intraocular tumours

nevus, malignant melanoma of uvea and retina, retinablastoma

1. Intraocular tumours Nur Aisyah Binti Idris 068

2. Contents Tumours of uvea tract Tumors of retina Tumors of optic nerves

3. Tumours of uveal tract

4. Classification Tumours of choroid : Benign 1) naevus 2) hemangioma 3) melanocytoma 4) choroidal osteoma Malignant 1) melanoma Tumours of ciliary body : Benign : 1) hyperplasia 2) benign cyst 3) medulloepithelioma Malignant : 1) melanoma Tumours of iris : Benign : 1) naevus 2) benign cyst 3) naevoxanthoendothelioma Malignant : 1) melanoma

5. Tumours of choroid Naevus Asymptomatic lesion Diagnose: fundus examination Flat, dark grey lesion with feathered margin a/w overlying colloid body May undergo malignant change: Increase pigmentation/ height of naevus Appearance of orange patches of lipofuscin Appearance of serous detachment

6. Choroidal hemangioma 2 forms: Localised choroidal heamangioma Raised, domeshaped , salmon pink swelling Situated at the posterior pole of the eye Serous detachment, cystoid degeneration, pigment epithelial mottling Diffuse choroidal haemangioma a/w sturge -weber syndrome Diffuse deep red discoloration of fundus

7. Melanocytoma Rare tumor Jet black lesion around the optic disc Choroidal osteoma Very rare benign tumor Elevated, yellowish-orange lesion Affect young women

8. Malignant melanoma of choroid Most common primary IOT 40-70years of age Rare in black, > common in white Arise from neural crest unilateral Gross Pathology: pre-existing naevus / denovo 2 form: circumscribed, diffuse

9. Histopathology : Modified Callender’s classification Spindle cell melanomas : spindle shape cells (best prognosis). Epitheloid cell melanomas : large, oval or round, pleomorphic cells with larger nuclei and abundant acidophilic cytoplasm (worst prognosis). Mixed cell melanomas : both spindle & epitheloid tumours (intermediate prognosis) Necrotic melanomas: predominant cell type is unrecognizable.

10. Clinical features Quiescent stage : Symptoms depend upon the location and size of tumour . Small tumour located in the periphery may not produce any symptoms tumours arising from the post. pole present with early visual lost . Sign: appearances of orange patches in the pigment epithelium. large tumour penetrate through Bruch’s membrane grows in subretinal space characterised by exudative retinal detachment produces marked loss of vision and gradually tumour fills the whole eye. Other associated features : sub/ intraretinal hemorrhage, choroidal folds, & vitrous hemorrhage.

11. Glaucomatous stage : Glaucoma may develop due to obstruction of venous outflow by pressure on vortex veins, blockage of the angle of ant. chamber Sx : severe pain, redness, watering Signs : chemosed & congested conjunctiva, oedematous cornea, shallow anterior chamber, fixed & dilated pupil,lens opaque, increase IOP (stony hard eye), features of iridocyclitis .

12. Stage of extraocular lesion : the tumor may burst through sclera usually at the limbus. Rapid fungation and involvement of extraocular tissues resulting in marked proptosis. Stage of distant metastasis : Hematologic spread commonly occurs in liver & commonest cause of death.

13. Differential diagnosis During quiescent stage : Small tumour w/o exudative retinal detachment : naevus , melanocytoma , hyperplasia of the pigment epithelium. Tumour with exudative retinal detachment : simple retina detachment, choroidal haemangioma . During glaucomatous stage : acute glaucoma

14. Investigation Indirect opthalmoscopic examination Transillumination test USG : A and B scan Fluorescein angiography Radioactive tracer MRI

15. Treatment Observation : in small and asymptomatic lesion with absence of suspicious features. Conservative : Brachytheraphy External beam radiotheraphy Transpupillary thermotheraphy Trans-scleral local resection Stereotactic radiosurgery Enucleation : > 16mm x 10mm Exenteration or debulking with chemotherapy Palliative treatment with chemotherapy & immunotherapy : distant metastasis

16. Prognostic indicators increasing age. large tumour . Involvement of extrascleral or vortex veins. Ciliary melanoma worst than choroidal melanoma. Cell type : spindle A (best prognosis) > mixed > epitheloid (worst). Prognosis worsen with nucleolar size variation, vascualar loops and mitotic activity. Monosomal 3 and partial duplication of chromosomal 8 increase risk of metastasis.

