PREOPERATIVE IMAGING TO PREDICT ORBITATINVASION BY TUMOR

Marc D. Eisen, BA,1 David M. Yousem, MD,t' ' Laurie A. Loevner,MD,t' 'Erica R. Thaler, MD,1 Warren B. Bilker, PhD,3 Andrew N. Goldberg, MD1

1 Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania Medical Center,Philadelphia, Pennsylvania2 Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce Street,Philadelphia, Pennsylvania 191043 Department of Biostatistics and Epidemiology, University of Pennsylvania Medical Center,Philadelphia, Pennsylvania

Accepted 4 October 1999

Abstract: Background. Our purpose was to examine the ac-curacy of preoperative imaging in assessing tumor invasion ol theorbit and nasolacrimal system.

Methods. Nineteen preoperative CT and 17 preoperative MRimages from patients at risk for orbital invasion were retrospec-tively reviewed. Invasion was corroborated by pathologic and in-traoperative assessment.

Resu/ts. Tumor adlacent to the periorbita was the most sen-sitive predictor of orbital invasion (90%) for both CT and MRl.Extraocular muscle involvement on MRI (100%) and orbital fatobliteration (80% MRl, 86% CT) had the highest positive predic-tive values ol the criteria evaluated. Extraocular muscle displace-ment and enhancement were less accurate (<65%) predictors.No one criterion was>79o/o accurate in predicting orbital invasion.Six or more positive criteria predicted invasion with 67% sensi-tivity and 80% specificity (accuracy, 72o/"). CT was more accuratethan MRI in seven of nine criteria. Invasion of the nasolacrimalsystem was predicted accurately (89%).

Conclusions. Although preoperative imaging can aid in sur-gical planning, it should not replace intraoperative assessment inambiguous cases of orbital invasion. @ 2000 John Wiley & Sons,lnc. Head Neck 22: 456-462, 2OOO.

Correspondence loj L. A. Loevner, Department of Radiology, University ofPennsylvania Medical Center, 3400 Spruce Street , Phi ladelphia, PA'1 91 04.

@ 2000 John Wi ley & Sons, Inc.

456 lmaging to Assess Orbi ta l Invasion

Keywords: sinonasal; orbital invasion; imaging; tumor; nasolac-rimal fossa

T.r*orr of the paranasal sinuses present late intheir course, often with extensive disease. Exten-sion to the orbit and nasolacrimal system has animpact on patient prognosis and the surgical ap-proach to these tumors. If orbital invasion is sus-pected, the surgeon and the patient are con-fronted with the difficult decision of exenteration.Orbital exenteration can be emotionally trau-matic for patients, yet it may be required for com-plete oncologic resection. The difficult decision re-garding the eye cannot be made on the basis ofophthalmic symptoms alone. In cases in whichthe clinical examination and imaging are unclear,preoperative patient counseling regarding the eyeis complex. A more accurate assessment of tumorinvasion of the orbit and nasolacrimal system pre-operatively would benefit both the surgeon andthe patient. Patients may be better informed withregard to their prognosis because tumors that in-

HEAD & NECK August 2000

vade the orbit carry a worse prognosis than thosethat do not.1 In addition, accurate preoperativeassessment may help the surgeon plan the extentof resection in those cases irt which invasion waspreviously unclear. Most surgeons use the rela-tionship between the tumor and the periorbita todetermine whether exenteration is necessary; tu-mor invasion through the periorbita may warrantexenteration, whereas an intact periorbita typi-cally warrants preservation.2 When tumor abutsthe periorbita, however, assessing periorbital con-tinuity may be diffrcult.

The nasolacrimal system is also susceptible toinvasion by paranasal sinus tumors. Tumor maytrack along the nasolacrimal duct and thereby re-quire more extensive resection than would havebeen anticipated by the bulk disease evident pre-operatively.

The purpose of this study was to determinewhether preoperative imaging could offer an ac-curate assessment of tumor extension to the orbitand nasolacrimal system. Involvement of the or-bital fat manifest as soft tissue stranding in thefat is the current imaging criterion suggestive ofneoplastic invasion. However, the accuracy withwhich imaging predicts invasion into these struc-tures is poorly studied. In this study we evaluatethe accuracy of various imaging criteria in pre-dicting tumor invasion of the orbit and nasolacri-mal system. We also sought to compare the efii-cacy between magnetic resonance imaging (MRI)and CT imaging with regard to assessing orbitalinvasion.

