Preoperative Imaging to Predict Orbital Invasion by Tumor

PREOPERATIVEIMAGING TO PREDICT ORBITAT INVASION 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, Pennsylvania 2 Department of Radiology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104 3 Department of Biostatistics and Epidemiology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania

Accepted 4 October 1999

Keywords: sinonasal;orbital invasion; imaging; tumor; nasolac- Abstract: Background. Our purposewas to examinethe ac- rimalfossa curacy of preoperativeimaging in assessingtumor invasionol the orbit and nasolacrimalsystem. Methods. Nineteenpreoperative CT and 17 preoperativeMR imagesfrom patientsat risk for orbitalinvasion were retrospec- T.r*orr of the paranasal sinuses present late in reviewed.Invasion was corroboratedby pathologicand in- tively often with extensive disease. Exten- traoperativeassessment. their course, Resu/ts. Tumor adlacentto the periorbitawas the most sen- sion to the orbit and nasolacrimal system has an sitive predictorof orbital invasion(90%) for both CT and MRl. impact on patient prognosis and the surgical ap- Extraocularmuscle involvementon MRI (100%) and orbitalfat proach to these tumors. If orbital invasion is sus- (80% the highestpositive predic- obliteration MRl, 86% CT) had pected, the surgeon and the patient are con- tive valuesol the criteriaevaluated. Extraocular muscle displace- ment and enhancementwere less accurate(<65%) predictors. fronted with the difficult decision of exenteration. No one criterionwas>79o/o accurate in predictingorbital invasion. Orbital exenteration can be emotionally trau- Six or more positivecriteria predicted invasion with 67% sensi- matic for patients, yet it may be required for com- tivityand 80% specificity(accuracy, 72o/"). CT was moreaccurate plete oncologicresection. The difficult decision re- than MRI in seven of nine criteria.Invasion of the nasolacrimal systemwas predictedaccurately (89%). garding the eye cannot be made on the basis of Conclusions. Althoughpreoperative imaging can aid in sur- ophthalmic symptoms alone. In cases in which gicalplanning, it shouldnot replaceintraoperative assessment in the clinical examination and imaging are unclear, ambiguouscases of orbitalinvasion. @ 2000 John Wiley & Sons, preoperative patient counseling regarding the eye lnc. Head Neck 22: 456-462, 2OOO. is complex. A more accurate assessment of tumor invasion of the orbit and nasolacrimal system pre- Correspondenceloj L. A. Loevner,Department of Radiology,University of PennsylvaniaMedical Center,3400 Spruce Street,Philadelphia, PA operatively would benefit both the surgeon and '1 9104. the patient. Patients may be better informed with @ 2000John Wiley & Sons,Inc. regard to their prognosis becausetumors that in-

