intraocular tumors according to who 2018

1. INTRAOCULAR
TUMORS
PRESENTER : Dr MADHURI REDDY
MODERATOR : Dr JYOTHI A RAJ

2. Anatomy of the eye

3. • The choroid lies between
the sclera and the retinal
pigment epithelium.
• Uveal tissue spills out
into most scleral canals,
as into this scleral canal
of the long posterior
ciliary artery.
HISTOLOGY OF THE CHOROID

4. The choroid is
composed, from outside
to inside, of
• The suprachoroidal
(potential) space and
lamina fusca,
• The choroidal stroma
(which contains uveal
melanocytes,
fibrocytes, collagen,
blood vessels,and
nerves)
• The fenestrated
choriocapillaries &
• The outer aspect of
Bruch’s membrane.

5. • The capillaries of the
choriocapillaries -the largest
capillaries in the body-permit
simultaneous passage of
numerous erythrocytes.
• The choriocapillaries ,BM and
associated connective tissue
compose the outer half of
bruch’s membrane,
• The inner half is composed of
the BM and associated
connective tissue of the RPE
• The pigment granules are
larger in the retinal pigment
epithelial cells than in the
uveal melanocytes

6. 1. Internal limiting
membrane,
2. Nerve fiber layer
3. Ganglion cell layer,
4. Inner plexiform layer,
5. Inner nuclear layer
6. Outer plexiform layer;
7. Outer nuclear layer;
8. External limiting
membrane
9. Photoreceptors
10. Retinal pigment
epithelium
im
Nf
gc
Ip
In
op
on
Pr
rpe
c
mm
em
nr
HISTOLOGY OF RETINA

7. WHO CLASSIFICATION (2018)
Tumours of the iris, ciliary body, and choroid (uveal
tract)
Tumours of the retina and retinal pigment epithelium
Tumours of the optic disc and optic nerve

8. Tumours of the Iris
Pigmented epithelial cyst
Implantation cyst
Ectopic lacrimal gland
Melanocytic naevus
Ocular melanocytosis
Lisch nodule
Iris melanoma
Histiocytic tumours

9. Tumours of the ciliary body
Adenomatous hyperplasia
Reactive epithelial hyperplasia
Ciliary body adenoma
Leiomyoma
Schwannoma
Glioneuroma
Medulloepithelioma
Uveal melanocytoma
Adenocarcinoma

10. Tumours of the choroid
Bilateral diffuse uveal melanocytic hyperplasia
Choroidal and ciliary body naevi
Neurofibroma and ganglioneuroma
Schwannoma
Haemangioma
Osteoma
Choroidal and ciliary body melanomas
Primary choroidal lymphoma
Secondary lymphomatous infiltration
Leukaemic infiltration
Secondary tumors

11. Tumours of the Retina & RPE
Tumours of the neurosensory
retina
 Nodular and massive retinal
gliosis
 Astrocytic hamartoma and
astrocytoma
 Haemangioblastoma
 Cavernous haemangioma
 Retinocytoma
 Retinoblastoma
 Vitreoretinal lymphoma
 Leukaemic infiltration
 Secondary tumours
Tumours of the retinal
pigment epithelium
 Reactive hyperplasia
 Congenital hypertrophy
 Simple and combined
hamartomas
 Adenoma
 Adenocarcinoma

12. Tumours of the optic disc and
optic nerve
Primary tumours
◦ Astrocytoma and glioblastoma
◦ Meningioma of the optic nerve
◦ Medulloepithelioma
◦ Solitary fibrous tumour/haemangiopericytoma
◦ Melanocytoma
Secondary tumours

13. Broadly can be classified as
Tumor like lesions
Epithelial tumours
Melanocytic tumors
Mesenchymal tumors
Neural tumors
Glial tumors
Retinoblastoma
Histiocytic tumors
Haematolymphoid tumours
Secondary tumors

14. TUMOR LIKE
LESIONS

15. INTRAOCULAR LACRIMAL
GLAND CHORISTOMA
 The pink colored lesion,
with a clear cyst in the
inferior part of the mass.
 FNAB -Benign epithelial
cells consistent with
lacrimal gland.
 Relatively stable ;if large -
local resection

16. Lesion showing dense fibrous tissue (above) and normal
lacrimal gland tissue (below)

17. Normal lacrimal acini and ducts

18. Photomicrograph of the solid portion of the lesion,
showing glandular tissue identical to normal lacrimal
gland.

19. FUCHS ADENOMA
(FUCHS’ REACTIVE HYPERPLASIA,CORONAL
ADENOMA, FUCHS’ EPITHELIOMA, BENIGN CILIARY
EPITHELIOMA)
 Age
Elderly
 Site
Pars plicata of the ciliary body
 Microscopy
The tumor is proliferative rather than neoplastic
Benign proliferation of cords of the nonpigmented ciliary
epithelium
Intervening stroma shows abundant, amorphous,
eosinophilic, acellular basement membrane material, acid
mucopolysaccharides, and glycoprotein.

