uveal melanoma; diagnosis and differentiation by magnetic

Sc. J , Ai. iMeil. Fnc. (Crr1.s ), Vol. 20, No. 1, J(itiiriiry. 19'19: 601 - 611.

UVEAL MELANOMA; DIAGNOSIS AND DIFFERENTIATION BY MAGNETIC

RESONANCE IMAGING.

By

Gouda M. khalifa, Hatem H. Sherif, Nailia M . Abdel-Ateif,

Alla M.Bader, Mahmoud K. El-Gendy and Tarek A. Mostafa.

Radiology and Ophihaltt~ology depal-~~nrtrr.s, Al-Hirssei~i

und Al-Zahraa University Hospirols. Ali tzhor rrtriversiry.

ABSTRACT

It is sometimes difficult to establish

correct diagnosis of an atypical uveal le-

sion. Enucleation of eyes with suspected

uveal melanomas that have simulating le-

sion on histologic examination are un-

common, however, some incorrect diag-

nosis still occurs even after clinical

examinations; fluorescein angiography,

ultrasonography or fine needle aspiration

biopsy.

In this study, we evaluated (26) pa-

tients with intraocular diseases by mag-

netic resonance imaging. Malignant uveal

melanoma was diagnosed in (16) patients

(5) underwent surgery with histopatholog-

ical confirmation of melanoma.

MRI is alloived detection of uveal

melanoma with their characteristic signal

intensity sccondary to the paramagnetic

properties of the melanin. In addition

tumor characterization improved detec-

tion of tumor margins and cxuaocular

extension.

MRI also can be proved valuablc for

differentiating uvcal melanoma from asso-

ciated subretinal effusion, choroidal de-

tachment and other tumors (choroidal he-

mangioma, metastases & retinoblastoma).

INTRODUCTION:

Malignant weal melanomas are the

most common primary malignant intraoc-

ular tumors in adult, Uveal melanomas

are rare in blacks, the white: black ratio

being about 15:l. Uveal melanomas in

blacks are larger, more pigmented and

rr~orc necrotic. Bilalcral uvcni mca lnom;~ ilu!i~e~cein angiography or ultrasono~r;~-

arc cxircrnely raic (Egar: ! O i i i i ) . It is phy, niirdiagnc>si.; is pus\iblc partic~~I:~rIy

thought to originate from pre-existing \vhen opnquc ~nedia pi-ecluile dircct vizu-

ncvi which arc congenital and usually ali7.atic)1i (Zimrnc~n~an 1988). C7' scan 11;ls

recognized lalc i n thc firs1 dccadc of life been uscd extcnsively to diagnose intrac~c-

with predo~ninarit locnticln at the posterior cular lesions. It has ;~ccuratcly dunon-

rhird of thc choroid. strated thc uveal melanoma and a variety

Benign ~nelanoma of thc choroid arc

congenital. acquire their pigmentation he-

tween thc age of 6-10 Scars, arc ftiund

chiefly in thc posterior pole and may raise

some fear of malignancy. (Reichcrt et al

1996).

Thc turnor arises as a suhsequcn~ ma-

lignant transformation of uveal melmocy-

tes that are found in thc iris, ciliary body

and choroid (Shammas ct al 1977). Extra-

ocular cxtcnsioiis, occurs i n 15-30 percent

of cases which arc oltcn of the flat diffuse

type. It usually takcs placc through the

emissary channels of the posterior or ante-

rior cilciary \,csscls. Extension of beyond

the glohc can occur, thereby worsening

the prognosis and necessitating changes i n

the ilierapeutic appl-oach (Kel-sten 1985).

hictastasi: is l'rcqucnt bccausc of the ease

\r,ith which thc tumor cclls invade the \.;IS-

culiir channels.

