and formation for the rest of the bony facial structures. It should be kept in mind that there are many local and humoral factors that affect the development of the skull base and therefore many opportunities for malformations along the way (152).  Growth and final development of the skull and skull base continue for at least 10 years after birth, and the degree of development of the anatomy for any individual patient must be taken into account when planning any invasive surgical therapy.

 

Part I.  Tumors of the Skull

 

Tumors of the skull are quite rare in pediatric patients and have been difficult to study to the fact that most studies include skull tumors as well as soft tissue tumors which invade the skull secondarily.  Most commonly calvarial tumors are benign, although they can occur as malignant or metastatic lesions.  When soft-tissue tumors and primary intracranial tumors are excluded dermoid and epidermoid tumors are the most common skull tumors, and account for up to 60% of pediatric skull lesions (159).  These are followed by Langerhans Cell Histiocytosis as the next common tumor (65).  Other benign tumors included in the differential diagnosis include ossifying fibroma, osteoblastoma, myofibroma, hemangioma, osteoma, and intradiploic meningioma.  The most common primary malignant tumors of the skull are angiosarcoma, osteogenic sarcoma, and fibrosarcoma, although these are exceedingly rare.  Non-hodgkin’s lymphoma, leukemia, Ewing’s sarcoma, neuroblastoma, and osteogenic sarcoma can metastasize to the skull (169).  Metastases are somewhat more common than primary skull tumors and therefore should be fully explored for a primary source when identified (65). 

 

These lesions most commonly present symptoms as a mass of the head (painless or painful) and soft tissue swelling with or without headache.  With the increasing use of imaging in clinical practice, they are occasionally identified as an incidental finding on imaging for another reason.  Diagnostic imaging is essential, as up to 37% of these lesions may have some intracranial involvement (159).

 

Epidermoid and dermoid cysts most commonly present as a painless subcutaneous swelling.  They differ only hystologically by the presence of dermal elements in dermoid cysts.  They have a tendency to occur on or near suture lines.  They only occasionally extend intracranially to involve dura or other intracranial structures.  Treatment consists of en bloc resection and recurrence is relatively rare.  Langerhans cell histiocytosis (eosinophilic granuloma) is the second most common tumor of the skull and most commonly presents as a tender, enlarging mass lesion of the skull (65, 125, 159).  Radiographs reveal a well-circumscribed, lytic bone lesion.  Needle biopsy can establish the diagnosis based on defined histologic and immunohistoligic criteria (165).  A skeletal survey should be obtained to rule out multifocal disease.  Lesions involving the orbit, mastoid bone, and temporal bone are known as high CNS risk areas and carry a higher risk of diabetes insipidus or other endocrinopathy when treated with monotherapy (69).  Solitary lesions of the skull are usually treated with surgical resection, although radiation and chemotherapy may also be effective (101).  Radiation therapy can also be effective, but is usually reserved for patients with recurrent disease (19).

 

Intraosseous hemangiomas are thought to make up between 1 and 5% of pediatric calvarial neoplasms (65, 151).  These vascular tumors may have a propensity for the spine and skull due to the extensive supply of vascular networks in these areas (14).  Both a rare globular form, originating at the skull base, and a more common sessile form, originating at the calvarium have been described (166).  The globular form is more likely to have intracranial extension and may cause neurological symptoms or elevated ICP.  Radiographs can aid in diagnosis with a trabecular or sunburst pattern occurring in over half of the cases (119).  For the globular form occurring at the skull base, embolization is the treatment of choice (166).  For cranial vault lesions, resection is usually curative.  Radiation may be useful for recurrent disease or incomplete resection.  Prognosis is generally good.

 

Osteomas are rare in children but are the most common benign bony neoplasm in adults (169).  Cranial vault lesions usually present as painless swelling while paranasal lesions may present with sinusitis or exophthalmos.  Radiographs show a well circumscribed hyperostotic lesion (169).  CT scan may help to delineate the extent of the lesion.  Multiple lesions suggest Gardener’s syndrome or hereditary polyposis syndrome (20, 199).  Prognosis is excellent with local resection (119, 151).  Paranasal lesions can be more difficult and may require anterior fossa skull base approaches for total resection.

 

Fibrous dysplasia is a developmental anomaly where transformation of woven bone to lamellar bone does not occur properly and results in overgrowth of well-vascularized stroma arranged around osseous trabeculae (77).  Aggressive surgical approaches have been advocated early after diagnosis to control disease progression and avoid encroachment on neurological structures (29).  This disease can occur in a polyostotic form in multiple sites as part of the McCune-Albright syndrome (77).  Surgery can be difficult in larger lesions and may require extensive cranial reconstruction.  Gross-total resection of the abnormal bone is the treatment of choice as there is a 25% recurrence rate associated with a partial resection (98).  Spontaneous malignant transformation is rare (186) and this is usually associated with adjuvant radiotherapy.  Prognosis is good with total resection and most complications occur by encroachment of the hyperostotic bone on vital structures such as the optic nerve.

 

Malignant lesions of the skull are relatively rare but include osteosarcoma, neuroblastoma, Ewing’s sarcoma (ES), fibrosarcoma, angiosarcoma, leukemia and lymphoma.  Neuroblastoma is the most common extracranial solid tumor in children and accounts for nearly 15% of pediatric cancer fatalities (67).  It can involve the skull base and orbit by hematogenous spread or contiguous extension.  This tumor should be highly suspected in a child with periorbital eccymoses and an abdominal mass.  Many staging systems have been used over the years, the newest being the International Neuroblastoma Staging System (INSS) (26).  The International Neuroblastoma Classification System is a modification (135, 176) of a stratification system introduced by Shimada et al (175) and is used in conjunction with the INSS to place patients into risk categories for treatment purposes.  For children with low-risk disease, surgery with gross-total resection is the treatment of choice.  Adjuvant chemotherapy may be helpful to decrease tumor burden and salvage vital organs.  Children with intermediate-risk disease are most often treated with chemotherapy and surgical resection (185).  Multimodal therapy is often used as a last resort in children with high-risk disease (126) but still carries a very poor prognosis.  Generally prognosis varies from excellent to poor with the extent and staging of neuroblastoma.

