choroidal melanoma
TRANSCRIPT
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CHOROIDAL MELANOMA
DR K HARIPRIYASSSIHMS
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• Choroidal melanomas are the most common primary intraocular malignancies
in adults.• It is the second most common type of
primary malignant melanoma in the body• Choroidal melanoma is a subtype of uveal
melanoma
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Epidemiology• Incidence of primary choroidal melanoma
is about 6 cases per 1 million population in USA.
• Perhaps because of increased sunlight exposure, there appears to be a higher incidence of uveal melanoma in the southern latitudes of the United States
• Other countries has almost same incidence.
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Etiology• Risk factors are people with light-colored
iris, whites, median age-55 yrs, men • Sunlight exposure is a contributory factor. • Predisposing diseases1)family history of uveal melanoma2) uveal nevus3)congenital ocular melanocytosis4)dysplastic nevus syndrome5) xeroderma pigmentosum.
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Pathophysiology• Primary choroidal melanoma arises from
melanocytes within the choroid• Three distinct cell types are recognized:(1) spindle A cells(2) spindle B cells (3) Epithelioid cells The last cell type usually has the most
aggressive behavior and carries a poorer prognosis for the patient’s long-term survival.
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• Choroidal melanomas may be darkly pigmented or amelanotic.
• They are typically dome-shaped. • As they enlarge, they break through the
Bruch membrane and assumes a mushroom configuration.
• Other shapes found are bilobular, multilobular, and diffuse. The diffuse type is characterized by lateral growth throughout the choroid with minimal elevation.
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• Fig. 12.24 Choroidal melanoma. (A) Highly pigmented melanoma; (B) amelanotic melanoma; (C) melanoma with surface orange pigment; (D) ‘collar-stud’ melanoma with intrinsic vessels; (E) diffuse melanoma; (F) large melanoma with subtotal retinal detachment(Courtesy of B Damato – figs A, C and F); AD Singh, from Clinical Ophthalmic Pathology, Elsevier, 2007 – fig. E)
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• Choroidal melanomas affect the retinal pigment epithelium as they push against it and deprive it of normal choroidal circulation.
• Overlying retinal pigment epithelium usually develops areas of atrophy, drusen, and localized pigment epithelial detachments.
• These changes can lead to choroidal neovascularization over the tumor, with consequent subretinal exudation, hemorrhage, and fibrous plaque formation
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• The tumor disrupts choroidal circulation leading to ischemia typically cause degeneration of retinal photoreceptors and other retinal neurons.
• The retina overlying the tumor can separate into cystoid spaces and larger schisis cavities (cystoid macular edema).
• Exudation of fluid into the subretinal space with consequent retinal detachment.
• Rarely, choroidal melanomas can impinge into underlying posterior ciliary nerves, causing severe ocular pain
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• Tumor grows anteriorly, involving the ciliary body, trabecular meshwork, and lens, with consequent ocular hypotension or hypertension, cataract, iris rubeosis, vitreous hemorrhage or hyphema.
• Its metastatic potential depends on the histopathologic aggressiveness of the tumor cells.
• It can only spread hematogenously, because there are no lymphatic vessels in the eye. It most often metastasizes to the liver, lung, bone, skin, and CNS.
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• Less frequently, tumor can grow transsclerally, through emissary channels, and metastasize locally into the orbit or rarely the conjunctiva.
• Choroidal melanoma almost never extends through the optic nerve; when it does, it is usually in juxtapapillary tumors or in diffuse choroidal melanomas
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Histologic Findings• Histologic evaluation of the tumor after
enucleation can confirm the diagnosis and determine the prognosis
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Spindle A cells have elongated nuclei and uncommonly have mitotic figures
Spindle B cells have a prominent
nucleolus. They are found more
commonly and also have an elongated
profile but are slightly larger than
spindle A cells.
