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Transcript
8/1/2013
You Can’t Afford to Miss This!
Understanding Posterior
Ocular Tumors
Lauren L. Richards, OD
Carlo J. Pelino, OD, FAAO
Disclosure Statement:
• Nothing to disclose
Please silence all mobile devices.
Unauthorized recording of this
session is prohibited.
You Can’t Afford
To Miss This!
Understanding Posterior
Ocular Tumors
Lauren L. Richards, OD
Carlo J. Pelino, OD, FAAO
The Pennsylvania College of Optometry at Salus University
Squamous Cell Carcinoma
tumor /tu·mor/ (too´mer)
also called neoplasm. a new growth of tissue characterized by
progressive, uncontrolled proliferation of cells. The tumor may be
localized or invasive, benign or malignant. A tumor may be named
for its location, for its cellular makeup, or for the person who first
identified it.
Mosby's Medical Dictionary, 8th edition. © 2009, Elsevier.
Basal Cell Carcinoma
Tumor Definition
• Eyelid Tumors
• Iris / Ciliary Body / Choroidal Tumors
• Retina / ONH and Pigment Epithelium
• Conjunctival Tumors
Ocular Tumors
•
•
•
•
•
•
•
•
•
•
Choroidal Nevus
Choroidal Melanoma
Congenital Hypertrophy of the RPE
Choroidal Metastasis
Melanocytoma
Combined Hamartoma of the Retina & RPE
Choroidal Hemangioma
Choroidal Osteoma
Retinal Astrocytic Hamartoma
Retinoblastoma
Lecture Outline
1
8/1/2013
Ocular Anatomy
NFL
ELM
NFL: Nerve Fiber Layer
ILM: Inner Limiting Membrane
GCL: Ganglion Cell Layer
IPL: Inner Plexiform Layer
INL: Inner Nuclear Layer
ILM
IS
GCL
IPL
IS/OS
OS
Retinal Anatomy
INL
RPE
OPL: Outer Plexiform Layer
ONL: Outer Nuclear Layer
ELM: External limiting membrane
IS: Photoreceptor Inner Segment
OPL
ONL
Choroid
IS/OS: Junction of inner and outer
photoreceptor segments
OS: Photoreceptor Outer Segment
RPE: Retinal Pigment Epithelium
Cirrus HD-OCT Healthy Macula
www.studyblue.com
Melanocyte vs Melanosome
• Most common
intraocular tumor
• Proliferation of
choroidal melanocytes
• Present in ~ 7.9% of
Caucasians
CHOROIDAL NEVUS
• Growth is rare after
puberty ????
Choroidal Nevus
2
8/1/2013
As we age:
• Nevi are less than 2mm
in thickness
• Nevi increase in
number and
thickness
• No known relationship
to sunlight exposure
• Pigment changes
• Have indistinct borders
• Metaplasia
• May undergo
malignant change into
melanoma
• Drusen / lipofuscin
Choroidal Nevus
Choroidal Nevus
• Typically do not cause
visual symptoms
• Signs of Suspicion
•
•
•
•
•
http://www.eyetumour.co.uk
Population by Race for the US: 2012
Vision changes
> 2 mm in thickness
Orange pigment
Proximity to optic disc
Subretinal fluid
RACE
1 in 8845 transform
into melanoma
Total population . . . . . . . . . . . . 313,914,040
100.0%
Caucasian . . . . . . . . . . . . . . . . . 244,852,951
78.%
Retina. 2005 Apr-May;25(3):243-52. westcoastretina.com
eyecancer.com
Clinical Findings
Source: quickfacts.census.gov
To Find Small Ocular Melanoma
Nevoma?
•
•
•
•
•
T= thickness
F= subretinal fluid
S= symptoms
O= orange pigment
M= tumor margin
touches disk
•
•
•
•
No risk factors (<4%)
1 risk factor (36%)
3 risk factors (50%)
5 risk factors (70%)
DOCUMENTED GROWTH - MEANS EVERYTHING
Using Helpful Hints = Ultrasound hollow, Halo
3
8/1/2013
Nevus in 2004
Nevus in 2009 ?
Nevus vs Melanoma?
