uveal melanoma; diagnosis and differentiation by magnetic
TRANSCRIPT
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.
Uveal Melanoma; Diagnosis 609
~ 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 oc- cur 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 tu- mor detection and delineation.
Kersten et al 1985 reported that diag- nosis 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 exten- sion 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 dem- onstrated 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 tu- mor. Moreover, the shape may be helpful, since the fluid collection often demon- strated 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 cres- cent or ring shaped area in T I and T2 weighted hyperintensity anatomically lo- cated to the choroid or suprachoriodal space. Such collection occurred by sur- gery, penetrating trauma or inflammation. This ability is helpful in the treatment. Malignant tumor is the most common oc- ular tumor associated with retinal detach- ment. (Peyter et al 1988) observed such association in (8%) of their cases. Our re- sult 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 heman- gioma, retinoblastoma or choroidal de- tachment) both in clinical and MRI crite- ria. They reported three choroidal hemangiomas with T1 weighted hyperin- tensity and T2 weighted iso- or hypoin- tensity. In contrast Mafee et al 1987 not- ed one case of choroidal metastases from breast carcinoma to have T I and T2 weighted hyperintensity images.
Unlike uveal melanoma, choridal he- mangioma 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 ex- plained 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 imag- es. (7.5%) two cases were diagnosed as choroidal metastases, uveal metastasis can be confused clinically and radiologi- cal with uveal melanoma, a most com- mon source of secondary carcinoma within the eye is from breast or lung (rare). They showed T1 weighted isoin- tensity and T2 weighted hypointensity
612 Gouda M, khulifu, er al.
~mages and (50 %) of them were associat- ed 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 sec- ondary to high mucin content.
Choroidal lymphoma and leukamic in- filtration of the uveal tract can be mistak- en for choroidal tumor. The process may be bilateral and may cause retinal detach- ment. On MR imaging, choroidal lympho- ma 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 differ- entiate 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, chron- ic 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 intra- ocular blood or proteninous subretinal ef- fusion.
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 in- formation's about the extraocular tumor extension.
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