Al:hough uveal mclanomas can bc ac-

culi~.tcly diagnc~scd hy ophthalmoscopy.

of patlioIogic;il cii!iditions. It can casily

dctcct Ihc calcificntiori wilhin thc tu111o1-

cspeci3lly i n retinohlastoma. that is nor

cvaluatcd by MR. In atldition dyna~riic CT

scan can provide information about lesion

vascularity arid perfusion and hclp to dis-

tinguisli uvcul nielanonias from other Ic-

sions such as choroidal hemangiomas

(Mafe 1984). MRI other technology that

also demonstrated potential in evaluating

intraoccular tuniol-s. Elcctron spin reso-

nance studies l~ave shown that mclanin

produces a stahle free radical signal under

all known conditions.Thcse stable radical?

cause a proton rclaxalion enhancement

that shortens both TI and T2 relaxation

tirnes vaiues (Hostin et a1 1997). U\,eal

melanomas thercforc arc uniquc amon2

malignant tumors i n that 1'1 and T2 relax-

ation values are shol.tencd owing to the

paramagnetic propcrty of mclanin (Plito

1995j.

RIATERIAI, and iMETHODS

Diagnustic MR !radiograph and

Uveal Melanoma; Diagnosis 603

/

medical records of patients with intraocu-

lar tumors were retrospectively reviewed.

Our patients and data collection were per-

formed from Columbia university, New

yo& & Illinois university, Chicago and

AL-Azhar university hospitals. Their

,umbers, percentages, age, sex and eye

affected distributions are summarized in

table I

Our study contained group of (26) pa-

tients, all had been diagnosed ophthalmo-

followed by coronal and occasionally sag-

ittal images. Tlweighted images were ad-

ditionally acquired after application of

(0.1 ml) Gd. DTPA /kg body weight. The

following MU values were recorded in-

cluded (tumor detection, tumor size, tu-

mor location, signal intensity relative to

that of vitreous, tumor extension, associat-

ed retinal detachment and subretinal hem-

orrhage or serous collections.

RESULTS logically (by indirect ophthamoscope,

Table 2 and 3 are summarized the re- ultrasonography and fluorescein angiogra-

sults and MU appearances of uveal meal- phy) as having an intraoccular mass.' nomas without1 with associated lesions

They were (I6) men and (I0) and simulating intraocular mass lesions.

with an age ranged from ,&IS.) years.

With MRI (16) were diagnosed as uveal In this study,TI weighted spine echo

melanoma, (3) choroidal hemangioma, (2) series (TR400-700m sec)& (TE 15-20111

retinoblastoma, (2) choroidal metastases

and (3) choroidal detachment. Five pa-

tients underwent surgery with histopatho-

logical confirmation of melanoma. MU

imaging was ,performed using (siemens

magnet and general electric magnet) sys-

tem operating at 1.5 tesla, with head coils

and some images were obtained using sur-

face coil. Partial saturation and spin echo

techniques were commonly used with sec-

tion thickness (3-5 mm) both on TI and

T2 weighted images. The majority of

studies were begun with axial sections,

sec) provided optimal contrast between

diseased tissues and normal structures. T2

weighted spine echo series (TR1500-

3000m sec) & (TE30-80m sec) provided

decreases signal to noise characteristics

and less spatial resolution. However most

of melanotic melanoma patients showed

characteristic M R appearance due to the

paramagnetic properties of melanin. On

T1 weighted images, they revealed very

hyperintensity .and T2 weighted images

revealed very low signal intensity (Fig 1).

They enhanced after administration of

604 Gouda M. kiialija, ei a/.

Gd-DPTA and enhancement may vary in

the samc tumor depcnding on the content

of melanin. Some patients showed typi-

cally hyperintensity in Tlweighted imag-

es, but they had isointensity in T2 wcight-

ed images, thcy wcre hypomelanotic.

Trans-sclerai extension into the retro-

bulbar space was observed in two cases

(12.50%) while optic nerve invasion was

noted in onc casc (6.25%) (Fig 2).

Extra-ocular extension was best seen

on thc unenhanced TI weighted images

with exception of the optic nerve infiltra-

tion, which be diagnosed after enhance-

ment in two cases (Fig3). Additionally,

widening of the subarachnoid space close

to the entry of the optic nerve into the

globe was observed in T2 weighted imag-

es. Discontmuity of the wall of thc globe

was depicted in two patients without evi-

dence of an extra-ocular mass extension.

Unusual high signal within the vitre-

ous was observed in one casc and this

was believed the result of protein leakage

owing the impaircd retinal blood barrier

(Fig 4).

In two cases subretinal effusion (of

high protein content) was detected as an

associated finding with high signal inten-

sity in T1 weighted images and high sig-

nal in T2 wcighted images (Fig 4).

