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CLINICAL STUDIES

MANAGEMENT OF INVASIVE JUVENILE


NASOPHARYNGEAL ANGIOFIBROMAS:
THE ROLE OF A MULTIMODALITY APPROACH
Pierre-Hugues Roche, M.D. OBJECTIVE: Juvenile nasopharyngeal angiofibromas involving the cranial base and
Department of Neurosurgery, intracranial compartment are challenging tumors. We reviewed our experience of these
Sainte Marguerite University Hospital,
tumors and analyzed the efficacy of a multimodality management.
Marseille, France
METHODS: Between 1981 and 2000, 15 extensive juvenile nasopharyngeal angiofibro-
Jerôme Paris, M.D. mas (Fisch Grade III or IV) were treated at our institution. The mean age of the patients was
Federation of Ear, Nose, 14.5 years, and the mean interval between the first symptom and diagnosis was 12.9
and Throat Surgery, months. Initial management included preoperative embolization of the external carotid
La Timone University Hospital,
Marseille, France
artery feeders, followed by tumor removal. A maxillofacial procedure was performed in
eight cases, a combination of maxillofacial and neurosurgical approach was performed
Jean Régis, M.D., Ph.D. in four cases, and a neurosurgical cranial base approach was performed in three cases.
Department of Stereotactic and RESULTS: Total removal after the initial procedure was obtained in eight patients.
Functional Neurosurgery, Subtotal removal justified additional surgery in one case, gamma knife radiosurgery in
La Timone University Hospital,
Marseille, France two cases, and fractionated irradiation in four cases. True recurrences were observed
in four cases at a mean interval of 37 months (range, 24–46 mo) and required tailored
Guy Moulin, M.D. multimodality management. No cases of perioperative death were observed. One
Department of Radiology, patient underwent hemiparesis after embolization in the early period of our experi-
La Timone University Hospital, ence. Permanent facial numbness was reported in four cases, moderate cosmetic prob-
Marseille, France
lems were reported in three cases, and hyposmia was reported in three cases. Except
for one patient who was lost to follow-up at 18 months, 12 patients were free of dis-
Michel Zanaret, M.D.
ease and two patients were free of tumor progression. All patients had normal or near-
Federation of Ear, Nose,
and Throat Surgery, normal daily life at the last check-up, with a median follow-up period of 108 months
La Timone University Hospital, (mean, 117 mo; range, 91–252 mo).
Marseille, France
CONCLUSION: Extensive juvenile nasopharyngeal angiofibromas are efficiently man-
Jean-Marc Thomassin, M.D. aged with a multimodal protocol in which preoperative embolization is followed by
Federation of Ear, Nose,
optimal surgical removal using various transcranial or transfacial approaches. Adjunctive
and Throat Surgery, gamma knife radiosurgery is a valuable option for intracavernous residual tumor. Our
La Timone University Hospital, protocol offers long-term cure with acceptable morbidity.
Marseille, France
KEY WORDS: Angiofibroma, Cranial base surgery, Neurosurgery, Radiosurgery, Skull base surgery
William Pellet, M.D.
Neurosurgery 61:768–777, 2007 DOI: 10.1227/01.NEU.0000280077.89703.AD www.neurosurgery-online.com
Department of Neurosurgery,
Sainte Marguerite University Hospital,
Marseille, France

Reprint requests:
Pierre-Hugues Roche, M.D.,
Service de Neurochirurgie,
J uvenile nasopharyngeal angiofibromas
(JNA) are benign tumors affecting young
adolescent males and originating from the
posterolateral wall of the nasal cavity. In the
tumor to the critical neurovascular structures
and to extensive vascular recruitment. There-
fore, a high neurological morbidity and a high
rate of incomplete resection may be expected.
Hôpital Sainte-Marguerite, situation of early diagnosis, the tumor exten- Most neurosurgeons have little experience
Assistance Publique des sion is limited and radical cure can be expected with this disease. In this retrospective study,
Hôpitaux de Marseille, using noninvasive surgical approaches (23). we sought to identify the patterns of intracra-
Boulevard de Sainte-Marguerite, However, in 20 to 40% of the cases, the tumor nial extension of JNAs. We attempted to clarify
Marseille, France.
Email: prochemail.ap-hm.fr
is diagnosed at the time of cranial base exten- the respective indications of cranial base tech-
sion with a potential involvement of intracra- niques and the potential role of adjunctive
Received, December 26, 2006. nial structures. In these cases, management is noninvasive procedures with special interest
Accepted, May 1, 2007. challenging because of the relationship of the to radiosurgery.