 

Osteosarcoma is the most common malignant tumor of bone, but only rarely occurs in the skull (88, 196).  This tumor may occur with malignant degeneration in fibrous dysplasia.  These tumors are fast growing and most commonly present with pain and local swelling.  There is very little prospective data on treatment of head and neck osteosarcoma due to the rarity with which it occurs.  Generally gross total excision is thought to be the best treatment.  Adjuvant radiation and chemotherapy are somewhat controversial and should be considered on a case to case basis based on the degree of resection that was performed (36, 102).  These tumors are difficult to resect and extensive facial reconstruction is often necessary.

 

Ewings sarcoma and primitive peripheral neuroectodermal tumor are now part of a group of tumors that comprise the ES Family of tumors.  ES is the second most common primary bone malignancy affecting children (184).  ES can develop in almost any bone or tissue, but the most common site is flat or long bone.  Primary ES of the skull is rare with less than 50 cases described in the literature (74); metastasis to the skull is more common.  The most common presentation in children is localized pain and swelling.  Fewer than 25 percent of patients have overt metastatic disease at the time of diagnosis, but it is surmised that there is a fair degree of subclinical spread given the 80-90 percent relapse rate with local therapy alone.  Therefore, localized tumors are treated with multimodal therapy usually involving chemotherapy and local excision with very good 5- and 10-year survival rates (136, 144, 170).  Radiotherapy is also sometimes used as an adjunct to surgery with localized disease (50).  For obvious reasons, tumors at the skull base can be much more difficult to treat with more iatrogenic complications.  Overall, Ewing’s tumors of the calvarium are very amenable to surgery followed by chemotherapy and/or radiation (74). 

 

Fibrosarcoma is one of the least common tumors of bone, and is even more rare in the skull (89).  The therapy of choice is wide local excision and treatment outcomes vary with the extent of disease (46).  Angiosarcoma is a tumor that originates in blood or lymphatic vessels.  It usually presents as a blue or purple lesion on the scalp that is present for several months prior to treatment (120).  This tumor is more commonly described in the adult population and pediatric literature is rare.  Prognosis for these tumors in adults is generally poor with 5 year survival ranging from 10-40 percent (62, 84, 120).  Size and resectabliliy are the largest prognostic factors (52, 84, 120).  Adjuvant chemotherapy and radiation are also used with some success.

 

Although Lymphoma and leukemia are common cancers of childhood, skull involvement is rare.  These may present with pain or nasal congestion or the common clinical picture of infection with fever and anemia.  Surgical treatment should be limited to biopsy.  Therapy then consists of chemotherapy or radiation, the scope of which is beyond the focus of this chapter.  Outcomes range with the grade and stage of disease.

 

In summary, tumors of the skull in pediatric patients are most commonly benign.  Dermoids/epidermoids and eosinophilic granuloma are the most common diagnoses.  Osetosarcoma is the most common malignant tumor diagnosed in the skull.  The usual therapy consists of local excision.  This may be combined with adjuvant chemotherapy and radiation for malignant tumors.  Overall, prognosis is very good with chance at a cure in most cases.

Part II.  Tumors of the Orbit and Optic Nerve

 

The orbit is the space containing the globe and optic nerve as well as the intrinsic eye muscles and is confined by the frontal, lacrimal, ethmoid, sphenoid, and maxillary bones.  This is a somewhat common location for a myriad of tumors in the pediatric population.  Given the confined space, any mass lesion is likely to cause symptoms such as visual disturbance or proptosis.  Knowing this it is somewhat surprising that many of these tumors go undiagnosed for months or years since small children do not often complain of visual changes.  Depending on the tumor type and treatment options, visual preservation may be possible.

 

There are many benign cystic and developmental lesions that can present as orbital masses.  Dermoid and epidermoid cysts are the most common benign tumors involving the orbit in children comprising 30-50% of all orbital tumors (28, 73, 172, 198).  These cysts rarely cause visual compromise unless rupture occurs and orbital cellulitis develops.  They may be simply observed if no symptoms exist or excised in toto if large and treatment is necessary.  Teratomas can also occur in the orbit and, unlike other sites in the body, tend to be benign (31).  These can also be either observed or excised.

 

Vascular tumors as a group make up about 15% of orbital lesions making them the second most common orbital tumors in children (31).  Capillary hemangioma or “strawberry nevus” is the most common (28, 75, 172) and makes up about 4% of orbital biopsies in children (174).  This tumor is usually superficial or intradermal, but may present within the orbit.  If visual compromise and lid involvement is minimal these can be treated with close observation only as they usually involute spontaneously by 2-3 years of age.  In cases with visual compromise topical or intralesional corticosteroids may be beneficial (109) or they can be excised with laser therapy (80).

 

Other vascular lesions include cavernous hemangioma, lymphangioma, hemangiopericytoma, and arteriovenous malformation (AVM).  Lymphangioma represents 1-3% of orbital tumors and (91, 173) and is invasive making complete surgical excision impossible.  These tumors are generally treated with steroids and surgical excision for the debulking of larger tumors.  AVMs can usually be embolized endovascularly and may have lasting effects based on their size.  Hemangiopericytoma is rare in children and can  be treated with surgical excision; however, incomplete excision can result in malignant transformation (31).