Epithelioid melanoma cells are highly anaplastic, poorly cohesive, polygonal and contain frequent mitotic figures
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• Fig. 12.23 Histology of choroidal melanoma. (A) Spindle cells – tightly arranged fusiform cells with indistinct cell membranes and slender or plump oval nuclei; (B) epithelioid cells – large pleomorphic cells with distinct cell membranes, large vesicular nuclei with prominent nucleoli, and abundant cytoplasm; (C) fascicular pattern – vasocentric; (D) necrotic tumour – cell type cannot be determined; (E) penetration of Bruch membrane in a ‘collar-stud’ fashion; (F) extraocular extension and an embolus of neoplastic cells within a blood vessel(Courtesy of J Harry – figs A and B; J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001 – figs C, D, E and F)
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• AFIP Classification of uveal melanomas. 1)Spindle cell nevi 2)Spindle cell melanomas (mixture of
spindle A and B cells). 3)Mixed cell melanomas in which there is a
mixture of spindle and epithelioid cells. 4)Epitheloid cell melanomaLast two types has poorer survival prognosisOther type- necrotic melanoma
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Adverse prognostic factors 1)Histological features include large numbers of epithelioid cells, long and wide nuclei, multiple nucleoli, closed vascular loops within the tumour and lymphocytic infiltration.2)Chromosomal abnormalities: loss of chromosome 3 and gains in chromosome 8, are associated with a poor prognosis. Gains in the short arm of chromosome 6 carry a favourable prognosis.
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3)Size. Large tumors have a worse prognosis than small tumors.
4)Extrascleral extension as tumor is more likely to be advanced and aggressive.
5)Location. Anterior tumors involving ciliary body have a worse prognosis.
6)Local tumor recurrence after conservative treatment is associated with poor survival. This is probably because the recurrence is an indication that the original tumor was relatively aggressive
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Clinical Presentation
Patient history
• Choroidal melanomas remain asymptomatic for long time; they may be
found incidentally during ophthalmoscopy.
• Blurred visual acuity
• Paracentral scotoma
• Painless and progressive visual field loss
• Floaters
• Severe ocular pain
• History of weight loss, marked fatigue, cough, or change in bowel or
bladder habits
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CLINICAL APPEARANCE- on ophthalmoscopic examination• COLOUR• SHAPETYPES- 1) Solid mass leision 2)Flat,diffuse type -Ring melanomaADVANCED STAGES:a)Extraocular extensionb)Invasion of optic nerve
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c)glaucomad)Uveitis, pthisis bulbie)Orbital invasion f)Metastasis
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classification Based on thickness and basal size. The tumour is termed -small (<10 mm diameter),-medium (10-15 mm diameter,<10mm
height) -large (>15 mm diameter, >10mm height)
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Diagnosis
• Clinical appearance• FFA• Ultrasound • Radiography• Laboratory tests• Transillumination• Invasive technique• New diagnostic tests
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CLINICAL APPEARANCEFeatures helpful in diagnosis:1)Pigmented mushroom shaped tumor2)Orange pigmentation(due to lipofuscin)3)Associated elevated retinal detachment4)Globular elevated mass
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Differential Diagnosis
Choroidal neoplasms:
• choroidal nevus
• Choroidal Metastasis
• Choroidal hemangioma
• Melanocytoma
• Choroidal lymphoid tumors
Hemorrhagic processes:
• Extramacular disciform degeneration
• Choroidal haemorrhage
• Haemorrhage into retinal cyst
Retinal pigment epithelium • Retinal pigment epithelial hyperplasia and hypertrophy
• Retinal pigment epithelial Adenocarcinoma
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Fundus Fluorescein angiography
• Fluorescein angiography and are not diagnostic. They heip to differentiate
between choroidal melanoma and pseudomelanoma .
• Small choroidal melanomas with intact RPE shows no changes.
• Larger melanomas with disrupted RPE may showArterial phase-mottled hyperfluorescenceVenous phase-pinpoint hyperfluorescenceLate venous phase- late staining due to SRF
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• Large dome shaped melanoma Mottled hyperfluorescence in Early venous
phase with late hyperfluorescence• Mushroom shaped melanoma During late arterial or early venous phase
the prominent vessels are seen within dome of the tumour, thereby allowing both retinal and choroidal vessels seen simultaneously(double circulation pattern)
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ultrasonography
A-SCAN:
• A-scan ultrasonography is useful for tumors thicker than 2-
3 mm.