20. A. Grossly -white tumor in the pars plicata of the ciliary body
B. Histologic section shows a proliferation of nonpigmented ciliary
epithelium that is elaborating considerable basement
membrane material

21. Fuchs adenoma; generally incidental lesions
comprised of nonpigmented ciliary epithelial cells
and amorphous, hyaline material.

22. IRIS PIGMENT EPITHELIAL CYST
 Each of the IPE cysts is lined by a monolayer of IPE cells
and usually has clear fluid in the lumen

23. EPITHELIAL
TUMORS

24. MEDULLOEPITHELIOMA
 Medulloepithelioma is a congenital neuroepithelial tumor
 Origin -primitive medullary epithelium (ie, the inner layer of the
optic cup).
 Site –CB>Retina>Optic nerve
 Presentation -lightly pigmented or amelanotic cystic mass
 Types
 Nonteratoid medulloepithelioma (diktyoma)
Benign
Malignant
 Teratoid medulloepithelioma
Benign
Malignant

25. Microscopy
 Undifferentiated round to oval
cells with little cytoplasm
 Arranged in ribbons cords
sheets
 Cell nuclei are stratified in 3 to
5 layers, and the entire
structure is lined on one side
by a thin basement
membrane.
 Mucinous substance, rich in
hyaluronic acid
 Mucinous cysts
 Homer wright and flexner-
wintersteiner rosettes may
also be present.

26. Malignant large, round cells.
Positive for desmin and muscle-
specific actin, confirming that
they represent rhabdomyoblasts
Large focus of hyaline cartilage
lined by skeletal muscle

27. Photomicrograph of the lesion,
showing a vitreous-filled cyst
near the surface
Closely compact cells with
malignant features

28. Tumor showing tissue
compatible with brain
Tubules and acini of proliferating
epithelial cells and extracellular
mesenchyme-like tissue

29. Positive histochemical stain for
mucin sensitive to hyaluronidase
Colloidal iron stain showing
large amounts of
mucopolysaccharide
surrounding the
neuroepithelial elements

30. CYTOGENETICS
◦ Associated with pleuropulmonary blastoma family tumor and
dysplasia syndrome caused by DICER -1 mutations
IHC
◦ Positive -LIN28A,Vimentin,NSE,Pancytokeratin & CK18
◦ Equivocal-Chromogranin,synaptophysin,S100,HMB45,GFAP
◦ Negative -CK7,CK20,EMA
DD
◦ Retinoblastoma
◦ Persistent fetal vasculature
◦ Cataract

31. ADENOMA
 Site –Cb>choroid>rpe
 Tubular (papillary) pattern,
vacuolated (solid) pattern, or
mixture of both;
 The heavily pigmented cells
are frequently vacuolated.
 Nuclear atypia is common,
mitotic figures are rare.

32. IHC
RPE adenoma
Positive
 S-100,
 Neuron-specific enolase,
 Synaptophysin,
 Ema,
 Vimentin
CB adenoma
Positive
 S-100 protein,
 LMW CK
Negative
 Melanoma-specific antigen
 HMB45
 Cytokeratin.

33. Differential Diagnosis
Reactive prolioferations of PE
 The cells of the adenoma are variably pigmented and are
packed together tightly with little or no stroma
 The individual cells in pseudoadenomatous hyperplasia
are separated by an amorphous basement membrane-
like material and show little atypia and no mitotic figures

34. ADENOCARCINOMA
Site - Ciliary body >RPE
Tumor cells showing tubular
and papillary pattern
HP showing round to oval tumor
cells with vesicular nuclei,
prominent nucleoli, scant
cytoplasm, and high N:C ratio

35. MELANOCYTIC
TUMORS

36. NEVUS
 Most common primary
intraocular tumor.
 Localized proliferation of
melanocytic cells
 Darkly pigmented lesion
 <2 mm in thickness
 If >10 mm (giant choroidal
nevus)
 Site –iris,CB,choroid
Microscopy
 Accumulation of branching dendritic cells or spindle cells with
melanin granules in the cytoplasm.
 The nuclei are oblong or ovoid,bland with indistinct nucleoli.

