EYE & ORBITAL TUMORS

ANATOMYEPIDEMIOLOGY

PATHOLOGY

DR HIMANI ( MDRT)

ANATOMY OF ORBIT

• Quadrangular truncated pyramids

• Volume around 30 cc• The orbital entrance

averages about 35 mm in height and 45 mm in width. & depth 40-45 mm in adults

Bony Orbit Seven bones make

up the bony orbit:– Frontal– Zygomatic– Maxillary– Ethmoidal– Sphenoid– Lacrimal– Palatine

CONTENTS OF THE ORBIT

• Eye ball • Optic nerve• EOM• Lacrimal glands,

lacrimal sac• Ophthalmic artery &

branches• III, IV, VI CN; V1, V2 ;

sympathetic nerve• Orbital fat & fascia

BLOOD SUPPLY

Internal carotid arteryOphthalmic artery

Central retinal AShort post ciliary ALong post ciliary AAnterior ciliary A

Lacrimal ASuperior muscular AInferior muscular APosterior ethmoidal AAnterior ethmoidal ASupraorbital ASupratrochlear A

VENOUS DRAINAGE

SUP OPH VEIN INF OPH VEIN

FACIAL VEIN PTERYGOID VENOUS PLEXUS

CAVERNOUS SINUS

JUGULAR VEINS

ANATOMY OF EYE

3 coats

1. fibrous coat

2. vascualr coat (uveal tissue )

3. nervous coat (retina)

SEGMENTS & CHAMBERS OF EYEBALL

1. Anterior segment contains Lens , iris, cornea, ant & post chambers

2. Posterior segment contains vitreous, retina, choroid, optic disc

EYE LIDS• Mobile tissues placed infront of eye balls, act as shutters

protecting the eyes• Orbital & tarsal part by a horizontal sulcus• Layers from ant to posterior

1. skin2. subcutaneous areolar tissue3. layer of striated muscles (orbicularis m/s, LPS)4. submuscular areolar tissue (nerves, vessels)5. fibrous layer 6. non striated m/s fibre layer – mullers m/s7. palpebral conjunctiva

GLANDS OF EYE LIDS • 1. meibomian glands / tarsal glands in stroma of tarsal

plate of fibrous layer ; modified sebacious glands2. glands of zies3. glands of Moll : modified sweat glands4. accessory lacrimal glands of wolfring : near upper border of tarsal plate

• Arterial supply by marginal & superior arterial arcade• Veins : post tarsal plexus into ophthalmic veins& pretarsal

plexus into subcut veins• Motor N - Facial, occulomotor, sympathetic fibres

sensory – trigeminal N

CONJUNCTIVA

• 3 Partsa) Palpebralb) Bulbarc) conjunctival fornix

• 3 layers histologicallya) epitheliumb) adenoid layerc) fibrous layer

• 2 types of glands- mucin secretory & accessory lacrimal

CONJUNCTIVA

• Arterial supply by peripheral arterial arcade, marginal arcade of the eye lid, anterior ciliary arteries

• Venous drainage into venous plexus of the eyelid & into anterior ciliary veins

• Lymphatic drainage into preauricular LN, submandibular LN

• Circum corneal zone – by br of long ciliary NRest by Br of lacrimal, supra, infra trochlear, supra orbital & frontal N

CORNEA• Occupies the center of the

anterior pole of the globe. In the adult, it measures about 12 mm in the horizontal meridian & about 11 mm in the vertical

• Transparent & form a positive lens of about 40 D & constitute the main refractive element of the eye

CORNEA

5 Layers• Epithelium• Bowman’s layer• Stroma• Descemet’s membrane• Endothelium

• Avascular structure• Ant ciliary N V1

SCLERA• Sclera is opaque and white• Covers the posterior surface

of the globe, with an anterior opening for the cornea and a posterior opening for the optic nerve

• 3 layers histologicallya) episcleral tissueb) sclera properc) lamina fusca

• Nerve supply by Br of long ciliary N

LENS

• Transparent, biconvex, crystalline structure b/n iris & vitreous with RI 1.39 & Dioptric power 18D

