Globe Tumours and mimics

CASE 1 Epilepsy Intellectual impairment Adenoma sebaceum

Retinal based lesion Flat base Endopytic with smooth outline No invasion of ocular coats

lesion

Pink fibrillar, process bearing cells with calcification calcium

DIAGNOSIS ?

Retinal astrocytoma Bad term because not a tumour, but hamartoma=tissue that should be there but in abnormal amounts or aberrant architecture.

CASE 2 Epilepsy Intellectual impairment glaucoma

sclera Choroid space lesion

DIAGNOSIS ?

Diffuse Choroidal haemangioma Actually a hamartoma Back to back thin walled vascular profiles containing blood. Sporadic and that associated with Sturge-Weber, as in this case Second commonest primary intraocular tumour Capillary and cavernous types according to size of vessels.

CASE 3

Mass in eye

Spindle cells arranged in syncitium ie. poorly defined cell boundaries Spindle shaped nuclei and cytoplasm

or

Epithelioid cells Draw a pencil line around each cell Cells-rounder/ ovoid Nucleoli Well defined cell boundaries Note melanin brown pigment

DIAGNOSIS ?

Ciliary body uveal melanoma

UVEAL MELANOMA Risk factors: Age, race (white: black 10:1), light irides, dysplastic naevus syndrome, neurofibromatosis 1, familial tendency, uveal naevi, oculodermal or uveal melanocytosis

GROSS PROGNOSTIC FACTORS SITE: Iris melanoma-10 x less mortality than ciliary and choroidal MM Tumour size-The bigger (height and scleral base) the tumour the worse the prognosis (COMMS study). Growth pattern-Ring and diffuse worse prognosis than focal elevating mass Extraocular spread-worse prognosis

Direct through sclera into orbit

MICROSCOPIC PROGNOSTIC FACTORS CELL TYPE-CALLENDER CLASSIFICATION The more epithelioid cells, the worse the prognosis Presence of loops and networks matrix patterns (Folberg et al), with PAS stain

CYTOGENETIC PROGNOSTIC FACTORS (FOR CILIARY BODY AND CHOROIDAL MELANOMA) MONOSOMY 3-POOR PROGNOSIS ISOCHROMOSOME 8q (+/- amplification)-POOR PROGNOSIS THESE CHANGES CORRELATE WITH CILIARY BODY LOCATION AND EPITHELIOID CELL PHENOTYPE. REDUCED SURVIVAL AND REDUCED DISEASE FREE INTERVAL

melanoma Serous fluid Between RPE and neural retina Migrating and proliferating RPE cells Tumour related serous RD

CASE 4

Optic nerve Basophilic intraocular mass

Optic nerve Another example of the same lesion

Flexner-Wintersteiner rossettes -lumen surrounded by rosette of primitive neuroblastic cells Pathognemonic of this lesion Homer Wright-rosette=solid pink Centre without lumen

Loads of Homer-Wright Rosettes Remember-not specific For this lesion

Fleurettes-indicate photoreceptor differentiation Eosiniphilic finger-like processes protruding From tumour cells-sign of high differentiation

Lamina cribrosa

Invasion of optic nerve by tumour cells

multifocality

Tumour growth around blood Vessels. Pink areas are necrotic tumour

Necrotic tumour-pink Arrows=dystrophic calcification

Dystrophic calcification Fractured during processing

Choroidal invasion

Ectropion uveae Anterior iris Posterior iris

Rubeosis-note vessels on anterior iris stromal surface

Secondary angle closure, from peripheral anterior synaechiae, secondary to rubeosis Trabecular meshwork

RETINOBLASTOMA

Retinoblastoma Occurs in 1: live births. Commonest paediatric intraocular malignant tumour. 94 % of affected children have no family history. 6 % have family history-usually autosomal dominant inheritance, with incomplete penetrance. Of these cases, 30 % bilateral.

Retinoblastoma Retinoblastoma gene-Rb1-180 kb-chromosome 13. Encodes anti-oncogenic protein. Only one Rb1 gene (heterozygous) is required to suppress the formation of retinoblastoma tumour. Two abnormal Rb1 genes (homozygous) required for retinoblastoma tumour development. This is basis of Knudson’s 2 hit hypothesis.

Retinoblastoma Children with a germinal mutation, inherit the first ‘hit’ Only one additional genetic event (somatic mutation) required for retinoblastoma development.

Patterns of inheritance Familial and Sporadic Familial-germline mutations in all body cells. Early onset tumour, bilaterality or multifocal retinoblastoma. Risk of pinealoblastoma, fibrosarcoma and osteosarcoma.

