Treatment of large juvenile nasopharyngeal angiofibroma DANIEL G. DESCHLER, MD, MICHAEL J. KAPLAN, MD, and ROGER BOLES, MD,S a n Francisco, California

The management of large juvenile nasopharyngeal angiofibromas with intracranial extension is controversial. We review our experience since 1980 with eighteen patients with juvenile nasopharyngeal angiofibroma. A diagnostic and treatment approach consisting of preoperative magnetic resonance imaging, embolization of feeding branches from the external carotid artery, and attempted complete resection was used in seven patients with intracranialdisease since 1987. Serial magnetic resonance images were used for followup. lntracranial disease that was persistent or recurrent and demonstrated subsequent growth was irradiated(35 to 45 cGy).Extracranial tumor recurrences were reexcised. We advocate this approach as a safe and effective alternative to primary irradiation and its sequelae. (OTOLARYNGOLHEAD NECKSURG 1992: 106:278.)

T h e management of juvenile nasopharyngeal angiofibroma (JNA) has evolved as a result of more refined diagnostic techniques, improved embolization, and increased familiarity with skull base surgical approaches. Controversy persists regarding the proper roles of surgery and irradiation, especially in larger tumors or those with intracranial extension. Unilateral nasal obstruction or bleeding in an adolescent male should raise the suspicion of a juvenile nasopharyngeal angiofibroma. Magnetic resonance imaging (MRI) is today the initial diagnostic method of choice, as the Aow voids as a result of the marked hypervascularity and the marked gadolinium enhancement of a mass that extends from the base of the sphenoid sinus are characteristic of little besides JNA. If surgery is to be performed, carotid angiography should be used both to confirm the diagnosis and embolize feeding vessels from branches of the external carotid artery. Because of the potential long-term risks of irradiation of an adolescent, most otolaryngologists agree that surgery is to be preferred for small JNAs with no intra-

From the Department of Otolaryngology-Head and Neck Surgery, University of California at San Francisco. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery. Kansas City, Mo., Sept. 2226, 1991. Received for publication Sept. 24, 1991; accepted Dec. 5 , 1991. Reprint requests: Michael J . Kaplan, MD, Department of Otolaryngology -Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143. 2311135332

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cranial involvement. Most otolaryngologists use either a transsphenoethmoid approach (TSE) or a transpalatal approach. Because of the risks of surgery at the cranial base and the fear of massive blood loss, some authors prefer radiation as the primary modality for larger tumors.5-’ We review our evolving experience and rationale for initial complete surgical resection (when possible) of JNAs at a medical center with both excellent neuroradiologic interventional capabilities and experienced skull base surgeons. Radiation is reserved for intracranial recurrent or residual tumors that are unresectable and that show evidence of subsequent growth. METHODS AND MATERIAL

Between January I980 and September 1991, eighteen cases of juvenile nasopharyngeal angiofi broma were treated at the University of California at San Francisco (UCSF). Twenty-one procedures were performed. The charts, radiographs, and histology of these patients were reviewed with attention to age and symptoms at presentation, use of preoperative embolization, extent of tumor radiographically and intraoperatively, procedures performed with estimated blood loss and complications, residual and recurrent tumor, the use of radiation therapy, and other pertinent facts concerning specific cases. Patient followup included postoperative visits, correspondence with the refemng physicians, and postoperative MRIs in cases of intracranial involvement or residual disease. Case numbers were assigned in chronologic order of diagnosis and the series was then divided by the presence or absence of intracranial involvement (Table 1).

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Table 1. Patient roster ~~~

Patient no./oge

Date

Procedure

Extracranial 8-80 TSE 1/45

~~

EBLlTransfusion (no. of units)