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INVASIVE JUVENILE NASOPHARYNGEAL ANGIOFIBROMAS

patients harbored focal tumors (Class I or II). Fourteen of these patients


TABLE 1. Fisch system for the grading of juvenile nasopharyngeal were managed from the onset, and one patient came from another cen-
angiofibromas ter after tumor recurrence. Operative records, neuroimaging results,
and clinical histories, including postoperative follow-up data, were
Type I Tumor limited to the nasopharynx and nasal cavity. reviewed. The mean age of patients at the time of diagnosis was
Bone destruction negligible or limited to the spheno- 14.5 years (range, 11–20 yr), and the mean interval between the first
palatine foramen. symptom and diagnosis was 12.9 months (range, 1–26 mo). The initial
Type II Tumor invading the pterygopalatine fossa or the maxillary, evaluation of the patient included a general history, physical examina-
ethmoid, or sphenoid sinus with bone destruction. tion, and endoscope examination of the nasal and pharyngeal cavities.
The first symptoms were epistaxis (12 patients) and nasal obstruction
Type IIIa Tumor invading the infratemporal fossa or orbital region (13 patients), followed by proptosis, pharyngeal obstruction, hearing
without intracranial involvement. loss, and trigeminal symptoms. The details of the clinical presentation
Type IIIb Tumor invading the infratemporal fossa or orbit with before our management are shown in Table 2.
intracranial extradural (parasellar) involvement.
Type IVa Intracranial intradural tumor without infiltration of the Radiological Evaluation
cavernous sinus, pituitary fossa, or optic chiasm. Contrast-enhanced computed tomographic (CT) scans, magnetic res-
Type IVb Intracranial intradural tumor with infiltration of the onance imaging (MRI) scans, or both were studied before surgery for
cavernous sinus, pituitary fossa, or optic chiasm. all patients. The tumor mass was characterized by a well-delineated
and high-density lesion that displayed a homogeneous enhancement.
The bony deformation and the erosion of the cranial base were shown.
MRI scans were particularly useful in analyzing the intracranial and
PATIENTS AND METHODS intraorbital extension. For each patient, tumor extension (Fisch class) is
given in Table 2. In addition, detailed radiological extensions to the dif-
Patient Population ferent compartments of the cranial base are analyzed and displayed in
This series represents our surgical experience with 15 patients Table 3. In all patients, a carotid arteriogram was performed, with selec-
treated at the University Hospital of Marseille between 1981 and 2000. tive catheterization of external and internal carotid arteries on both
This subgroup of patients was extracted from a larger population of sides. Data available in 14 cases indicated that main feeders came from
35 consecutive patients with JNAs who had been treated during the the ipsilateral internal maxillary artery in all patients with a predomi-
same period. The present review encompasses 15 male patients harbor- nant role played by the sphenopalatine artery. Tumor feeders came
ing an extensive tumor mass involving the cranial base or the intracra- from the ascending pharyngeal artery in four cases, the ipsilateral inter-
nial compartment that could be classified as Class III or IV tumors nal carotid artery in five cases (mainly intracavernous branches), the
based on the Fisch (13) classification (Table 1), whereas the 20 other contralateral external carotid artery in five cases, and the contralateral

TABLE 2. Summary of clinical findings of juvenile nasopharyngeal angiofibromas in 15 patientsa


Patient Age at Initial Other Physical Interval between symp- Fisch
no. diagnosis (yr) symptom symptoms findings tom and diagnosis (mo) stage
1 11 E FD 30 IVa
2 12 E NO 18 IVa
3 15 E NO FD, P hypoacousia 14 IVa
4 11 NO 2 IIIa
5 13 E NO, headaches P, FD 1 IIIa
6 18 E NO 5 IIIa
7 17 E NO, HS 12 IIIa
8 12 E Headaches FD 9 IIIa
9 17 E NO 24 IVa
10 15 E FD, HS Pharyngeal mass 12 IVa
11 14 E NO 3 IIIa
12 13–20b E NO Hypoacousia 26 IIIa
13 16 E NO, headaches P, visual deficit, FD 19 IVb
14 13 NO HS 12 IIIa
15 14 E NO FD, facial numbness 6 IVa

a
E, epistaxis; FD, facial deformity; HS, hyponasal speech; NO, nasal obstruction; P, proptosis.
b
Thirteen-year-old boy at first management in another center and 20 years old at the time of our management.

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TABLE 3. Tumor extensions shown by preoperative radiological workup


Radiological extension of the 15 juvenile nasopharyngeal angiofibromas
Orbit
Cranial base structures Intracranial structures
Pterygoid plate 15 Extradural temporal fossa 5 6
Pterygomaxillary fissure 15 Intradural temporal fossa 1
Infratemporal fossa 8 Superior orbital fissure 2
Posterior parapharyngeal space 6 Cavernous sinus 4
Sphenoid sinus 12
Inferior orbital fissure 10

internal carotid artery in two


cases. Postoperative MRI or CT
scans were obtained within 2
months of surgery to determine
the extent of resection in each
patient and in the long-term fol-
low-up period to assess a poten-
tial recurrence.

Extent of Resection
The determination of extent of
resection was based on the intra-
operative assessment, postopera-
tive findings of the fiberoptic
examination of the nasal and pha-
ryngeal cavities, and postopera-
tive images (Fig. 1). Gross total
removal was defined as a patient
displaying no intraoperative evi-
dence of residual tumor, normal
fiberoptic examination, and no
evidence of contrast-enhancing
tumor on postoperative imaging.
The cases of residual tumor were
considered as partial removal.
Tumor recurrence was defined as
any newly identified enhance-
ment after gross total removal.

Preoperative Embolization FIGURE 1. Diagram illustrating the treatment protocol used in our population. JNA, juvenile nasopharyngeal
angiofibroma; MF, maxillofacial; PLN, paralateronasal; MD, midfacial degloving; mPSIT, modified preauricular sub-
Several agents were used to
and infratemporal approach; ETP, epidural temporopolar approach; GKR, gamma knife radiosurgery; FUp, follow-
selectively occlude the feeders that
up; RT, radiotherapy
came from the external carotid
artery from one or both sides:
Histoacryl glue (B-Braun, Melsungen, Germany), resorbable Gelfoam tumor resection, taking into consideration the high vascularity, the
(Upjohn Co., Kalamazoo, MI), or a combination of Gelfoam with flower locoregional extension, and the fibrous consistency of the tumor. We
microcoils (Guerbet Biomedical, Louvres, France). The procedure was always attempted to achieve an en bloc extracapsular resection using
delivered within the 72 hours before surgical removal (Fig. 2). extensive surgical corridors. A meticulous hemostasis was permanently
performed to reduce blood loss. The attempt of intracavernous resec-
tion of tumor fragments was never undertaken, avoiding the mobiliza-
Approach Selection and Operative
tion of critical neurovascular structures.
Technique in First Intention Ear, nose, and throat approaches were the transfacial approach with
The surgical approach was predicated on the location of the epicen- a paralateronasal skin incision, the transmaxillary transantral approach,
ter of the tumor, direction of tumor extension, and tumor size (Table 4). and the transmaxillary approach via midfacial degloving. These
Regardless of the approach, we used the same general principles of approaches have been extensively detailed in other articles (19).