• Structure:1. lens capsule 2. anterior eppithelium3. lens fibres ( nucleus , cortex )

• Avascular

UVEAL TRACT• Middle vascular coat of

eyeball with 3 parts IRIS, CB, CHOROID

• Arterial supply by short, long posterior ciliary arteries, ant ciliary arteries

• Venous drainage by a series of small veinsjoin to form 4 vortex veins – sup, inf temporal, sup , inf nasal sup & inf ophth veins cavernous sinus

RETINA

• Inner most layer ; from oraserrata to optic disc• 2 regions : post pole, peripheral retina• Optic disc : 1.5 mm d, all layers termiante

except nerve fibres( lamina cribrosa)

BLOOD SUPPLY OF RETINA

• Arterial supply by choroidal vessels – outer 4 layerscentral retinal artery – inner 6 layers

• Venous drainage by central retinal vein into cavernous sinus

OPTIC NERVE• 2ND CN • Backward cont of nerve

fibre layer, From optic disc to chiasma

• 47-50 mm length

LACRIMAL APPARATUS• 1. Main lacrimal gland

2. accessory lacrimal glands (krause, wolfring)3. lacrimal passages

• Blood supply by lacrimal artery

• Sensory supply – lacrimal N• Symp by – carotid plexus of

cervical symp chain• Secretomotor fibres from sup

salivary nuclues (pons)

EYE LID SKIN TUMORS

• Classification :1. Benign : simple papilloma (Sq papilloma & sebacious keratosis ) , naevus, angioma, haemangioma, NF, sebacious adenoma2. pre cancerous : solar keratosis, CIS, XP3. malignant : SCC, BCC, malignant melanoma, sebacious gland adenocarcinoma

CONJUNCTIVAL TUMORS CLASSIFICATION:• Non pigmented :

1. cong – dermoid & lipodermoid2. benign – simple granuloma, papilloma, adenoma, fibroma, angiomas3. premalig – bowen’s disease4. malig – SCC, BCC

• Pigmented:1. benign – naevi 2. precancerous melanosis – SSM, LMM3. malig – Primary melanoma

UVEAL TRACT TUMORS• CLASSIFICATION

I. TUMORS OF CHOROIDA) Benign : neavus, haemangioma, melanocytoma, choroidal osteomaB) malignant : melanoma

II. TUMORS OF CBA) Benign : hyperplasia, benign cyst, medulloepitheliomaB) Malignant : Melanoma

III. TUMORS OF IRISA) Benign : naevus, benign cyst, naevoxantho endotheliomaB) Malignant : Melanoma

RETINAL TUMORS• CLASSIFICATION

A) primary tumors 1. neuroblastic tumors : RB, astrocytoma, benign epithelioma, malignant melanoma 2. mesodermal angiomata ex: cavernous hemangioma 3. phakomatoses: angiomatosis retinae , NF & encephalo trigeminal angiomatosis

B) secondary tumors mets from choroid melanoma, mets from GIT, GUT, lungs, pancreas, mets from sarcomas, malignant melanoma from skin

TUMORS OF LACRIMAL GLANDS• CLASSIFICATION

1. epithelial tumors a) benign mixed tumors(50%) b) malignant : adenoid cystic ca, mucoepidermoid ca, adenoid ca, mixed

2. non epithelial a) lymphoproliferative tumors b) inflammatory cond like idiopathic orbital infla disease, sarcoidosis, mikulicz syndrome

TUMORS OF ORBITA) Primary

1. Developmental : dermoid, epidermoid, lipodermoid, teratomas2. vascular3. mesenchymal : RMS4. neural : ON gliomas, meningiomas5. lymphoproliferative : benign reactive lymphoid hyperplasia, malignant lymphomas, LCH

B) secondary tumors from eye ball, eye lids, nose, PNS, nasopharynx, cranial cavity

TUMORS OF ORBITC) Metastatic orbital tumors

1. in children NB from adrenals, symp chain; nephroblastoma from kidney, Ewing’s from bone, leukemic infiltration

