INTRAOCULAR TUMORS(1)

Choroidal Melanoma

M. Akhlaghi MDAssociate professor of Isfahan university of medical science

Feiz Hospital

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INTRAOCULAR TUMORS

• Intraocular tumors of childhood• Intraocular tumors in adults• Vascular tumors

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INTRAOCULAR TUMORSI. Intraocular tumors of childhoodA. Retinal tumors

Retinoblastoma

B. Iris and ciliary body lesionsMedulloepithelioma

C. Choroidal and RPE lesionsCongenital hypertrophy of the retinal pigment epitheliumCombined hamartoma of the retina and retinal pigment epitheliumCongenital melanocytosis

D. Other benign tumors

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INTRAOCULAR TUMORSII. Intraocular tumors in adultsA. Choroidal and RPE lesions

Choroidal nevusChoroidal melanoma

B. Iris and ciliary body lesionsFuchs adenomaIris nevusCiliary body nevusIris melanomaCiliary body melanoma

C. Metastatic disease to the choroid

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INTRAOCULAR TUMORS

• III. Vascular tumorsA. Retinal capillary hemangiomaB. Retinal cavernous hemangiomaC. Choroidal hemangioma

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INTRAOCULAR TUMORS

Common Malignancies • Metastatic tumors are the most common

intraocular malignancy

• Choroidal melanoma is the most common primary malignant intraocular tumor

• Retioblastima is the most common malignancy in chailhood

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CHOROIDAL MELANOMA

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CHOROIDAL MELANOMA Etiology

• Develop from preexisting melanocytic nevi

• De novo growth

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CHOROIDAL MELANOMAEpidemiology

• Incidence: about 5-7 cases per 1 million population

• Incidence of choroidal melanoma is highest around age 60 years

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CHOROIDAL MELANOMA

Risk FactorsPredisposing factors:

• uveal nevus Estimated rate of malignant transformation is 1 in 5000/year

• dysplastic nevus syndrome

• Ocular or oculodermal melanocytosis [nevus of ota]. The incidence of choroidal melanoma in oculodermal melanocytosis is 1 in 400

• family history of uveal melanoma Despite a few reports of sporadic family clusters, most patients with posterior uveal melanoma have no known family history of the disease.

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CHOROIDAL MELANOMA

Risk Factors cont.

• Age• Gender • Race • Eye color• Sun light exposure• Smoking• Mobile use

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CHOROIDAL MELANOMA

Clinical Presentation

• Choroidal melanomas remain asymptomatic for prolonged periods of time.– The more anterior their origin, the longer the delay of any

symptoms. • Choroidal melanoma symptoms:

– Blurred visual acuity…– Paracentral scotoma…– Painless and progressive visual field loss…– Floaters…– Severe ocular pain…

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• Anterior choroidal melanomas might show sentinel vessels that feed the metabolically active tumor

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CHOROIDAL MELANOMA

Clinical Presentation

• small subconjunctival area of abnormal hyperpigmentation due to transscleral growth of an anterior choroidal melanoma

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CHOROIDAL MELANOMA

Clinical Presentation

CHOROIDAL MELANOMA

Diagnostic EvaluationIndirect ophthalmoscopy • Ophthalmoscopy is typically adequate for

diagnosis. Ultrasound, CT, MRI and FA can be used to aid in diagnosis,

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CHOROIDAL MELANOMA

Diagnostic Evaluation• Ophthalmologic examination may reveal the following:

• Small choroidal melanomas typically take the form of a nodular, dome-shaped, and well-circumscribed mass under the retinal pigment epithelium

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• As choroidal melanomas grow, they may adopt more irregular configurations (mushroom shapes)

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CHOROIDAL MELANOMA

Diagnostic Evaluation

• Diffuse choroidal melanoma, characterized by lateral growth throughout the choroid with minimal elevation, are more difficult to diagnose and often cause significant exudative retinal detachment

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CHOROIDAL MELANOMA

Diagnostic Evaluation

• Choroidal melanoma may remain undetected underneath a large exudative retinal detachment, a subretinal hemorrhage, or a vitreous hemorrhage

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CHOROIDAL MELANOMA

Diagnostic Evaluation

• Choroidal melanomas may have variable coloration, ranging from amelanotic to darkly pigmented; some are partially pigmented

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CHOROIDAL MELANOMA

Diagnostic Evaluation

CHOROIDAL MELANOMA

Diagnostic Evaluation• Overlying the choroidal melanoma, there are usually

retinal pigment epithelial changes (eg, drusen), patches of atrophy, and orange discoloration; orange changes can occur in both malignant and benign lesions

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CHOROIDAL MELANOMA

Diagnostic Evaluation

• Ultrasonography• Choroidal melanoma characteristically shows an

initial prominent spike, followed by low-to-medium internal reflectivity with diminishing amplitude