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INVASIVE JUVENILE NASOPHARYNGEAL ANGIOFIBROMAS

Neurosurgical approaches consisted of various temporobasal cran-


iotomies. We initially adopted a modified preauricular sub- and
infratemporal approach, derived from Sekhar et al.’s (26) technique.
The approach included a preauricular skin incision followed by the
mobilization of the temporal muscle after zygomatic deposition. The
temporomandibular joint was translocated anteroinferiorly and a tem-
poral bone flap was made, including the optimal resection of the floor
of the middle fossa as far as the pterygoid plate. The dissection of the
upper neck was then undertaken, which exposed the division of the
A B facial nerve inside the parotid gland and the internal carotid artery
under the petrous bone. After optimal resection of the tumor, including
the components that involved the infratemporal fossa and the parapha-
ryngeal space, meticulous reconstruction and closure were performed.
More recently we adopted a less invasive technique, the epidural tem-
poropolar approach, derived from the description of Hakuba et al. (15).
The patient was positioned supine with the head rotated 45 degrees to
the opposite side. The skin incision was started 1 cm inferior to the
zygoma and 1 cm anterior to the tragus, prolonged upward in a ques-
tion mark fashion, ending behind the hairline in the frontal area. The
pericranial flap was elevated and turned downward and forward. The
C D supraorbital nerve was freed from the supraorbital foramen and
FIGURE 2. Radiological data from Patient 9. A, preoperative angiogram reflected within the flap. The temporalis muscle and fascia were dis-
showing the numerous feeders coming from the branches of the internal sected subperiosteally. A temporopterional bone flap was made and
maxillary artery. B, coronal CT scan indicating the extension of the tumor included an orbitozygomatic deposit in a “one-piece” manner (Fig. 3).
mass to the paranasal sinuses, inferior orbital fissure, and temporal fossa The frontotemporal dura, periorbit, and superior orbital fissure were
on the right side. C, after selective embolization of the internal maxillary widely exposed and could be opened in the case of intradural involve-
artery by coils, feeders are still coming from the intracavernous branches ment. The floor of the temporal fossa was drilled extensively to expose
of the internal carotid artery. D, postoperative CT scan showing the extent the foramen rotundum and ovale. The upper part of the infratemporal
of resection and lack of residual tumor. fossa, pterygopalatine fossa, sphenoid sinus, and posterior wall of the
maxillary sinus could also be exposed, depending on tumor extension.

TABLE 4. Synopsis of the management and follow-up of patientsa


Patient First Extent of Adjunctive Delay of recurrence/ Length of follow- MRI at
no. treatment resection treatment additional treatment up (yr after surgery) last follow-up
1 PLN STR RT —/— 1.5 (LFU)
2 PLN and mPSIT STR GKR —/— 4 DRT
3 mPSIT STR RT —/— 20 NRT
4 Transmaxillary GTR — 46 mo/MD and GKR 7 DRT
5 PLN GTR — 44 mo/PLN and mPSIT 23 NRT
6 MD GTR — —/— 8 NRT
7 PLN GTR — 30 mo/PLN 11 NRT
8 PLN STR RT —/— 8 NRT
9 MD and mPSIT GTR — —/— 5 NRT
10 mPSIT GTR — 24 mo/PLN 4 NRT
11 PLN GTR — —/— 11 NRT
12 PLN GTR — —/— 12 NRT
13 PLN and mPSIT STR RT —/— 12 NRT
14 mPSIT STR MD —/— 12 NRT
15 PLN and ETP STR GKR —/— 5 NRT

a
MRI, magnetic resonance imaging; PLN, paralateronasal approach; STR, subtotal removal; RT, radiation therapy; LFU, lost to follow-up; mPSIT, modified preauricular sub-
and infratemporal approach; GKR, gamma knife radiosurgery; DRT, decreased residual tumor; NRT, no residual tumor; GTR, gross total removal; MD, midfacial degloving;
ETP, epidural temporopolar approach.

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ROCHE ET AL.

A B

C D

FIGURE 3. Interoperative photograph of Patient 15


showing the epidural temporopolar approach that was
conducted simultaneously to the paralateronasal proce-
dure. One-piece orbitozygomatic pterional bone flap is
achieved (inset), allowing an access to the infratempo-
ral fossa. The upper and lateral pole of the tumor is in
the inferior orbital fissure (white arrow). GSW, great FIGURE 4. MRI scans of Patient 15. A, the sphenoid sinus, infratempo-
sphenoid wing; OF, orbital fascia. ral fossa, and intracranial parasellar compartment are involved by the
tumor. B, preoperative axial view, the whole ethmoid is involved. C, early
postoperative axial view indicating a residual tumor mass (arrow) in the
Case Selection for External Beam Radiation right cavernous sinus. D, MRI scan obtained 5 years after GKR showing
that there is no evidence of residual tumor mass.
Therapy and Gamma Knife Radiosurgery
From 1981 to 1992, before the development of radiosurgery in our
institution, external beam radiation therapy was delivered in case of
residual tumors unable to be extirpated. Delivered doses ranged from RESULTS
25 to 50 Gy (mean dose, 40 Gy; median dose, 37.5 Gy), with a 2 Gy per
fraction protocol. From 1992 to 2000, gamma knife radiosurgery
One patient (Patient 1) was lost to follow-up at 28 months
(GKR) was administered after incomplete resection when the residual after surgery. For the 14 remaining patients, the median clinical
tumor mass did not exceed a 3 cm diameter and the optic pathway and radiological follow-up period was 108 months (mean, 117
was not in the close proximity of the lesion (Fig. 4). Tumors were mo; range, 91–252 mo) after the first treatment in our institution.
treated using a multi-isocentric protocol. The dose that was deliv-
ered at the tumor margin ranged from 14 to 16 Gy, corresponding to Embolization
the 50% isodose (Table 5). Thirteen patients (all patients except Patients 5 and 8) under-
went preoperative endovascular tumor embolization. The fol-
Follow-up Protocol lowing arteries were embolized: internal maxillary artery on
Insofar as it was possible, the patients underwent a sequential fol- one side in 10 patients, internal maxillary artery on both sides
low-up evaluation by our team, including iterative clinical and fiberop- in five patients, ascending pharyngeal artery in nine patients,
tic controls and CT or MRI scans. For the purpose of this study, we facial artery in two patients, and accessory meningeal artery in
were able to collect recent information for all patients except one, with four patients. This management allowed a significant reduction
particular attention to their level of autonomy and quality of life. of the blood loss during surgery. Permanent hemiparesis was

TABLE 5. Summary of juvenile nasopharyngeal angiofibroma cases who underwent a gamma knife radiosurgical procedurea
Patient Location of
Indication of GKR Dosimetry Outcome
no. remnant tumor
2 Residual tumor after initial surgery MCC 16 Gy at the 50% peripheral Decrease at 4 yr
isodose (isodose 50) NC
4 Residual after second surgery MCC, inferior orbital fissure 14 Gy isodose 50–11 Decrease at 3 yr
for recurrence isocenters NC
15 Residual tumor after initial surgery Whole cavernous sinus 14 Gy isodose 50–36 No residual at 5 yr
isocenters NC

a
GKR, gamma knife radiosurgery; MCC, medial cavernous compartment; NC, no complication.