2. adults ca from lungs, breast, prostate, thyroid, rectum, MM from skin

MOST COMMONS• IN CHILDREN

• MC intra ocular tumor – RB• MC intra orbital – RMS

IN ADULTS• MC intra ocular – malignant melanoma choroid• MC intra orbital – cavernous hemangioma• Mc tumor which metastasize to eye – NB• MC tumor of eye lids – BCC• MC tumor of lacrimal gland – Benign mixed tumor

EPIDEMILOGY & PATHOLOGY OF

OCULAR TUMORS

EYE LID SKIN TUMORS

Sq cell ca

Basal cell ca

EPIDEMIOLOGYBasal and squamous cell carcinomas of the periorbital skin most frequently occur on the lower eye lid & medial canthus •RISK FACTORS : sun exposure & immuno compromised pts•90% BCC & 10% Sq CC

PATHOLOGY• Regional LN involvement – 24 % pts with SCC & is mc for larger, recurrent & those tumors with perineural invasion• pts with recurrent , perineural invasivon may have tumors cells produce more peripherally than clinically apparent • tumors located in embryological fusion planes have been found to be more deeply infiltrating

SEBACIOUS GLAND CA OF EYELID• Sebacious gland adeno ca is

locally aggressive & can metastasize to reg LN & distant organs

• Usually in older but in earlier age pts having hereditary RB treated with RT

• Main systematic association Muir- Torre synd

PTERYGIUM• Benign growth of

fibrovascular tissue• R/F : excessive exposure to

wind, sunlight, sand, UV exposure

• Most pterygia are located nasally and occur in patients aged 20 to 50 years

• Beta irradiation with Strontium 90, mitomycin C

CAPILLARY HAEMANGIOMAS• Benign endothelial cell neoplasms

on eye lids or skin of the orbit• Undergoes spontaneous

regression• Retinal haemangiomas represent

a component of VHL synd or SW syndrome

• Choroidal haemangiomas probably congenital in all cases, undetetcted until 2nd decade; circumscribed or diffuse type

UVEAL MELANOMA• MC primary malignant intraocular neoplasm EPIDEMIOLOGY• Arise from melanocytes of uveal tract• Incidence around 1500 pts / year in USA &

average age at the time of diagnosis is 60 yrs• Mc in lightly pigmented persons• M:F equal• Rarely B/L• Risk factors : prolonged sunlight exposure &

light colored irises• Predisposing diseases : melanoma, XP,

oculodermal melanocytosis & dysplastic nevus syndrome

PATHOLOGY

• Arise from melanocytes that are of neuroectodermal origin• Melanoma cells have a large nuclear to cytoplasmic ratio,

prominent or multiple nucleoli, and frequent mitotic figures

• Generally composed of either spindle cells or epithelioid cells

• Classification : 1) spindle cell melanoma2) mixed type3) epitheloid cell melanoma

• Other type – necrotic

UVEAL MELANOMA CONT

UVEAL MELANOMA CONT

• Prognostic indicators: Type of histology, tumor dimension, thickeness, location of anterior tumor margin

• Variable rate of growth ; usually tend to be slow growing ; rapidly growing tumors which have worst prognosis tend to be anaplastic, composed of epitheloid cells

• EOM extension can occur through emissary canals; with worst prognosis

• Mc sites of mets – liver lungs by hematogenous route

UVEAL MELANOMA CONT

UVEAL MELANOMA STAGING IRIS

T1 – limited to IrisT1a - < 3 clock hrs in sizeT1b - >3 clock hrs in size T1c - with secondary glaucoma

T2 – tumor confluent with or extending to CB, choroid, or both

T3 – CB, choroid, or both with scleral extension

T4 – with extra scleral extension T4a - <5 mm in diameterT4b - >5 mm

CB & CHOROID

• T1 – tumor size cat 1T1a – without CB involvement & extraocular extension T1b – with CB involvementT1c – without CB , with extraocular extension ≤5mm in diameterT1d – with CB involvement, extraocular extension ≤5 mm