37. NEVUS CELLS - TYPES
 Plump polyhedral: abundant cytoplasm is filled with
pigment and has a small, round to oval nucleus with
appearance
 Slender spindle: cytoplasm contains scant pigment and a
small, dark, elongated nucleus
 Plump fusiform dendritic: morphology is intermediate
between plump polyhedral and slender spindle
 Balloon cells: abundant, foamy cytoplasm lacks pigment
and has a bland nucleus

38. Choroidal nevus, showing closely
compact benign spindle cells.
Iris nevus with a surface plaque. The
surface plaque is composed of bland
spindled cells. The iris stroma is diffusely
populated by nevus cells.

39. MELANOCYTOMA
 Variant of melanocytic nevus
 Site -optic disc,ciliary body
choroid ,iris
 No specific diagnostic criteria
 Deeply pigmented due to
abundant large melanosomes
in the cytoplasm
 Magnocellular nevus
 Necrosis is a common feature,
sometimes with pseudocysts
containing free-floating
melanophages.

40. Dense cytoplasmic melanin that
precludes a view of cell detail
Bleached section of the lesion
allowing better visualization of
cell detail

41. This bleached section shows
plump, round cells with relative
uniform nuclei
Area of necrosis within the
tumor

42. OCULAR MELANOCYTOSIS
(MELANOSIS OCULI )
Congenitally increased population of non
proliferating hyperpigmented melanocytes
U/L (occasionally bilateral) hyperpigmentation of the
sclera and uveal tract
Flat, gray-to brown patches of pigmentation on
sclera
Heterochromia iris

43. The presence of foci of orange pigment over
choroidal melanocytosis is a suggestion that the
lesion is becoming thicker and potentially evolving
into choroidal melanoma
FORME FRUSTE (iris mammillations )
Cell of origin
Abnormal migration of neural crest derived
melanocytes to the eye

44. Increased choroidal thickness and
hyperpigmentation secondary to increased
number of choroidal melanocytes

45. LISCH NODULE
(IRIS HAMARTOMA ;MELANOCYTIC HAMARTOMA)
It is an iris hamartoma consisting of proliferation of
melanocytes occurring in the setting of NF-1
Risk factors
NF1 mutation
UV radiation
Iris color

46. Lisch nodule, showing an elevated lesion composed of
spindle nevus cells on the anterior surface of iris in a
patient with NF type 1.

47. UVEAL MELANOMA
Most frequent primary intraocular neoplasms in
adults; rare in adolescents and children.
Most common in the choroid, with less than a
quarter found in ciliary body or iris
Risk factors
• Fair complexion
• Light irides
• Oculodermal and ocular melanocytosis
• Von recklinghausen disease
• Preexisting benign nevi

48. Site
Iris
Ciliary body
Choroid
Cell of origin
Neural crest derived melanocytes
Modified callender classification:
1. Spindle cell melanoma
2. Epithelioid melanoma
3. Mixed-cell type (mixture of spindle and epithelioid cells)

49. Clinical features
Presents as
• An elevated mass with varying degrees of
pigmentation
• Multiple small nodules (tapioca iris melanoma)
• A broad carpet of growth on the surface
An irregular, slate-gray, solid, subretinal tumor
producing an overlying retinal detachment
Decreased vision
They generally appear as a discoid, globular, or
mushroom-shaped mass
Sometimes spread diffusely or extend out along
scleral canals into the orbit.

50. Melanoma of iris
encroaching the pupil
Malignant melanoma of
choroid erupting through
Bruch’s membrane forming a
mushroom-shaped subretinal
mass.

51. Fundus photograph of the
same individual several years
later; the tumor has grown
and has ruptured through the
Bruch membrane.
Fundus photograph with a
relatively flat pigmented lesion
of the choroid near the optic
disc.

