GRAND GRAND ROUNDSROUNDS

Desirée Ong, M.D.Desirée Ong, M.D.

Vanderbilt Eye Institute Vanderbilt Eye Institute

June 28, 2007June 28, 2007

Our PatientOur Patient

CC: “My appearance has changed”CC: “My appearance has changed”

HPI: 57 yo F HPI: 57 yo F Left eye has progressively “pulled Left eye has progressively “pulled

outward” outward” Binocular diplopia x 3 yrsBinocular diplopia x 3 yrs Lashes rub against her sunglassesLashes rub against her sunglasses Students said they did not know who she Students said they did not know who she

was looking at was looking at

HistoryHistory POHX: POHX:

Narrow-angle glaucoma OU s/p LPI OUNarrow-angle glaucoma OU s/p LPI OU Eye muscle surgery x 3 within last two years Eye muscle surgery x 3 within last two years Revision of lower eyelid OS for post-surgical Revision of lower eyelid OS for post-surgical

scarringscarring

PMHX: PMHX: HypothyroidHypothyroid ArthritisArthritis DepressionDepression Concussion x 2Concussion x 2

FHx: Daughter has strabismusFHx: Daughter has strabismus

HistoryHistory Social Hx: Social Hx:

Married with grown childrenMarried with grown children No tobacco or ETOHNo tobacco or ETOH 88thth grade teacher grade teacher

Meds: Meds: WellbutrinWellbutrin SynthroidSynthroid Hormone replacement therapyHormone replacement therapy Alphagan BID OUAlphagan BID OU

Allergies: DarvocetAllergies: Darvocet

ExamExam

BCVA: OD 20/15, OS 20/25-2BCVA: OD 20/15, OS 20/25-2

CVF: full OUCVF: full OU

Ishihara: 15/15 OUIshihara: 15/15 OU

Hertel: 7 mm of proptosis OSHertel: 7 mm of proptosis OS

Pupils: 3Pupils: 32mm OU, no RAPD2mm OU, no RAPD

Motility

ExamExam

L/L: quiet OD, inferior symblepharon L/L: quiet OD, inferior symblepharon OSOS

S/C: quiet OUS/C: quiet OU K: quiet OD, PEE OSK: quiet OD, PEE OS A/C: narrow angles OUA/C: narrow angles OU Iris: patent superior LPI OUIris: patent superior LPI OU Lens: 1+ NSC OULens: 1+ NSC OU Ant vitreous: quiet OUAnt vitreous: quiet OU

Differential Diagnosis?Differential Diagnosis?Proptosis with extraocular motility Proptosis with extraocular motility

limitationlimitation

Differential DiagnosisDifferential DiagnosisProptosis with extraocular motility Proptosis with extraocular motility

limitationlimitation Neoplastic Neoplastic

Sphenoid wing meningiomaSphenoid wing meningioma Lacrimal gland tumorLacrimal gland tumor Schwannoma Schwannoma MucoceleMucocele Nasopharyngeal tumorNasopharyngeal tumor Dermoid cystDermoid cyst MetastasisMetastasis Solitary fibrous tumorSolitary fibrous tumor Fibrous histiocytomaFibrous histiocytoma HemangiopericytomaHemangiopericytoma LymphoproliferativeLymphoproliferative NeurofibromaNeurofibroma LeiomyomaLeiomyoma Glioma Glioma

Differential DiagnosisDifferential DiagnosisProptosis with extraocular motility Proptosis with extraocular motility

limitationlimitation AutoimmuneAutoimmune

TED – 60% of all orbital diseaseTED – 60% of all orbital disease Inflammatory Inflammatory

PseudotumorPseudotumor Sarcoid granulomaSarcoid granuloma

Vascular Vascular Cavernous hemangiomaCavernous hemangioma Varix Varix A-V fistulaA-V fistula

InfectiousInfectious Orbital cellulitisOrbital cellulitis Tuberculosis granulomaTuberculosis granuloma

TraumaTrauma Retrobulbar hematomaRetrobulbar hematoma

What is next?What is next?