17. Tumor of ciliary body Hyperplasia and benign cyst Insignificant lesion of ciliary body Medulloepithelioma Rare congenital tumor arising from non pigmented epithelium of CB Present in 10 years of life

18. Malignant melanoma of CB Usually diagnosed very late Extent anteriorly, posteriorly or circumferentially Clinical features: Slight hypotony , unaccountable defective vision, localised sentinel dilated episcleral vein Anterior spreading: Anterior displacement, subluxation & cataract formation of lens Secondary glaucoma Epibulbar mass

19. Posterior spread: Exudative retinal detachment Pathological feature: same as choroidal melanoma Treatment: enuclation , local resection

20. Tumors of iris Naevus Most common lesion Flat, pigmented, circumscribed lesion of variable size Rare of malignant change Naevoxanthoendothelioma Rare fleshy vascular lesion Seen in babies Cause recurrent hyphaema treat: x-ray & steroids

21. Malignant melanoma Single/ multiple rapidly growing vascular nodule Spread in angle  2° glaucoma May penetrate through limbus epibulbar mass Treat: wide iridectomy Iridocyclectomy enuclation

22. Tumours of retina

23. Primary tumours Neuroblastic tumours . Arise from sensory retina ( retinoblastoma & astrocyotoma ) and pigment epithelium ( benign epithelioma & melanotic malignant tumours ). Mesodermal angiomata : cavernous haemangioma . Phakomatoses : angiomatosis retinae( von hippel -Lindau disease ), tuberous sclerosis ( Bourneville’s disease ), neurofibromatosis ( Von Recklinghausen’s disease ), encephalofacial angiomatosis ( Sturge -Weber syndrome ).

24. Secondary tumours Direct extension : from malignant melanoma of choroid. Metastatic carcinoma from GIT, genitourinary tract, lungs, & pancreas. Metastatic sarcomas Metastatic malignant melanoma from skin

25. Retinoblastoma Most common IO tumour in childhood occurring 1 in 15000-20000 of childbirth age between 1-2 years old. 25-30% effects bilaterally where one eye is affected more and earlier than the other. Due to deletion of 14 band on the long arm of chromosome 13 (13q 14) 10% are hereditary and 90% are sporadic.

26. Origin: Arises as malignant proliferation of immature retinal neural cells which are small round cells with large nuclei Histopathology Small round cells with large nuclei (resemble cells of nuclear layer of retina) Highly undifferentiated/ well- differentiated tumour - Microscopic – Flexner- Wintersteiner rosettes, Homer-Wright rosettes, pseudorosettes , fluorettes formation . Pathology

27. Clinical features Leucocoria 60% Strabismus 20% Painful red eye 7% Poor vision 5% Orbital cellulitis 3% Unilateral mydriasis 2% Heterochromia iridis 1% Hyphema 1%

28. Intraocular stage of RB Stage of extraocular exntension Stage of distant metastasis Stages of retinoblastoma

29. Intraocular stage Quiescent presentation Leucocoria Yellowish- white pupillary reflex( amaurotic cat’s eye) commonest presentation Squint Usually convergent, 2 nd commonest presentation Nystagmus Rare features, noticed bilateral Defective vision Endophytic Exophytic Diffuse infiltrating Ophthalmoscopic features Very rare, late manifestation (3-5 years)

30. Endophytic retinoblastoma Grows inwards from retina into vitreous cavity Tumour like well circumscribed polypoid mass of white or pearly pink In presence of calcification, typical “cottage cheese” Exophytic retinoblastoma Grows outwards and separate retina from choroid Appearance of exudative retinal detachment Diffuse infiltrating tumours Placoid thickness of retina and not a mass Usually diagnose late