MATERIALS AND METHODSTwerrty-frve patients (19 merr and 6 women) withtumors of the paranasal sinuses, anterior cranialfossa, or skin surrounding the orbit seen over a10-year period (1988-1998) were chosen from therecords of the University of Pennsylvania CancerCenter database. Six patients had tumors origi-nating in the maxillary sinusl six in the ethmoidsinus; six in the nasal cavity; and one each in thesphenoid sinus, cavernous sinus, maxilla, frontalsinus, forehead, eyelid, and anterior cranial fossa.Tumor histologic frndings included 12 carcino-mas; 6 inverted papillomas; 3 melanomas; and 1each fibroma, sarcoma, odontogenic keratocyst,and meningioma. Patients selected from the da-tabase had preoperative imaging, surgery, andpathologic correlation. Preoperative imagingstudies included MRI (n : 6), CT (n : 8), or both(ru : 11). Individual studies were reviewed inde-

lmaging to Assess Orbital Invasion

pendently and randomly, and thus a total of 36(17 MRI, 19 CT) imaging studies were evaluated.

MRI was performed on a 1..5 T system (Signa;General Electric Medical Systems, Milwaukee,WI). The MRI protocol consisted of conventionalspin-echo sagittal Tl-weighted images and axialand coronal T1' and T2-weighted images. Con-trast-enhanced (0.1 mmol/kg of gadopentetatedimeglumine lMagnevist; Schering, Berlin, Ger-manyl) axial Tl-weighted images with frequency-selective fat suppression techniques were also ac-quired. Other imaging parameters includedsection thickness of 5 mm, 2 excitations, and a256 x 192 matrix.

CT scans were performed with 3- to 5-mm sec-tion thickness in axial and coronal planes. Imageswere photographed for soft tissue and bone detail.Three patients received iodinated contrast beforeCT scanning. The other patients'studies were un-enhanced.

Eleven criteia involving the tumor, orbit, andnasolacrimal fossa were used to assess eachstudy: three criteria for the tumor's relationshipto the periorbita (abutting, displacing, or bowingthe periorbita laterally); one for the interface be-tween the tumor and periorbita ("nodular" if themargin had focal irregularity or "smooth" if it didnot); one for orbital fat invasion (soft tissuestranding or infiltration within the extraconal fatcontiguous with the primary tumor); three for theextraocular muscles (displaced, enlarged, or ab-normal signal intensity/density); one for orbitalbone integrity; and one for nasolacrimal systeminvasion (tumor extensiorr into the nasolacrimalsac or duct). For studies in which contrast wasadministered (n : 20; 17 MRI, 3 CT), extraocularmuscle enhancement was also evaluated. Twoneuroradiologists unaware of the surgical find-ings carried out retrospective image analysis in-dependently and blindly. Each reader was re-quired to choose whether each criterion was met.The strength of interobserver consensus for allthe criteria was determined by kappa analysis.s

Table 1. Definitions ol crileria evaluation

Term Definit ion

Sensit ivi tySpecif ici tyPosit ive predict ive valueNegative predict ive valueAccuracy

TP/(TP + FN)TN/(TN + FP)IP/(TP + FP)IN/(TN + FN)T P + T N / ( T P + F N + T N + F P )

Abbreviations: FN, false negative; FP, false positive; TN, true negative: TP,true posrtive.

HEAD & NECK August 2000 457

Table 2. Radiologic-pathologic correlat ion for evaluating tumor invasion of orbit with MRl.

Adlacent toPeriorbita

Periorbitadisplaced

Periorbitabowedlateral ly

Extraconal fatinvolved

EOMdisplaced

N l n n f d i c a n r o o m o n t q

U C T V V U U I I I U d U U I >

True posit ivesTrue negativesFalse posit ivesFalse negativesSensit ivi ty (%)Specif ici ty (o/.)Posit ive predict ive value (9"7Negative predict ive value (%)Accuracy (%)

19251

9029646765

2B342

BO43676065

07343

7043645059

146.1

640B6BO5059

27433

70577057A 1

Differences between the two readers' evaluationswere resolved by consensus.

The operative and/or pathologic reports wereused as the "gold standard" for orbital and naso-lacrimal invasion. Positive invasion was definedas tumor extension through the periorbita andinto orbital fat. If the periorbita remained uncom-promised, the orbit was considered to be free fromneoplastic invasion. Fourteen of the 25 patientshad confirmed orbital invasion. The sensitivity,specifrcity, positive and negative predictive value,and accuracy were used to evaluate each criterion(Table 1).