 

Lymphoid masses can also occasionally be seen in the orbit.  These can range in scope from eosinophilic granuloma to leukemia and lymphoma.  Eosinophilic granuloma has been discussed already in the previous section.  This can represent 1-3% of orbital masses in children (157, 172).  Once the periosteum is penetrated by the mass, a wide inflammatory reaction often occurs which can be confused with orbital cellulitis.  Like eosinophilic granuloma of the skull, treatment may include a wide array of modalities including surgery, radiation, chemotherapy, and corticosteroids (106).  Leukemia is occasionally seen in the orbit and may involve the globe with or without proptosis (31).  Granulocytic sarcoma is a variant of acute myelogenous leukemia and may occur in isolation in the orbit without systemic evidence of leukemia (31).  This tumor can be differentiated from rhabdomyosarcoma by the absence of osteolysis on imaging.  The only lymphoma which is common in the orbital region of children is Burkitt’s lymphoma.  This usually presents around 6 months after infection with Epstein Barr Virus and may occur in the abdomen, lymph nodes, and head and neck region (31).  For all of these hematologic malignancies, prompt recognition and initiation of chemotherapy provides fair prognosis.

 

Orbital mesodermal tumors include rhabdomyosarcoma, fibroma, sarcoma, and lipoma.  Rhabdomyosarcoma is easily the most common mesodermal malignancy of the orbit (157, 172).  This tumor often has some relation to minor head trauma.  This grows from the undifferentiated mesenchymal cells within the orbit and most commonly occurs in the superomedial quadrant (31, 96).  They often present with proptosis and drooping eyelids.  Metastasis occurs via hematogenous route and often spreads to lung and bone.  Surgical biopsy for tissue confirmation is followed by chemotherapy and radiation.  With this regimen prognosis is good with a 91% 3-year survival rate (3).

 

Optic nerve glioma (Juvenile Pilocytic Astrocytoma) represents 2-3% of orbital tumors in children (28, 172).  These are often very slow growing tumors and 90% are evident by the second decade (35).  These patients most often present with visual symptoms or are found to have optic disc atrophy or edema.  These tumors are strongly associated with neurofibromatosis type 1 (NF1) and are found in 10-20% of patients with NF-1.  50% of unilateral optic gliomas and nearly 100% of bilateral lesions are associated with NF-1 (183).  Since the tumors are slow growing, treatment is usually conservative.  Surgery is considered once vision declines or if the lesion begins to extend intracranially, but this always leads to at least unilateral blindness.  Chemotherapy and radiation have been useful in some patients with fast growing lesions.

 

Retinoblastoma occurs in 1 in 15000 births and is by far the most common intraocular malignancy of childhood (145).  This tumor has been extensively studied as it is a flagship in the discovery of the tumor suppressor gene (Rb) and the two-hit hypothesis of some cancers.  Once any retinal cell loses function of both Rb alleles, the cell is transformed into retinoblastoma.  The disease occurs in both a non-familial form and a heritable form where one allele is genetically dysfunctional at birth.  This leaves every cell in the patient’s retina vulnerable to the second hit which occurs in 80-90% of patients before the age of 3 giving the tumor an autosomal dominant appearing pattern of inheritance.  The average age of onset is 1 year for bilateral and 2 years for unilateral tumors (187).  The familial form is thought to occur in all patients with bilateral disease and 15% of patients with unilateral disease (31).   Genetic counseling is necessary in all of these patients and at-risk family members should be screened.  The most common presenting sign is leukocoria (2), but strabismus, glaucoma and apparent orbital cellulitis also commonly occur (31).  Management used to consist of enucleation, however many advances in chemotherapy, radiation, and focal laser therapy have given globe salvage rates of 66-78% (87, 171).  The most common route of metastasis occurs to the brain via the optic nerve (123).  The children with familial retinoblastoma are at high risk for other malignancies.  Ten percent of them present with retinoblastoma and pinealoblastoma in the first decade of life (31).  Second malignancies in the second decade occur at 1% per year (204) and include head and neck sarcomas most commonly.  These patient should continue to have frequent exams throughout life in order to diagnose second malignancies early.

 

Part III.  Tumors of the Skull Base

 

Tumors of the skull base are rare in children and therefore class I evidence regarding prevalence, prognosis, and treatment is lacking.  These tumors are also somewhat difficult to classify and are on a continuum with the tumors previously discussed in the sections on the skull and orbit.  We will classify them by the most common site of occurrence, although it is important to remember that many of these tumors may occur in multiple sites within the skull base.

 

Skull base tumors in children can be very large and extensive.  The utility of surgery is determined by the anatomical extent of the tumor with large consideration to the pre-operative neurological condition of the patient.  A complete and extensive neurological examination must be performed to delineate the functional status of sight and smell as well as hearing and facial function.  This may help to determine which approach will be used and also help to predict the morbidity of the proposed procedure for the patient.  Multimodal imaging including CT and MRI should also be obtained to determine the anatomical extent of the tumor.  If the tumor has extension into the neck or middle skull base, contrast angiography with CT or MR can define the important vascular anatomy and its relationship to the tumor.  If the tumor is significantly vascular, pre-operative embolization may have a role.  Evaluation by ENT and plastic surgery is also advisable prior to surgery as these specialists will likely have a prominent role at the time of surgery.

 

Significant discussion should take place with the child and parents explaining the gravity of the tumor and the procedure proposed to cure it.  Often these procedures require surgery elsewhere on the body to obtain fat or bone grafts for reconstruction and this should also be discussed pre-operatively.  The need for blood transfusion is frequent and some families wish to self-donate prior to surgery to minimize transfusion risk.  These procedures are very complex and it is necessary to take significant time to be sure that the family understands what is proposed and the significant morbidity and even mortality imposed by the tumor and the treatment.