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CHOROIDAL MELANOMA

Diagnostic EvaluationAngiography• Fluorescein angiography and indocyanine green

angiography do not show pathognomonic signs of choroidal melanoma but can help point to its diagnosis

• Small choroidal melanomas may show fluorescein angiographic changes similar to some choroidal nevi, (ranging from normal angiography to hypofluorescencesecondary to blockage)

• Larger melanomas may show a patchy pattern of early hypofluorescence and hyperfluorescence followed by late intense staining

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CHOROIDAL MELANOMA

Diagnostic Evaluation

FA typically shows mottled fluorescence during the arteriovenousphase and then progressive leakage and staining

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Choroidal MelanomaDiagnostic Evaluation

ICG provides more information about the extent of the tumour, because there is less interference caused by RPE changes

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Choroidal MelanomaDiagnostic Evaluation

Choroidal melanoma, transillumination shadow

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CHOROIDAL MELANOMA

Diagnostic Evaluation• MRI of the globe and orbit can be used to determine

extrascleral extension of the melanoma and distinguish surrounding fluid from the tumor

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CHOROIDAL MELANOMA

Differential DiagnosisThe differential diagnosis for pigmented lesions in the ocular fundus most commonly includes the following:

• choroidal nevus • atypical disciform scar associated with AMD• suprachoroidal hemorrhage • RPE hyperplasia• congenital hypertrophy of the retinal pigment epithelium (CHRPE)• choroidal hemangioma with RPE hyperpigmentation• Melanocytoma• metastatic carcinoma with RPE hyperpigmentation• choroidal osteoma

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Choroidal Melanoma Differential Diagnosis

Differential Diagnosis of Amelanotic Choroidal Mass

• Amelanotic melanoma• Choroidal metastasis• Choroidal hemangioma• Choroidal osteoma• Age-related macular or

extramacular degeneration• Choroidal detachment• Uveal effusion syndrome• Posterior scleritis• Chorioretinal granuloma

• Toxoplasmic retinochoroiditis• Rhegmatogenous retinal

detachment• Degenerative retinoschisis• Presumed acquired retinal

hemangioma• Neurilemoma• Leiomyoma• Retinal cavernous hemangioma• Combined hamartoma of the

retinal pigment epithelium

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Large choroidal naevus Metastatic tumour Localized choroidalhaemangioma

Choroidal detachment Choroidal granuloma Dense sub-retinal orsub-RPE haemorrhage32

CHOROIDAL MELANOMA

Differential DiagnosisNevus vs. melanoma• Virtually all choroidal melanocytic tumors thicker than

3 mm are melanomas, and virtually all choroidal melanocytic lesions thinner than 1 mm are nevi

• Many lesions 1-2 mm in thickness may be benign, although the risk of malignancy increases with height

• Flat lesions with a basal diameter of 10 mm or less are almost always benign.

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CHOROIDAL MELANOMA

Differential DiagnosisNevus vs. melanomaClinical risk factors for enlargement of choroidal melanocytic lesions:

• Clinical symptoms such as metamorphopsia, photopsia, visual field loss• absence of drusen or RPE changes• presence of orange pigmentation• associated subretinal fluid• larger size at presentation• juxta papillary location• hot spots on fluorescein photography • documented increase of 0.3 mm in thickness and 0.5 mm in basal

diameter

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Typical choroidal nevus• Common - 2% of population

• Round slate-grey withindistinct margins

• Surface drusen

• Flat or slightly elevated

• Diameter less than 5 mm

• Location - anywhere

• Asymptomatic

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Suspicious choroidal naevus• Diameter more than 5 mm

• Elevation 2 mm or more

• Surface lipofuscin

• Posterior margin within3 mm of disc

• May have symptoms dueto serous fluid

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• The recommended management of choroidal nevi is photographic documentation for lesions less than 1 mm in thickness and photographic and ultrasonographic documentation for lesions greater than 1 mm in thickness, coupled with regular, periodic reassessment for signs of growth.

• Uveal Nevus estimated rate of malignant transformation is 1 in 5000/year (Rayan: However, the available literature suggests that the risk of choroidal and ciliary body melanomas associated with nevi of the uveal tract is low. Each year, only 1 in 5000 persons with such nevi develop a melanoma. with these conditions, current guidelines and recommendations for management and follow-up may not be cost-effective

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CHOROIDAL MELANOMA

Classification The modified Callender classification of uveal melanomas:

• spindle cell nevus• spindle cell melanoma • epithelioid melanoma• mixed-cell type

This classification can only be used in cases in which the eye has been removed

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CHOROIDAL MELANOMA

Classification Classification based on size:

• Small: <10 mm in diameter and <3 mm in height

• Medium: 10–15 mm in diameter and 3–5 mm in height

• Large: >15 mm in diameter and >5 mm in height

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genetic melanoma type

• It was discovered that uveal melanomas tend to develop several non-random chromosomal abnormalities, particularly chromosome 3 loss (monosomy-3) and gains in 6p and 8q…..