OCT
• Can detect retinal edema, subretinal fluid,
retinal thinning and RPE detachment
• Helpful in determining presence of drusen
FA
• Findings depend on the amount of pigment
within nevus and the overlying RPE
• Hypofluorescence due to blockage of
choroidal filling
• Hyperfluorescence of surface drusen
Special Testing
CAN J OPHTHALMOL—VOL. 42, NO. 2, 2007
• Baseline fundus photography
• Consider OCT if location permits
• Consider B-Scan if suspicious
• Yearly dilated fundus examination
CHOROIDAL MELANOMA
Treatment & Management
4
8/1/2013
• Accounts for 90% of
all uveal melanomas
• Cells undergo
neoplasia, reproducing
at a faster rate than
usual
• Typically large
• Although 30% are
less than 3 mm thick
• Orange pigment
• May be amelanotic
• Look for subretinal
fluid
• 91% vs 14% of nevi
• Intermittent blurred
vision or flashes
secondary to fluid
shift
• Fluid = significant
risk of metastasis
Choroidal Melanoma
Clinical Findings
Choroidal Melanoma
Choroidal Melanoma
Retinal Arterial Macroaneurysm
5
8/1/2013
Asymptomatic
Caucasian ethnicity
Flashes
Systemically
well
Light colored eyes (blue)
Fair skin
Pain is rare
Propensity to burn when
exposed to UV light
Scotoma
Cutaneous nevi or freckles
Vitreous
hemorrhage
Iris nevi
VF defect
www.abouttrend.com
Welders
Presentation of Melanoma
Risk Factors of Melanoma
www.sightnation.com
Quadrant Uveal Melanoma in 8100 patients
OCT
• Can detect sub-retinal fluid
• Has been shown to detect early seeding
• Helpful in monitoring response to treatment
Superior 22%
•
Macula 4%
Nasal 21%
Temporal 28%
•
•
•
•
B Scan
Acoustically hollow
Choroidal excavation with orbital shadowing
Classic mushroom appearance (less common)
Can identify extraocular extension
FA
• No pathognomonic pattern
• Typically, mottled fluorescence during
arteriovenous phase, followed by leakage
and staining
Diffuse 3%
Inferior 22%
Special Testing
CAN J OPHTHALMOL—VOL. 42, NO. 2, 2007
Shields CL, et al. Uveal melanoma analyses in 8100 consecutive patients. Report #1
Sentinel Vessels
Intrinsic Blood Vessels
6
8/1/2013
Collaborative Ocular Melanoma Study
• Organized and funded in 1985 to address issues related to the
management of choroidal melanoma. > 4000 patients. 65% pts eligible
• Primarily to study the overall survival of patient following treatment
Small melanomas
< 2.5 mm in height
Medium melanomas
Extraocular Extension
2.5 – 10.0 mm in height
Large melanomas
> 10.0 mm in height
• Secondary outcomes = metastasis-free survival, years of useful vision
Eye 2001 Vol: 15(4):550-551.
Sinead Fenton; Teresa Sandinha; William R Lee; Ewan G Kemp
Risk factors for metastasis
• Enucleation
• Radioactive
plaques
• Proton beam
radiotherapy
• Transpupillary
thermotherapy
• Local resection
Most widely
accepted
Less common
• Thickness > 2 mm
• Symptoms: Flashes, floaters,
loss of vision
• Proximity to the optic nerve
• Documented growth
Treatment & Management
Uveal Melanoma
Shields Cl Shields JA. Risk factors for metastasis of small choriodal melanocytic
Lesions. Ophthalmology 1995
• 10 year mortality for
uveal melanoma
• Large 50%
• Medium 25%
• Small 12%
• Most common sites of
metastasis for uveal
melanoma
•
•
•
•
Liver 89%
Lung 29%
Bone 17%
Skin / Subcutaneous 12%
• Pattern of metastasis
• Uveal: hematogenous
• Cutaneous: lymphatic
• Median survival after dx
of metastasis - 6 months
Choroidal Melanoma
• Using fluorescence in situ hybridization and molecular
assay techniques, several genetic abnormalities in uveal
melanoma were found on chromosomes 1, 3, 6, and 8
• Monosomy 3
• Found in up to 50% of
uveal melanomas
• Imparts a worse prognosis.