 

Tumors of the Anterior Fossa

 

Olfactory Neuroblastoma (Esthesioneuroblastoma)

 

Olfactory neuroblastoma is one of the better described tumors of the skull base.  There are several relatively large case series published (57, 85, 100, 134, 142, 181), and therefore the data regarding treatment and outcomes is somewhat better than that in other pediatric skull base tumors.  This malignant tumor arises from the olfactory placode is thought to represent about 3% of all true nasal tumors (169).  These tumors arise from the basal epithelium of the superior third of the nasal septum, cribiform plate, and superior turbinates (15, 193).  They can present over a wide range of age, but are most common in a bimodal distribution of 10-20 years and then again at 50-60 years (27, 142).  Presenting symptoms usually consist of epistaxis, nasal obstruction, soft tissue mass around the nose, pain, and anosmia (169).  Contrast-enhanced CT or MR are the most useful radiologic adjuncts for defining the extent of the lesion.  Both early and late metastasis to the cervical lymph nodes, lungs, and bone occur in 8% to 30% of patients (11, 131, 142).  The Kadish staging system (100) (Table 1) has been the most reliable system used in predicting outcome and prognosis.  In 1992 a TNM staging system was also proposed which is based on CT and MR findings (53).  This system is useful but has not yet been accepted as a replacement for the Kadish system.  A histopathologic staging system which was proposed by Hyams (90) has seen mixed results as a reliable predictor of outcome (100, 128, 142). 

 

Multiple treatment algorithms have been proposed in the treatment of olfactory neuroblastoma.  The most common treatment algorithm currently in use (116, 142) is both multimodal and multidisciplinary.  Olfactory neuroblastoma is proven to be radiosensitive (100, 116, 142, 195) and therefore both pre- and post-operative radiation therapy can be of use.  Preoperative radiation has been shown to decrease tumor burden and increase the chance of gross total resection at surgery (142, 146). In patients with Kadish Stage C disease, metastases, recurrent disease, or those with surgical contraindication adjuvant chemotherapy has also been used (116, 142, 200).  Surgical therapy must be carried out with the multidisciplinary team approach for best results.  This team should consist of the neurosurgeon, otolaryngologist, plastic surgeon, radiation oncologist, and medical oncologist amongst others for individual cases.  A combined surgical approach is usually necessary with a bifrontal craniotomy for resection of tumor from the cribiform plate, dura, and olfactory tracts followed by some variation of a facial degloving procedure for resection of the intranasal and sinus component.

 

Outcomes for olfactory neuroblastoma have been widely reported and largely dependent on the treatment algorithm used.  Elkon initially reported the five-year survival in patients with Kadish stage A, B, and C disease to be 75, 60, and 41% respectively (57).  More recently, the 5-year survival for patients with Stage A and B disease has been reported to be 86% with only 72% of patients with stage C disease living 5 years (117).  Local recurrence rates are high with rates ranging from 20-40% (142), although it is thought that perioperative adjuvant radiation may decrease this risk.  Overall the worst prognostic indicator is the presence of metastatic disease with the 5 year survival reported at virtually zero (104).  In the absence of metastatic disease and with the use of the multidisciplinary approach, olfactory neuroblastoma is a disease with a fairly high cure rate.

 

 

Table 1: Kadish staging for olfactory neuroblastoma

 

 

 

 

Juvenile Nasal Angiofibroma

 

Juvenile Nasal Angiofibroma is a histologically benign but locally destructive tumor found most commonly in prepubescent males.  This rare tumor originates from the nasopharynx and can grow to involve most of the bony structure of the face as well as the skull base (54).  Histologically, it is composed of a dense fibrous stroma interspersed with vascular channels (55).  The most common presenting symptoms include obstructing nasal lesion, epistaxis, facial deformity, proptosis, sinusitis, and visual changes (10, 169, 193).  Although most commonly confined to their nasopharyngeal site of origin, they can invade the intracranial space in nearly 40% of cases (93).  Staging is carried out by the system originally proposed by Chandler in 1985 (34) or a modification thereof (169).  Appearance on neuroimaging is accepted as pathognomonic which obviates the need for tissue biopsy.

 

Therapy of Juvenile Nasal Angiofibroma often requires a multimodal approach.  Radiotherapy has shown to be effective used as both a primary therapy (43, 202) or as an adjunct to surgery (55, 72).  For stage 1 and 2 lesions, surgical therapy seems to be the best option (10, 55, 76).  Surgical therapy may be best accomplished after endovascular embolization to help minimize blood loss (10, 55).  The tumor takes its blood supply from the external carotid artery in nearly 80% of cases (55); however the internal carotid may be involved in intracranial extensions or larger tumors and balloon test occlusion may be wise prior to surgery (10).  There are a paucity of chemotherapeutic studies due to the rarity of the tumor and various agents have been used as adjuncts to surgery with varying degrees of success (63, 193).  Although overall outcomes data is lacking, it seems that the tumor has a relatively high cure rate with combined radiotherapy and surgery.

 

Rhabdomyosarcoma

 

Rhabdomyosarcoma is the most common soft tissue sarcoma found in children (48, 182).  Approximately 350 new cases are diagnosed in the United States each year, with an incidence of 4.3 cases per 1 million patients less than 20 years of age (155).  The head and neck is the most common location for these tumors to occur and 26% of these occur in the orbit, and 40% in the anterior skull base (48).  Presenting symptoms vary widely and depend largely on tumor size and location.  Radiographic appearance is non-specific and may be confused with many other tumors occurring in the same area.  There have now been several Intergroup Rhabdomyosarcoma Study Group (IRSG) reports detailing the classification and treatment of rhabdomyosarcoma (39-41, 82, 149).  Several histologic subtypes are described including leiomyomatous, embryonal, alveolar, and undifferentiated.  Of these, alveolar and undifferentiated have the worst prognosis.  Staging is accomplished via the system developed by IRSG I and II (CG staging system) which classifies the disease into stage I through IV based on the amount of tumor spread and the amount of tumor left after initial surgery (39, 41).  A newer TNM system has also been developed and incorporated in the IRSG IV protocol (40) (Table 2).