Sporadic- 2 environmental (somatic) hits in retinal cell triggers tumour. Such mutations affect 1 eye only, unifocal tumour and develop later than familial RB. No risk of other malignancies

Clinical features Usually child before 3 years Leukocoria, strabismus (squint) or visual symptoms.

Pathology Micro-”small round blue cell tumour”, arising from retinal parenchyma. Differentiating towards photoreceptors. Cytological differentiation indicated by: Flexner-Wintersteiner rosettes Flexner-Wintersteiner rosettes Homer-Wright rosettes Homer-Wright rosettes Fleurettes Fleurettes

Modes of spread Invade optic nerve-brain Invasion of meninges-CNS Direct transcleral spread to orbital soft tissues-paranasal sinuses, nasopharynx and cranial cavity Haematogenous-brain, bone and lungs Lymphatic-associated with conjunctival infiltration.

Gross / Clinical Prognostic factors MetastasisTrilateralBilateralMultifocal Orbit invasion Optic nerve invasion Scleral invasion Choroidal invasion Above if present-bad prognosis Remember that a trilateral, bilateral and multifocal Retinoblastoma generally means germ cell mutation in Rb gene. The histological factors have much less significance compared to above gross / clinical prognostic factors.

DIFFERENTIAL FOR RETINOBLASTOMA ROPPHPV Congenital cataract ToxocariasisToxoplasmosis Retinal astrocytoma Coat’sMedulloepithelioma Retinal angiomas Coloboma Retinal detachment Norrie’s disease

Prognostic factors Extent of optic nerve invasion The mortality increases with increasing extent of optic nerve invasion. Magramm proposed the following grading system for the degree of optic nerve invasion: Grade 1 superficial invasion of the optic nerve head only (prelaminar). Grade 1 superficial invasion of the optic nerve head only (prelaminar). Grade 2 involvement up to and including the lamina cribrosa (laminar). Grade 2 involvement up to and including the lamina cribrosa (laminar). Grade 3 involvement beyond the lamina cribrosa (retrolaminar). Grade 3 involvement beyond the lamina cribrosa (retrolaminar). Grade 4 involvement up to and including the surgical margin. Grade 4 involvement up to and including the surgical margin. Grade 3 and 4 optic nerve invasion carry the worst prognosis, with respect to metastatic rate and mortality.

OTHER IMPORTANT INTRAOCULAR TUMOURS

ATYPICAL EPITHELIUM-CONTAIN MUCIN

GLANDULAR STRUCTURE CONTAINING NECROTIC MATERIAL

DIAGNOSIS ?

METASTATIC ADENOCARCINOMA TO CHOROID Always remember this for cause of intraocular mass

Metastases and the choroid Mets=commonest intraocular tumour 90% choroid, 10% iris and ciliary body because uvea is vascular bed. Shield’s and Shield’s-520 cases (1997 Ophthalmology 104; ) Breast 47 % Lung 21% GIT 4% Skin melanoma 3% Kidney 2% Prostate 2% Others 21%

Uveal mets. Often multi-focal Clinical differential diagnosis-uveal melanoma

Uveal mets. 25 % of cases of patients with uveal mets have no history of primary cancer -the ophthalmologist is the first to make a diagnosis of metastatic disease.

Tumour mimics

CASE 1

History Doctor, when I eviscerated this eye, there was a rock hard mass at the posterior pole…..? ?? Malignant tumour

Lamellar bone with osteocytes

Polarisation microscopy shows boney seams

DIAGNOSIS ?

Phthisis with intraocular bone formation Bone arises from RPE transdifferentiation to fibroblasts- lay down collagen-then ossify

CASE 2

History leukocoria

sclera Optic nerve Subretinal pink exudate RD

Cholesterol clefts and foamy macrophages

Some macrophages contain shed RPE melanosomes

Very dilated retinal vessels containing eosinophilic exudate

DIAGNOSIS?

Coat’s disease Saccular vascular aneurysmal malformations-subretinal exudation Simulate RB Remember-Norrie’s disease gene contribution in some cases.

CASE 3

HISTORY Leukocoria

DIAGNOSIS?

PHPV Microphthalmic eye Unilateral Retrolental fibrovascular mass, with elongated ciliary processes Cataract formation Retinal tractional changes Persistence of primary vascularised vitreous with hyaloid vessel

CASE 4

HISTORY MALE 75 YEARS OLD MASS POSTERIOR POLE

Subneural retinal heamorrhage

DIAGNOSIS ?

Haemorrhage from sub- retinal neovascular membrane Can mimic melanoma