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INVASIVE JUVENILE NASOPHARYNGEAL ANGIOFIBROMAS

observed immediately after embolization in Patient 1 and was


caused by the migration of the embole product to the middle
cerebral artery during the early stage of our experience. In
another patient (Patient 13), the embolization may have con-
tributed to the formation of a limited scalp necrosis that
occurred after surgery; however, the long-term cosmetic result
was acceptable and did not require any additional procedures.

Tumor Removal
The first-intention surgical strategy was distributed as fol-
lows (Fig. 1; Table 4): four patients underwent a combined max-
illofacial and neurosurgical approaches in a one- or two-stage
procedure. Eight patients were managed by a single maxillofa-
cial approach, and a single neurosurgical procedure was per-
formed in the three remaining patients.
FIGURE 5. Histological features of JNA showing that
Gross total removal of the tumor mass was obtained in eight
the tumor was composed of fibrocollagenous stroma
of the 15 patients (53.3%; confidence interval, 26.6–78.7). containing vascular spaces (hematoxylin and eosin;
Subtotal removal was observed in seven of the 15 (46.7%) original magnification, ⫻40).
patients after the first procedure and mainly involved patients
with Fisch Class IV tumors. In six patients, the remnant tumor
was not eligible for a more aggressive attempt of resection after and infratemporal approach. Cosmetic problems (unesthetic
careful consideration of the risk of additional cranial nerve skin scar) were encountered in two of the 10 patients who
injury and potential vascular damage. Fractionated radiation underwent operation via a paralateronasal approach. One of
therapy was performed in four patients, and GKR was per- them displayed a permanent enophthalmia after removal of
formed in two patients (Table 5). In the last patient, a new sur- the intraorbital tumor fragment. Another patient had perma-
gical step (midfacial degloving) was performed without nent rhinitis with hyposmia and a bird-like nose deformation
adjunctive irradiation. On average, the estimated blood loss responsible for psychoaffective disturbances after a midfacial
during surgery was 1037.5 mL (standard deviation, 1091 mL). degloving. Permanent hyposmia was experienced by two other
Recurrence patients after a maxillofacial procedure. Chewing difficulties
were reported by one patient who had undergone a modified
True recurrence of the disease was observed in four of the preauricular sub- and infratemporal approach with resection of
eight patients (50%) in whom gross total removal was the mandibular condyle.
achieved. The mean interval between the first treatment and No deaths were reported during the exhaustive follow-up
recurrence was 37 months (range, 2–4 yr) after surgery. In all period for 14 patients, and all patients are now living with
cases, new symptoms (epistaxis and nasal obstruction) were what they estimate as a satisfactory level of quality of life,
contemporary with this event. On the basis of the endoscopic although a dedicated questionnaire has not been filled out.
evaluation and postoperative CT and MRI scans, the location
of recurrence was focal in two patients (choana and ptery-
gopalatine fossa) and more extensive (middle cranial base DISCUSSION
and infratemporal fossa) in the other two patients. Treatment
of the recurrence consisted in additional surgical procedure in General Considerations
all patients, followed by GKR in one patient. In this small The term “juvenile nasopharyngeal fibroma” was introduced
group of patients, it was not possible to identify predictive by Chaveau (4) in 1906 to describe a nodular and dark tumor
factors that may have influenced the recurrence, particularly of the choana. JNA is a nonencapsulated, highly vascular lesion
in respect to the age of the patient, tumor extension, and Fisch originating from the mesenchymal tissue. Compression of sur-
class at the time of management. Among the four recurrent rounding normal tissue produces a pseudocapsule of fibrous
cases, three patients had undergone a single maxillofacial tissue. The tumor is histologically benign and composed of a
approach as the initial procedure. connective tissue stroma with a matrix of a dilated vascular
structure (Fig. 5). The blood vessels usually lack a complete
Complications muscular layer, which may account for the lesion’s well-known
Eight patients from this series displayed at least one perma- hemorrhagic tendencies (28). JNAs occur almost exclusively in
nent problem resulting from the surgical treatment of their dis- adolescent males and account for only 0.5% of all neoplasms of
ease. Trigeminal hypesthesia, especially in the area of the max- the head and neck, but they remain the most common benign
illary branch, was observed in four patients, three of whom tumor of the nasopharynx. The main symptoms are nasal
had undergone an extensive combined maxillofacial and neu- obstruction in 90% of the patients and spontaneous epistaxis
rosurgical approach, including a modified preauricular sub- (atraumatic recurrent epistaxis) in 60% of the patients. When

