Transcript Grand rounds - LSUHSC Shreveport

Grand rounds
Clay Bundrick, MD
5.15.2012
LSU Dept of Ophthalmology
Presentation
 CC: “eye doctor told me I had retinal detachment”
 HPI: 55yo WM no sig PMH presented to LSU eye clinic
2/2012 with 2 year history of progressively deteriorating
vision left eye.
 + metamorphopsia, photopsia, “ball of light would travel
across VF 3x/day
 almost sudden acute drop in VA brought him to optometrist
in Alexandria who referred him to LSU
 SH: skidder operator, smokes 1.5ppd, 4+ EtOH
 POH: none
 FH/FOH: noncontributory
exam
 Vitals: BP 144/86, HR 78, RR 16, T 98f
 VAsc: 20/20 OD, 20/400 OS
 Pupils: APD left eye
 CF: constricted OS
 EOMs: full
 Ta: 17 OU
exam
 SLE
 LLL: no proptosis, no masses, +anterior blepharitis
 C/S: trace injection OU
 K: clear ou
 AC: deep/ quiet OU
 Lens: N1 nsc ou
DFE
Differential Dx:
 Choroidal nevus
 Choroidal melanoma
 Focal choroidal hemangioma
 Melanocytoma
 Metastasis
 ARMD
 CHRPE
 Suprachoroidal detachment
Choroidal melanoma?
 Next steps in diagnosis?
 Gonioscopy to check for anterior tumors
 FA
 US
 CT/ MRI/ bloodwork
 Biopsy
 ** Gold standard: indirect ophthalmoscopy usually
sufficient for diagnosis
FA
 Usually limited dx value bc
no pathognomonic pattern
 Late hyperfluorescence
classically found
 Collar stud tumors show
“dual circulation” of tumor
vessels and retinal vessels
Collar stud – when tumor breaks through bruch’s membrane
US

US useful with opaque media and to measure
the lesion

Also ID’s extraocular extension

Classic findings:



Acoustic hollowness
Choroidal excavation
Orbital shadowing

Top: US of dome shaped tumor that
demonstrates choroidal excavation

Bottom: collar stud tumor
IMAGING
 MRI shows hyperintensity in T1-
weighted images and
hypointensity in T2
 Gadolinium enhances optic
nerve and orbital invasion
 This is a T1 saggital view
Labs/ other imaging
 CBC/ BMP WNL
 AST slightly elevated relative to ALT
 No obvious mets in liver/ lungs
Choroidal Melanoma
 Incidence 5/1,000,000 per year
 No gender preference
 Main peak age 55-65, smaller peak age 20-40
 Can occur in children but rare (better px)
 Most common primary intraocular malignancy in
adults
 **cutaneous melanoma 20x more common than intraocular
 Accounts for 90% of uveal melanomas
Choroidal melanoma
 Risk factors
 Ocular melanocytic conditions (oculodermal