 

Treatment varies widely and is based on the above mentioned staging systems.  Rhabdomyosarcoma is one of the tumors where great strides have been made in treatment over the last 2 decades.  Previously, skull base tumors had terrible prognosis and could not be resected without severe morbidity.  With the advent of better skull base surgical techniques, more of these tumors are amenable to surgery (47).  Wide margins (>1cm) are optimal for achieving disease control; however these are difficult to achieve in the skull base.  Adjuvant therapy is based on histologic subtype and stage, but generally all children should receive chemotherapy and radiation.  With multimodal therapy, 60-70% of children with localized tumors attain cure control of their disease (39, 40, 148).  This compares with only 20% in previous years.  Overall, rhabdomyosarcoma can be a very devastating disease, especially when occurring in the skull base, but with improved surgical techniques and treatment regimens, it is becoming a more curable disease.

 

Table 2: IRS clinical group and TNM staging systems for rhabdomyosarcoma

 

IRS Clinical roup and TNM Staging Systems for rhabdomyosarcoma. These are used in conjunction for prognosis in children with rhabdomyosarcoma. Adapted from Charous S and Brockstein B. Head and Neck sarcomaa. UpToDate  article.  www.utdol.com  2007.

 

 

Tumors of the Middle Fossa and Sellar Region

 

Pituitary Adenoma

 

Although pituitary adenomas are common in the adult population, they are rare in children comprising less than 3% of supratentorial tumors with a mean annual incidence of 0.1 per million children (21).  Prolactinomas are the most common subtype of pituitary adenoma in children followed by ACTH secreting tumors and GH secreting tumors (94).  Non-functional tumors are even more rare in children accounting for around 3-6% of all pituitary tumors (21, 132).  These tumors may be somewhat easier to diagnose in children given their immature growth and endocrine state.  They are often diagnosed when children have slow growth for their age or in females who have failure of menarche (1).  The symptom of bitemporal hemianopia is often pathognomonic of pituitary lesion and is secondary to tumor compression on the optic chiasm.  Close collaboration with a pediatric endocrinologist is necessary during the workup and post-surgical hormone replacement phase.  Hormone replacement in these patients is even more crucial than in adults as normal development cannot proceed without normal levels of many pituitary hormones.

 

Workup is extensive including multiple endocrinologic studies as well as imaging.  Several prolactin levels should be obtained at different times and the mean value used in diagnosis.  Cushings may present with growth failure, hypertension, abdominal stria, diabetes, and osteoporosis.  Patients should have both a fasting and stimulated cortisol to aid in diagnosis.  In children, hypersecretion of GH results in gigantism due to hypogonadism and delayed epiphysial closure.  Patients should have 24 hour GH levels as well as insulin-like growth factor-I level measured for diagnosis.  All children with suspected pituitary adenoma should undergo contrast enhanced MRI of the sella.  Due to the small size of the pituitary in children and the already likely small size of the tumor, it is not uncommon for imaging to be non-diagnostic with suspicion for tumor still high.  If the diagnosis is still uncertain, inferior petrosal sinus venous sampling can guide further therapy but may also be difficult in the pediatric population (108, 113).

 

Treatment depends on the overall size of the tumor and endocrinologic subtype.  Transsphenoidal resection is preferred in ACTH and GH secreting tumors.  Studies have quoted long-term remission rates of 50-98% in Cushings related to pituitary adenoma (122, 139).  The success is somewhat less impressive in GH secreting tumors with only around 60% achieving normal GH levels (94).  Management of prolactin secreting tumors is first attempted with dopamine agonists such as bromocriptine.  These have been shown to be effective at decreasing tumor volume in children (23).  Management of non-secreting tumors is surgical and focused on decompressing the para-sellar structures which allows visual improvement in most cases (113, 114).  As with any procedure, results are better when the neurosurgeon is well versed in performing the transsphenoidal procedure in children.  Radiosurgery may be a useful adjunct in patients who have failed surgical resection (49, 97).

 

Craniopharyngioma

 

Craniopharyngioma is a tumor which usually arises from the Rathke’s pouch and comprises 1.8-6% of all expanding intracranial lesions during the childhood years (99, 110, 154).  These tumors usually involve both the intrasellar and suprasellar region with solely suprasellar and solely intrasellar localizations occurring in only 20% and 10% of patients, respectively (4, 23).  Headache, visual disturbance and endocrinologic disturbance are the most common presenting symptoms.  These tumors can be quite large at presentation and may obstruct the cerebral aquaduct and/or foramen of Monro necessitating a shunting procedure (110, 127).  Endocrine abnormality is found in up to 80% of patients (180) with reduced GH secretion being the most common.  Diabetes insipidus occurs in 9-17% of patients (180).  Like patients with suspected pituitary adenoma, all craniopharyngioma patients should have a contrast enhanced MRI scan which can make the diagnosis in a relatively high number of patients (79).  These tumors have a very characteristic appearance on imaging including cystic, solid, and calcified components (132, 164).

 

Treatment of craniopharyngioma has been extensively studied.  In smaller tumors without significant extrasellar extension total excision is often easily accomplished and curative (59).  The morbidity and mortality of the therapy are largely dependent on the size and extent of the tumor at diagnosis.  Morbidity is minimized and longevity maximized after near-total resection followed by fractionated radiotherapy (81, 97, 121).  Morbidity is further reduced with the advent of gamma knife and other localized radiotherapy modalities.  If the transsphenoidal approach can be used, it is advisable over any other approach even if the completeness of resection cannot be completely assured as the risk of hypothalamic injury with the transcranial approach is high.  Other therapies such as intracystic injection of yttrium or phosphorus-32 have been used with some success in recurrent disease (94).  Overall, the benefit of any additional radiotherapy should be heavily weighed in children as the risk of hypopituitarism is significantly elevated (59).