• Choroidal melanoma shows an initial prominent spike,
followed by low-to-medium internal reflectivity with
diminishing amplitude and a significant echo.
• Performing sequential A-scans, with accurate dimension
measurements, in cases of diagnostic uncertainty is
important.
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B-SCAN:
• B-scan is a routine test used in the evaluation of any posterior segment mass.
• It is especially needed in patients with media opacity.
• B-scan helps in -establishing the diagnosis, -to evaluate possible extraocular extension -to estimate tumor size for periodic observation -to plan therapeutic intervention.
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Intraocular melanomas have several distinctive features on B scan:
• Low-to-medium reflectivity
• Excavation of underlying uveal tissue
• Shadowing of subjacent soft tissues
• Internal vascularity
• An acoustic quiet zone at the base of the tumor called acoustic hollowing
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Ultrasound biomicroscopy (UBM) • It can differentiate very anterior choroidal
melanomas from those of ciliary body origin.
• It is also helpful in assessing angle-closure glaucoma
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RadiographyComputed Tomography• CT scan is more expensive and is not as
sensitive as ultrasonography.• It is useful for visualizing extraocular
extension and may help differentiate between choroidal or retinal detachment and a solid tumor.
• CT scan also is sensitive in detecting calcium (characteristically choroidal osteoma).
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Magnetic Resonance Imaging
• MRI is more expensive and still remains less sensitive .
• Use of surface coil imaging and gadolinium as a contrast material greatly
improves its resolution.
• Pigmented melanomas are seen as a high-density image in T1 and as a
low-density image in T2 .
• MRI also can be used to determine extrascleral extension and
distinguish surrounding fluid from the tumor.
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Laboratory Studies
• Liver enzyme levels are indicated in any patient with uveal melanoma,
because the liver is the most common site of choroidal melanoma
metastasis.
• The most sensitive tests of hepatic function are serum levels of the
following:
-Alkaline phosphatase
-Glutamic-oxaloacetic transaminase
-Lactate dehydrogenase
-Gamma-glutamyl transpeptidase
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Transillumination• Rarely done these days.• Transillumination can be used to find the
borders of the tumor, especially if it is surrounded by exudative retinal detachment.
• Its precision is dependent on even tumor pigmentation and if associated hemorrhage is present
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Invasive technique• Fine-needle biopsy and incisional biopsy
are not usually required but may be helpful in case where diagnosis is not established.
• particularly for distinguishing amelanotic melanomas from metastatic tumors.
• Fine-needle biopsy is increasingly being performed for prognostic purposes
• In opaque medias, ultrasound guided approach is essential.
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• It is done by 25 guage needle via transvitreal or transcleral route.
• Risk of spread of cancerous cells in the case of fine-needle biopsy is small
• Genetic analysis and karyotyping of biopsy specimens have gained increasing attention.
• Other test- radioactive phosphorus uptake test- used less commonly.
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New diagnostic tests
• Colour doppler• Positron emission tomography• P-31 magnetic resonance spectroscopy• Monoclonal antibody tagged with a short
lived radioactive technicium-99m tracer
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TreatmentThe methods of patient management
depend on several factors:-size, location, and extent of the tumor-visual status of the affected eye and of the
fellow eye-age and general health of the patient-patient's wishes and fears
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• Observation may be acceptable for posterior uveal tumors where
diagnosis is not well established.
• In particular, tumors of less than 2-2.5 mm in elevation and 10
mm in diameter can be observed until growth is documented.
• Photography and sequential ultrasonography for precise
measuring of the tumor’s dimensions are usually necessary.
• Choice of treatment of choroidal melanoma remains controversial
in many respects.
• Although enucleation has been the treatment of choice in the
past, it appears that vision-sparing approaches might offer similar
degrees of ocular and metastatic tumor control particularly
because it is clear that in many patients at the time of diagnosis,
posterior uveal melanomas already have spread through
micrometastasis.