RESULTS

The two observers agreed on 336 of380 readings(88.4Vo of 11 criteria from 20 contrast-enhancedstudies and 10 criteria from 16 noncontrast-enhanced studies). The strength of the interob-server agreement was excellent (rc : 0.77).4 Thecriterion with the smallest number of disagree-ments was a laterally bowed periorbita (z : 0 of36), and the highest number of disagreementswas the assessment of the tumor interface(smooth vs nodular) with the periorbita (n : Il of36).

A summary of the results for evaluating or-bital invasion is shown in Table 2 for the MRIstudies and Table 3 for the CT studies. Of thecriteria used to assess the orbit for possible tumorinvasion, tumor adjacent to the periorbita was themost sensitive finding for invasion (907o). How-ever, this criterion suffered from low specificity(297o MRI, 44Eo CT). Displaced and laterallybowed periorbita had lower sensitivities butgreater specificity (437o MRI, 677o CT for both cri-teria). The accuracy ofeach ofthese criteria was

458 lmaging to Assess Orbital Invasion

less than 70Vo. Orbital fat invasion was radiologi-cally suspected in only one MRI and one CT scanin which orbital invasion was absent pathologi-cally (false positives), and thus this criterion hadboth a high specifi city (>857o) and positive predic-tive value (80% MRI, 867o CT) (Fig. 1 and 2). Yetorbital fat involvement was a less than 607o sen-sitive imaging criteria for orbital invasion.

Extraocular muscle (EOM) involvementtended to be a specific, yet insensitive, finding. AllMRI images showing enlargement, enhancement,or abnormal EOM signal had pathologically con-firmed orbital invasion (PPV : I00Va) and a bet-ter result than CT, although a considerable num-ber of confirmed cases of invasion had negativecriteria. Figure 3 is an example of proven orbital

FIGURE 1. Axial enhanced CT scan shows a mass (arrows)anterior and lateral to the orbit, displacing the periorbita medially.The orbital fat is normal in appearance (arrowheads), without softt issue stranding. Tumor was found invading through the perior-bita, despite evidence of orbital fat invasion on imaging.

HEAD & NECK August 2000

Tabfe 2. (continued)

n = 1 7EOM

ennanceoEON/

enlargeo

EOIVaonormal

srgnal

Nodular tumorinterface with

orortBony

dehiscence

No. of disagreementsh ^ + , r , ^ ^ ^ - ^ ^ A ^ t ^U E T V V U C I I I U d U U I 5

True posit ivesTrue negativesFalse posit ivesFalse negativesSensit ivi ty (%)Specif ici ty (%)Posit ive predict ive value (%)Negative predict ive value (%)Accuracy (%)

2170B

1 l1 0 01 0 04765

I

1709

1 01001004447

66524

607 1755665

2170I

1 01001004450

27433

7057705765

invasion despite negative imaging criteria forEOM involvement (no muscle enlargement, dis-placement, or signal abnormality). EOM displace-ment had a higher sensitivity (7O%oMRI,607o CT)but had more false positives than the other EOMcriteria. Consequently, these EOM findings wereat best 657o accwrate for predicting orbital inva-sion.

A nodular (Fig. 3) as opposed to a smooth (Fig.4) interface of the tumor with the periorbita was7l7o (MRI) and787o (CT) specifrc for orbital inva-sion, with a positive predictive value of 757o. Fourcases in which a nodular interface was recordedbut no neoplastic extension to the orbit was re-corded at pathologic examination (ie, false posi-tives) were from two patients who each had bothMRI and CT imaging. Although both patientswere free from tumor invasion through the peri-orbita and thus negative for invasion by our im-aging criteria, tumor involved but did not invadethrough the periorbita in one ofthe cases. In thatcase, a portion of the periorbita was removed aspart of the tumor margin, and the eye was pre-served. Invasion in both of these cases was bor-derline and thus may account for the low accuracyof this finding (<707o). The accuracy of bony de-hiscence to predict invasion was similar betweenMRI and CT, which was 657o and 687o, respec-tively.

The association between each criterion andconfirmed invasion was assessed using odds ra-tios,5 and a \Vo level of signifrcance was used inthis study. For each criterion considered individu-ally, no statistically significant association wasfound. Multiple logistic regressionss were frt toassess the possibility that the results of multi-ple tests considered simultaneously predictedorbital invasion. No combination of test results

lmaging to Assess Orbital Invasion

was found to improve the prediction of invasron(p > .B).