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locoregional extension to the cranial base is observed, patients treatment. Clinical examination is followed by an endonasal
may display facial deformation, proptosis, and cranial nerve fiberoptic endoscopy. Taken together, CT scans with bone win-
deficits. Jafek et al. (18) reported proptosis in 20% and cranial dow and MRI scans evaluate the infratemporal, paranasal,
neuropathy in 33% of 15 patients with JNAs involving the mid- intraorbital, and intracranial extensions of the disease. A bilat-
dle cranial fossa. eral carotid digital substraction angiography with selective
catheterization of the external and internal carotid arteries is
Natural History and Tumor Extension required to describe the tumor blood supply. Preoperative
JNAs are thought to arise at the site of the junction of the embolization of the external carotid artery is the first step of the
membranous viscerocranium (palatine, vomer, pterygoid) and treatment. The occlusion of the tumor’s feeders provokes the
the cartilaginous neurocranium (sphenoid). Anatomically, the progressive development of thrombosis in the small distal ves-
site of development is the posterolateral wall of the nasal cav- sels of the tumor, allowing for tumor shrinkage and an easier
ity, close to the sphenopalatine foramen. JNAs tend to extend en bloc removal. McCombe et al. (22) stated that the quality of
along natural foramina and fissures, spreading toward the preoperative embolization was essential to prevent recurrence.
paranasal sinus (ethmoid, sphenoid, maxillary) and through In the present series, embolization did not involve the feeders
the pterygopalatine fossa laterally. This growth in soft tissue coming from the internal carotid artery because of high risk of
spaces is relatively unrestricted, limited only by bone that is stroke. This explained the remnant tumor vascularity and
usually not invaded but rather eroded by pressure. This phe- residual bleeding during the surgical step. Cranial nerve
nomenon is well illustrated by CT images of “maxillary antrum palsies, cutaneous and subcutaneous necrosis, and local pain
bowing,” usually observed in cases involving the pterygomax- lasting a few days are sometimes reported after embolization
illary fissure. If there is further progression, regional involve- (29). In a study by Zhang et al. (29) no permanent sequela was
ment laterally joins the infratemporal fossa, backward toward noted after 20 embolized JNA cases, but one patient experi-
the parapharyngeal space. Upward, the extension to the orbit is enced a partial visual loss that was recovered within 7 days. In
done through the inferior orbital fissure, but the orbital fascia the early stage of our experience, one of our patients experi-
is not involved in most cases. enced a hemiparesis as the result of agent migration in the
Intracranial extension was reported in 10 to 20% of all cases internal carotid artery.
before the era of modern neuroimaging. With the use of high- The essential step of the management is surgical removal. It
resolution CT and MRI scans, this incidence increases to 36%. has clearly been shown that the extent of initial surgery is cru-
Several routes of intracranial involvement are described. The cial to prevent recurrence (21). However, this surgery is chal-
tumor may involve the parasellar compartment through the lenging because of the depth to reach, the pattern of vascular-
superior orbital fissure. In many cases, the orbital involvement ity, and the multiplicity of extensions to the skull base and
lies outside the rectus muscle cone and may extend to the mid- intracranial structures. Because almost all tumors remain
dle fossa without involving the dura. As outlined in previous extradural, single-stage maxillofacial extracranial approaches
studies (17, 21), deep extension into the cancellous bone at the have been proposed for even very large tumors (20). However,
base of the pterygoid process is often associated with expan- the depth of the operative field, difficulties controlling the
sion and invasion of the greater sphenoid wing leading to a bleeding from the cavernous space, and potential disturbance
direct invasion of the middle fossa. Several natural channels, of bony facial development are well-known limitations of this
namely, the vidian canal, foramen rotundum, and foramen strategy. In our personal experience, these approaches provided
ovale, perforate the middle fossa and represent the natural a satisfactory rate of radical resection with acceptable compli-
pathway of intracranial invasion. It is of note that intradural cations in selected cases.
invasion is rare and brain invasion has never been observed. In Wide cranial base and intracranial extension of JNAs may
a review of 84 cases of intracranial JNA by Jones et al. (20), only require extensive cranial base procedures. The infratemporal
one case of dural penetration was reported. In our own expe- approaches pioneered by Andrews et al. (1), Fisch (13), Fisch
rience, we observed a unique case of intradural extension and Mattox (14), and Zhang et al. (29) offer a direct and wide
among 15 cases of invasive JNAs, and histological examination exposure of the infratemporal fossa and parapharyngeal space
did not show differences in the subgroup of focal JNAs com- together with the middle fossa and cavernous sinus with a
pared with the subgroup of invasive JNAs (data not shown). shortened working distance. Such procedures resulted in an
80% rate of radical cure and a 6% incidence of recurrence.
Primary Treatment of Invasive JNAs However, resection of the glenoid fossa is responsible for mal-
The rate of radical cure of focal JNAs is approximately 100%. occlusion and long-term mandibular dysfunction. The division
This result can be achieved with reduced morbidity and using of the mandibularly and possibly of the maxillary branch of the
ear, nose, and throat approaches, such as lateral rhinotomy, the trigeminal nerve entails facial anesthesia and sometimes
transpalatal approach, or more recently, endoscopic excision. dolorosa anesthesia. Slight temporal depression and conductive
The purpose of this article is to show how a multimodality hearing loss are also two notable permanent symptoms in a
management is able to achieve satisfactory results in invasive Type C approach. The same principle, efficacy, and drawbacks
JNAs. This study outlines the importance of a thorough preop- may be attributed to the preauricular sub- and infratemporal
erative workup of the disease to plan the different steps of the approach described by Sekhar et al. (26). An alternative to these