52. Iris melanoma – Cytology
showing melanoma cells with
with atypia and prominent
nucleoli
Cytopathology, showing
pigmented spindle melanoma
cells

53. FNAC : Epithelioid type

54. Gross photograph of a
choroidal melanoma that has
ruptured the Bruch
membrane. The overlying
retina is detached.
Pigmented ciliary body
melanoma causing subluxation
of the lens

55. Spindle-A cells have slender, elongated nuclei with small
nucleoli. A central stripe may be present down the long
axis of the nucleus

56. Spindle-B cells -higher N:C ratio, more coarsely
granular chromatin, and plumper, large nuclei. Nucleoli
are prominent, and mitoses are present,

57. A choroidal melanoma comprised predominantly of
epithelioid cells.

58. IHC
 S-100(cytoplasmic and nuclear)
 HMB-45 (cytoplasmic)
 Mart-1 (Melan-A)(cytoplasmic)
 Tyrosinase (cytoplasmic)
 SOX10 (nuclear)
 BAP1(nuclear)
 MITF(nuclear )
CYTOGENETICS
 Chromosome 3 loss
 Chromosome 6p & 8q gain
 Mutations in the GNAQ or GNA11
 Mutations in BAP1

59. Differential diagnosis
◦ Metastatic carcinoma
◦ Localized hemorrhage beneath the retina or
between the pigment epithelium and choroid,
◦ Focal areas of proliferation of the RPE
◦ Posterior scleritis,
◦ Nevi
◦ Hemangiomas
◦ Melanocytoma
◦ Bilateral diffuse uveal melanocytic proliferation
(BDUMP).

60. PROGNOSTIC FACTORS
 The mean of the 10 largest melanoma cell nucleoli (MLN)
 Intrinsic tumor extravascular matrix patterns ;tumors
containing more complex extravascular matrix patterns
as closed loops or networks (3 back-to-back loops)
 Microvascular density
 Tumor infiltrating macrophages
 Extrascleral extension
 Anterior or juxtapapillary location of the tumor
 The presence of tumor-infiltrating lymphocytes

61. Extravascular matrix patterns in uveal melanoma.
 Closed loop (L) (PAS stain).
 Network (3 or more back-to-back loops) (PAS stain).

62. IRIS
 T1 Tumour limited to iris
T1a not more than 3 clock hours in size
T1b more than 3 clock hours in size
T1c with secondary glaucoma
 T2 Tumour confluent with or extending into the CB, choroid, or both
T2a Tumour confluent with or extending into the CB without
secondary glaucoma
T2b Tumour confluent with or extending into the choroid without
secondary glaucoma
T2c Tumour confluent with or extending into the CB and/or choroid
with secondary glaucoma
 T3 Tumour confluent with or extending into the CB, choroid or both, with
scleral extension
 T4 Tumour with extrascleral extension
T4a ≤ 5mm in diameter
T4b > 5 mm in diameter
TNM CLASSIFICATION OF UVEAL MELANOMA

63. Classification for ciliary body and choroid uveal melanoma
based on thickness and diameter.
CILIARY BODY AND CHOROID

64. T1 Tumour size category 1
T1a without CB involvement and extraocular extension
T1b with CB involvement
T1c without CB involvement but with extraocular extension ≤ 5
mm in diameter
T1d with ciliary body involvement and extraocular extension ≤ 5
mm in diameter
T2 Tumour size category 2
T2a without CB involvement and extraocular extension
T2b with ciliary body involvement
T2c without ciliary body involvement but with extraocular
extension ≤ 5 mm in diameter
T2d with ciliary body involvement and extraocular extension ≤5
mm in diameter

65.  T3 Tumour size category 3
T3a without ciliary body involvement and extraocular extension
T3b with ciliary body involvement
T3c without ciliary body involvement but with extraocular ≤ 5
mm in diameter
T3d with ciliary body involvement and extraocular ≤5 mm in
diameter
 T4 Tumour size category 4
T4a without ciliary body involvement and extraocular extension
T4b with ciliary body involvement
T4c without ciliary body involvement but with extraocular
extension ≤5 mm in diameter
T4d with ciliary body involvement and extraocular extension ≤ 5
mm in diameter
T4e Any tumour size category with extraocular extension > 5 mm
in diameter

66. N – Regional Lymph Nodes
 NX Regional lymph nodes cannot be assessed
 N0 No regional lymph node metastasis
 N1 Regional lymph node metastasis
M – Distant Metastasis
 M0 No distant metastasis
 M1 Distant metastasis
 M1a Largest metastases 3 cm or < in greatest
dimension
 M1b Largest metastases is >3 cm in greatest
dimension but not > 8 cm
 M1c Largest metastases is >8 cm in greatest
dimension

