2016, Volume 32, Number 3, Page(s) 186-192
Management and Outcome of Uveal Melanoma in a Single Tertiary Cancer Center in Jordan
Ahmed ZEWAR1, Ibrahim NAWAİSEH1, Imad JARADAT2, Jakub KHZOUZ3, Khaleel ALRAWASHDEH1, Ghadeer ABDEEN4, Mustafa MEHYAR1, Samer KHURMA1, Yacoub A YOUSEF1
1Departments of Ophthalmology, King Hussein Cancer Centre (KHCC), Amman, Jordan
2Departments of Radiotherapy, King Hussein Cancer Centre (KHCC), Amman, Jordan
3Departments of Pathology, King Hussein Cancer Centre (KHCC), Amman, Jordan
4Departments of Medical Oncology, King Hussein Cancer Centre (KHCC), Amman, Jordan
Keywords: Choroid, Enucleation, Melanoma, Radioactive plaque therapy
The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an
example of a referral tertiary cancer center in the Middle East.
Material and Method: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required
access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor
location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality.
Results: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary
enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary
body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system
(UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis
(N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were
epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two
(10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for
uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was
equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes.
Conclusion: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate
tumors for radioactive plaque therapy were successfully controlled in 93% of cases
Uveal melanoma is the most common primary intraocular
malignancy in adults and accounts for 5% of all melanomas1
. It is seen more frequently in Caucasians in comparison
with Hispanics, Asians and Africans. For the Whites in the
United States, uveal melanoma has an incidence of 0.69
and 0.54 per 100,000 person-year for males and females
consecutively with a mean age of 601
Uveal melanoma mostly appears in the choroid (85-91%
of cases), and it is localized to the ciliary body or the iris in
9-15% of cases2. Iris melanomas are associated with the
earliest detection and overall best prognosis while ciliary
body melanomas are associated with the worst prognosis3,4.Around 50% of patients diagnosed with uveal
melanoma will develop metastasis, despite treatment, with
survival time after metastasis averaging 6-12 months5,6.
The Collaborative Ocular Melanoma Study (COMS)
concluded that there was no significant difference between
brachytherapy and enucleation in terms of prevention of
metastasis and mortality for medium sized melanomas.
Globe and vision-preserving radiation therapy is therefore
currently the primary treatment of choice for most uveal
melanomas in the developed world1,7,8.
There is limited data about the features and outcome of
management of uveal melanoma in the Middle East in
general and in Jordan specifically. The aim of this study is
to describe the features and outcome of uveal melanoma
management in a single tertiary cancer center in Jordan
(King Hussein Cancer Center (KHCC), Amman, Jordan)
in a developing country in the Middle East.
This study was approved by the Institutional Review Board
in KHCC. It was a retrospective case series of 46 eyes of
46 consecutive patients from July 2006 to April 2014 who
had intraocular uveal melanoma. Selection required access
to patients' medical charts, pathologic records, radiology
reports, and laboratory results.
Outcome measures included: patient's age at diagnosis,
gender, laterality, smoking, presenting symptoms and
visual acuity at presentation. Evaluated tumor clinical
characteristics included: tumor location, surface features,
shape, thickness, largest basal diameter, size, pigmentation,
presence of subretinal fluid, vitreous hemorrhage, cataract,
neovascular glaucoma, rubeosis, MRI features, TNM
staging, presence and site of metastasis. For tumors treated
by brachytherapy, additional features included plaque
size, apex dose, rate of radiation, distance between tumor's
edge and the optic nerve and the fovea, tumor thickness
and visual acuity after treatment.
Inclusion and Exclusion Criteria: The eligibility criteria
for inclusion were eyes with clinical and/or pathologic
diagnosis of intraocular uveal melanoma treated either by
radioactive plaques or by enucleation.
Pathological Characteristics and Definitions: In this study,
the tumors were classified according to the Collaborative
Ocular Melanoma Study (COMS) classification. The
COMS divided uveal melanomas based on size into small,
medium and large tumors9. Small melanoma; 5-16
mm at the largest basal diameter (LBD) and 1-3 mm in
apical height. Medium-sized melanoma; 16 mm or less
at the LBD and had an apical height between 3 mm and
10 mm and uveal melanomas more than 16.0 mm at the
LBD and more than 10 mm in height were defined as large
tumors. Pathologically; and according to the Callender
Classification, mixed tumors have been defined as tumors
that had less than 50% of cells as epithelioid in type, while
epithelioid tumors are those with more than 50% of cells
as epithelioid in type10,11. TNM staging was according
to the 7th edition of the American Joint Committee on
Cancer (AJCC) staging system12.
Reviewed data from the medical records regarding treatment
included the following: complications of brachytherapy,
and histopathological features of enucleated eyes. The
histopathology was further reviewed regarding extraocular
extension of the tumor such as extrascleral and/or optic
nerve involvement at the time of enucleation.
Follow-up of these patients was documented including
period, evidence of metastasis and patient status during the
period of the follow-up.
In our center, indications for enucleation included a tumor
involving or touching the optic nerve, large-sized tumor,
recurrence of tumor after brachytherapy, associated total
retinal detachment and secondary neovascular glaucoma
Seventy-six eyes were diagnosed with uveal melanoma in
King Hussein Cancer Center (KHCC) between July 2006
and April 2014. Thirty patients were excluded from the
data analysis because of inadequate data and/or because
the patients refused treatment and were lost for follow up.