456 lmaging to Assess Orbital Invasion HEAD& NECK August2000 vade the orbit carry a worse prognosis than those pendently and randomly, and thus a total of 36 that do not.1 In addition, accurate preoperative (17 MRI, 19 CT) imaging studies were evaluated. assessmentmay help the surgeonplan the extent MRI was performed on a 1..5T system (Signa; of resectionin those casesirt which invasion was General Electric Medical Systems, Milwaukee, previously unclear. Most surgeons use the rela- WI). The MRI protocol consistedof conventional tionship between the tumor and the periorbita to spin-echo sagittal Tl-weighted images and axial determine whether exenteration is necessary;tu- and coronal T1' and T2-weighted images. Con- mor invasion through the periorbita may warrant trast-enhanced (0.1 mmol/kg of gadopentetate exenteration, whereas an intact periorbita typi- dimeglumine lMagnevist; Schering, Berlin, Ger- cally warrants preservation.2 When tumor abuts manyl) axial Tl-weighted images with frequency- the periorbita, however,assessing periorbital con- selectivefat suppressiontechniques were also ac- tinuity may be diffrcult. quired. Other imaging parameters included The nasolacrimal system is also susceptibleto section thickness of 5 mm, 2 excitations, and a invasion by paranasal sinus tumors. Tumor may 256 x 192 matrix. track along the nasolacrimal duct and thereby re- CT scans were performed with 3- to 5-mm sec- quire more extensive resection than would have tion thickness in axial and coronal planes. Images been anticipated by the bulk diseaseevident pre- were photographed for soft tissue and bone detail. patients operatively. Three received iodinated contrast before patients'studies were The purpose of this study was to determine CT scanning.The other un- whether preoperative imaging could offer an ac- enhanced. Eleven criteia involving the tumor, orbit, and curate assessmentof tumor extensionto the orbit nasolacrimal fossa were used to assess each and nasolacrimal system. Involvement of the or- study: three criteria for the tumor's relationship bital fat manifest as soft tissue stranding in the to the periorbita (abutting, displacing, or bowing fat is the current imaging criterion suggestive of the periorbita laterally); one for the interface be- neoplastic invasion. However, the accuracy with tween the tumor and periorbita ("nodular" if the which imaging predicts invasion into these struc- margin had focal irregularity or "smooth" if it did tures is poorly studied. In this study we evaluate not); one for orbital fat invasion (soft tissue the accuracy of various imaging criteria in pre- stranding or infiltration within the extraconal fat dicting tumor invasion of the orbit and nasolacri- contiguous with the primary tumor); three for the mal system. We also sought to compare the efii- extraocular muscles (displaced,enlarged, or ab- cacy between magnetic resonanceimaging (MRI) normal signal intensity/density); one for orbital and CT imaging with regard to assessingorbital bone integrity; and one for nasolacrimal system invasion. invasion (tumor extensiorr into the nasolacrimal sac or duct). For studies in which contrast was MATERIALSAND METHODS administered (n : 20; 17 MRI, 3 CT), extraocular (19 Twerrty-frvepatients merr and 6 women) with muscle enhancement was also evaluated. Two tumors of the paranasal sinuses,anterior cranial neuroradiologists unaware of the surgical find- fossa, or skin surrounding the orbit seen over a ings carried out retrospective image analysis in- (1988-1998) 10-yearperiod were chosenfrom the dependently and blindly. Each reader was re- records of the University of Pennsylvania Cancer quired to choosewhether each criterion was met. Center database. Six patients had tumors origi- The strength of interobserver consensus for all nating in the maxillary sinusl six in the ethmoid the criteria was determined by kappa analysis.s sinus; six in the nasal cavity; and one each in the sphenoid sinus, cavernoussinus, maxilla, frontal sinus, forehead, eyelid, and anterior cranial fossa. Table 1. Definitionsol crileriaevaluation Tumor histologic frndings included 12 carcino- Term Definition mas; 6 inverted papillomas; 3 melanomas;and 1 each fibroma, sarcoma, odontogenic keratocyst, Sensitivity TP/(TP+ FN) and meningioma. Patients selected from Specificity TN/(TN+ FP) the da- Positivepredictive value IP/(TP + FP) tabase had preoperative imaging, surgery, and Negativepredictive value IN/(TN + FN) pathologic correlation. Preoperative imaging Accuracy TP+TN/(TP+FN+TN+FP) (n : (n : studies included MRI 6), CT 8), or both Abbreviations: FN,false negative;FP, falsepositive; TN, true negative: TP, (ru : 11). Individual studies were reviewed inde- true posrtive.

lmagingto AssessOrbital Invasion HEAD& NECK August2000 457 Table 2. Radiologic-pathologiccorrelation for evaluatingtumor invasion of orbitwith MRl.