A comparison between the results of the MRIand CT findings for orbital invasion demon-strated that CT was more accurate than MRI inseven of nine criteria for orbital invasion. Extra-ocular enhancement was not included in this com-parison because there were too few contrast-enhanced CT studies to make an accuratecomparison between the two modalities for thisfinding.

Nasolacrimal involvement could be confirmedonly in the nine cases that contained pathologicfindings and/or operative report informationabout the nasolacrimal fossa. In one of these stud-ies, nasolacrimal invasion was recorded incor-

FIGURE 2. Maxil lary sinus squamous cel l carcinoma with orbitalinvasion. A coronal CT scan shows imaging l indings consistentwith orbital invasion, which was confirmed pathologically. Thereis destruction of the lamina papyracea, with displacement of theperiorbita laterally. There is soft tissue replacing the extraconalorbital fat with elevation of the inferior rectus muscle complex(arrow).

HEAD & NECK August 2000 459

Table 3. Radiologic-pathologic correlat ion for evaluating tumor invasion of orbit with CT

n = 1 9Adjacent toperiorbita

Periorbitadisplaced

PeriorbltaDOWeOlateral ly

Extraconal fatinvolved

EOMdisplaced

I \ l ^ n f d i c r ^ r a a m a n t a

between readersTrue posit ivesTrue negativesFalse posit ivesFalse negativesSensit ivi ty (%)Specif ici ty (%)Posit ive predict ive value (9",Negative predictive value ("/")Accuracy (%)

09451

904464BO6B

0I631

906775B679

08632

BO67737574

26B14

60B9B66774

36544

6056605642

rectly as positive (i.e., false positive). In eight ofnine of these studies, however, the nasolacrimalfossa involvement was correctly predicted on im-aging, rendering the finding of nasolacrimal fossainvasion more sensitive (100o/o) than specific(757o). The accuracy of this finding was 89Vo.

DrscusstoNThe orbit is a cone-shaped space comprised ofseven bones that include the frontal bone, thegreater and lesser wings of the sphenoid, the zy-

goma, the maxilla, the lacrimal bone, and the eth-moid bone. The condensed periosteum of thesebones makes up the periorbita, which is continu-ous with the dura mater at the optic foramen andsuperior orbital fissure.6 During the first half ofthe twentieth century, radical excision with or-bital exenteration was the standard treatment forcancers of the paranasal sinuses abutting theeye.2 In recent decades, however, the periorbitahas been considered an effective barrier to tumorextension into the orbit.2 Tumors that do not in-

FIGURE 3. Magnif ied, enhanced T1-weighted MR image with appl icat ion of fat suppression shqws anodufar margin of the sinonasal tumor with the periorbita and involved extraconal fat (arrows). Themedial rectus muscle does not appear enlarged; however, it is displaced laterally. Tumor was con-firmed at surgery to invade through the periorbita, but the eye was preserved and a portion of theinvolved periorbita resecteo.

460 lmaging to Assess Orbital Invasion HEAD & NECK August 2000

Tabfe 3. (continued)

n - 1 0

EOMennanceo

EOMenrargeo

EOMaEnormal

s igna l

Nodular tumorinterface with

orbitBony

dehiscence

N l n n f d i c a n r o o m o n i c

A ^ + r ^ , ^ ^ ^ " ^ ^ i ^ " ^U U L V V U V I I I E A U S I J

True positivesTrue negativesFalse positivesFalse negativesSensit ivi ty (%)Specif ici ty (%)Posit ive predlct ive value (%)Negative predict ive value (%)Accuracy (%)

2072

1 00

7B0

A 1

5B

33B17

30B9755325

4

01120

500

335B

'l

B542

BO56677 16B

56724

607875646B

vade through the periorbita can be removed with-out exenteration and have reduced risk of localorbital recurrence.t-e In general, if tumor has notextended through the periorbita, the eye may besurgically preserved.l0 Two studies from thesame institution have retrospectively examinedthe orbital recurrence rate in patients with ma-lignant sinonasal tumors. The eye was preserwedin 27 patients who had malignant sinonasal tu-mors that eroded through orbital bone and dis-placed the globe but did not invade the periorbita.Of these patients, three had local recurrence de-velop. Simple exenteration in these three pa-tients, however, would not have changed their

FIGURE 4. Coronal enhanced T1-weighied MR image of a pa-tient with sinonasal melanoma. Tumor invaded orbital bone butnot the periorbita. The mass (m) results in mild lateral bowing ofthe periorbita but no involvement oi the extraocular muscles ororbital fat. The margin of the mass with the periorbita was inter-preted as smooth.

lmaging to Assess Orbital Invasion

outcome because extensive skull base resectionswould have been required. With these results, theauthors advocate orbital preservation unless theperiorbita is extensively invaded.2'tt The decisionto exenterate also may involve additional factorssuch as the strength ofthe patient's contralateralvision and evidence of distant metastases.