Retinal detachment. associated with

choroidal melanoma is better seen by

MR imaging as a crescent hypointensc

line in TI weighted images and of isoin-

tense (hyperintense) to vitreous in T?

(Fig 5).

Chronic exudative choroidal detach-

ment was noted in two cases as modcr-

atcly hyperintense in TI weighted images

and hypointense in T2 weighted images.

Chronic choroidal hemorrhagic dc-

tachment diagnosed in one case and

demonstrated as marked hyperintensity

in T1 and T2 weighted images (Fig 6),

Unlikc uvcal melanoma, choroidal

hemangioma noted in three pa-

tients,showed areas of moderately

hypointense in TI wcighted images and

hypcrintense in T2 weighted images

(Fig. 7).

Two patients who had choroidal me-

tastases showed isointcnsity in TI

weighted images and hypointensity i n T2

weighted images. Two patients were di-

agnosed as retinoblastoma mimicking

the melanoma and showed slight hyper-

intense in T1 and hypointcnse in T2

wcighted images.

Uveul Melanornu: Dia~nosis 605

/

Table 1 Orbital mass lesion & age & sex and eye affected distribusion.

Table 2 MRI apperance of orbital lesions simulating melanomas

- Choroidal detachment 3

26

Orbital lesion

Choroidal hemangioma

Retinoblastoma

Choroidal metastases

Choroidal detachment

* Serous.

"emorrhagic.

11.5%

100%

Enhanced fat-

supp T1

Intense enh.

Moderate enh.

slight enh.

T1

Iso or slight hperintense

Slight hyperintense

Mottled Iso intense

Iso or slight hyperintense

Hyperintense.

30-56Ys

2-78Ys

T2

Hyperintense

Hypointense

Hypointense

Hyperintense

Hyper orvariable

according to age of

heg.

3

16

--

10

2

17

1

9 -

Noof

Pat.

3

2

3

I

2

2

2

1

%

ls.75".

1250%

la75'/.

6.25

"/a

1233%

1250'/.

12.M'/.

6.25

Yo

Associated lesions T I T2 Enhanced fat-

supp-T1

Uveal melanoma without associated lesion Hyperintense Hypointense Moderateenh.

Retinal detachment. Cresent hypointense line Isointense with - associat. hyperitense mass viterous

h,n hemorrhagic sub - retinal emusion Hyperintense Hyperintense -- (of high protein content ).

Prntien leakage within the vitreous Hyperintense Hyperintense - + vitreous hemorrhage.

- ---

Trans-scleral extension into reterobulbar ffyperintense Isointense Enhancment

space.

Discontinuity uf the wall of the globe Hyperintense Isointense Enhancment

without extra-oculnr extension.

Extra-ocular extension. Heterogenous hyperintense Hypointense Enhancment.

Optic nerve invasion Hyperintense Hypointense Enhancment

Fig. ( I i : Choroidal melanoma with mild sub-retinal tluid. ,\xial T I : - There is ;In "void of nyper~niene moss i n the I~.nlporal aspect of thc right optic globe

associated w ~ t h mild sub-retinal iluid (hypcrintensc) extend to posterior aspect of the glohc.

Axi;ll T1:- The m:iss appears CIS hypointensity compared to vitreous. sub-retinal tluid is isointense (hyperintense) to viteruus.

F1g ( 2 ) :

Axial TI:-

Right melanoma with optic nerve

invasion.

A well defined hyperintense mass

resting at the posterior aspect of the

right globe with optic nerve

invasion.

Fig. 3 Melanoma \vith retro-bulbar cxtcnsion. Sagittal TI : -Shows a large well defined slight hyperintense rc~ro-bullar Inass related to tumor

extension. Aul:rl T?:. Shows a small intm-ocular hypointcnsc mass in the nasal aspect with retro-bulbar

cnicnsmn

Fig. (6):

Axial TI:-

Chronic choroidal hemorrhagic

detachment.

A crescent shape hyperintensity

at the posterior aspect of the

right globe.


~ i g . (7): Choroidal hemangioma.

Sagittal T1:- Shows a slight hyperintense mass mimic melanoma.

Axial T2:- Shows no discernible mass because the lesion is isointense (hyperintense) to vitreous.