67. Stage I T1a N0 M0
Stage IIA T1b–d,
T2a N0 M0
Stage IIB T2b,
T3a N0 M0
Stage IIIA T2c–d N0 M0
T3b–c N0 M0
T4a N0 M0
Stage IIIB T3d N0 M0
T4b–c N0 M0
Stage IIIC T4d–e N0 M0
Stage IV Any T N1 M0
Any T Any N M1
PATHOLOGICAL STAGING

68. MESENCHYMAL
TUMORS

69. LEIOMYOMA
 Female preponderance
 Site -CB> anterior choroid
 DD-amelanotic spindle cell nevus
low-grade melanoma
 IHC -muscle-specific antigen,
smooth muscle actin,
vimentin
Mesectodermal leiomyoma
 Cell of origin –neural crest derived
CB muscle
 DD –Astrocytic tumors

70. Mesectodermal leiomyoma
Widely spaced tumor cell nuclei set in a
fibrillar cytoplasmic matrix

71. OSTEOMA
 Female preponderance ;
 20-30yrs
 Site –M/c-choroid
 Slightly elevated, yellow-white
juxtapapillary lesion
 HPE-choroid is replaced by
mature bone that contains
marrow spaces.

72. The plaque of mature bone at the level of the choroid.

73. HEMANGIOMA
 Site :M/C –Choroid ;followed by
retina
 Occurs in 2 specific forms:
circumscribed (ie, localized) and
diffuse.
 Circumscribed - occurs in
patients without systemic
disorders;
 Diffuse-seen in patients with
Sturge-Weber syndrome
 Rx –Photodynamic therapy

74. Microscopic section through a
superficial aspect of the mass,
showing dilated veins compatible
with choroidal hemangioma and
overlying fibrous metaplasia of the
retinal pigment epithelium and
cystoid retinopathy
Section through the main aspect of
the tumor, showing large, thin-
walled vascular channels filled
with blood, compatible with
choroidal hemangioma.

75. Cavernous hemangioma of retina
A grape like cluster of clumped
vascular saccules

76. HEMANGIOBLASTOMA
(ANGIOMATOSIS RETINAE ,RETINAL
CAPILLARY HEMANGIOMA)
 Site –retina,rarely optic nerve
 Sporadic /AD
 Red to orange tumors arising
within the retina with large-
caliber, tortuous afferent and
efferent blood vessels
 Associated with VHL syndrome
 Rx -photocoagulation for smaller
lesions; cryotherapy for larger
and more peripheral lesions

77. Hemangioblastoma
• The pale, vacuolated
neoplastic cells are
interspersed with
proliferating vessels.
• Secondary bone
formation is present
in this case.

78. NEURAL TUMORS

79. MENINGIOMA
 The tumor (primary or
secondary) is usually
meningothelial
 Composed of plump cells with
indistinct cytoplasmic margins
(syncytial growth pattern)
 Arranged in whorls.
 Psammoma bodies are sparse

80.  Meningioma (between arrows) of the optic nerve (ON) originates
from the arachnoid
 The whorls of tumor cells, characteristic of meningothelial
meningioma

81. Low-power photomicrograph of
the sectioned eye, showing
elevated choroidal mass.
Whorls of benign spindle cells
SCHWANNOMA

82. Intraocular and orbital plexiform
neurofibroma, showing diffuse
thickening of the choroid
The cells that thicken the uveal
tract are believed to represent a
combination of neurons and
melanocytes.
NEUROFIBROMA

83. GLIAL TUMORS

84. GLIONEUROMA
Tumor shows tissue similar to brain tissue, containing ganglion
cells
GLIONEUROMA

85. ASTROCYTOMA
 Site -optic nerve head , optic nerve,retina
 1st decade of life
 M/C -Low-grade juvenile pilocytic astrocytomas
 Associated with NF1
 The nerve shows fusiform or sausage-shaped
enlargement
 Primary malignant gliomas of the anterior visual pathways
occur mainly in adults and show
Nuclear pleomorphism,
High mitotic activity
Necrosis
Hemorrhage

86. Cytopathology of the lesion demonstrating ovoid to round cells with
benign nuclear features.
IHC showed positive reaction to glial fibrillary acidic protein and negative
reaction to the melanoma-specific antigen HMB-45, and epithelial
markers, supporting the diagnosis of astrocytic neoplasm