REGIONAL LN(N)•Nx •N0• N1 – RLN

DISTANT METSM0M1M1a – largest diameter of distant met ≤3 cmM1b – 3-8 cmM1c - ≥ 8 cm

STAGINGI – T1a N0M0IIA – T1b-d N0M0

T2a N0 M0IIB – T2b N0 M0

T3a N0 M0IIIA – T2c-d N0 M0

T3b-c N0 M0 T4a N0 M0

IIIB – T3d N0 M0 T4b-c N0 M0

IIIC – T4d-e N0 M0IV - any T N1M0

any T anyN M1a-c

CHOROIDAL/ UVEAL METS EPIDEMIOLOGY Choroidal mets are most frequently from breast > lungs

> GIT > kidney = skin = prostate PATHOLOGY• MC Pathological type is adeno ca from breasts > non

small cell ca lungs• Disease extent can be localized to choroid• The avg no of lesions seen in the choroid in one large

series was 2, in this situation involvement of opp choroid can be 50% of pts

• Orbital mets can occur & usually U/L

A) Multifocal amelanotic mets with overlying brown lipofuscin deposits from breast ca

B )Unifocal amelanotic mets with overlying brown lipofuscin deposits & subretinal fluid from lung ca

C) Multifocal orange-colored mets with overlying brown lipofuscin deposits from lung carcinoid tumor.

D) Multifocal pigmented mets from skin malignant melanoma

RHABDOMYOSARCOMA• MC orbital malig tumor in children PATHOLOGY• Histologic sub types in the order of worse prognosis:

a) ERMS (MC; spindle , botryoid variants; LOH on 11p)

b) ARMS ( small, round, blue cells forming alveolar like spaces; t(2,13) or t(1,13); PAX+FKHR fusion protein diagnostic )

c) Undifferentiated• IHC staining positive for Myo D• Other genetic synd asso with RMS : NF1, LF , BWS

LACRIMAL GLAND TUMORS

EPIDEMIOLOGY• Rare• M:F equal incidence• Age group : 10-73 yrs• Mostly malignant• Benign pleomorphic adenomas , benign

lymphoid hyperplasia can also occur

PATHOLOGY• MC histological variant is Adenoid cystic ca >

muco epidermoid ca > Adeno ca• Prognosis depends on presence of necrosis,

haemorrhage, perineuaral invasion, mitotic counts

LACRIMAL GLAND TUMORS CONT

Adenoid cystic ca of lacrimal gland

Benign pleomorphic adenoma

LYMPHOMAS EPIDEMIOLOGY• Primary orbital lymphomas rare, <1% of all

lymphomas• In the orbit can occur anteriorly in conj /

retrobulbar region• In primary intra ocular lymphomas, malignant

lymphoid cells involve retina, vitreous, ON head with or without CNS involvement

• Pts with lymphomas at other sites can also present with eye involvement in the course of their disease

LYMPHOMAS CONT

• Increased incidence over past 15 yrs in both immunocompromised & immunocompetant pts; reason unknown

• Disease of 5th, 6th decade• Male > female

LYMPHOMAS CONT

PATHOLOGY• Orbital lymphomas are of mostly B cell origin• Low & intermediate grade by working formulation• Mc subtype of ocular adnexal lymphoma – MALT• Intraocular lymphomas – diffuse large B cell type &

usually aggressive ; tend to disseminate into/ be a component of disease within the CNS thus carry a more omnious prognosis

Conjunctival lymphoma

OPTIC NERVE TUMORS OPTIC NERVE MENINGIOMAS

EPIDEMIOLOGY & PATHOLOGY• From meningothelial cap cells of arachnoid villi & can

develop any where• Meningiomas from other locations can also extend to

involve ON• U/L, B/L, multifocal• Pts with NF2 predispose to B/L, multifocal lesions• F > M• Age of presentation – 40 yrs