Imaging: MRIImaging: MRI T1: isointense to brainT1: isointense to brain

T2: hyperintense to brain, T2: hyperintense to brain, isointense to CSFisointense to CSF

Marked enhancement on T1 with Marked enhancement on T1 with gadoliniumgadolinium ““Peripheral ring”Peripheral ring” Cavitary change or heterogeneityCavitary change or heterogeneity

Our PatientOur Patient

Excisional biopsyExcisional biopsyUnderwent anterior orbitotomy with Underwent anterior orbitotomy with

image-guided excision of a well-image-guided excision of a well-encapsulated mass 4/20/07encapsulated mass 4/20/07

Gross PathologyGross Pathology Yellow-tan lesion with Yellow-tan lesion with

varicose vessels on the varicose vessels on the surfacesurface

Cone-shaped > dumbbell Cone-shaped > dumbbell > oval > round> oval > round

True capsule composed True capsule composed of perineuriumof perineurium

Eccentric position within Eccentric position within capsulecapsule

Wt. 3.58 g, dimensions: 3.4 x 2 Wt. 3.58 g, dimensions: 3.4 x 2 x 1.4 cmx 1.4 cm

PathologyPathology

Antoni A pattern: compact Antoni A pattern: compact palisading nucleipalisading nuclei

Verocay bodies: dense whorls

PathologyPathology

PathologyPathology

Antoni B pattern: ovoid clear cells, loose Antoni B pattern: ovoid clear cells, loose pattern of myxoid stromal degeneration, pattern of myxoid stromal degeneration, cystic spacescystic spaces

PathologyPathology Most common pattern: Most common pattern:

mixed Antoni A and B (47%)mixed Antoni A and B (47%)

No axons present within the No axons present within the substance of the tumor substance of the tumor

Fibrosis and hyalinization Fibrosis and hyalinization around blood vessels, vessel around blood vessels, vessel walls contain xanthoma walls contain xanthoma cellscells

““Ancient” lesions can have Ancient” lesions can have calcification, cystic changescalcification, cystic changes

upload.wikimedia.org/wikipedia/commons/thumb/...

http://www.histopathology-india.net/Schwannoma.htm

‘Ancient’

Luse bodies: cytoplasmic collagen fibrilsLuse bodies: cytoplasmic collagen fibrils

ImmunohistochemistryImmunohistochemistry

S-100 positiveS-100 positive

Vimentin positiveVimentin positive

Leu7 positiveLeu7 positive

Progesterone-receptor positiveProgesterone-receptor positive May account for increased proptosis during May account for increased proptosis during

pregnancypregnancy Possible place for hormonal txPossible place for hormonal tx

http://www.emedicine.com/derm/topic285.htm

Diffuse S-100 positivity

DiagnosisDiagnosis

Orbital SchwannomaOrbital Schwannoma

SchwannomaSchwannoma (Neurilemoma)(Neurilemoma)

Benign tumor of Schwann cell Benign tumor of Schwann cell sheaths of peripheral sensory nervessheaths of peripheral sensory nerves

First described by Verocay in 1910First described by Verocay in 1910

Well-defined, slowly progressive and Well-defined, slowly progressive and non-invasive with low malignant non-invasive with low malignant potentialpotential

SchwannomaSchwannoma

No racial predilectionNo racial predilection

Female predominanceFemale predominance

22ndnd to 5 to 5thth decades (mean: 40 yrs) decades (mean: 40 yrs)

18% associated with 18% associated with neurofibromatosisneurofibromatosis

SchwannomaSchwannoma

55% of all peripheral nerve tumors 55% of all peripheral nerve tumors

Predilection for the head/neck, flexor Predilection for the head/neck, flexor surfaces of extremities surfaces of extremities

Solitary except for in NF-1 or 2Solitary except for in NF-1 or 2

Orbital SchwannomaOrbital Schwannoma

1-2% of orbital tumors1-2% of orbital tumors

Extraconal > intraconalExtraconal > intraconal

Superior > medial superior > apexSuperior > medial superior > apex

Orbital SchwannomaOrbital Schwannoma

Most common: sensory branches of CN V1 Most common: sensory branches of CN V1 (supratrochlear/supraorbital)(supratrochlear/supraorbital)

Rarely from motor nerves: CN III (superior Rarely from motor nerves: CN III (superior division, ciliary nerve), CN VIdivision, ciliary nerve), CN VI

Optic nerve never involved since an extension Optic nerve never involved since an extension of the CNSof the CNS

Rarely intramuscular, epibulbar or intraosseusRarely intramuscular, epibulbar or intraosseus

SymptomsSymptoms Initially asymptomaticInitially asymptomatic

DiplopiaDiplopia

HeadacheHeadache

Decreased visionDecreased vision Direct optic nerve compressionDirect optic nerve compression Induced hyperopiaInduced hyperopia

Numbness or pain in distribution of Numbness or pain in distribution of involved nerve – rare unless large tumorinvolved nerve – rare unless large tumor