1-81 Caldwell-Luc

2000 14

3116

3-81 Transpalatal

110012

4116 5/16

10-84 Transpalatal 11-84 Transpalatal 6-85 9-85 7-89 4-86 12-89 10-90 7-91

TSE Transpalatal Transpalatal TSE Transpalatal TSE Transpalatal

lntracranial 9/16 5-87 TSEIMM

10116

6-87 TSEIMM

11/16

12-87 TSE/MM

14/16 -/same

6-90 TSE/MM/lateral maxillotomy 8-90 MM

~

Second Complications Residual/recurrence ProcedurelRT

1 unit bleed postoperative day 5

700lNone 250013

Only case w l o embolrzation

750iNone lOOlNone 25/None 7001None 95012 7001None 5001None

Recur 7-89

See next line

150012

Recurrence 1-88: Cavernous sinus, ITF Temporal bone,

RT 3500 cGy

80012

Recurrence 9-87: Cavernous sinus, Temporal fossa

RT 4500 cGy

8-90: Immediate, extracranial only

120011

3000 14

16/16

12-90 CF 1, TSEiMM

230012

-117 17/11

9-91 TSE 4-91 CF 2, TSEIMM

See next line RT 3600 cGy

8751None

10-90 TSE/MM

7-89 Temporal encephalocele 18 mo S I P RT; repaired w l o further sequelae

Initial question of recurrence, but no change on later MRls

400/None

15/14

Comments

Diagnosis possibly incorrect Prolonged epistaxis history

15001None

2/29

6119 718 -112 8116 12/13 13112 18116

~

Transient Ill nerve

95OlNone 750/None

Residual at MCF Recurrence 9-91: 2 cmz sphenoid sinus

2 cm2 Cavernous sinus

See next line

Question of angiosarcoma No growth on MRls No intracranial or cavernous sinus recurrence; and easily re-resectable Stable, hence no RT

EBL, Estimated blood loss, RT, radiation therapy. TSE. transsphenoethrnoid, MM, Medial rnaxillectomy, ITF, lnfratemporaf fossa, MCF, Medial middle cranial fossa, CF 7 , orbitozygomatic frontal osteoromy. bicoronal ternporofronlal craniotomy, CF 2, Bicoronal frontal craniotomy

RESULTS

The most common presentations were nasal obstruction and epistaxis (72% each). Other symptoms included facial numbness, rhinorrhea, ear-popping, sinusitis, and headache. All patients treated were male, and average age at presentation (excluding the 45-year-

old patient) was 15 years, with a range from 8 to 29 years. Computed imaging was used for radiographic assessment in all cases. Since 1987, MRI has replaced CT with contrast. The advantages of MRI include multiplanar imaging, improved definition at the cribriform

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280 DESCHLER et al.

plate and cavernous sinus, improved differentiation of tumor from inflamed mucosa and fluid in the paranasal sinuses, and avoidance of diagnostic radiation in young patients who require serial follow-up studies. Preoperative embolization was used before 20 of the 21 surgical procedures. Polyvinyl alcohol particles of appropriate size were used to embolize major feeding vessels from the external carotid arteries. Balloon occlusion and assessment of collateral cerebral flow was performed in two cases in which the internal carotid artery was involved by tumor or provided significant tumor blood supply. There were no complications of embolization. Definitive surgical treatment was planned in all cases. All but two tumors (cases 15 and 17) were believed to be grossly excised completely at the time of surgery. Extracranial lesions were excised by means of transpalatal, transantral or external transsphenoidectomy (TSE) approaches, extended as necessary to include medial maxillectomy (MM). Cases with intracranial involvement were approached by means of TSE, with or without MM (supplemented with transantral lateral maxillectomy in one case), from below and, when necessary, combined craniofacial resection from above. Two cases required combined neurosurgic-otolaryngologic approaches. Case 16 underwent a bicoronal frontal craniotomy with cerebrospinal fluid leak (CSF) repair by means of dural closure and a pericranial flap. An orbitofrontozygomatic approach was used in case 17 to expose an especially large tumor with cavernous sinus and possible internal carotid artery involvement; the CSF leak was similarly repaired. There were no cases of postoperative CSF leaks or meningitis. Two postoperative complications occurred in the series. A nasopharyngeal bleed that required a one-unit transfusion after the removal of packing occurred in case 3. The patient was repacked and had no further bleeding. A transient oculomotor nerve palsy in case 15 was the only complication in the cases with intracranial tumor. There were no deaths in the series. A temporal encephalocele was discovered 2 years postoperatively and 1 year after radiation therapy for recurrent tumor in case 9. After presenting at that time with a CSF leak, the patient underwent succesful repair by the neurosurgery service by means of a temporal craniotomy. No residual tumor was identified and the patient has had no further CSF leak. The average estimated blood loss (EBL) for the twenty-one procedures was 1100 ml; ten were transfused. The average transfusion was 2.4 units. Larger tumors or those with intracranial extension had, as expected, both a greater average EBL (1300 ml; range:

400 to 3000 ml) and transfusion rate (66%). The cases without intracranial extension had an average EBL of 960 ml (range: 25 to 2500 ml) with a transfusion rate of 33%. Seven patients had residual or recurrent disease. All recurrences, except one, occurred in cases with initial intracranial extension. Two patients (cases 7 and 16) presented with epistaxis at 48 and 9 months, respectively, after initial surgery. Each had extracranial recurrence only, and underwent repeat complete excision from below through the initial approach. Two patients with intracranial tumor (cases 15 and 17) had subtotal resections. Each had extensive cavernous sinus involvement and, intraoperatively, complete resection was considered unwise. Both patients currently have stable disease and are being followed by serial MRI; radiation therapy will be given if there is future evidence of tumor growth. Three patients (cases 9, 10, and 14) have undergone irradiation for MRI-determined recurrent intracranial disease, receiving 3500,4500, and 3600 cGy, respectively, of external beam megavoltage radiation therapy. All are presently without evidence of active disease. (Case 14 was of particular interest because the recurrence was so large and rapid in growth, that an angiosarcoma, though extremely rare, was suspected. Repeat resection again appeared complete, but immediate radiation therapy was considered prudent.) All cases with recurrent disease are being followed closely with serial MRI. Similarly, the cases of intracranial JNA without recurrence are screened with serial MRI. DISCUSSION

The epidemiology and presentation of the patients in our series is consistent with previously reported series.'".'' Although two patients, diagnosed 10 years ago, were beyond adolescence (which has been noted in other series),'*.13 JNA is predominantly a diagnosis of adolescent males. When similar lesions are noted in older males or in females, an expanded differential diagnosis must be considered. Brooker et aI.l4 reviewed the pathology of seventeen cases of purported JNA in Ireland, finding seven patients (5 female, one 36-yearold male) that required change of diagnosis. l4 Once the diagnosis of JNA is suspected in the adolescent male, we agree with Lloyd and Phelps15 that MRI, with and without gadolinium, is the most valuable and productive diagnostic test. JNA has a characteristic appearance on MRI: flow voids representing the large vessels are seen in this highly vascular tumor. MRI provides excellent soft tissue definition and delineates tumor from inflamed mucosa, mucus, and brain. Mul-

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Large juvenile nosopharyngeal angiofibroma 281

Fig. I.Cme 77. Coronol T,-weighted MRls (A, C , and D with gadolinium).A, Preoperatiie study with tumor extent to floor of middle cranial fossa (MCF) and into ptetygomaxillary space. B, Three months postoperatively with question of scar vs. residualtumor effacing MCF at root of nosopharynx. inferior to cavernous sinus and medial to cavernous sinus in superolaterai sphenoid sinus @rows).C and D, Studies at 21 and 31 months later, respectively, show stable gadolinium enhancement at roof of nosopharynx, consistent with fibrosis. The area of concern in the sphenoid sinus has resolved.

282 DESCHLER et 01.

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Fig. 2. Case 16. Coronal T,-weighted MRls [A, B, and C with gadolinium]. A, Preoperativeextent of large tumor filling nosopharynx to floor of anterior cranial fossa and to temporalis muscle (small arrow). The presence of tumor transgressing dura (/argearrow) necessitated bicoronal frontal craniotomy. B, Five months postoperatively with no residualdisease. C,Ten months postoperativelywith area (arrow) suggestive of recurrence at junction of nosopharynx and sphenoid sinus on right. D, Angiogram of right ECA verifies recurrent tumor to accessible exhacranial site, embolized before resection.

Volume 106 Number 3 March 1992

tiplanar imaging enhances the surgeon’s preoperative three-dimensional assessment of the tumor. As intracranial involvement is the crucial factor on which operative morbidity and success rests, the advantages of MRI at the cavernous sinus and planum sphenoidale are especially important (Figs. 1 and 2 ) . Accumulating experience with paranasal tumors extending superiorly and meningiomas extending inferiorly to involve the skull base has demonstrated that skull base surgery can be performed safely. In our opinion, skull base surgery in adolescents, with its attendant risks, is preferable to radiation therapy and its longterm sequelae. For this reason, after complete discussion of the treatment alternatives, surgery with preoperative embolization is recommended. Although we favor an external transsphenoethmoid approach (with medial maxillectomy, if necessary) because of its excellent exposure, ease of packing, and patient comfort, transpalatal approaches have also been used, especially for small tumors confined to the nasopharynx and nose. Angiography confirms the vascularity of JNA but is rarely necessary diagnostically. The major role of angiography is preoperative embolization. The complete blood supply of the tumor is demarcated and feeding vessels from the external carotid arteries are identified and embolized in one procedure. Angiography may also assist in differentiation of scar from recurrent tumor when suspicious areas are noted on follow-up MRI (Fig. 2 ) . As in other series,‘ all but one patient received preoperative embolization of the major external carotid artery branches supplying the tumor, notably the internal maxillary and ascending pharyngeal arteries. Balloon occlusion studies of the internal carotid and its branches can also be performed with angiography to assess the feasibility of resecting tumors involving these vessels. Average EBL was similar to other series with e m b ~ l i z a t i o n Average .~ blood replacement (2.4 units) was markedly lower than series not using embolization.2 Every effort was made to make autologous transfusions possible. The major controversy in the management of JNA is how best to treat those lesions with intracranial extension. Operative complications, tumor recurrence, and mortality are all closely linked to intracranial extension.16Nee1 et al.” reported five deaths in 120 patients, all of whom had intracranial extensions. Ward et a1.I3 described the death of one patient with intracranial extension in a series of 35 patients. Although not currently considered more aggressive histologically, intracranial angiofibromas have an increased vascularity accordant with their increased tumor size. Blood supply recruited from the intracavernous internal carotid artery cannot be embolized, adding to the difficulty of hemostasis. Because current imaging techniques accurately assess