87. Cytopathology with IHC of a fine-needle aspiration biopsy
specimen demonstrating positive reaction to glial fibrillary acidic
protein. (×200.) Markers for epithelial cells were negative

88. Photomicrograph of the lesion, showing
well-differentiated astrocytes

89. The right side of this photomicrograph demonstrates a normal
optic nerve (asterisk); the left side shows a pilocytic astrocytoma

90. The neoplastic glial cells are elongated to resemble hair

91. Degenerating eosinophilic filaments, which are known as
Rosenthal fibers (arrows), may be observed in these tumors.

92. RETINOCYTOMA
Retinocytoma is characterized histologically by
numerous fleurettes admixed with individual cells
that demonstrate varying degrees of photoreceptor
differentiation .
Retinocytoma should be differentiated from the
spontaneous regression of retinoblastoma that is the
end result of coagulative necrosis.

93. Retinocytoma
HP : Cells have bland round nuclei and poorly defined
clear cytoplasm

94. Retinocytoma.
The exquisite degree of photoreceptor differentiation with
apparent stubby inner segments (arrow) (H&E stain).

95. Retinocytoma differs from retinoblastoma in the
following ways:
Retinocytoma cells have more cytoplasm and
more evenly dispersed nuclear chromatin than
retinoblastoma cells.
Mitoses are not observed in retinocytoma
Although calcification may be identified in
retinocytoma, necrosis is usually absent

96. RETINOBLASTOM
A

97. Mc intraocular malignancy in children
Cell of origin -retinal precursor cells
Familial /sporadic
U/L or B/L
Trilateral –B/L retinoblastoma with pinelaoblastoma

98. Clinical features
Leukocoria
Strabismus
Poor vision
Buphthalmos
Neovascular glaucoma
Iris neovascularisation

99. Types
◦ Exophytic (into the subretinal area)
◦ Endophytic (into the vitreous)
◦ Diffuse infiltrating (tumor grows in a flat,infiltrating
pattern and does not appear as an elevated mass)

100. Bilateral leukocoria in a 3-month-
old child
Total retinal detachment with
iris neovascularization
secondary to exophytic
retinoblastoma.

101. Gross appearance of the
retrolental area, showing
characteristic seeding of white
tumor cells in the ciliary body
and zonule
Fluorescein angiogram of the
eye depicting the dilated retinal
blood vessels over the tumor
and leakage of dye from the
abnormal iris vasculature.

102. Bilateral retinoblastoma showing a white mass consisting
of detached retina and neoplastic tissue immediately behind
the lens in each eye.

103. Cytology of the vitreous fluid.
Neoplastic cells forming loosely cohesive clusters with scant
cytoplasm, high N : C ratio,“salt-and-pepper” chromatin
pattern,nuclear molding and small single conspicuous nucleoli

104. Retinoblastoma. Sheets of cells with suggestions of
rosette formation. The cytoplasm is scant. The nuclei are
round with occasional nucleoli and numerous mitotic
figures (MGG)

105. Gross
Chalky white mass, often friable
Can present with different growth patterns
exophytic, endophytic, mixed and diffuse.
Extension to the uvea, epibulbar structures and optic
nerve is grossly visible in advanced cases.
Choroidal invasion may also be grossly visible

106. Gross photograph of
retinoblastoma
Section of the enucleated eye
the hyphema and the diffuse
irregular
white mass involving the entire
sensory retina

107. Dystrophic
calcification
necrosis

108. Flexner-
Wintersteiner
rosettes
Homer Wright rosettes
Fleurette
ROSETTES IN RETINOBLASTOMA

109. Highly differentiated retinoblastoma with
photoreceptor differentiation;the eosinophilic “stalks”
representing photoreceptors.

110. Anaplastic retinoblastoma with highly
pleomorphic cells showing angular molding and
wrapping as well as prominent nucleoli.