Periorbita Adlacentto Periorbita bowed Extraconalfat EOM Periorbita displaced laterally involved displaced

Nln nf dicanroomontq

UCTVVUUII IUdUUI> 1 2 0 1 2 Truepositives 9 B 7 4 7 Truenegatives 2 3 3 6 4 .1 Falsepositives 5 4 4 3 Falsenegatives 1 2 3 6 3 Sensitivity(%) 90 BO 70 40 70 Specificity(o/.) 29 43 43 B6 57 Positivepredictive value (9"7 64 67 64 BO 70 Negativepredictive value (%) 67 60 50 50 57 Accuracy(%) 65 65 59 59 A1

Differencesbetween the two readers' evaluations less than 70Vo.Orbital fat invasion was radiologi- were resolvedby consensus. cally suspectedin only one MRI and one CT scan The operative and/or pathologic reports were in which orbital invasion was absent pathologi- used as the "gold standard" for orbital and naso- cally (false positives),and thus this criterion had lacrimal invasion. Positive invasion was defined both a high specifi city (>857o)and positive predic- as tumor extension through the periorbita and tive value (80% MRI, 867oCT) (Fig. 1 and 2). Yet into orbital fat. If the periorbita remained uncom- orbital fat involvement was a less than 607osen- promised,the orbit was consideredto be free from sitive imaging criteria for orbital invasion. neoplastic invasion. Fourteen of the 25 patients Extraocular muscle (EOM) involvement had confirmed orbital invasion. The sensitivity, tended to be a specific,yet insensitive,finding. All specifrcity,positive and negative predictive value, MRI images showing enlargement,enhancement, and accuracywere used to evaluate eachcriterion or abnormal EOM signal had pathologically con- (Table 1). firmed orbital invasion (PPV : I00Va)and a better result than CT, although a considerablenum- RESULTS ber of confirmed cases of invasion had negative The two observersagreed on 336 of380 readings criteria. Figure 3 is an example of proven orbital (88.4Voof 11 criteria from 20 contrast-enhanced studies and 10 criteria from 16 noncontrast- enhanced studies). The strength of the interobserver agreement was excellent (rc : 0.77).4The criterion with the smallest number of disagreements was a laterally bowed periorbita (z : 0 of 36), and the highest number of disagreements was the assessment of the tumor interface (smoothvs nodular) with the periorbita (n : Il of 36). A summary of the results for evaluating orbital invasion is shown in Table 2 for the MRI studies and Table 3 for the CT studies. Of the criteria used to assessthe orbit for possibletumor invasion, tumor adjacentto the periorbita was the most sensitive finding for invasion (907o).How- ever, this criterion suffered from low specificity (297o MRI, 44Eo CT). Displaced and laterally FIGURE 1. Axial enhanced CT scan shows a mass (arrows) lateral periorbita bowed periorbita had lower sensitivities anteriorand to the orbit,displacing the medially. but The orbitalfat is normalin appearance(arrowheads), without soft (437o greater specificity MRI, 677oCT for both cri- tissuestranding. Tumor was foundinvading through the perior- teria). The accuracyofeach ofthese criteria was bita, despiteevidence of orbitalfat invasionon imaging.

458 lmagingto AssessOrbital Invasion HEAD& NECK August2000 Tabfe 2. (continued)