 

Tumors of the Posterior Fossa

 

Chordoma

 

Chordoma is an uncommon malignant primary bone tumor which is thought to arise from embryonic notochordal remnants (83, 141, 143).  These tumors are most commonly found in adults and tumors diagnosed in children make up only 5% of all chordoma diagnoses (178).  In adults the most common site is the sacrum, however in children they are more likely to develop in the skull base (95, 161, 162, 178) (Figure 1) and account for around 15% of all intracranial tumors in children (107, 203).  Frequent presenting symptoms include pain, neurological dysfunction, failure to thrive, and obstruction of the neck structures (16, 138, 153).  Much of the literature regarding childhood chordomas comes from isolated case reports, therefore the morphology and natural history of these lesions is somewhat difficult to predict.  There has been some suggestion throughout the literature that chordoma occurring in children tends to be “atypical” and more aggressive than that occurring in adults.  Newer studies have suggested that this may not be the case (83).  Histologically they have an overall lobular arrangement of large eosinophilic cells growing in chords, irregular bands, or an acinar pattern (154).  Several histologic subtypes exist including conventional, chondroid, cellular, and poorly differentiated (83).  Much of the morbidity is from local invasion; however, they are known to metastasize to lung, lymph node, liver, bone, kidney and adrenals (24).  The rate of metastasis at diagnosis is nearly 60% for patients less than 5 years old, but drops to less than 10% in patients over 5 years old (83).  The aggressive behavior previously mentioned is most common in the cellular and poorly differentiated subtypes.

 

Treatment usually centers on surgical resection, although these tumors are known to be very difficult to achieve gross-total resection.  It is not currently possible to take quick frozen sections of bone, further complicating complete resection (167).  Care is taken to remove all intradural extension of tumor, avoiding encased vessels and brainstem.  Adjuvant radiotherapy is often used both pre- and post-operatively.  Proton beam therapy seems to be particularly effective in children giving them a better prognosis than adults with similar tumors (12, 83).  Overall survival ranges from 23 to 81%, although this does include some mixing of adult and pediatric literature (83, 133, 140).  Chemotherapy has not shown great results and this is generally reserved for patients who have failed more conventional therapy (92).  In general, patients seem to do best with surgical resection followed by local proton beam therapy.  For the more “atypical” subtypes of tumor, prognosis is dismal and new therapies are needed.

 

 

 

Figure 1

10 month old boy presented with bilateral 6th nerve palsies.  MRI revealed clivus chordoma compressing the brainstem and displacing the basilar artery (A and B).  The child underwent 2-stage bilateral retromastoid craniectomy for tumor resection.  This approach was chosen based on the fact that this child was the youngest known patient treated with surgery for clivus chordoma, and the danger of violating the skull base in a child this age.  3-month post-operative MRI shown (C and D).  Postoperative course was complicated by transient diabetes insipidus.  He also underwent proton beam radiation.  At 3-years follow-up there were no cranial nerve deficits and he was developing normally.

 

Meningioma

 

While meningiomas are fairly common tumors in the adult population, they are relatively rare in pediatric patients and have wide rates of incidence reported across many communities.  In general, meningiomas are thought to comprise between 1.9 and 8% of childhood intracranial tumors (9, 13, 33, 64, 105) with an incidence of 2 per 100,000 (156).  The average age of presentation is between 8 and 15 years (51).  The literature varies widely on the common locations with some studies citing parasagittal and convexity as the most likely area for tumor occurance (45, 58) and others finding them up to 70% of the time in the skull base (9).  Common signs and symptoms include increased head circumference, increased ICP, seizure and focal neurological deficit.  Common radiographic findings include hyperostosis of the adjacent skull and the much discussed “dural tail” seen on MRI (32, 42, 44, 188).  There has also been a larger size at diagnosis associated childhood meningioma with up to 50% of tumors over 5 cm (7, 9, 32, 150).  These children should also be screened for neurofibromatosis which is associated up to 23% of the time (194).  It has been suggested that childhood meningiomas show faster growth and higher propensity for invasion than those in adults, but this literature is inconsistent.

 

Typical meningiomas treated with gross-total resection have very good outcomes and good chance for long-term survival (9).  These outcomes have improved with the improvement in surgical techniques and pre- and post-operative intensive care.  Adjuvant radiotherapy has been beneficial in adults with meningiomas (66), however it is difficult to justify using radiotherapy in children for a benign slow-growing lesion (58).  It can be concluded then, that surgery with aim at gross-total resection including wide margins of the involved dura should be the initial goal.  Radiotherapy may be used judiciously as an adjunct if there is tumor recurrence or sub-optimal resection with significant tumor burden invading eloquent areas.

 

Acoustic Schwannoma

 

Acoustic schwannomas (neuroma) comprise about 10% of all intracranial tumors and primarily occur in adults (103).  These tumors are rare in children, and almost always associated with neurofibromatosis type 2 (NF-2) in this population.  Very few pediatric acoustic neuromas have been presented in the literature and are mostly relegated to case reports.  These tumors generally present between the ages of 7 and 16 years (6, 111, 160, 197).  Children with NF-2 and bilateral acoustic schwannomas present after the age of 15 years (124).  These tumors grow from the vestibular component of cranial nerve VIII and are seen as mass lesions in the cerebellopontine angle.  Presenting symptoms include sensorineural hearing loss, headache, facial weakness, obstructive hydrocephalus, nystagmus, and ataxia.  Like the other tumors described above, pediatric patients tend to present later in the disease with very large tumors since their underdeveloped skull can expand with the tumor for some time.  These tumors are generally adherent to surrounding structures and much more vascular than the adult version making them difficult to resect.  MRI is the diagnostic test of choice as these tumors enhance dramatically with gadolinium contrast (70).  Approximately 10% of patients with NF-2 have acoustic schwannomas and bilateral schwannomas are nearly diagnostic of this disease (56).

