1. Globe Tumours and mimics

2. CASE 1 Epilepsy Intellectual impairment Adenoma sebaceum

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

4. lesion

5. Pink fibrillar, process bearing cells with calcification calcium

7. DIAGNOSIS ?

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

9. CASE 2 Epilepsy Intellectual impairment glaucoma

10. sclera Choroid space lesion

12. DIAGNOSIS ?

13. 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.

14. CASE 3

15. Mass in eye

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

17. or

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

19. DIAGNOSIS ?

20. Ciliary body uveal melanoma

21. 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

22. 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

23. Direct through sclera into orbit

24. 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

25. 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

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

27. CASE 4

30. Optic nerve Basophilic intraocular mass

31. Optic nerve Another example of the same lesion

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

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

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

35. Lamina cribrosa

36. Invasion of optic nerve by tumour cells

37. multifocality

38. Tumour growth around blood Vessels. Pink areas are necrotic tumour

39. Necrotic tumour-pink Arrows=dystrophic calcification

40. Dystrophic calcification Fractured during processing

41. Choroidal invasion

43. Ectropion uveae Anterior iris Posterior iris

44. Rubeosis-note vessels on anterior iris stromal surface

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

46. RETINOBLASTOMA

47. Retinoblastoma Occurs in 1: 20-30 000 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.

48. 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.

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

50. 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.

51. 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

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

57. 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

58. 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.

59. 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.

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

62. 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.

63. OTHER IMPORTANT INTRAOCULAR TUMOURS

65. ATYPICAL EPITHELIUM-CONTAIN MUCIN

66. GLANDULAR STRUCTURE CONTAINING NECROTIC MATERIAL

67. DIAGNOSIS ?

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

69. 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; 1265-1276) Breast 47 % Lung 21% GIT 4% Skin melanoma 3% Kidney 2% Prostate 2% Others 21%

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

71. 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.

72. Tumour mimics

73. CASE 1

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

76. Lamellar bone with osteocytes

77. Polarisation microscopy shows boney seams

78. DIAGNOSIS ?

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

80. CASE 2

81. History leukocoria

82. sclera Optic nerve Subretinal pink exudate RD

83. Cholesterol clefts and foamy macrophages

84. Some macrophages contain shed RPE melanosomes

85. Very dilated retinal vessels containing eosinophilic exudate

87. DIAGNOSIS?

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

89. CASE 3

90. HISTORY Leukocoria

95. DIAGNOSIS?

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

97. CASE 4

98. HISTORY MALE 75 YEARS OLD MASS POSTERIOR POLE

99. Subneural retinal heamorrhage

103. DIAGNOSIS ?

104. Haemorrhage from sub- retinal neovascular membrane Can mimic melanoma