31. When left untreated, some patient may present with severe pain, redness and watering These symptoms occur either due to acute secondary glaucoma or apparent intraocular inflammation or orbital cellulitis Painful red eye presentation

32. Stage of extraocular extension progressive enlargement of tumour , the globe burst through the sclera, usually near limbus or optic disc followed by rapid fungation and involvement of extraocular tissue resulting in mark proptosis. Stage of distant metastasis Lymphatic spreads first occurs in preauricular & neighbouring LN. Direct extension by continuity to the optic nerve & brain is common.

33. Classification : ICRB Group A (very low risk) include all small tumours <3mm in greatest dimension, confined to retina, located >3mm from fovea, and >1.5mm from optic disc margin. Group B (low risk) include large tumours >3mm in dimension , and any size tumours located <3mm from fovea , & <1.5mm from optic disc margin. Group C (moderate risk) include retinoblastoma & focal seeds characterized by subretinal and or vitreous seeds ≤3mm from RB . Group D (high risk) include retinoblastoma & diffuse seeds characterized by subretinal and or vitreous seeds >3mm from RB . Group E (very high risk) include extensive RB characterized by any of the following : Tumour touching the lens, neovascular glaucoma, tumour anterior to anterior vitreous face involving ciliary body and anterior segment, diffuse infiltrating tumours , opaque media with haemorrrhages

34. Differential diagnosis Leukoria : congenital cataract, inflammatory deposits following a plastic cyclitis or choroiditis, coloboma of choroid, retrolental fibroplasia, toxocara endophthalmitis, exudative retinopathy of Coats. Endophytic RB : retinal tumour in tuberous sclerosis, neurofibromatosis, astrocytoma, exudative choroiditis. Exophytic RB : Coat’s disease.

35. Diagnosis Examination under anaesthesia Plain x-ray orbit Lactic dehydrogenase Ultrasonography and CT/MRI Performed on suspected case. Measure intraocular pressure & corneal diameter Show calcification which occurs 75% cases of retinoblastoma Level is raised in aqueous humour Useful diagnosis CT/MRI demonstrate extension to optic nerve, orbit and CNS

36. Treatment A ) Conservative tumour destructive therapy : if diagnosed early Chemotherapy : Focal therapy : cryotherapy, laser photocoagulation, thermotherapy, plaque radiotherapy, external beam radiotherapy.

37. B ) E nucleation for group E patients when : Tumour involve more than half of retina. Optic nerve is involved. Glaucoma is present and ant chamber is involved. C ) Palliative therapy : when prognosis is bad in spite of aggressive treatment. RB with orbital extension RB of intracranial extension RB with distant metastasis Should include combination of :

38. Prognosis untreated prognosis -always bad rarely spontaneous regression of the eyeball get shrunk due to necrosis by immunological action . enucleated before occurrence of extraocular lesion, survival rate is 70-85%. Poor prognosis when optic nerve involvement , undifferentiated tumour cells, massive choroidal invasion.

39. Phacomatoses Group of familial condition which characterized by development of neoplasm in eye, skin, and CNS . 1. Angiomatosis retinae (Von H ippel L indau’s syndrome ) Involve retina, brain, spinal cord, kidneys, and adrenals. C/F : vascular dilatation, aneurysm( balloon-like angiomas ), hemorrhage and exudates leading to retinal detachment . Treat: cryopexy / photocoagulation.

40. 2. Tuberous sclerosis (Bourneville disease) Triad of adenoma sebaceum , mental retardation, and epilepsy associated with hamartomas of brain, retina, and viscera. potato-like appearance 2 tyepe : relatively flat & soft appearing white / grey lesion (posterior pole), large nodular tumor common seen in optic disc

41. Neurofibromatosis ( Von Recklinghausen’s disease ) Multiple tumours in the skin, nervous system, and other organs . Cutaneous manifestation : vary from café-au- lait spots to Neurofibromata Ocular manifestation : neurofibromas of lids and orbits, glioma of optic nerve, and congenital glaucoma . Encephalofacial angiomatosis ( Sturge -Weber syndrome ). Angiomatosis in the form of port-wine stain ( naevus flammeus ), involving one side of the face which may be ass with choroidal hemangioma , leptominingeal angioma , and congenital glaucoma on affected side.