 

Surgery is the treatment of choice with these tumors and gross-total resection is a cure, although patients with NF-2 are at risk on the contralateral side.  The primary concern with surgery in children is hearing preservation.  It has been recommended that tumors greater than 2.0 cm in diameter be resected with attempt at hearing preservation.  Tumors 2.0 to 3.5 cm may be treated with subtotal resection followed by stereotactic radiosurgery as gross total resection may risk loss of what little hearing remains (5).  The choice of approach is very dependent on the state of hearing the patient already has, and the translabrynthine approach should be reserved for patients with unilateral deafness.  As mentioned above, pediatric tumors have a tendency toward vascularity and so pre-operative embolization may have a role (6, 160).  It has also been proposed that all pediatric patients with acoustic neuromas undergo surveillance MRI after initial resection as they may develop a contralateral lesion associated with NF-2 (38).  Adult studies report the overall tumor removal rate at 97-99% (68, 163) with facial nerve preservation in 85% and cochlear nerve preservation in 36% (163).  Based on the current literature it is impossible to know if this data could be reproduced in pediatric patients.

 

Cholesteatoma

 

A cholesteatoma, also known as epidermoid cyst, can be congenital or acquired and are believed to occur from an abnormal rest of epithelial tissue trapped in bone (usually temporal) (22).  These tumors consist of stratified squamous epithelium with keratinous debris (129).  Acquired lesions are thought to arise from migration of epithelial cells after otitis media or tympanic membrane perforation (22).  Congenital cholesteatoma has a reported incidence of 0.12 per 100,000 people (192).  Cholesteatomas usually present as an incidental white placque seen in the ear canal, but occasionally present with hearing loss (179).  Vertigo and facial palsy are rare, but do occur with larger tumors (177).  CT scan is the radiographic imaging of choice as bony involvement can be easily determined.  MRI can be used to rule out intracranial complications.  All children should have pre-treatment audiologic examination and exam by qualified otolaryngologist unless there is surgical urgency.

 

The mainstay of treatment is surgery with a goal of gross total resection of the abnormal epithelium.  Two main surgical strategies have been in use: the canal-wall-down mastoidectomy which externalizes the affected ear (61) and the canal-wall up procedure (61).  The canal-wall-down mastoidectomy provides better surgical exposure, as well as post-operative surveillance of the disease (61).  The canal-wall-up tympanomastoidectomy does not provide equal surgical exposure and therefore less assurance of complete resection, but does provide for preservation of hearing.  It is not surprising then that recurrent occurs as much as 57% of the time with this procedure after 5 years (158).  Medical therapy plays a role only to the point of preventing systemic infection.  Patients are usually treated topically with antimicrobials aimed at pseudomonas species (177).  Several medical therapies have been attempted including cyclophosphamide and hyaluronic acid, but these have had little, if any, success (147, 201).  Surveilance is a must after surgery, and some surgeons even perform repeat operations to look for recurrent disease (191).  With total excision, the prognosis is fairly good.

 

Part IV.  Skull Base Approaches, Outcomes, and Pediatric Pitfalls

 

 As with any aspect of care of pediatric patients, size difference and growth are the major components which make pediatric skull base surgery difficult when compared with the same procedures in adults.  It was thought for many years that the smaller size of the head made resection of many pediatric tumors easier and that virtually all pediatric tumors could be removed via a standard craniotomy.  As skull base surgery evolved in adults, so too the concept that removal of bone was better than retraction of brain became adapted to pediatrics.  The data has taken a very long time to evolve due to the proportionally smaller numbers of pediatric skull base tumors in children and many of these spring up at isolated institutions making large case series impossible.  Thus, it is not surprising that many pediatric skull base tumors are still treated under multiple treatment regimens at any given institution.

 

Tessier initially described transfacial approaches in pediatric patients in 1967 for the repair of birth defects involving the face and anterior cranial base (190).  This has now been expanded by several other case series all involving less than 100 patients (25, 78, 189).  Virtually all of the approaches used in adults can be used in pediatric patients with appropriate modifications.  It is important to consider that given the small size of pediatric patients, meticulous surgical technique and minimization of blood loss are a must.  A few hundred milliliters of blood loss in a child can be a significant percentage of the blood volume requiring transfusion.  The type of approach should be carefully selected and confirmed with radiographs as many more peripheral or superficial lesions can be accessed via a standard craniotomy as mentioned above.  Need for brain retraction must also be minimized as this will cause undue injury to normal brain. 

 

There are certain anatomical differences that also must be considered.  In their review of 55 pediatric skull base procedures, Brockmeyer et. al. made mention of several anatomic differences frequently encountered (25).  First, the supraorbital notch is absent in children less than 8 years of age, making orbital dissection difficult.  The pterion is also displaced in a forward direction, making a burr hole placed in the traditional “keyhole” fall into the periorbital region rather than the anterior fossa. It is also felt that the brain is generally more compact making the dissection of the arachnoid cisterns such as the sylvian and interhemispheric fissures more difficult in younger children.