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INVASIVE JUVENILE NASOPHARYNGEAL ANGIOFIBROMAS

invasive procedures is to perform a fronto-orbitozygomatic for intracavernous residual tumors and choose an adjunctive
craniotomy with an epidural temporopolar approach, as illus- radiation therapy technique. Efficacy of radiation therapy in
trated in one of our cases. This allows the control of large JNAs was initially documented in studies in which it had been
intracranial and cranial base involvement but offers a restricted used in first intention (2, 6, 10). On average, an 80% long-term
approach to the intrapetrous and parapharyngeal space. Di tumor control rate was obtained using doses between 30 and 35
Rienzo et al. (8) recently proposed a modification of this latter Gy. However, in the series of 55 cases reported by Cummings
approach. In their experience, the so-called open-mouth fronto- et al. (6), one patient developed a thyroid carcinoma and one
orbitozygomatic approach allowed the joining of the sphenoid patient developed a facial basal cell carcinoma. More recently,
sinus, pterygoid plate, and pterygopalatine fossa using a more Reddy et al. (25) reported three cases of cataracts and one case
downward retraction of the coronoid process. They published of basal cell carcinoma of the skin in a series of 15 patients.
three cases of high-grade JNAs that were totally removed using Because of these potential complications and the risk of radia-
this technique. tion-induced neuropathy, hypophyseal insufficiency, or inter-
As shown by our experience and depending on the tumor ference with development on facial skeleton, radiation therapy
extension, it may be necessary to associate both maxillofacial should be reserved for unresectable remnant disease in this
and cranial base neurosurgical approaches simultaneously or in age group. In our population, adjunctive radiation therapy was
a two-stage strategy. These combined procedures offer multiple motivated by the extent of the residual tumor despite an opti-
operative corridors, better vascular control, and a better chance mal attempt of resection and considering the growing potential
to achieve radical resection. However, such procedures add to of these lesions. This treatment was given at the initial step of
the risk and morbidity of both approaches. our practice and, although we did not have to experience any
radio-induced complication, the use of stereotactic radio-
Management of Residual Tumor after Surgery surgery was later preferred in our group. Well-vascularized
After the initial surgery, a thorough clinical and radiological and delineated residual tumors seem to be a suitable target for
workup should be conducted because incomplete cure can lead the gamma knife, particularly in cases of an intracavernous
to potential regrowth of the remnant tumor. In published location (Fig. 4). Recently, Dare et al. (7) reported their experi-
works, the treatment of residual tumor is debated, most likely ence of two patients treated with GKR using 20 Gy at the tumor
because the biological behavior of such remnants is difficult to margin in both cases. Both tumors were small residual cranial
predict. In their series, Herman et al. (16) observed residual base JNAs treated in the months after surgery. The follow-up
tumors in nine out of 44 patients, and a prolonged follow-up periods were 2 and 3 years after GKR, respectively, and the
period showed a stable or decreasing mass in all of these. In the tumor size remained unchanged. In our experience with infe-
same manner, English et al. (11) described four cases of incom- rior doses, we can obtain long-term control of the treated target
plete extracranial resection with angiographically proven with no complications.
regression of residual tumor. Dohar and Duvall (9) also
reported the same experience. Zhang et al. (29) deliberately left Management of Recurrent Tumor after Surgery
intracavernous remnant tumors in four out of 20 patients Continuous follow-up after radical removal is justified by
undergoing operation and did not observe any tumor growth potential recurrence. The actual recurrence rate is difficult to
on serial imaging during a 46- to 53-month follow-up period. assess, even in the era of modern neuroimaging. This rate
This favorable behavior is not always observed, particularly in may range between 6 and 39% of all cases (12, 16, 21, 24, 29).
young patients. We personally consider that, in the case of The interval between radical removal and recurrence is usu-
symptomatic tumors occurring in young adolescents, the JNA ally short, with only one case reported at 4 years in the liter-
is in an active state of growth and, thereby, justifies active treat- ature (29). Herman et al. (16) observed that no recurrence was
ment of the residual fragment. Therefore, we systematically recorded after 24 months. In the 72 patients managed by
undertook adjunctive treatment. For extracavernous tumors Lloyd et al. (21), 46.5% of recurrences presented within 1 year
able to be extirpated, we preferred additional surgery. The and some within 6 months. In our own series, we clearly dis-
problem is more debatable for intracavernous remnant tumors tinguished the situation of regrowth after subtotal resection
because they are usually poorly symptomatic and difficult to from true recurrences after GTR, which may explain why our
remove safely. Close et al. (5) reported six cases of JNAs pre- findings of later recurrence (2 and 4 yr after surgery) do not
senting with cavernous sinus involvement for which the match previous reports. Several studies have shown that the
patients underwent radical surgery. Total removal was incidence of recurrence correlates to the degree of cranial base
obtained in all patients using various approaches. However, extension and the quality of initial resection (16, 17, 21).
the authors reported a postoperative permanent trigeminal Special interest has been brought to the involvement of the
hypesthesia in three patients and oculomotor palsy in one. This basisphenoid. Howard et al. (17) compared the recurrence
experience was not reported elsewhere in the literature and rate in two consecutively operated cohorts of 20 patients each.
was conducted before the advent of magnetic resonance neu- In the most recent group, additional surgical exploration of
roimaging, giving an imprecise view on the actual intracav- the basisphenoid was conducted with exposition of the ante-
ernous location of the tumor. As advocated by Fisch (13) and rior part of the pterygoid canal and drilling of the basisphe-
Jafek et al. (18), it may be safer to adopt nonsurgical treatment noid. In this latter group, no recurrence was observed,

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ROCHE ET AL.