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Brachytherapy
• Brachytherapy (episcleral plaque radiotherapy) with ruthenium-106 or an iodine-125 applicator is usually the treatment of first choice 1.Indications
-Tumours less than 20 mm in basal diameter in which there is a reasonable chance of salvaging vision.
-5 mm thick with a ruthenium plaque -10 mm thick with an iodine plaque.
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2)Techniquea.The tumour is localized by transillumination or
binocular indirect ophthalmoscopy.b. A template consisting of a transparent plastic
dummy or metal ring with eyelets is sutured to the sclera with a releasable bow
c.The sutures are loosened and used to secure the radioactive plaque.
d. The plaque is removed once the appropriate dose has been delivered, usually within 3–7 days. At least 80 Gy should be delivered to the tumour apex.
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3)Tumour response is usually gradual Tumour regression starts about 1–2 months after
treatment and continues for several years, leaving a flat or dome-shaped pigmented scar.
4)Complications Excessive irradiation causes cataract,
papillopathy and maculopathy. The irradiated tumour can cause macular edema , retinal hard exudates, serous retinal detachment, rubeosis and neovascular glaucoma (‘toxic tumour syndrome’).
5)Survival: similar to that following enucleation for comparable tumors
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External beam radiotherapy Irradiation with charged particles such as
protons achieves a high dose in the tumour with a relatively small dose in the superficial tissues.
Indications: tumours unsuitable for brachytherapy either because of large size or posterior location making positioning of a plaque unreliable.
Survival results: similar to brachytherapy or enucleation
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Transpupillary thermotherapy • Transpupillary thermotherapy uses an infrared
laser beam to induce tumour cell death by hyperthermia but not coagulation. It is useful
adjunct to radiotherapy. Indications :1)Small, pigmented choroidal
tumour(<3mm), away from macula, when differentiation between naevus and melanoma is not possible 2)Small choroidal melanoma when radiotherapy is inappropriate because of poor general health or reduced life expectancy. 3)After radiotherapy, as a treatment for exudation threatening vision.
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Laser photocoagulation• Is of limited value • It is used to treat selected small choroidal melanomas.
• when the lesions are located away from the fovea and are
less than 3.8 mm in thickness,<10mm in diameter.
SOURCES: xenon arc
krypton laser
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Enucleation Indications: -large tumour size, -optic disc invasion, -extensive involvement of the ciliary body or angle,-irreversible loss of useful vision and -poor motivation to keep the eye.Modified Technique: It is essential to perform ophthalmoscopy after draping
the patient to ensure that the correct eye is treated. No touch cryosurgical enucleation(minimal trauma
technique) Pre-enucleation radiotherapy
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Orbital exenteration
• Reserved for cases with widespread orbital
extension.
• Patients with such advanced melanomas are likely to
have extensive distant metastases and poor
prognoses.
• The procedure should be considered only in rare
cases where marked discomfort is associated with
massive orbital spread of the melanoma.
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Other procedures:
Pars plana vitrectomy endoresection
endoresection for posterior choroidal melanomas
Block excision
It is reserved for small tumors covering less than one third of the globe’s
circumference.
Trans-scleral choroidectomy Indicated for tumours too thick for radiotherapy but
usually less than 16 mm in diameter.
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• Systemic chemotherapy and immunotherapy
- No distinct role
• Photoirradiation
• Ferromagnetic hyperthermia
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Further outpatient care
• Irrespective of the treatment modality chosen, patients with choroidal
melanomas need to be observed carefully for many years.
• This is particularly true for small tumors, when the diagnosis is not
established clearly.
• Close observation and measurement of the dimensions of the tumors is
critical.
• Repeat examinations usually are performed about every 3 months initially,
and if no changes are seen, follow-up care is performed every 6 months.
If growth of the lesion is detected, consider further treatment.
• The goal of successful treatment is not necessarily reduction in size but
long-term arrest of the tumor’s growth.
• The possibility of intraocular or extraocular tumor recurrence should be
kept in mind.
• Early detection of distant metastases may affect management and
survival.
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Dr. Finger suggests that you "Think of Sunglasses as
Sun Block for your Eyes" and start wearing your UV
blocking sunglasses. They make great gifts too!
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THANK YOU