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CHOROIDAL MELANOMA

Classification

Metastatic Evaluation• The Collaborative Ocular Melanoma Study (COMS)

reported an incidence of metastatic disease of 25% at 5 years after initial treatment and 34% at 10 years

• clinically evident metastatic disease at the time of initial presentation can be detected in less than 2% of patients

• It is now known that micrometastases may occur several years before the diagnosis of a choroidal melanoma

• In general, survival with metastatic uveal melanoma is poor, with a median survival of less than 6 months

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• An assessment of metastatic disease patterns in COMS revealed liver involvement in 89% , lung involvement in 24%, bone involvement in 17%, and skin and subcutaneous tissue involvement in 12%.

• In cases that were autopsied, liver involvement was found in 100% and lung involvement in 50% of the patients with metastatic disease.

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CHOROIDAL MELANOMA

Metastatic Evaluation

All patients require metastatic evaluation prior to definitive treatment of the intraocular melanoma

why?

• To rule out the possibility of detectable metastatic melanoma If metastatic disease is clinically present during the pretreatment evaluation of the eye tumor, enucleation is inappropriate unless the eye is painful.

• To determine whether the patient has any other medical conditions For example, the COMS found preexisting independent primary cancers in about 10% of patients

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CHOROIDAL MELANOMA

Metastatic Evaluation

metastatic evaluation should be performed on all patients on a yearly follow-up basis and should include:

• comprehensive physical examination• liver function tests• Chest x-ray, although its yield was found to be low.

• Liver imaging studies: Ultrasound of the abdomen is usually sufficient

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CHOROIDAL MELANOMA

Metastatic Evaluation

CHOROIDAL MELANOMA

ManagementThe methods of patient management currently in use 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

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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 mm in elevation and 10 mm in diameter

• in very elderly and systemically ill patients who are not candidates for any sort of therapeutic intervention

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CHOROIDAL MELANOMA

Management

• Enucleation is the classic approach for some medium-sized, many large, and all extra-large choroidal melanomas and complicated tumors, which compromise visual function and for which other therapies tend to fail

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CHOROIDAL MELANOMA

Management

Plaque brachytherapy is probably the most common method of treating uveal melanoma• brachytherapy is a widely accepted alternative to

enucleation for medium-sized posterior uvealmelanomas

• iodine 125 is the isotope most frequently used• local tumor control rates to as high as 96%.• Regrowth: 4%-5% • Late radiation complications: optic neuropathy and

retinopathy, are visually limiting in as many as 50% of patients

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CHOROIDAL MELANOMA

Management

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Charged-particle radiation (proton beam radiotherapy)• High -linear-energy transfer radiation with charged particles

(protons and helium ions) has been used effectively in managing and choroidal melanomas.

• The technique requires surgical attachment of tantalum clips to the sclera to mark the basal margins of the tumor prior to the first radiation fraction. The charged-particle beams deliver a more homogeneous dose of radiation energy to a tumor than does a radioactive plaque, and the lateral spread of radiation energy from such beams is less extensive

• Local tumor control rates of up to 98% have been reported. • Radiation complications, most commonly anterior, lead to

uncontrolled neovascular glaucoma in 10% of treated eyes and vision loss in approximately 50%.

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CHOROIDAL MELANOMA

Management

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CHOROIDAL MELANOMA

Management

• External beam irradiation Conventional external-beam radiation therapy is ineffective as a single-modality treatment for malignant melanoma.

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CHOROIDAL MELANOMA

Management

• Pars plana vitrectomy endoresection

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CHOROIDAL MELANOMA

Management

A 37-year-old woman treated by endoresection. (A) Left eye before treatment, with visual acuity of 20/20 . (B) Fundus appearance 10 years later

• Block excision (sclerouvectomy) is an alternative treatment method reserved for small tumors covering less than one third of the globe’s circumference

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CHOROIDAL MELANOMA

Management

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• Laser photocoagulation and transpupillarythermotherapy (TTT) are used to treat selected small choroidal melanomas that are located away from the fovea and are less than 3 mm in thickness

• Orbital exenteration is a radical treatment reserved for cases with widespread orbital extension; it should be considered only in rare cases where marked discomfort is associated with massive orbital spread of the melanoma

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CHOROIDAL MELANOMA

Management

• Adjuvant systemic chemotherapy is not advocated

• When distant metastases are found in the initial systemic workup, palliative systemic chemotherapy is the primary treatment

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CHOROIDAL MELANOMA

Management

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