111. GRADING OF ANAPLASIA IN RETINOBLASTOMA
Retinocytoma Mild anaplasia
Moderate anaplasia Severe anaplasia

112. Artefactual seeding of the choroid
Intact retinoblastoma in the upper and
left portion of the micrograph.
Toward the lower right side of the,
scattered tumor cells appear to have
no relationship to the collagenous
strands of the choroid.
Retinoblastoma with true invasion
into the choroid.
The RPE is evident as a pigmented
demarcation extending from upper
left to lower right.
The choroid is beneath the retinal
pigment epithelium

113. DIFFERENTIAL DIAGNOSIS
Retinocytoma
Neuroblastoma
Medulloblastoma
Leukemia
Retinal dysplasia
Small round blue cell tumor metastases

114. IHC
 Synaptophysin,
 Retinal-binding protein,
 Retinal s-antigen,
 Interphotoreceptor retinal-binding protein,
 Cone opsin, and rod opsin

115. Cytogenetics
Somatic or germline mutation of chromosome 13
 Alfred Knudson’s two-hit model
Retinoblastoma arises as a result of two mutational
events involving the RB1 gene(13q14)(27 exons)
Autosomal dominant

116.  In the hereditary form,
The first mutation occurs in a germinal (prezygotic) cell
The second mutation occurs in a somatic (postzygotic)
neural retinal cell,
 Resulting in multiple neural retinal tumors (multifocal in
one eye,bilateral, or both), as well as in primary tumors
elsewhere in the body (e.g., Pineal tumors ,sarcomas and
tumors in the lung, bladder, bone, soft tissues, skin,
brain )

117. In the sporadic form;
If both mutations occur in the same somatic
(postzygotic) cell, a single, unifocal, unilateral
retinoblastoma results.
Because the mutations occur in a somatic cell,the
resultant condition is nonheritable.

118. PATHOGENESIS OF RETINOBASTOMA

119.  New constitutional mutations arise mostly in a parental
germ cell, usually paternal.
 Less frequently, the RB1 mutation arises in one cell of the
multicell embryo, resulting in mosaicism in the proband.
 RB1mutations include the full range of deleterious
mutations: point mutations, small and large deletions, and
deep intronic and splice mutations.
 2 common mutations are
Methylation (addition of a methyl group at CpG sites) of the
promoter in somatic cells,
Translocation leading to transcriptional silencing in germ cells

120. ◦ Most RB1 mutations result in an inactive retinoblastoma
protein (pRB)
◦ Compared with completely inactive pRB, partly inactive
pRB reduces penetrance (fewer affected gene carriers) and
expressivity (fewer tumours in those affected, with more
unilaterally affected)
◦ Children with loss of RB1 and flanking genes because of
large deletions on chromosome 13q can also have
developmental anomalies (eg, facial dysmorphia,
congenital abnormalities, mental retardation, and motor
impairment).

121. The International classification of Retinoblastoma

122. T – Primary Tumour
pTx Primary tumour cannot be assessed
pT0 No evidence of primary tumour
pT1 Tumour confined to eye with no optic nerve or
choroidal invasion
pT2 Tumour with intraocular invasion
pT2a Focal choroidal invasion and pre or intralaminar
invasion of the optic nerve head
pT2b Tumour invasion of stroma of iris and/or trabecular
meshwork and/or Schlemm’s canal
TNM CLASSIFICATION OF RETINOBLASTOMA

123. pT3 - Tumour with significant local invasion
pT3a Choroidal invasion >3 mm in diameter or multiple
foci of invasion totalling >3 mm or any full thickness
involvement
pT3b Retrolaminar invasion of optic nerve without
invasion of transected end of optic nerve
pT3c Partial thickness involvement of sclera within the
inner 2/3rd
pT3d Full thickness invasion into 1/3rd of the
sclera and/or invasion into or around emissary
channels
pT4 - Extraocular extension: Tumour invades optic nerve at
transected end, in meningeal space around the optic
nerve, full thickness invasion of the sclera with invasion of
the episclera, adipose tissue, extraocular muscle, bone,
conjunctiva, or eyelid.

124. pN– Regional Lymph Nodes
pNx Regional lymph nodes cannot be assessed
pN0 No regional lymph node involvement
pN1 Regional lymph node involvement
pM – Metastasis
cM0 No distant metastasis
pM1 Distant metastasis
pM1a Single or multiple metastasis to sites other
than CNS
pM1b Metastasis to CNS parenchyma or CSF
fluid

125. Stage I T1,T2, T3 N0 M0
Stage II T4 N0 M0
Stage III Any T N1 M0
Stage IV Any T Any N M1
PATHOLOGICAL STAGE

126. HISTIOCYTIC
TUMORS

127. Juvenile xanthogranuloma
Rosai dorfmann disease
Langerhans cell histiocytosis
Erdheim chester disease

128. JUVENILE
XANTHOGRANULOMA
 Touton giant cells with ring
of nuclei, inner eosinophilic
cytoplasm, and outer
vacuolated or foamy
cytoplasm
 Foamy histiocytes
 Lymphocytes