DISCUSSION

The uvea is the middle layer of the eye wall between the sclera and the retina. It

is derived from mesoderm and neuroecto- dcrm, thus it may harbor tumors of either

origin.

Being the most vascular portion of the eyeball, it provides a suitable substrate for tumor cells. In adult, it is the commonest

site for primary and metastatic ocular neo- plasm's, mostly are malignant melanoma.

(Mc Mohon 1980).

Although ophthalmologists are usually correct in their diagnosis of uveal melano-

ma, serous misdiagnosis continues to occur when clear view of visualization ob- scured by vitreous hemorrhage or large

amount of subretinal effusion.

Orbital MR imaging has been possible

in the past few years and currently techni-

cal advances allow thinner sections and

innovative surface coil increases signal

to noise ratio resulting in better spatial resolution.

In this series we studied (26) patients

using a high magnetic field imager

which demonstrated all intraocular le-

sions that were elevated more .than (3

mm). Out of them (16) were uveal mela-

noma, (2) retinoblastoma, (3) choroidal

hemangioma, (2) choroidal metastases

and ( 3) choroidal detachment.

Our cases all showed hyperintensity

in TI weighted images and hypointensity

in T2 weighted images. Such MR ap-

pearance consisting with melanotic mela-

noma and as (Plito et al 1995) stated that

unique behavior is due to the paramag-

netic properties of melanin that shorten

TI&T2 relaxation times.

Our results support (Peyster et al

1988) who reported such criteria in 93%

of their cases while the remainder

showed variable signality either T1

weighted hyperintensity or T2 weighted

isointensity and they explained this vari-

ation due to the presence of hypomela-

notic tissues.

610 Gouda M. khalqa, er al.

With Gd-DTO-PA administration im-

ages demonstrated superiority in the tumor detection and delineation.

Kersten et al 1985 reported that diagnosis of a mass in the retrobulbar space

adjacent to the tumor with signality differ- ent from retrobulbar fat should considered

extraocular extension.

In our cases (12.50 %) showed this exten-

sion and support those authors who ob-

served such extension in (10-15%) of

their cases.

Murphy et a1 1995 reported this extension in (4%) of their cases and they ex-

plained ultrasound false interpretation to diagnose such extension due to the fol-

lowing items.

One- Insertion of the extra-ocular muscles.

Two- Tumor located at posterior pole

near the optic nerve head is difficult to be

large at their site of extension.

Three- Vortex veins, which drain

blood from the globe and penetrate its wall, may be large at their site of entry.

Four- Post-therapeutic states with im- planted applications result in scarred ret-

rohulbar space.

Extraocular extension described as a

tumor growth through the sclera and pres-

ence of tumor nodule outside the globe. It

was best seen on the unenhanced T1 weighted images.

Transscleral extension and infiltration

of the optic nerve was demonstrated in

(12.50 %) of our cases. Its diagnosis

was achieved as the tumor enhancement

extended into the proximal part of the

nerve. Additionally widening of the sub-

arachnoid space close to the entry of the

optic nerve into the globe was observed

in T2 weighted images. In two patients

without an extraocular mass lesion, dis-

continuity of the globe wall was ob-

served. MR was surprised in differentiat-

ing uveal melanoma from subretinal

fluid, this is not only important for tumor

detection but also for obtaining reliable

measurements of the tumor size which

has a prognostic value for primary mela-

noma both at the initial evaluation and in

post-therapeutic follow up.

Okaba et a1 1986 studied the signal

characteristics of subretinal fluid on MR

in comparison to their chemical composi-

tion, they found that protein content

which varied considerably was principal-

ly responsible for the signal intensity.

With non -hemorrhagic effusion, high

protein content shorten T l relaxation

times, thus the fluid becomes hyperin-

tense on T1 and T2 weighted images

more than the vitreous.

Hemorrhagic effusion has variable

appearance depending on the age of he-

matoma.

Uveal Melanoma; Diagnosis 61 1

In three (1 1.5%) of our cases we demonstrated serous subretinal effusion with hyperintensity signal in T1 and T2 weighted images. Our result support (Au-

et al 1987), who observed that intraocular tissue that is hyperintense in

and T2 weighted images is very likely to represent subretinal fluid rather than tumor. Moreover, the shape may be helpful, since the fluid collection often demonstrated dependent pooling with straight or concave smooth surface against the vitre-

ous body.