melanocytosis)
Cigarette smoking
Northern European background
Light irides (inferior ½)
Sun? probably, but no definitive data
Classification by cell type
 Spindle cell
 Arranged in tight bundles
 Cell membranes indistinct
 Granular cytoplasm
Classification by cell type
 Epithelioid cells
 Larger
 More pleomorphic
 Polyhedral
 Abundant cytoplasm
 Distinct cell membranes
 Large nuclei/nucleoli
 More abundant mitotic
figures
 Collar stud tumor
 Penetration of bruch’s
Callender classification system
 Best to worst prognosis:
 Spindle cell nevus: only spindle A cells
 Spindle cell melanoma: spindle A+B cells
 Mixed melanoma: spindle + epithelioid
 Epithelioid melanoma: exclusively ep cells
Categorize by size
Diameter
(mm)
Thickness
(mm)
5 year survival
%
Small
4-8
1-2.4
88
Medium
6-16
2.5-10
70
Large
>16
>10
50
Poor prognosticators
 Histology: epithelioid
 Chromosomal abnormalities within melanoma
cells:
 Loss in chm 3 and gains in chm 8 bad
 Gains in chm 6 short arm good
 Size: big is bad
 Extrascleral extension, scleral contact
 Location: anterior tumors (ciliary body) worse,
more likely to have spread.
Metastasize?
 It is not known at what stage melanomas begin
to spread
 2% of ocular melanoma have demonstrable
mets at time of diagnosis
 COMS found that 10% of patients harbored a
second malignancy
 If suspicion of metastatic disease is high bc of
large tumor size / systemic symptoms- common
to get PET scan, more sensitive
Metastasize?
 Pattern of spread:
 Hematogenous
 Via bruch’s penetration invasion of scleral channels
for blood vessels vortex veins
 Primarily to the liver, occasionally lungs, bone, skin,
brain
 Rarely invades optic nerve
 7 years median duration from Rx to Dx of mets
 6 months from dx of mets to death
Fundus exam
 Elevated
 Subretinal dome-shaped mass
 From highly pigmented to amelanotic
Fundus exam
 Lipofuscin/ orange pigment clumps commonly seen
in RPE overlying tumor
 Collar stud with visible intrinsic blood vessels
Fundus exam
 Diffuse tumor
 Rare
 Characterized by
extensive flat grayish
brown irregular
discoloration
 Extraocular extension
common bc this type
tends to be aggressive
Fundus exam
 Subtotal retinal
detachment
 Unlike RRD:
 Subretinal fluid shifts with
ocular movement and
gravity
 Retina does not show the
fine silvery rippling that
occurs in the presence of
a tear
treatment
 Goals:
 1. conserve as much useful vision as possible
 2. avoid development of painful and unsightly eye
 Observation alone is acceptable if:
 1. tumor is <1mm thick
 2. pt cannot tolerate tretment
 Risks involved in delaying Rx are uncertain, so it is
essential to confirm dx and obtain proper
consent from an understanding pt
treatment
 Enucleation
 - treatment of choice for all large
tumors and many medium size
tumors
 If there is optic nerve invasion
 Extensive involvement of ciliary
body or angle
 Irreversible loss of useful vision
 Poor motivation to keep the eye
 Crucial to operate on the correct
eye
 Orbital recurrence is rare if there is
no extraoc tumor spread
Radiation Therapy
 BRACHYTHERAPY
 With ruthenium-106 or iodine 125
 Indications
 Tumors <20mm in basal d
 +chance of salvaging vision
 Can treat tumors up to 5mm thick with ruthenium
plaque and 10mm thick with iodine plaque
 COMS- pre enucleation XRBT:
 no effect on overall survival
 Did significantly reduce orbital recurence
 TECHNIQUE
 Tumor localized by
transillumination
 Template with transparent metal
ring with eyelets sutured to sclera
 Sutures are loosened and used to
secure the radioctive plaque
 Plaque is removed 3-7 days after
the appropriate dose has been
delivered
 Usually >80Gy
 Tumor regression starts abt 1-2 mo
after rx
 Brachytherapy
 Tumor response usually gradual
 Amelanotic tumors tend to
become more pigmented
 Complications
 Cataract
 Papillopathy
 Macular edema (refractory to grid
laser)
 NVG
 Toxic tumor syndrome
 Complications worse in diabetics
Radiation therapy
 Plaque radiotherapy
 Radiation focused on tumor by aiming beams
from different directions sequentially or
concurrently
 Good tumor control rate
 Adverse effects include
 Radiation retinopathy
 Optic neuropathy
Radiation therapy
 CHARGED PARTICLE IRRADIATION
 Irradiate with protons achieves high dose in
tumor and small doses in superficial tissues
 Indications
 Tumors unsuitable for brachytherapy bc too large
or posterior (unreliable plaque placement)
 Tumor regression slower than brachyrx
 Complications more anterior (cataracts/ NVG)
Chemo?
 Concern for undetected mets common
 adjuvant systemic treatment is not advocated.
 This consensus comes from treatment trials with
extrapolation of the experience with cutaneous
melanoma, where adjuvant treatment has
shown no benefit.
 In cases where distant metastases are found
during the initial systemic workup, treatment of
the intraocular melanomas becomes palliative..
COMS
 Collaborative Ocular Melamoma Study
 Three subgroups based on tumor size:
 1. Small tumors
 Treatment vs observation
 Results: ?? Enrollment in Rx branch too low for comparison
 2. Medium tumors
 Enucleation vs plaque RT
 Rx modality did not affect 5 year survival
 3. large tumors
 Enuclation with preop RT vs no preop RT