• In small melanoma it
provokes the argument for
earlier treatment than
observation.
Role of Cytogenetics
7
8/1/2013
Interesting Case…
8
8/1/2013
• Common benign
lesion
CONGENITAL HYPERTROPHY
OF THE RETINAL PIGMENT
EPITHELIUM
• Focal area in which
the RPE cells are
taller and more
densely packed
with melanosomes
Congenital Hypertrophy of
the Retinal Pigment Epithelium
• These lesions are not
true tumors
• Discrete margins,
typically near the
equator
• No growth
• No subretinal fluid
• Lacunae are common
• Ultrasound will
show flat lesion
• Multiple lesions may
be confined to one
sector of the fundus –
bear tracks
• No intrinsic vessels
dro.hs.columbia.edu, mrcophth.com, webeye.ophth.uiowa.edu
eyedrd.org
Clinical Findings
Congenital Hypertrophy RPE
9
8/1/2013
Familial Adenomatous
Polyposis (FAP)
• Typically remains
stationary
• AD inheritance
• Adenomatous polyps
throughout rectum &
colon
• Starts to develop in
adolescence (15-40 yrs)
• If untreated – all pts
will develop colorectal
cancer
• May occasionally
increase in diameter
or spawn an elevated
nodule that may
represent adenoma or
adenocarcinoma
>80% of patients with
FAP have atypical
CHRPE lesions
Systemic Association
Treatment & Management
•Most common site for
uveal metastases -90%
•Estimated incidence
of 30,000 cases/year
• Choroidal melanoma
2,500 cases per year
•Primary site
• Breast (women)
• Lung (men)
CHOROIDAL METASTASIS
http://www.eyecancer.com, Dr. Shivan Maini
Br J Ophthalmol 2008;92:156-157
Choroidal Metastasis
Lung Metastasis
• Creamy-white, placoid
choroidal lesion
• Fast growing
• Usually found in
posterior pole
• Exudative RD common
• Tumors may
metastasize elsewhere
Clinical Findings
Eye Cancer Network
Choroidal Metastasis
10
8/1/2013
Breast Metastasis
Metastatic Prostate Cancer
Choroidal Metastasis
OCT
• Dome shaped elevation of retina and RPE
with adjacent subretinal fluid
• Can detect retinal edema, RPE thickening
and RPE detachment
B Scan
• Shows diffuse choroidal thickening
• Moderately high internal acoustic reflectivity
FA
• Shows early hypofluorescence and diffuse
late staining
Metastatic Breast Cancer
Special Testing
Dr. Aaron Gold
• Observation
• Ocular metastases
are the most common
ocular malignancies
• Radiotherapy
• TTT
• Estimated incidence
of 30,000 cases per
year
• Systemic therapy
• Enucleation
Treatment & Management
• Choroidal melanoma
2,500 cases per year
Choroidal Metastasis
11
8/1/2013
• Breast cancer is the most common tumor to
metastasize to the eye - followed by lung cancer
• 85% of patients with breast cancer metastases will
have a known history of breast cancer
• Breast cancer metastases tend to be bilateral and
multiple
• Breast cancer in 2010
• (< 1%) new cancers in men
• 192,400 (27%) new cancers in women
• Metastasis from breast cancer occurs in
25% of women at a median of 5 years.