OPTIC NERVE GLIOMA EPIDEMIOLOGY• 1-5% intra cranial gliomas & 4% of orbital tumors• Most freq in children with 75% in 1st decade , 90% in

first 2 decades PATHOLOGY cell of origin unknown in pedia ON glioma• Classified as grade I Astrocytomas / pilocytomas• Slow growing, do not tend to metastasize• 10-38% with NF1• When B/L pathognomic of NF1

PATHOLOGY CONT

• Adult form of ON glioma – diffusely infiltrating type including astrocytomas , anaplastic astrocytomas, GBM (WHO II, III, IV resp )

RETINOBLASTOMA EPIDEMIOLOGY• 3% of pediatric malignancies, with 2 to 5 cases / million

children / yr in USA• The incidence is higher (6 to 10 cases per million

children) in Africa, India, and children of Native American descent in North America

• increased incidence primarily in U/L cases & Associated with poverty & low levels of maternal education, that suggests environmental factors in its etiology

• (HPV) Viral oncoprotein E7 binds to & inactivate RB gene product (pRB)

PATHOLOGY• Macroscopically, soft and friable,

tending to outgrow its blood supply with resultant necrosis and calcification.

• microscopic appearance depends on the degree of differentiation.

• Undifferentiated RB is composed of small, round, densely packed cells with hypochromatic nuclei and scant cytoplasm

PATHOLOGY CONT

Flexner- Wintersteiner rosettes

clusters of low columnar cells arrangedaround central lumens

Fleurettes

composed of larger cells with abundant eosinophiliccytoplasm

Reese-Ellsworth Grouping• I (Very Favorable for maintenance of sight)

Ia - Solitary tumor < 4 dd at orbehind the equator

Ib - Multiple tumors, none > 4 dd,all at or behind equator

• II (Favorable) IIa - Solitary tumor 4-10 dd, at or behind

equator IIb Multiple tumors 4-10 dd, at or behind

equator

• III (Doubtful) IIIa - Any lesion anterior to equator IIIb - Solitary tumor > 10 dd behind

equator• IV (Unfavorable) IVa -Multiple tumors, some > 10 dd IVb - Any lesion extending anteriorly to the

oraserrata• V (Very Unfavorable) Va - Massive tumors involving more than half

the retina Vb- Vitreous seeding

International RetinoblastomaStaging System

• 0 - Patients treated conservatively• I - Eye enucleated, completely resected

histologically• II - Eye enucleated, microscopic residual tumor• III - Regional extension IIIa - Overt orbital disease IIIb - Preauricular or cervical lymph node

extension

• IV Metastatic disease Iva - Hematogenous metastasis (without CNS

involvement) 1. Single lesion 2. Multiple lesions IVb CNS extension (with or without any other site of

regional or metastatic disease) 1. Prechiasmatic lesion 2. CNS mass 3. Leptomeningeal and cerebrospinal fluid

disease

RADIATION TOLERANCE • EYE LIDS

20 Gy- loss of eye lashes24-26 Gy – Xerophthalmialate – telengiectasia, atrophy

• CONJUNCTIVA>30 Gy- acute conjunctivitssecondary bacterial & viral inf

• CORNEA30-35 Gy – punctate epithelial keratitis40-50 – corneal oedema60 Gy – corneal perforation

RADIATION TOLERANCE • IRIS ( relatively radio resistant)

hypofractionated RT with 30-40 Gy or conventional RT with >70 Gy – persistant Iritis- very late effect – neovascular glaucoma

• LENSchildhood 1Gy – 50% risk of developing cataractAdults 2.5 – 6.5 Gy – 33% with 8 yrs latent period6.5 – 11.5 Gy – 66% with 4 yrs latent period

RADIATION TOLERANCE • RETINA

30-35 Gy – radiation retinopathy after 6 m-3 yrs Rx• OPTIC NERVE

RION – radiation induced opt neuropathy

< 50Gy – 0 % risk55-60 Gy- 3-7% risk>60 Gy – 7-20 % risk

RION depends on fraction size1.9 Gy is safe

• LACRIMAL SYSTEM30-35 Gy – dry eye synd after 4-11 yrs Rx>57 Gy – dry eye synd in 9-10 m