Transcript Globe tumours and mimics

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
Serous fluid
Between RPE
and neural retina
Tumour
related
serous RD
melanoma
Migrating and
proliferating
RPE cells
CASE 4
Basophilic intraocular
mass
Optic nerve
Another example
of the same lesion
Optic nerve
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
Anterior
iris
Ectropion uveae
Posterior
iris
Rubeosis-note
vessels on
anterior iris
stromal surface
Trabecular
meshwork
Secondary angle closure , from
peripheral anterior synaechiae,
secondary to rubeosis
RETINOBLASTOMA
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.
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:
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Flexner-Wintersteiner rosettes
Homer-Wright rosettes
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
Metastasis
Trilateral
Bilateral
Multifocal
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
ROP
PHPV
Congenital cataract
Toxocariasis
Toxoplasmosis
Retinal astrocytoma
Coat’s
Medulloepithelioma
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:
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Grade 1 superficial invasion of the optic nerve head only (prelaminar).
Grade 2 involvement up to and including the lamina cribrosa (laminar).
Grade 3 involvement beyond the lamina cribrosa (retrolaminar).
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; 1265-1276)
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 fibroblastslay down collagen-then ossify
CASE 2
History
leukocoria
Subretinal pink exudate
RD
sclera
Optic nerve
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 subretinal
neovascular membrane
Can mimic melanoma