3 years if ocular metastasis
• 40% of these patients have a brain metastasis
• The most common location is the lung,
bone, lymph nodes and liver
Metastatic Tumors
Metastatic Tumors
http://www.nationalbreastcancer.org/metastatic-breast-cancer
• Lung cancer metastasis rarely bilateral and multifocal
• They often produce pain
• Lung cancer metastasis 70%
of patients don’t know they
have cancer
MELANOCYTOMA
• Chest x-ray very important
www.medicalartstudio.com
Metastatic Tumors
• Benign melanocytic
uveal tumor
• Patients are usually
asymptomatic
• Composed of large,
plump magnocular
nevus cells that are
heavily pigmented
• Adjacent to or within
the optic nerve
• Can present in all age
groups and races
•
•
African-Americans
Females
Melanocytoma
• Black in color with
feathery margins
• Visual field defect
may be present
• APD may be present
Clinical Findings
12
8/1/2013
OCT
• Disruption of the internal limiting membrane
• Disorganization of involved retina
• Visualization of subretinal surface
FA
• Shows hypofluorescence of deep vessels
due to blockage
• The disc margin may stain in late phases
Special Testing
Melanocytoma
Dr. Aaron Gold
CAN J OPHTHALMOL—VOL. 42, NO. 2, 2007
• No systemic
association
• Typically stationary
• 2% of cases develop
into melanoma
COMBINED HAMARTOMA OF
THE RETINA & RPE
• No treatment is
recommended
Treatment & Management
• Grey pigmentation
with superficial gliosis
• Rare, benign tumor
• Likely congenital
• Involves retina, RPE
and overlying
vitreous
• Typically presents in
late childhood or
early adulthood
•
•
•
•
Strabismus
Blurred vision
Metamorphopsia
Loss of vision
• Secondary retinal
wrinkling and vessel
tortuosity
• Lesions can be
• Juxtapapillary
• Peripapillary
• Within posterior pole
Can be
Asymptomatic
Wills Eye Resident Case Series, April 2007
Combined Hamartoma of the Retina & RPE
Absence of retinal detachment,
hemorrhage,
exudation or
Wills Eye Resident Case Series, April 2007
vitreous inflammation
Clinical Findings
13
8/1/2013
OCT
• Neurofibromatosis
Type 1
•
•
•
•
•
• Shows retinal disorganization and elevation
with overlying ERM
• Abilty to monitor macular changes 2° to
traction
Café-au-late spots
Neurofibromas
Lisch nodules
Short stature
Scoliosis
B Scan
• Can be used to rule out compressive lesions
• May be unable to pick up depth of
hamartoma
• Findings not characterisitc
• Neurofibromatosis
Type 2
•
•
•
•
Acoustic neuromas
Hearing loss
Balance problems
Cataracts
FA
• Rarely diagnostically important
• Findings are characteristic
Systemic Association
Special Testing
• Patients are monitored annually for
• Growth of lesion
• Vision changes secondary to
macular traction
• Consider annual OCT of macula
• Ask pertinent history questions
in regards to NF-1 and NF-2
• Refer for vitrectomy with membrane peel in cases where
vision is significantly affected
CHOROIDAL HEMANGIOMA
Treatment & Management
CIRCUMSCRIBED
• Mass of vascular
channels within
choroid
Orange/red mass with
indistinct margins
• Circumscribed vs.
Diffuse [Sturge-Weber]
Usually peripapillary
• Symptoms in
adulthood secondary
to RD
Acoustically solid lesion
eyecancer.com
Choroidal Hemangioma
Subretinal fluid or macular
edema
webeye.ophth.uiowa.edu
Choroidal Hemangioma
14
8/1/2013
DIFFUSE
Affects over ½ the choroid
Enlarges slowly
Deep-red colored fundus
Found exclusively in patients
with Sturge-Weber Syndrome
Choroidal Hemangioma
Choroidal Hemangioma
Dr. Aaron Gold
Sturge-Weber Syndrome
OCT
• Acute leakage shows subretinal fluid with intact
photoreceptor layer and normal retinal thickness
• Chronic leakage shows loss of photoreceptors,
retinoschisis, and retinal edema
• Congenital hamartomatous
malformations
• May affect
• Eye
• Skin
• CNS
B Scan
• Acoustically solid lesion
• High internal reflectivity
• Motor seizures – 85%
• Mental retardation – 60%
• Facial cutaneous venous dilation
(port-wine stain) present in 96%
FA
• Rapid spotty hyperfluorescence in the early arterial phase
• Diffuse intense late hyperfluorescence
Systemic Association
Diffuse
•
•
•
•
•
Observation
Amblyopic therapy
Laser photocoagulation
Irradiation
Retinal detachment
surgery
• Enucleation seconday to
neovascular glaucoma
Special Testing
Circumscribed
• Transpupillary
thermotherapy
• Photodynamic therapy
for secondary retinal
detachment
CHOROIDAL OSTEOMA
Treatment & Management
15
8/1/2013
• Benign ossifying
tumor of the choroid
•
•
•
•
• Composed of mature
bone
Orange-yellow lesion
Typically unilateral
Well-defined
Usually juxtapapillary
• Young females
• Vision loss 2° to
• Benign – may grow
•
•
•
• VA < 20/200 in
56-58% after 10 yrs
Subretinal Fluid
Neovascularization
Photoreceptor loss
telemedicine.orbis.org, eyewiki.aao.org
archopht.ama-assn.org
Choroidal Osteoma
Clinical Findings
OCT
• Inner retina preserved
• No systemic
association
B Scan
• Highly reflective anterior surface
• Orbital shadowing
• No malignant
potential
FA
• Irregular, diffuse mottled hyperfluorescence in
the early and late phases
• Neovascularization may be present.