Preop RT did not affect 5 year survival
prognosis
 Guarded
 About 30-50% of patients with choroidal melanoma
will die within 10 years from diagnosis and treatment.
 Death is usually secondary to distant metastases, and
the risk is greatest in larger tumors.
 For large melanomas, the Collaborative Ocular
Melanoma Study found that the 10-year rates of
death secondary to metastasis were 45% in the preenucleation radiation group and 40% in the
enucleation alone group.
DDX
 Choroidal nevus
 5-10% of whites, rare in blacks
 Assd with NF1 and dysplastic nevus syndrome
 Growth usually prior to puberty, rare in adulthood
 For this reason a growing lesion in an adult should
be worrisome
 Usually asymptomatic, detected on routine
exam
Choroidal nevus
 Usually <5mm basal diameter and 1mm thick
 Slate blue or grey, not sharp borders
 Histologically demonstrate spindle cell melanocytes in the
choroid but spare the choriocapillaris
Choroidal nevus
 Surface drusen may be present, particularly in central area
 FA findings depend on amount of pigmentation
 Most nevi are avascular and pigmented
 Hypofluor caused by blockage of background choroidal
fluorescence
 Surface drusen will result in dots of hyperf
 FA is not helpful in dist bt small melanoma and a nevus,
althought pinpoint areas of hyperf may predict future growth
Choroidal nevus
 ICG shows hypofluorescence
 US shows localized flat/ slightly elevated lesion
with hight internal acoustic reflectivity
 Low internal reflectivity on a-scan suggests
malignancy
Suspicious nevus
 Fishy features
 Symptoms of blurred vision etc
 Dimensions > 5mm/ 1mm
 Orange pigment
 Margin near optic nerve
 Serous RD over surface of lesion
Amelanotic nevus
Halo nevus
Ddx… melanocytoma
 Magnocellular nevus
 Rare, distinctive heavily pigmented tumor
 MC in optic nerve head
 Rarely arises elsewhere in uvea
 More common in dark skinned females
 Usually stationary with little tendency to change
melanocytoma
 Histology
 Large deeply
pigmented polyhedral
spindle cells
 Small nuclei
melanocytoma
 Dark lesion with feathery edges
 Within NFL
 Extends over edge of disk
 Occasionally tumor is elevated and occupies
most of the disk surface
 APD may be present with good vision
melanocytoma
 FA
 Hypofluorescence of deep
vessels due to blockage
 RX:
 Rarely required
 Except in event of malignant
transformation
DDx choroidal hemangioma
 Not usually assd with systemic disease
 May be dormant thoughout life or may give rise
to s/o in adulthood secondary to exudative RD
 Slight progressive enlargement may occur over
many years
 Presentation usually in 4th/ 5th decades:
 Unilateral blurring of VA/ VF defect
 Hyperopia from subretinal fluid/ tumor
 Most asymptomatic
Circumscribed choroidal
hemangioma
 Histology shows congested vascular channels
 Oval mass with indistinct margins, same color as surrounding
choroid
 Usually posterior to equator in peripapillary area
 Median base diameter is 6mm, median thickness 3mm
Circumscribed choroidal
hemangioma
 FA
 Rapid, spotty hyperfluorescence in the prearterial phase and
diffuse intense late hyperfluorescence
 ICG
 Early hyperfluorescence
Circumscribed choroidal
hemangioma
 US
 Acoustically solid lesion with sharp anterior surface but without
choroidal excavation and orbital shadowing
 Complications:
 Fibrous metaplasia
 Retinal edema/ exudative RD/ NVG
Circumscribed choroidal
hemangioma
 Treatment
 Unnecessary in asymptomatic lesions
 PDT- same as for choroidal NVM
 TTT- transpupillary thermotherapy for lesions not
involving the macula- causes VF loss
 RT- low dose, causes collateral damage
Diffuse Choroidal Hemangioma
 Usually affects over half of the choroid
 Enlarges very slowly
 Almost exclusively in pts with SWS
 Ipsilateral to the nevus flammeus
Diffuse choroidal hemangioma
 Deep red tomato ketchup
fundus
 Most marked at posterior pole
 US shows diffuse choroidal
thickening
 Complications:
 Cystoid retinal degeneration
 Exdative rd
 Nvg
 Rx: external beam radiotherapy
 Rarely necessary
CHRPE
 Common benign lesion
of RPE
 May be typical or
atypical
 Discrete margins
 Depigmented lacunae
common
 Grouped bear tracks
alert clinician for polyps
references

1. Factors predictive of growth and treatment of small choroidal melanoma: COMS
Report No. 5. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. Dec
1997;115(12):1537-44.

2. Accuracy of diagnosis of choroidal melanomas in the COMS Arch Ophthalmol. Sep
1990;108(9):1268-73. [Medline]. Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH,
Becher R.

3. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. May 4
1996;347(9010):1222-5. [Medline].

4. Histopathologic characteristics of uveal melanomas in eyes enucleated from the
Collaborative Ocular Melanoma Study. COMS report no. 6. Am J Ophthalmol. Jun
1998;125(6):745-66. [Medline].

5. The Collaborative Ocular Melanoma Study (COMS) randomized trial of preenucleation radiation of large choroidal melanoma III: local complications and
observations following enucleation COMS report no. 11. Am J Ophthalmol. Sep
1998;126(3):362-72. [Medline].

6. The Collaborative Ocular Melanoma Study (COMS) randomized trial of preenucleation radiation of large choroidal melanoma II: initial mortality findings. COMS
report no. 10. Am J Ophthalmol. Jun 1998;125(6):779-96. [Medline].