Mafee et al 1988 proved that MR can differentiate choroidal melanoma from choroidal effusion or detachment. They published that effusion appears as a crescent or ring shaped area in T I and T2 weighted hyperintensity anatomically located to the choroid or suprachoriodal space. Such collection occurred by surgery, penetrating trauma or inflammation. This ability is helpful in the treatment. Malignant tumor is the most common ocular tumor associated with retinal detachment. (Peyter et al 1988) observed such association in (8%) of their cases. Our result showed this association in (12.50 %) of cases and was distinguished from the tumor by T I and T2 weighted images dif- ferent intensity.

MRI diagnostic limitation to evaluate amelanotic melanoma was described by (Peyter et al 1988) who observed the diffi- culty to differentiate (uveal melanoma,

choroidal metastases, choroidal hemangioma, retinoblastoma or choroidal detachment) both in clinical and MRI criteria. They reported three choroidal hemangiomas with T1 weighted hyperintensity and T2 weighted iso- or hypointensity. In contrast Mafee et al 1987 noted one case of choroidal metastases from breast carcinoma to have T I and T2 weighted hyperintensity images.

Unlike uveal melanoma, choridal hemangioma diagnosed in (1 1.5 %) of our cases demonstrated moderately iso-or slight hyperintense in T I weighted and hyperintensity in T2 weighted images. Mafee et al 1986 supported our results and demonstrated lack of signal void phenomena in this tumor and they explained to be the result of slow circula- tion (slow washout of the excited spins as demonstrated by dynamic CT).

Retinoblastoma was diagnosed in (7.5 %) two cases, they showed T1 weighted slight hyperintensity and T2 weighted hypointensity images.

Tumor calcifications, which easily seen at CT, were not seen on MR images. (7.5%) two cases were diagnosed as choroidal metastases, uveal metastasis can be confused clinically and radiologi- cal with uveal melanoma, a most common source of secondary carcinoma within the eye is from breast or lung (rare). They showed T1 weighted isointensity and T2 weighted hypointensity

612 Gouda M, khulifu, er al.

~mages and (50 %) of them were associated with widespread retinal detachment. (Spencer et al 1987) reported a case of

choroidal metastases from mucin- adenocarcinoma, it was hyperintense to vitreous in Tlweighted presumably secondary to high mucin content.

Choroidal lymphoma and leukamic infiltration of the uveal tract can be mistak- en for choroidal tumor. The process may be bilateral and may cause retinal detachment. On MR imaging, choroidal lymphoma and leukemia may have similar signal characteristics as uveal melanomas and they often bilateral, however, bilateral melanomas are extremely rare (Mafee MF. 1998).

Surnmaty and conclusion

In summary, the results of this study suggested that MRI has both high sensi- tivity and specificity to detect and differentiate intraocular tumors. Particularly uveal melanoma. Its sagittal images give graphic anatomic information's not other- wise available with US or CT. It provides characterization of acute, subacute, chronic choroidal or subretinal hemorrhage in a more sensitive fashion than do CT. Intra- tumoral vascularity or lack of it can be

better appreciated as well as the relation- ships and extension to the orbital muscles and optic nerve. Presence or absence of extrascleral growth can better determined in T I weighted spin echo before and after contrast while T2 weighted was less helpful.

MR helps to recognize the occult un- derlying tumor when the ophthalmoscop- ic examination is obscures by intraocular blood or proteninous subretinal effusion.

MR makes it ideally suited for meas- urement of the tumor size, volume. Early invasion of the sclera may sometimes were seen at histological examination. This invasion has an important point where uveal melanomas are diagnosed.

We do not routinely used MR scan- ning in patient with uveal melanoma. It is a relatively expcnsive study.

We usc it in-patients with atypical uveal tumors and in those in whom therc is possibility of extraocular tumor extcn- sion.

The rationale for this approach is threefold, first in atypical cases, addition- al non-invasive assay may be diagnostic before resorting to fine needle aspiration biopsy. Second in patients with uvcal metastases, the status of contiguous CNS is crucial for treatment planning made MR is the imaging of choice to assay that setting. Third MR adds valuable information's about the extraocular tumor extension.

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uveal melanoma; diagnosis and differentiation by magnetic

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