Imaging offers the hope of preoperatively de-termining tumor invasion of the orbit. We havepresented a uniform set of imaging criteria thatwe thought would predict periorbital invasion.These criteria included the relationship betweenthe tumor and the periorbita, an assessment ofthe orbital fat and extraocular muscles. and a de-termination of the bony integrity of the orbit.Nodularity of the tumor margin with the orbitwas another criterion used because focal noduleshave been shown to be associated with tumor in-vasion in other anatomic regions, such as thedura.12 No one criterion had an accuracy of morethan 797o. A nodular tumor-periorbita interfacewas a fairly accurate indicator of orbital invasion.This finding, however, had the greatest number ofdisagreements between the two readers, whichsuggests a high degree of subjectivity. A positiveEOM enhancement, enlargement, and abnormalsignal on MRI predicted orbital invasion in allcases. A number of criteria were particularly sen-sitive predictors of orbital invasion. These in-cluded tumor adjacent to periorbita (907o) anddisplaced periorbita (80% MRI, 907a CT). Specificpredictors included orbital fat involvement, EOMenhancement, and EOM.

Orbital fat involvement is typically used as thehallmark imaging finding for orbital invasion.Our results reveal a significant number of falsenegatives for orbital fat involvement, and thus a

HEAD & NECK August 2000 461

low sensitivity (40Vo MRI, 60% CT). This resultsuggests that although orbital fat involvementstrongly predicts orbital invasion, Iack of orbitalfat involvement cannot rule out invasion.

CT predicted orbital invasion somewhat moreaccurately than MRI. The strength of CT is itsability to assess both fat and bone. With CT, how-ever, it is difficult to differentiate between tumorinvading through versus compressing the perior-bita. In a study of 15 patients with paranasal si-nus malignancies, CT images from four of sevenpatients without orbital symptoms correctly as-sessed invasion. Two of the studies incorrectlypredicted that invasion was present, and one in-correctly predicted that it was not.13 We obtainedsimilar results in our study. MRI differentiatesperiorbita from bone poorly, both of which havelow signal intensity with T1- and T2-weighted se-quences. The strength of MRI, however, is itsmultiplanar capabilities and soft tissue contrast,yet MRI tended to underestimate orbital inva-sion. One potential problem with our study's com-parison of MRI and CT accuracy is that the pa-tients evaluated with the two modalities camefrom different, although overlapping, sets of pa-tients. The comparison between MRI and CTwould benefit from a larger set of patients whoreceived images from both modalities.

In conclusion, we have evaluated imaging cri-teria with which to assess orbital invasion by tu-mors. MRI underestimated orbital invasion morefrequently than CT. Six or more positive criteriapredicted orbital invasion with an accuracy of727o. Tumor adjacent to the periorbita was themost sensitive finding (g}Vo), whereas EOM en-Iargement was the most specific (1947o for both mo-dalities combined). Although orbital fat involve-ment is specific (86% MRI, B9Vo CT) and has ahigh positive predictive value (807o MRI, 867o CT)for orbital invasion, it is considerably less sensi-tive.

Most patients are willing to accept extra risksto save the eyela and endure the morbidity asso-ciated with extensive extirpation to preserve theorbital contents.ls Thus, patients deserve themost accurate assessment of orbital invasion. Im-

aging may aid in counseling patients regardingsurgical planning and prognosis. However, at pre-sent it is not sufficiently accurate to substitute forintraoperative assessment of orbital invasion inthose cases in which the preoperative examina-tion is unclear.

Acknowledgment. The authors would like to ex-press gratitude to Ara Chalian, Gregory Wein-stein, Randal Weber, Donald Lanza, and ScottBartlett for contributing cases to this study.

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462 lmaging to Assess Orbital invasion HEAD & NECK August 2000