 

Surgical approaches to the anterior cranial base include the transfacial, orbitozygomatic, and transsphenoidal craniotomies.  The transfacial approaches are generally limited in children by the budding teeth.  The transoral and transmaxillary approaches destroy the central incisors and may jeopardize other teeth in children less than 10 years old (112).  Furthermore, these approaches may not yield the best exposure due to the proportionally greater amount of tissue in the face and sinuses (118).  Surprisingly, most studies have found that the disruption of facial growth with the transfacial approaches is not often affected as most of the osteotomies do not pass through growth centers (18, 189).  Facial degloving procedures may increase exposure while preventing disfiguring incision, however this procedure is associated with lasting facial sensory disturbances (86, 118).  The orbitozygomatic approach, while not often indicated, may actually be technically easier in pediatric patients due to the shallow anterior fossa (112).  Transsphenoidal surgery has been successfully performed in children but is technically difficult due to the small sphenoid sinus and close proximity of the cavernous sinus and carotid artery.  It should be noted that all approaches that use the facial sinuses for access are more difficult in children and require more drilling of bone due to the fact that the sinuses are incompletely aerated and the air spaces that do exist are much smaller than those in adults.

 

Middle fossa approaches include frontotemporal, temporal, and preauricular infratemporal (193).  These approaches may also require differing degrees of resection of the orbit, zygoma, mandible, and the petrous portion of the temporal bone.  Many of the complications with these approaches are associated with CSF leak, wound infection, and meningitis (115).  There is also a relatively high frequency of facial paralysis due to damage of the facial nerve or its branches (30, 60).  These approaches have some advantage in children as there is less bone to resect from the skull base and the sphenoid wing and temporal ridge are generally less prominent making exposure somewhat easier.  The effects of mandibular resection in children is not well known and should be avoided if possible (103).  Resection of craniopharyngioma carries a high probability of post-operative diabetes insipidus due to the close proximity of the pituitary stalk.

 

There are many approaches to the posterior fossa and these are perhaps the most technically difficult and harrowing procedures in neurosurgery.  These include the transpetrosal, retrosigmoid, translabyrinthine, retrolabyrinthine, transcochlear, and far-lateral transcondylar.  The most frequent complications from these procedures involve CSF leaks and cranial nerve deficits (168).  The translabrynthine and transcochlear approaches by nature involve the loss of hearing on the affected side.  These approaches are sometimes modified in a manner set to preserve hearing with mixed results (193).  The complications of the far-lateral transcondylar approach is not well described in children and it is unclear what effect the hemilaminectomy of C1 and the partial resection of the occipital condyle have on future craniocervical growth and stability.

 

Overall, outcomes are very difficult to classify given that the data comes from many separate isolated reports with a mix of different approaches and lesions.  In a series published by Brockmeyer, et. al. (25), 55 patients underwent orbitozygomatic, transfacial, Dolenc’s approach, transpetrosal, and far-lateral craniotomies for various skull base pathology.  Ninety-six percent of these patients had Glasgow Outcome Scores of 4 to 5 with most only suffering minor complications.  Hanbali, et. al. (78), published a series of 30 skull base procedures in 24 children.  In this series the overall survival of patients with benign tumors at 1- and 5-years was 100% compared with 77% in patients with malignant tumors.  Surgical complications developed in 42% of patients and were persistent in 50% of these.  Teo et. al. (189), followed 26 patients who underwent orbitozygomatic, retrosigmoid/translabyrinthine, anterior craniofacial, transcondylar, transoral, transsphenoidal, and transpetrosal craniotomies for mixed pathology.  In 24 of these patients, complete radiological tumor removal was achieved.  Five patients died, 3 of primary disease and 1 of postoperative complications.  Fifty-seven percent of patients had immediate postoperative complications, most of which were minor, and 30.7% had permanent complications.  Overall 62% of patients had a good outcome, 15% were graded as fair, and 8% had poor outcomes.  Lang et. al. (112), reported results in 20 children who underwent multiple different surgical procedures.  Eighteen patients had a good outcome on the Glasgow Outcome Scale, one had moderate disability, and one suffered severe disability. Several other studies have reported outcomes that vary as greatly as those mentioned above (8, 118).

 

Figure 1

 

A standard pterional craniotomy.

 

The first cut divides the root of the zygoma. The second (A and B) divided the zygoma just above the level of the malar eminence.

 

The third cut just lateral to the supraorbital notch carried posteriorly towards the  superior orbital fissure.

 

Fourth cut connecting the superior and inferior orbital fissures.

 

Dural exposure gained by orbitozygomatic craniotomy.

 

Bony piece removed including zygoma and supralateral orbit.

 

Conclusion

 

As evidenced by the preceding chapter, good data with solid conclusions on pediatric skull base surgery is rare.  This will likely improve as some specialty centers accumulated and publish larger series.  Overall, it can be said that pediatric skull base surgery is a field that is yet in its infancy but will likely expand in the future.  Tumor diagnoses differ between pediatrics and adults as there are many more sarcomas diagnosed in children.  The push toward better surgical techniques will continue as total resection is curative for large benign pediatric tumors; which obviates the need for further detrimental adjuvant therapy.  Multiple anatomic and logistical differences exist that make pediatric skull base surgery difficult.  Outcomes are variable, and depend largely on the tumor type, approach, overall condition of the patient, need and type of adjuvant therapy, patient age, and stage and grade of tumor.  The planning for skull base procedures in children must occur on an individual case basis as generalizations are difficult.  A large an specialized multidisciplinary team is necessary in order to maximize outcome while limiting surgical morbidity in this population.  There will be much room for growth in this field in the future.

 

 

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Corresponding Author:

 

Mustafa K. Başkaya, MD

Department of Neurological Surgery

University of Wisconsin Hospitals and Clinics

600 Highland Avenue

UWHC-Neurosurgery F4/315, CSC-8660

Madison, WI  53792

E-mail:  m.baskaya@neurosurg.wisc.edu

Phone: (608) 262-0090

Fax: (608) 263-1728

 

 

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