EOIV Nodulartumor EOM EON/ aonormal interfacewith Bony n=17 ennanceo enlargeo srgnal orort dehiscence No. of disagreements h^+,r,^^^ -^^A^t^ UETVVUCII IUdUUI5 2 2 I 6 2 Truepositives 1 1 1 6 7 Truenegatives 7 7 7 5 4 Falsepositives 0 0 0 2 3 Falsenegatives B I 9 4 3 Sensitivity(%) 1l 10 10 60 70 Specificity(%) 100 100 100 71 57 Positivepredictive value (%) 100 100 100 75 70 Negativepredictive value (%) 47 44 44 56 57 Accuracy(%) 65 50 47 65 65 invasion despite negative imaging criteria for was found to improve the prediction of invasron EOM involvement (no muscle enlargement, dis- (p > .B). placement,or signal abnormality). EOM displace- A comparisonbetween the results of the MRI ment had a higher sensitivity (7O%oMRI,607oCT) and CT findings for orbital invasion demon- but had more false positives than the other EOM strated that CT was more accurate than MRI in criteria. Consequently,these EOM findings were seven of nine criteria for orbital invasion. Extra- at best 657o accwratefor predicting orbital inva- ocular enhancementwas not included in this com- sion. parison because there were too few contrast- A nodular (Fig. 3) as opposedto a smooth (Fig. enhanced CT studies to make an accurate 4) interface of the tumor with the periorbita was comparison between the two modalities for this 7l7o (MRI) and787o (CT) specifrcfor orbital inva- finding. sion, with a positive predictive value of 757o.Four Nasolacrimal involvement could be confirmed casesin which a nodular interface was recorded only in the nine cases that contained pathologic but no neoplastic extension to the orbit was re- findings and/or operative report information corded at pathologic examination (ie, false posi- about the nasolacrimalfossa. In one of these stud- tives) were from two patients who each had both ies, nasolacrimal invasion was recorded incor- MRI and CT imaging. Although both patients were free from tumor invasion through the periorbita and thus negative for invasion by our imaging criteria, tumor involved but did not invade through the periorbita in one ofthe cases.In that case,a portion of the periorbita was removed as part of the tumor margin, and the eye was preserved. Invasion in both of these caseswas bor- derline and thus may account for the low accuracy of this finding (<707o).The accuracy of bony de- hiscenceto predict invasion was similar between MRI and CT, which was 657o and 687o,respec- tively. The association between each criterion and confirmed invasion was assessedusing odds ra- tios,5 and a \Vo level of signifrcancewas used in this study. For eachcriterion consideredindividu- FIGURE2. Maxillarysinus squamous cell carcinoma with orbital ally, no statistically significant association was invasion.A coronalCT scanshows imaging lindings consistent found. Multiple logistic regressionsswere frt to with orbitalinvasion, which was confirmedpathologically. There is destruction papyracea, assessthe possibility that the results of multi- of the lamina withdisplacement of the periorbitalaterally. There is soft tissue replacingthe extraconal ple tests considered simultaneously predicted orbitalfat with elevationof the inferiorrectus muscle complex orbital invasion. No combination of test results (arrow).

lmagingto AssessOrbital Invasion HEAD& NECK August2000 459 Table3. Radiologic-pathologiccorrelation for evaluatingtumor invasion of orbitwith CT

Periorblta Adjacentto Periorbita DOWeO Extraconalfat EOM n= 19 periorbita displaced laterally involved displaced

I\l^ nf dicr^raamanta betweenreaders 0 0 0 2 3 Truepositives 9 I 8 6 6 Truenegatives 4 6 6 B 5 Falsepositives 5 3 3 1 4 Falsenegatives 1 1 2 4 4 Sensitivity(%) 90 90 BO 60 60 Specificity(%) 44 67 67 B9 56 Positivepredictive value (9", 64 75 73 B6 60 Negativepredictive value ("/") BO B6 75 67 56 Accuracy(%) 6B 79 74 74 42 rectly as positive (i.e., false positive). In eight of goma,the maxilla, the lacrimal bone,and the eth- nine of these studies, however, the nasolacrimal moid bone. The condensedperiosteum of these fossa involvement was correctly predicted on im- bones makes up the periorbita, which is continu- aging, rendering the finding of nasolacrimal fossa ous with the dura mater at the optic foramen and invasion more sensitive (100o/o)than specific superior orbital fissure.6 During the first half of (757o).The accuracyof this finding was 89Vo. the twentieth century, radical excision with orbital exenteration was the standard treatment for DrscusstoN cancers of the paranasal sinuses abutting the The orbit is a cone-shapedspace comprised of eye.2In recent decades,however, the periorbita seven bones that include the frontal bone, the has been considered an effective barrier to tumor greater and lesser wings of the sphenoid, the zy- extension into the orbit.2 Tumors that do not in-

FIGURE3. Magnified,enhanced T1-weighted MR imagewith application of fat suppressionshqws a nodufarmargin of the sinonasaltumor with the periorbitaand involvedextraconal fat (arrows).The medial rectus muscledoes not appear enlarged;however, it is displacedlaterally. Tumor was confirmed at surgeryto invadethrough the periorbita,but the eye was preservedand a portionof the involvedperiorbita resecteo.