Special Testing
• CNVM may develop
Treatment & Management
• Vascular and glial
tumor of the retina
• Rare and benign
• No threat to vision
RETINAL ASTROCYTIC
HAMARTOMA
• Frequently seen in
tuberous sclerosis
Optical Coherence Tomography of Retinal Astrocytic Hamartoma in 15 Cases
C. Shields, et al., utsouthwestern.edu, pconsupersite.com
Retinal Astrocytic Hamartoma
16
8/1/2013
• May be multiple or
bilateral
• Can be calcified
• Can be
• Endophytic
• Vitreous
• Exophytic
• Subretinal
Clinical Findings
OCT
• Inner retinal thickening and
disorganization with a gradual transition
to normal retina
• Retinal traction (27%)
• Intratumoral cysts (67%)
• Adjacent edema (47%)
FA
• Hyperfluorescence without leakage
Special Testing
• Solitary lesions may
be found in normal
individuals
• Tuberous Sclerosis
•
•
•
•
50% of patients
have astrocytomas
Multiple/bilateral
Rare genetic disease
Benign tumors grow
on skin, brain,
kidneys, and heart
Systemic Association
• Usually relatively
stable
• Can show progressive
growth
• Rare cases –
exudative retinal
detachment and
neovascular glaucoma
Treatment & Management
• The most common
primary, intraocular
malignancy in
childhood
• Results from malignant
transformation of
primitive retinal cells
before final
differentiation.
RETINOBLASTOMA
• Seldom seen after age 3
Retinoblastoma
17
8/1/2013
Retinoblastoma – life threatening disease
• Heritable
• germline
•
•
70% of cases
Pinealblastoma
• Non-heritable
• somatic
•
30% of cases
Retinoblastoma
Initial Features:
• Leukocoria
70 %
• Strabismus 25 %
• Other (VA) 5 %
~ 15 % will present with iris
neovascularization
Most common intraocular malignancy in children / dx=18 month
300 new cases of retinoblastoma diagnosed each year in the US
Leukocoria
• Retinoblastoma
• Coats disease
• Congenital
Cataract
• Coloboma
• Toxocariasis
• ROP
• PPHV
• Retinal
Detachment
Hyphema may also be present
Retinoblastoma
Retinoblastoma
In 75 % of cases enucleation is
performed
Special Testing
In 25 % of cases conservative
treatment is
administered
Treatment & Management
18
8/1/2013
Intravenous chemoreduction
(carboplatin, etoposide, vincristine)
International Classification of Retinoblastoma
Subconjunctival carboplatin
Plaque, TTT
Group A
Small RB < 3 mm size
Group B
Larger RB > 3 mm size
Plaque radiotherapy
Group C
Contained seeds
External beam radiotherapy
Group D
Diffuse seeds
Group E
Extensive > 50% globe, NVI, Opaque media
Transpupillary thermotherapy
Cryotherapy
Laser photocoagulation
Chemoreduction
W / WO EBRT
Intra-arterial Chemotherapy (IAC)
Retinoblastoma Treatment
Recurrences = within 1st year
Primary Intraocular
Uveal
LYMPHOID TUMORS
Char DH: Clinical Ocular Oncology. 2nd ed. Philadelphia, Lippincott-Raven, 1996.