SignsSigns Proptosis – most commonProptosis – most common

Lid swellingLid swelling

Restricted ocular motilityRestricted ocular motility

Globe displacementGlobe displacement

Afferent pupillary defectAfferent pupillary defect

Choroidal foldsChoroidal folds

Optic atrophy/disc edemaOptic atrophy/disc edema

http://content.lib.utah.edu/cgi-bin/showfile.exe?CISOROOT=/EHSL-WFH&CISOPTR=174

Diagnosis and Diagnosis and ManagementManagement

MRI with/without contrast: imaging MRI with/without contrast: imaging method of choicemethod of choice

Observation vs excision Observation vs excision

Radiation Radiation

Evaluation for NF with bilateral Evaluation for NF with bilateral vestibular schwannomas and age < vestibular schwannomas and age < 30 30

Surgical approach Surgical approach

Governed by location of tumor within the orbitGoverned by location of tumor within the orbit

Complete removal is recommended Complete removal is recommended Aspiration or piecemeal excision Aspiration or piecemeal excision Small risk of recurrence with incomplete removalSmall risk of recurrence with incomplete removal One reported case of recurrence and malignant One reported case of recurrence and malignant

transformation after incomplete excision in a pt transformation after incomplete excision in a pt with neurofibromatosis with neurofibromatosis

May strip tumor from nerve of origin via May strip tumor from nerve of origin via microsurgical techniquemicrosurgical technique

Our Patient at Follow-Up Our Patient at Follow-Up (6/19/07)(6/19/07)

Pt still complains of diplopia in primary gazePt still complains of diplopia in primary gaze Motility:Motility:

Plan: strabismus surgery to improve her Plan: strabismus surgery to improve her diplopiadiplopia

Teaching pointsTeaching points

Early diagnosis and accurate Early diagnosis and accurate evaluation of the extent of an orbital evaluation of the extent of an orbital schwannoma is critical for schwannoma is critical for restoration of vision and preserving restoration of vision and preserving extraocular eye movementsextraocular eye movements

Complete excision, if possible, is Complete excision, if possible, is recommended to prevent recurrence recommended to prevent recurrence and malignant transformation and malignant transformation

ReferencesReferences Chang BY, Moriarty P, Cunniffe G, Barnes C, Kennedy S. Accelerated Chang BY, Moriarty P, Cunniffe G, Barnes C, Kennedy S. Accelerated

growth of a primary orbital schwannoma during pregnancy. Eye. 2003 growth of a primary orbital schwannoma during pregnancy. Eye. 2003 Oct;17(7):839-41.Oct;17(7):839-41.

Cockerham KP, Cockerham GC, Stutzman R et al. The clinical spectrum Cockerham KP, Cockerham GC, Stutzman R et al. The clinical spectrum of schwannomas presenting with visual dysfunction: a clinicopathologic of schwannomas presenting with visual dysfunction: a clinicopathologic study of three cases. Surv Ophthalmol. 1999 Nov-Dec;44(3):226-34. study of three cases. Surv Ophthalmol. 1999 Nov-Dec;44(3):226-34.

Gunduz K, Shields CL, Gunalp I, Erden E, Shields JA. Correlation of Gunduz K, Shields CL, Gunalp I, Erden E, Shields JA. Correlation of magnetic resonance imaging and pathologic findings. Graefe’s Arch Clin magnetic resonance imaging and pathologic findings. Graefe’s Arch Clin Exp Ophthalmol 2003; 241: 593-597.Exp Ophthalmol 2003; 241: 593-597.

Rawlings NG, Brownstein S, Robinson JW, Jordan DR. Orbital Rawlings NG, Brownstein S, Robinson JW, Jordan DR. Orbital schwannoma: histopathologic correlation with magnetic resonance schwannoma: histopathologic correlation with magnetic resonance imaging. Can J Ophthalmol. 2007 Apr;42(2):326-8. imaging. Can J Ophthalmol. 2007 Apr;42(2):326-8.

Rootman J. Diseases of the Orbit. Philadelphia: J.B. Lippincott Rootman J. Diseases of the Orbit. Philadelphia: J.B. Lippincott Company, 1988: 319-325.Company, 1988: 319-325.

Shields JA, Shields, CL. Atlas of Orbital Tumors. Philadelphia: Shields JA, Shields, CL. Atlas of Orbital Tumors. Philadelphia: Lippincott Williams and Wilkins, 1999: 76-78.Lippincott Williams and Wilkins, 1999: 76-78.

Wang Y, Xiao LH.Wang Y, Xiao LH. Orbital schwannomas: findings from magnetic Orbital schwannomas: findings from magnetic resonance imaging in 62 cases. Eye. 2007 Apr 20; epublication.resonance imaging in 62 cases. Eye. 2007 Apr 20; epublication.