460 lmagingto AssessOrbital Invasion HEAD& NECK August2000 Tabfe 3. (continued)

EOM Nodulartumor EOM EOM aEnormal interfacewith Bony n - 10 ennanceo enrargeo signal orbit dehiscence

Nln nf dicanroomonic

A^+r^,^^^ 'l UULVVUVII IEAUSIJ"^^i^"^ 4 3 2 5 True positives 0 3 0 6 B Truenegatives 1 B 7 7 5 Falsepositives 1 1 2 2 4 Falsenegatives 2 7 10 4 2 Sensitivity(%) 0 30 0 60 BO Specificity(%) 50 B9 7B 78 56 Positivepredlctive value (%) 0 75 0 75 67 Negativepredictive value (%) 33 53 A1 64 71 Accuracy(%) 5B 25 5B 6B 6B

vade through the periorbita can be removed with- outcome becauseextensive skull base resections out exenteration and have reduced risk of local would have been required. With these results, the orbital recurrence.t-e In general, if tumor has not authors advocate orbital preservation unless the extended through the periorbita, the eye may be periorbita is extensivelyinvaded.2'tt The decision surgically preserved.l0 Two studies from the to exenterate also may involve additional factors same institution have retrospectively examined such as the strength ofthe patient's contralateral the orbital recurrence rate in patients with ma- vision and evidenceof distant metastases. lignant sinonasal tumors. The eye was preserwed Imaging offers the hope of preoperatively de- in 27 patients who had malignant sinonasal tu- termining tumor invasion of the orbit. We have mors that eroded through orbital bone and dis- presented a uniform set of imaging criteria that placed the globe but did not invade the periorbita. we thought would predict periorbital invasion. Of these patients, three had local recurrence de- These criteria included the relationship between velop. Simple exenteration in these three pa- the tumor and the periorbita, an assessmentof tients, however, would not have changed their the orbital fat and extraocular muscles. and a de- termination of the bony integrity of the orbit. Nodularity of the tumor margin with the orbit was another criterion used becausefocal nodules have been shown to be associatedwith tumor invasion in other anatomic regions, such as the dura.12No one criterion had an accuracyof more than 797o.A nodular tumor-periorbita interface was a fairly accurate indicator of orbital invasion. This finding, however, had the greatest number of disagreements between the two readers, which suggests a high degree of subjectivity. A positive EOM enhancement,enlargement, and abnormal signal on MRI predicted orbital invasion in all cases.A number of criteria were particularly sensitive predictors of orbital invasion. These included tumor adjacent to periorbita (907o) and displacedperiorbita (80% MRI, 907aCT). Specific predictors included orbital fat involvement, EOM FIGURE4. Coronalenhanced T1-weighied MR imageof a pa- enhancement,and EOM. tient with sinonasalmelanoma. Tumor invadedorbital bone but Orbital fat involvement is typically used as the not the periorbita.The mass (m) resultsin mild lateralbowing of the periorbitabut no involvementoi the extraocularmuscles or hallmark imaging finding for orbital invasion. orbitalfat. The marginof the mass with the periorbitawas inter- Our results reveal a significant number of false pretedas smooth. negatives for orbital fat involvement, and thus a