whereas it reached a 40% rate in the former group. In another 2. Briant TD, Fitzpatrick PJ, Book H: The radiological treatment of juvenile
study, Lloyd et al. (21) indicated a 93% rate of recurrence in nasopharyngeal angiofibromas. Ann Otol Rhinol Laryngol 79:1108–1113,
1970.
the group of patients displaying invasion at the base of the
3. Chandler JR, Goulding R, Moskowitz L, Quencer RM: Nasopharyngeal
pterygoid process compared with only 7% in the group in angiofibroma: Staging and management. Ann Otol Rhinol Laryngol
whom the sphenoid was not invaded. In our policy, we sys- 93:322–329, 1984.
tematically treated the four cases of recurrence using a new 4. Chaveau C: History of the diseases from the pharynx [in French]. Paris, Ballière,
surgical procedure with long-term cure. 1906, p 562.
5. Close LG, Schaefer SD, Mickey BE, Manning SC: Surgical management of
Tumor Classifications and Current Management nasopharyngeal angiofibroma involving the cavernous sinus. Arch Otolaryn-
gol Head Neck Surg 115:1091–1095, 1989.
Several classifications of JNA extension (3, 4, 13, 27) have 6. Cummings BJ, Blend R, Keane T, Fitzpatrick P, Beale F, Clark R, Garrett P,
been proposed, all of which were described before the advent of Harwood A, Payne D, Rider W: Primary radiation therapy for juvenile
modern imaging and were not based on the regular pattern of nasopharyngeal angiofibroma. Laryngoscope 94:1599–1605, 1984.
7. Dare AO, Gibbons KJ, Proulx GM, Fenstermaker RA: Resection followed by
tumor spread. Moreover, some degrees of overlapping between radiosurgery for advanced juvenile nasopharyngeal angiofibroma: Report of
the different stages were observed. In the Fisch grading sys- two cases. Neurosurgery, 52:1207–1211, 2003.
tem, Stage IV tumors are defined by an intracranial intradural 8. Di Rienzo A, Ricci A, Scogna A, Zotta D, Stati G, Galzio R, Tschabitscher M:
extension. Cavernous sinus, pituitary fossa, or optic chiasm The open-mouth fronto-orbitotemporozygomatic approach for extensive
involvement is included in the “IV b” tumors because we con- benign tumors with coexisting splanchnocranial and neurocranial involve-
ment. Neurosurgery 54:1170–1180, 2004.
sider that cavernous sinus is not intradural and that this fre- 9. Dohar JE, Duvall AJ 3rd: Spontaneous regression of juvenile nasopharyngeal
quent involvement cannot be compared with the rare optic angiofibroma. Ann Otol Rhinol Laryngol 101:469–471, 1992.
pathway involvement. 10. Economou TS, Abemayor E, Ward PH: Juvenile nasopharyngeal angiofi-
For each individual case, we suggest describing the exact broma: An update of the UCLA experience, 1960–1985. Laryngoscope
pattern of the tumor extensions and then adopting a tailored 98:170–175, 1988.
11. English GM, Hemenway WG, Cundy RL: Surgical treatment of invasive
surgery following simple rules. Focal JNAs may be approached angiofibroma. Arch Otolaryngol 96:312–318, 1972.
using noninvasive maxillofacial routes. JNAs that display a 12. Fagan JJ, Snyderman CH, Carrau RL, Janecka IP: Nasopharyngeal angiofibro-
discrete involvement to the cranial base (pterygopalatine fossa, mas: Selecting a surgical approach. Head Neck 19:391–399, 1997.
pterygoid plate, inferior compartment of the orbit) may be still 13. Fisch U: The infratemporal fossa approach for nasopharyngeal tumors.
operated on by regular maxillofacial approaches. Tumors Laryngoscope 93:36–44, 1983.
14. Fisch U, Mattox D: Microsurgery of the Skull Base. New York, Thieme Medical
spreading extensively to the cranial base or reaching the Publishers, 1988, p 350.
intracranial extracavernous regions are good candidates for 15. Hakuba A, Liu S, Nishimura S: The orbitozygomatic infratemporal approach:
neurosurgical cranial base techniques or for combined A new surgical approach. Surg Neurol 26:271–276, 1986.
approaches. Large JNAs that display intracavernous involve- 16. Herman P, Lot G, Chapot R, Salvan D, Huy PT: Long-term follow-up of juve-
ment require extracavernous surgery and adjunctive radiation nile nasopharyngeal angiofibromas: Analysis of recurrences. Laryngoscope
109:140–147, 1999.
technique for the intracavernous remnant tumor. 17. Howard DJ, Lloyd G, Lund V: Recurrence and its avoidance in juvenile
angiofibroma. Laryngoscope 111:1509–1511, 2001.
18. Jafek BW, Krekorian EA, Kirsch WM, Wood RP: Juvenile nasopharyngeal
CONCLUSIONS angiofibroma: Management of intracranial extension. Head Neck Surg
2:119–128, 1979.
Invasive JNAs remain challenging because of the difficulties 19. Janecka IP: Classification of facial translocation approach to the skull base.
eradicating the multiple extensions of the tumors to the cranial Otolaryngol Head Neck Surg 112:579–585, 1995.
base and intracranial structures. A thorough preoperative radi- 20. Jones GC, DeSanto LW, Bremer JW, Neel HB 3rd: Juvenile angiofibromas.
ological workup of these extensions is required to plan an indi- Behavior and treatment of extensive and residual tumors. Arch Otolaryngol
Head Neck Surg 112:1191–1193, 1986.
vidual tailored treatment. The satisfactory clinical results
21. Lloyd G, Howard D, Phelps P, Cheesman A: Juvenile angiofibroma: The les-
obtained from the present series strongly support the concept sons of 20 years of modern imaging. J Laryngol Otol 113:127–134, 1999.
of a multimodality management when preoperative emboliza- 22. McCombe A, Lund VJ, Howard DJ: Recurrence in juvenile angiofibroma.
tion is required and collaborative maxillofacial and neurosurgi- Rhinology 28:97–102, 1990.
cal management offer the best chances for optimal resection. In 23. Pryor SG, Moore EJ, Kasperbauer JL: Endoscopic versus traditional approaches
for excision of juvenile nasopharyngeal angiofibroma. Laryngoscope
the case of remnant or recurrent tumors, a second surgery is
115:1201–1207, 2005.
considered as the best option if the tumor can be reasonably 24. Radkowski D, McGill T, Healy GB, Ohlms L, Jones DT: Angiofibroma.
extirpated. Involvement of the cavernous sinus does not Changes in staging and treatment. Arch Otolaryngol Head Neck Surg
require aggressive surgery and can be advantageously treated 122:122–129, 1996.
with a radiosurgical procedure. 25. Reddy KA, Mendenhall WM, Amdur RJ, Stringer SP, Cassisi NJ: Long-term
results of radiation therapy for juvenile nasopharyngeal angiofibroma. Am J
Otolaryngol 22:172–175, 2001.
REFERENCES 26. Sekhar LN, Schramm VL Jr, Jones NF: Subtemporal-preauricular infratempo-
ral fossa approach to large lateral and posterior cranial base neoplasms.
1. Andrews JC, Fisch U, Valavanis A, Aeppli U, Makek M: The surgical manage- J Neurosurg 67:488–499, 1987.
ment of extensive nasopharyngeal angiofibromas with the infratemporal 27. Sessions RB, Bryan RN, Naclerio RM, Alford BR: Radiographic staging of
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INVASIVE JUVENILE NASOPHARYNGEAL ANGIOFIBROMAS