Large juvenile nosopharyngeal angiofibromo

283

the extent of intracranial tumor, intraoperative surprises and the “tip of the iceberg” effect13 should no longer occur. Cavernous sinus involvement, a common site of intracranial extension, also markedly increases risks of bleeding and neurologic complication. For these reasons many authors believed that JNA with intracranial, and specifically cavernous sinus, involvement should be treated solely with radiation therapy. Complete surgical excision, if necessary via combined neurosurgic-otolaryngologic approaches, is advocated by many as safe and e f f e ~ t i v e . ~ ~ ” . ’K~re.’~~~’ korian and Kempe22described a combined approach in 1969. Jafek et a1.” provided an excellent review of combined approaches in addition to a rare case of dural involvement. They noted a 3 1% recurrence for patients so treated, with no complications attributable to craniotomy per se. Close et a1.I’ reported success with combined neurosurgical-otolaryngologic treatment for JNA with involvement of the cavernous sinus. Fisch” used an infratemporal fossa approach for resection of especially large intracranial JNAs. Some authors believe extended approaches to reach intracranial tumor are unnecessary. Jones et al.,” citing a recurrence rate of only 50% for intracranial JNA treated solely extracranially (compared to the 31% Jafek et al.” reported), maintained that the reduction in recurrence did not warrant inclusion of craniotomy. We favor an approach based on initial attempted total surgical excision. The inferior exposure of choice is usually an external transsphenoethmoidectomy, with or without medial maxillectomy. Neurosurgical access is afforded by means of bicoronal frontal craniotomy; more lateral exposure is possible when necessary. Intraoperative assessment determines the extent of resection; complete excision may not be prudent at the cavernous sinus. Fisch agrees.” We prefer to use serial MRIs to follow patients with either known residual disease or in whom intracranial/skull base recurrence is a significant risk. The initial scan is obtained 2 months postoperatively, by which time perioperative inflammation and edema have largely resolved. This series presents two such cases (cases L 5 and 17) in whom tumor in the cavernous sinus was left. Follow-up MRIs have shown no increased size, and radiation therapy has not, to date, been used. Case 11 was considered on initial follow-up MRI to have an area suspicious for recurrence. The patient was followed closely, and subsequent MRIs showed no progression and were more consistent with postoperative changes and scarring rather than recurrent tumor (Fig. 1). In the case of growing intracranial tumor recurrence, radiation therapy is indicated. The recurrences in cases 9 and 10 involved the cavernous sinus and no reexcision

284 DESCHLER et 01.

was attempted. Neither has shown further tumor growth after radiation therapy. Case 14 had marked and rapid extracranial recurrence demonstrated on the initial postoperative scan. Because this recurrence was large, extracranial, and easily approachable through a small portion of the previous incision, the patient underwent reexcision. Resection was again determined to be complete, but because of the aggressive nature of this particular tumor and the concern for a more malignant histology-such as an extremely rare and difficult to diagnose angiosarcoma-radiation therapy was initiated. A combined neurosurgical-otolaryngologic procedure was necessary in two cases. There were no complications in these cases. Other series report similar results.".*' Note that craniotomy is not required in all cases of intracranial involvement. Extradural intracranial extension without internal carotid artery blood supply or cavernous sinus involvement can be completely removed solely through the inferior approach. If craniotomy may be warranted, we discuss this possibility with the patient and family and are prepared to add it at the initial operation.