okulistyka.com.pl, surgical-pathology.com
Lymphoid Tumors
• Proliferation of B
lymphocytes
• Accounts for 65% of
cases of intraocular
lymphoma
• 90% of the time it is
bilateral
• Increased incidence in
immunosuppressed
patients
Primary Intraocular Lymphoma
• Symptoms =
unilateral floaters,
blurred vision, red
eye or photophobia
• Patchy yellow lesions
• Secondary vitreous
cells - “clumps”
• Primarily affects the
retina and/or optic
disc
Clinical Features
19
8/1/2013
• Radiotherapy – if
tumor is confined
to the eye
• Intravitreal
methotrexate
• Systemic
chemotherapy
Rospond-Kubiak, I., Kocięcki, J. & Stopa, M.
Primary uveal lymphoma effectively managed
with oral chlorambucil: a case report. (2013).
• Uveal lymphoma
= systemic
• Typically nonHodgkin B-Cell
lymphoma
•
•
•
Treatment & Management
• Usually unilateral
• Yellow-orange lesions
• Can occur as a
solitary mass
• Vitreous is usually
clear
• Secondary exudative
retinal detachment
T-cell lymphoma
Hodgkin disease
Other forms of
lymphoma
Primary uveal lymphoma effectively managed with oral chlorambucil: a case report
Iwona Rospond-Kubiak*, Jarosław Kocięcki and Marcin Stopa
Uveal Lymphoma
Clinical Features
• Systemic
chemotherapy
• Whole-eye
irradiation
• Plaque radiotherapy
LEUKEMIA
A rare ocular manifestation of non-Hodgkins’ lymphoma
Michael S. Peterson, O.D. and Lori S. Kirwan, O.D.
Treatment & Management
20
8/1/2013
• Abnormal
proliferation of white
blood cells
• Ocular involvement
typically seen in the
acute form
• Most patients have
known systemic
disease
• Usually a sign of
severe disease
• Diffuse or patchy
thickening of the
retina and choroid
• Retinal hemorrhage
• Optic disc
infiltration
• Vitreous cells
imagebank.asrs.org
Leukemia
http://www.nejm.org
Clinical Features
• Management of
systemic disease
• Ocular
radiotherapy
http://www.aao.org
Treatment & Management
Ocular involvement in 80% of patients
choroidal nevus
choroidal melanoma
retinoblastoma
choroidal metastasis
choroidal hemangioma
retinoblastoma
choroidal osteoma
choroidal hemangioma
astrocytic hamartoma
choroidal melanoma
choroidal osteoma
lymphoid tumor
21
8/1/2013
Kanski, J. Clinical Ophthalology: A Systemic Approach. 6th Edition. Butterworth-Heinemann.
Palmar, M., Carney, M., and Combs, J. Combined Hamartomas of the Retinal Pigment Epithelium and Retina. Retina. Vol 10,
1990, pp. 33-36
Rospond-Kubiak, I., Kocięcki, J. & Stopa, M. Primary uveal lymphoma effectively managed with oral chlorambucil: a case
report. (2013
The End!
Say, E., et al. Optical Coherence Tomography of Retinal and Choroidal Tumors. Journal of Ophthalmology. Vol 2011, Article
ID 385058, 12 pages
Shields, C., Materin, M. & Shields, J. Review of optical coherence tomography for intraocular tumors. Current opinion in
ophthalmology 16, 141–54 (2005).
Shields, J. and Shields, C. Intraocular Tumors: An Atlas and Textbook. Second Edition. Lippincott Williams & Wilkins, 2008
Shields, J. and Shields, C. Tumors of the Retinal Pigment Epithelium. Retinal Physician. May 2005
Shields, Jerry. Ocular Oncology Essentials: Melanoma Update [based upon presentation at the 2006 Retinal Physician
Symposium] Retinal Physician. Sept 2006.
Sinead Fenton, Teresa Sandinha, William R Lee, and Ewan G Kemp. (2001). Massive extraocular extension as the presenting
feature of a choroidal melanoma. Eye. doi:10.1038/eye.2001.175
Tasman, W and Jaegar, E. Wills Eye Hospital Atlas of Clinical Ophthalmology, 2nd Ed. Chapter 7 Retinal Tumors.
References
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