28. Standefer J, Holt GR, Brown WE Jr, Gates GA: Combined intracranial and
extracranial excision of nasopharyngeal angiofibroma. Laryngoscope
93:772–779, 1983.
I n this very elegant series, the authors have described the multimodal-
ity treatment of extensive juvenile nasopharyngeal angiofibromas
(JNAs). I agree with the authors that extensive intracranial extensions
29. Zhang M, Garvis W, Linder T, Fisch U: Update on the infratemporal fossa can be removed by an infratemporal approach, without the manipula-
approaches to nasopharyngeal angiofibroma. Laryngoscope 108:1717–1723,
tion of the temporomandibular joint. Preoperative embolization is very
1998.
important in this group of patients because it can convert a very vas-
cular tumor to one that is not very vascular. In addition to embolization
through the external carotid artery branches, we have sometimes used
COMMENTS direct puncture of the tumor and embolization through this route.
When the cavernous sinus is involved by this tumor, this piece is very
I n our experience with these large extensive lesions, we too have
found that routine preoperative embolization helps with resection
(1, 5). However, our approach is slightly different from that of the
easily removed from the neurovascular structures. I would, therefore,
encourage the authors to pursue the remnants inside the cavernous
authors. We prefer anterior craniofacial resection via a modified trans- sinus more aggressively. Cosmetic considerations are very important
basal approach as a craniotomy-only type of craniofacial resection. for these patients because many of them are in the developmental stage
During surgery, if a radical resection is considered infeasible, a sub- when these tumors are removed. Some of the patients may require sec-
labial transfacial approach, consisting mostly of a medial maxillectomy ondary reconstruction. Extensive tumor devascularization before sur-
or a LeFort I osteotomy, is added (2, 4). We rarely use lateral cranial gery may allow a less invasive approach and a better cosmetic outcome
base approaches for these extensive tumors. We fully agree with the in the long term. The authors are commended for bringing this exten-
authors and do not resect tumoral components that invade the cav- sive and carefully studied series to the neurosurgical literature.
ernous sinus. They are either radiated postoperatively or later if the Laligam N. Sekhar
tumor progresses. Seattle, Washington
Using our approach, we have not encountered any significant cos-
metic deformities because facial incisions are avoided (2). Facial numb-
ness is also avoided during a lateral approach. Furthermore, anosmia
is effectively avoided by the addition of a cribriform plate osteotomy.
T his report by Roche et al. highlights the issues surrounding the
management of extensive JNAs. These tumors typically occur in
adolescent males and usually present with nasal obstruction, epistaxis,
Because these patients' tumors are benign, they are perfect candidates and Eustachian tube dysfunction. Delay in presentation is common
for an olfactory-preserving procedure (3). Using anterior craniofacial given the tendency to associate the indolent symptoms of JNA with
resection for these extensive tumors, our rate of recurrence or incom- common sinonasal inflammatory disease. Thus, many tumors are
plete resection is no higher than commonly reported in contemporary advanced at diagnosis, with intracranial and infratemporal fossa exten-
series. sion being common. Endovascular embolization of the tumor typically
We believe that a craniofacial approach is key. As the authors point precedes the judicial application and often a combination of varied
out, a significant number of these tumors receive their blood supply approaches to the sinonasal cavities, pterygopalatine and pterygomax-
directly from the cavernous portion of the internal carotid artery. These illary fissures, infratemporal fossa, and cranial base, including the cav-
feeders are best managed via an anterior transbasal procedure rather ernous sinus and parasellar region. This allows for the safe and com-
than via a transfacial approach. Potentially with the latter, a small plete removal of the vast majority of extensive tumors such as those
amount of residual tumor could be left. described by the authors. Combining anterior approaches with the
Iman Feiz-Erfan epidural temporopolar or modified subtemporal-infratemporal
Robert F. Spetzler approaches, as described by the authors, is optimal and can access
Phoenix, Arizona common sites of residual tumor. There is absolutely no need to induce
a conductive hearing loss by using any of the postauricular approaches
that have been described for the resection of these tumors. I completely
1. Deshmukh VR, Fiorella DJ, McDougall CG, Spetzler RF, Albuquerque FC: agree with the authors that patients with unexpected residual or recur-
Preoperative embolization of central nervous system tumors. Neurosurg Clin rence that is deemed resectable should be offered further surgery to
N Am 16:411–432, 2005. achieve complete tumor removal for these histologically benign
2. Feiz-Erfan I, Han PP, Spetzler RF, Porter RW, Klopfenstein JD, Ferreira MA, tumors. In my opinion, the uniform application of postoperative irra-
Beals SP, Joganic EF: Exposure of midline cranial base without a facial incision diation in the setting of “unresectable” residual tumor in this group of
through a combined craniofacial-transfacial procedure. Neurosurgery 56 young individuals is unwarranted given the uncertain biological nature
[Suppl 1]:28–35, 2005. of the tumor. Many residual tumors remain indolent and some, in fact,
3. Feiz-Erfan I, Han PP, Spetzler RF, Horn EM, Klopfenstein JD, Kim LJ, Porter
have been shown to spontaneously regress. The use of radiosurgery,
RW, Beals SP, Lettieri SC, Joganic EF: Preserving olfactory function in anterior
fractionated stereotactic radiotherapy, or intensity-modulated radia-
craniofacial surgery through cribriform plate osteotomy applied in selected
patients. Neurosurgery 57 [Suppl 1]:86–93, 2005. tion therapy should be reserved for instances of proven tumor growth
4. Feiz-Erfan I, Han PP, Spetzler RF, Horn EM, Klopfenstein JD, Porter RW, given our ability to carefully monitor these individuals with magnetic
Ferreira MA, Beals SP, Lettieri SC, Joganic EF: The radical transbasal approach resonance imaging scans, the uncertainty of tumor biology, and the
for resection of anterior and midline skull base lesions. J Neurosurg young age of these patients. Both hormonal and chemotherapeutic
103:485–490, 2005. treatments have been reported for JNAs, but their success remains
5. Kim LJ, Albuquerque FC, Aziz-Sultan A, Spetzler RF, McDougall CG: Low anecdotal.
morbidity associated with use of n-butyl cyanoacrylate liquid adhesive for pre-
operative transarterial embolization of central nervous system tumors. Franco DeMonte
Neurosurgery 59:98–104, 2006. Houston, Texas

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