SUMMARY Review of the eighteen cases of juvenile nasopharyngeal angiofibroma treated at our institution since 1980 supports the notion that attempted complete surgical excision as the initial treatment of JNA is a safe and appropriate management plan. Magnetic resonance imaging and angiography with embolization are critical to planning and completion of surgery with the greatest three-dimensional knowledge of tumor extent and the least loss of blood. Inferior surgical access, we believe, is best obtained by means of an external transsphenoethmoid approach, extended as necessary. Intracranial involvement may require an appropriate craniotomy. Patients with resected intracranial disease, residual disease, or large tumors are followed closely with examination and serial MRI. A baseline MRI is obtained 2 months postoperatively, and twice yearly scans are obtained through adolescence. Radiation therapy is reserved for intracranial persistent disease that has demonstrated subsequent growth on serial MRI. Recurrences that are extracranial are re-resected. This treatment rationale among 11 patients without intracranial involvement has resulted in one reoperation and no irradiation; among seven patients with initial intracranial tumor, there have been two second surgical procedures and three cases that required radiation therapy. REFERENCES 1. Boles R, Dedo H. Nasopharyngeal angiofibroma. Laryngoscope

1976;86:364-72.

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2. Bremer JW, Nee1 HB 111, DeSanto LW, Jones GC. Angiofibroma: treatment trends in 150 patients during 40 years. Laryngoscope 1986;96:1321-9. 3 , Duvall AJ, Moreano AE. Juvenile nasopharyngeal angiofibroma: HEAD NECK SURC diagnosis and treatment. OTOLARYNGOL 1987;97:534-40. 4. Economou TS, Abemayor E. Ward PH. Juvenile nasopharyngeal angiofibroma: an update of the UCLA experience, 1960-1985. Laryngoscope 1988;98:170-5. 5 . Ward PH. The evolving management of juvenile nasopharyngeal angiofibroma. J Laryngol Otol 1983;s:103-4. 6. Cummings BJ, Blend R, Keane T, et al. Relative risk factors in the treatment of juvenile nasopharyngeal angiofibroma. Head Neck Surg 1980;3:21-6. 7. Cummings BJ, Blend R. Primary radiation therapy for juvenile nasopharyngeal angiofibroma. Laryngoscope 1984;94:15991605. 8. Fields JN, Halverson KJ. Devineni VR, Simpson JR, Perez CA. Juvenile nasopharyngeal angiofibroma: efficacy of radiation therapy. Radiology 1990;176:263-5. 9. Makek MS, Andrews JC, Fisch U. Malignant transformation of a nasopharyngeal angiofibroma. Laryngoscope 1989;99:108892. 10. Maharaj D, Fernandes CMC. Surgical experience with juvenile nasopharyngeal angiofibroma. Ann Otol Rhino1 Laryngol 1989;98:269-72. 11. Roberts JK, Korones GK, Levine HL, Wood BG, Tucker HM, Lavertu P. Results of surgical management of nasopharyngeal angiofibroma. Cleve Clin J Med 1989;56:529-33. 12. Nee1 HB Ill, Whicker JH, Devine KD, Weiland LH. Juvenile angiofibroma: Review of 120 cases. Am J Surg 1973;126:54756. 13. Ward PH, Thompson R. Calcaterra T, Kadin MR. Juvenile angiofibroma: a more rational therapeutic approach based upon clinical and experimental evidence. Laryngoscope 1974; 84:2 18 1-94. 14. Brooker DS, Kenny B, Gibson RG, Primrose WJ. Juvenile nasopharyngeal angiofibroma in a static population: the implications of misdiagnosis. Clin Otolaryngol 1989: 14:497-502. IS. Lloyd GAS, Phelps PD. Juvenile angiofibroma: imaging by magnetic resonance. CT and conventional techniques. Clin Otolaryngol 1986;11:247-59. 16. Krekorian EA, Kato R. Surgical management of nasopharyngeal angiofibroma with intracranial extension. Laryngoscope 1977237:154-64. 17. Jones GC, DeSanto LW, Bremer JW. Nee1 HB 111. Juvenile angiohbroma: Behavior and treatment of extensive and residual tumors. Arch Otolaryngol Head Neck Surg 1986;112:1191-3. 18. Close LG, Schaefer SD, Mickey BE, Manning SC. Surgical management of nasopharyngeal angiofibroma involving the cavernous sinus. Arch Otolaryngol Head Neck Surg 1989;115: 109 1-5. 19. Fisch U. The infratemporal fossa approach for nasopharyngeal tumors. Laryngoscope 1983;93:36-44. 20. Gill G, Rice DH, Ritter FN, Kindt G. Russo HR. Intracranial and extracranial nasopharyngeal angiofibroma. Arch Otolaryngol 1976;l02:37 1-3. 21. Jafek BW, Krekorian EA. Kirsch WM, Wood RP. Juvenile nasopharyngeal angiofibroma: management of intracranial extensions. Head Neck Surg 1979;2:119-28. 22. Krekorian EA, Kempe LG. The combined otolaryngologyneurosurgery approach to extensive benign tumors. Laryngoscope 1969:79:2086-103.