lmagingto AssessOrbital Invasion HEAD& NECK August2000 461 low sensitivity (40VoMRI, 60% CT). This result aging may aid in counseling patients regarding suggests that although orbital fat involvement surgical planning and prognosis.However, at pre- strongly predicts orbital invasion, Iack of orbital sent it is not sufficiently accurate to substitute for fat involvement cannot rule out invasion. intraoperative assessmentof orbital invasion in CT predicted orbital invasion somewhat more those cases in which the preoperative examina- accurately than MRI. The strength of CT is its tion is unclear. ability to assessboth fat and bone.With CT, however, it is difficult to differentiate between tumor Acknowledgment. The authors would like to ex- invading through versus compressing the perior- press gratitude to Ara Chalian, Gregory Wein- bita. In a study of 15 patients with paranasal si- stein, Randal Weber, Donald Lanza, and Scott nus malignancies, CT images from four of seven Bartlett for contributing cases to this study. patients without orbital symptoms correctly as- sessedinvasion. Two of the studies incorrectly predicted that invasion was present, and one in- REFERENCES correctly predicted that it was not.13We obtained 1. Van TuyI R, Gussack GS. Prognostic factors in craniofa- similar results in our study. MRI differentiates cial surgery. Laryngoscope l99l;l0l:240-244. 2. Perry C, Levine PA, Williamson BR, Cantrell RW. Pres- periorbita from bone poorly, both of which have ervation of the eye in paranasal sinus cancer surgery. low signal intensity with T1- and T2-weightedse- Arch Otolary-ngolHead Neck Surg 1988;174:632-634. quences. The strength of MRI, however, is its 3. Fleiss JL. Statistical methods for rates and orooortions. multiplanar New York: Wiley; 1981. capabilities and soft tissue contrast, 4. Landis JR, Koch GG. The measurement ofobserver agree- yet MRI tended to underestimate orbital inva- ment for categoricaldata. Biometrics 1977;33:159-174. sion. One potential problem with our study's com- 5. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemio- parison MRI logic research: Principles and quantitative methods. BeI- of and CT accuracyis that the pa- mont, CA: Van Nostrand Reinhold; 1982. tients evaluated with the two modalities came 6. Weisman RA. Surgical anatomy of the orbit. Otolaryngol from different, although overlapping, sets of pa- CIin North Am 19BB;21:1-12. tients. The comparison between MRI and 7. Sisson GA. Symposium III: Treatment of malignancies of CT paranasal sinuses: Discussion and summary. Laryngo- would benefit from a larger set of patients who scope1970;80:945-953. receivedimages from both modalities. 8. Som ML. Surgical management of carcinoma of the max- In conclusion,we have evaluated imaging cri- iIIa. Arch Otolaryngol I97 4;99:270-27 3. 9. Xuexi W, Pingxhang T, Yongfa Q. Management of the teria with which to assessorbital invasion by tu- orbital contents in radical surgery for squamous cell car- mors. MRI underestimated orbital invasion more cinoma of the maxillary sinus. Chin Med J 1995;108: frequently than CT. Six or more positive criteria 123-125. 10. Maroldi R, Farina D, Battaglia G, et al. MR of malignant predicted orbital invasion with an accuracy of nasosinusal neoplasms. Frequently asked questions. Eur 727o.Tumor adjacent to the periorbita was the J Radiol 1997;24(3):181-190. most sensitive finding (g}Vo),whereas EOM en- 11. McOary WS, Levine PA, Cantrell RW. Presewation of the (1947o eye in the treatment of sinonasal malignant neoplasms Iargement was the most specific for both mo- with orbital involvement. Arch Otolaryngol Head Neck dalities combined). Although orbital fat involve- Surg 1996;122:657-659. ment is specific (86% MRI, B9VoCT) and has a 12. Eisen MD, YousemDM, Montone KT, et al. Use of preop- predict high positive predictive (807o erative MR to dural, perineural, and venous sinus value MRI, 867oCT) invasion of skull base tumors. AJNR Am J Neuroradiol for orbital invasion, it is considerablyless sensi- 1-996;17:1937-1945. tive. 13. Graamans K, Slootweg PJ. Orbital exenteration in sur- patients gery of malignant neoplasms of the paranasal sinuses. Most are willing to acceptextra risks Arch Otolaryngol Head Neck Surg 1989;115:977-980. to save the eyela and endure the morbidity asso- 14. Conley J. The risk to the orbit in head and neck cancer. ciated with extensive extirpation to preserve the Laryngoscope 1985;95:515-522. orbital contents.ls Thus, patients deserve 15. Larson DL, Christ JE, Jesse RH. Preservation ofthe or- the bital contents in caner ofthe maxillary sinus. Arch Oto- most accurateassessment of orbital invasion. Im- Iaryngol 1982;108:37 0-37 2.

462 lmagingto AssessOrbital invasion HEAD& NECK August2000