129. It is a granulomatous and infiltrative disorder of unknown
etiology with proliferation of cholesterol-containing
histiocytes and peculiar bone involvement.
ERDHEIM CHESTER DISEASE
ROSAI DORFMANN
DISEASE
 Intra ocular Rosai-Dorfman disease (RDD) is
an extremely rare disease .
 Proliferation of morphologically distinctive
histiocytes showing emperipolesis (large
histiocytosis with intact phagocytosed
lymphocytes),
 An inflammatory background of
lymphocytes and conspicuous numbers of
plasma cells

130. LANGERHANS CELL HISTIOCYTOSIS
Langerhans cells with folded or grooved nuclei and
moderately abundant pale cytoplasm are mixed with
a few eosinophils.

131. HEMATOLYMPHOID
NEOPLASMS

132. LYMPHOMA
 Site – Choroid,Retina
 Choroidal lymphoma is mostly secondary to systemic
disease,primary is rare
 Primary vitreoretinal lymphoma -about 65% of cases of
intraocular lymphoma. Bilateral in about 90% of cases
 Mostly malignant proliferation of B lymphocytes
 Cell of origin
Choroid –reactive lymphocytes
PVRL-cells at a late stage in germinal B cell
differentiation
◦ IHC-CD79a,CD20,PAX5,BCL2,BCL6,MUM1,IgM
◦ DD-Benign reactive lymphoid hyperplasia of uvea (BRLH)

133. CYTOLOGY
(Vitreous FNAB)
 Large cell lymphoma
 Necrosis

134.  Replacement of
the choroid by
lymphoma. The
overlying retinal
pigment
epithelium is intact
 HP –malignant
lymphoma cells

135. LEUKEMIA
Infiltration of the uvea, retina and optic disc by
leukemic blast cells with extensive hemorrhage.
◦ The tumor cells often fill the retinal and uveal blood
vessels and have a tendency to invade deep into the optic
nerve
 Leukemic retinopathy
intraretinal and subhyaloid hemorrhages,
hard exudates,
cotton-wool spots, and
white-centered retinal hemorrhages
 True leukemic infiltrates are less common
appear as yellow deposits in the retina and the
subretinal space.
Due to anemia
Hyperviscosity
thrombocytopenia

136. Cytopathology of a needle biopsy of the anterior chamber
material demonstrating leukemic blast cells.

137. Photomicrograph of the involved retina, showing intravascular and
extravascular infiltration of leukemic blast cells.

138. SECONDARY TUMORS
◦ Metastatic cancer probably represents the most common
form of intraocular malignancy.
◦ Metastatic cancer reaches the intraocular structures
through hematogenous routes
◦ Most common develops in the uveal tract,
 >90% involving the posterior aspect of the choroid
 <10% arising in the iris and/or ciliary body
◦ Metastases to retina,optic disc, and vitreous are very
uncommon

139. ◦ Most intraocular metastases are carcinomas, with
sarcomas and melanomas being less common.
◦ Most common
Men - Lung
Women –breast
◦ Less often, the primary malignancy arises from carcinoma
of the alimentary tract, kidney, thyroid gland, pancreas,
prostate, and other organs
◦ Others like cutaneous melanoma and bronchial carcinoids
tumors .

140. Lung carcinoma metastasis to the retina
Vitreous aspirate, showing an aggregate of tumor cells,
characteristic of adenocarcinoma of the lung.

141. GROSSING OF OCULAR SPECIMENS
Specimens
• Enucleation of eyeball
• Exenteration of orbital contents (for lid, ocular &
orbital tumors)

142. ◗ 1st cut: posteroanteriorly,starting
adjacent to the optic nerve to the
periphery of the cornea.
◗ 2nd cut: a second plane of section,
parallel to the first,to include the
neoplasm
◗ Both cuts are made in such a way
that the neoplasm is included in
central slice.
B
Identify as right or left eye by
locating the positions of insertion
of the superior and, inferior oblique
muscles and insertion of the optic
nerve which is inferomedial

143. FOR OCULAR TUMORS

144. A. The goal of sectioning is
to obtain a pupil–optic
nerve (PO) section that
contains the maximum
area of interest.
B. Two caps, or calottes,
are removed to obtain a
PO section.
C. The first cut is generally
performed from
posterior to anterior.
D. The second cut yields
the PO section
GROSS DISSECTION OF A GLOBE.

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