42. Retinal Astrocytoma Aka Retinal astrocytic hamartoma benign , acquired, retinal or papillary neoplasias , often found in association with the tuberous sclerosis complex also be associated with neurofibromatosis type 1 ( NF-1) rarely be found independently to any systemic diseases. Reti progressive lesions, always asymptomatic, detected either on routine or screening fundus examinations in patients with TSC or NF-1 usually located in the inner layers of the retina or the optic disc, obscuring the retinal vessels.

43. Dd (x): retinoblastoma, choroidal melanoma Funduscopy : a milky gray–white appearance, depending on their amount of calcification Histopathology: spindle-shaped or even pleomorphic retinal astrocytes and can have various amounts of calcification. Investigation : fluorescein angiography Treatment almost never required, growing lesions, where photodynamic therapy can be effective.

44. ( A) Small noncalcified astrocytic hamartoma in a patient with tuberous sclerosis complex. (B) Large heavily calcified astrocytic hamartoma in an otherwise asymptomatic patient .

45. Retinal cavernous hemangioma rare vascular hamartomas autosomal dominant pedigrees  Genotyping for three known cerebral cavernous malformation, or CCM, genes Usually unilateral and rarely increase in size always asymptomatic CF: Skin and central nervous system hemangiomas may co-exist Fundus examination : dark intraretinal aneurysms with characteristic " cluster-of-grapes" appearance . macular involvement or vitreous hemorrhage

46. Investigation: neuroimaging Treatment: observation is the best management. photocoagulation has been used in some cases prognosis localized cavernous hemangioma of the retina retain good vision visual loss secondary to vitreous hemorrhage or contraction of the preretinal membrane overlying the tumor may occur.

47. Tumours of optic nerve

48. Optic nerve tumor Optic nerve glioma Slow growing tumor, astrocytes First decade of life Solitary tumor/ part of Von Recklinghausen’s NF CF: gradual visual loss, painless unilateral axial proptosis, 4-8 years Fundus exm : optic atrophy / papilloedema & venous engorgement

49. Diagnosis : clinical diagnosis X-ray: uniform regular rounded enlargement of optic foramen CT scan & USG: fusiform growth Treatment: Observation Surgical excision radiotherapy

50. Meningiomas Invasive tumor arising from arachnoid villi 2 type: 1° & 2° Primary intraorbital meningiomas Aka optic nerve sheath meningiomas Rare benign tumor of meningoepithelial cells of meninges Mid-age, female>, a/w NF-2 CF: early visual loss a/w limitation of ocular movement, optic disc edema/ atrophy, slowly progressive unilateral proptosis

51. During intradural stage  indistinguishable from optic nerve glioma (clinically) Presence of opticociliary shunt (hallmark) ONSM Ct scan is diagnostic investigation Treatment: Observation Surgical excision Prognosis = good

52. Secondary intraorbital meningiomas Secondarily invade the orbit Arise from the sphenoid bone or involve it enroute to the orbit Orbital invasion : floor of ant. Cranial fossa, superior orbital fissure, optic canal Meningioma enplaque  affect greater & lesser wings of sphenoid taking origin in the region of pterion (common variety affecting orbit) Mid-age women

53. CF: greater proptosis, visual impairment, boggy eyelid swelling, ipsilateral swelling temporal region of face (ICT arise from lat. Part of sphenoid ridge) Ct scan useful in assessing extent of tumor Management: Observation Subtotal resection Postoperative radiotherapy

54. References Comprehensive ophthalmology, 6 th edition, AK Khurana http://atlasgeneticsoncology.org/Tumors/EyeTumOverviewID5272.html Thank you 