Demographics and clinical features: 46 eyes with uveal
melanoma from 46 patients were studied. The mean age
at diagnosis was 46 years (median 45 years, range; 1.5-75
years,). There were 21(45%) males and all (100%) patients
had single tumor. Eighteen (39%) eyes were treated by
primary enucleation, and 28 (61%) eyes were treated
by I-125 radioactive plaque therapy. Two of the eyes
treated by plaque therapy were consecutively enucleated.
Demographics are shown in Table I.
Tumor features: The melanoma was in the choroid in 40
(87%) eyes, in the ciliary body in 6 (13%) eyes, and no
single patient had iris melanoma in this series. According
to the 7th edition of the American Joint Committee on
Cancer staging system (UICC/AJCC); 8 (17%) were T1,
17(36%) were T2, 16 (35%) were T3, and 5 (11%) were
T4. One (2%) patient had lymph node metastasis (N1),
and 5 (11%) patients showed distant metastasis (M1). One
patient already had metastasis at time of diagnosis while
the others were discovered to have metastasis later after
the diagnosis by an average interval of 26 months. Details
of tumor features in both groups (enucleation and plaque
group) are shown in Table II.
Pathologic features of enucleated eyes: A definitive diagnosis
of uveal melanoma was confirmed by histopathology
in 20(43%) eyes after enucleation. On histopathological
examination, 2 (10%) tumors were spindle cell type uveal
melanoma, 4 (20%) tumors were epithelioid cell type, and
14 (70%) tumors were of mixed type uveal melanoma
(Figure 1A,B). Extrascleral extension was seen in 3 (15%)
eyes (Figure 1C), and optic nerve invasion was seen in 2
Click Here to Zoom
|Figure 1: Histopathologic appearance of choroid melanoma.
A) Spindle cell melanoma type B showing pigmented spindle
cells with vesicular oval large nuclei and prominent nucleoli with
prominent mitotic activity (H&E; x200), B) HMB-45 positivity
in case of epithelioid melanoma (HMB-45; x200), C) Mixed
type choroid malignant melanoma with perivascular extrascleral
extension (H&E; x40).
Plaque features: The radioactive plaques used had a
median size of 16 mm with a range between 12 mm and 20
mm. The total radiation apex dose was 85 Gy in all patients
(median radiation rate = 7.25, range: 4.5 to 13). The main
complications included 5 cases of cataract, 7 cases of NVG, 1 case of recurrence, 1 case of radiation optic neuropathy,
and 5 cases of radiation retinopathy. At last follow up after
therapy, tumor thickness was < 5 mm in 13 (46%)eyes, and
5-10 mm in 13 (46%) eyes. The median tumor thickness
after therapy was 4.5 mm (range; 2-8 mm), and the decrease
in tumor thickness was variable between the treated eyes
(Table III). Two eyes were consecutively enucleated; one
for tumor recurrence, and one for uncontrolled painful
NVG. After therapy, visual acuity was equal or better than
0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than
0.1 in 10 (38%) eyes. 2 (7%) eyes had better vision while 15
(54%) eyes had worse vision after treatment.
Outcome and follow up: Twenty eyes were enucleated; 17
(85%) eyes were large (more than 16.0 mm at the LBD and
more than 10 mm in height), 17 (85%) eyes had RD, 1 (5%)
eye had tumor recurrence after plaque therapy, 2 (10%)
eyes had neovascular glaucoma, and 2 (10%) tumors were
touching the optic nerve. Three (15%) patients required
additional external beam radiation post enucleation due to
extraocular tumor extension confirmed pathologically. At
a median follow up of 24 months in the plaque group, 26
eyes were salvaged while 2 eyes have been enucleated.
Five patients out of 46 patients (11%) included in our
series had metastasis (5 had liver metastasis, 1 had lung metastasis, 1 had lymph nodes metastasis and 1 had bone
metastasis). 3 patients had plaque therapy and the other
2 underwent enucleation (one found to have epithelioid
cell type and the other mixed cell type). 2 patients had a
large-sized tumor, all tumors located in the choroid, and
3 patients were dead from the metastasis at the last date
of follow up after an average of 30 months from time of
diagnosis. Details of outcome in enucleation and plaque
groups are shown in Table III.
Well-developed data about uveal melanoma in the Middle
East is missing except in the form of small local case series
and case reports. Our series showed 77 cases of uveal
melanoma documented between 2006 and 2014 in a tertiary
cancer center in Jordan, and this low number provides
the impression that uveal melanoma occurs with a low
frequency in our region. In Saudi Arabia, one study showed
only 40 cases of uveal melanoma diagnosed between 1983
and 2005, only 28 of them were of Saudi Arabian ancestry13
. Similarly, another report from the Shanghai Eye, Ear,
Nose and Throat Hospital in China showed only 103 cases
of uveal melanoma diagnosed between 1955 and 197914
. On the other hand, 688 cases of uveal melanoma
were diagnosed among New York State residents between
1975 and 198615,
and similarly, 2997 patients had been
registered to have uveal melanomas in Sweden during the period from 1960 to 199816
. Even statistics about the
incidence of uveal melanoma in the Middle East and most
of the developing countries are missed, it seems that the
incidence in the Middle East and in Asia is less than the
incidence of uveal melanoma in USA and Europe.
This wide variation in incidence can be attributed to the
light skin color in USA and Europe residents which is one
of the risk factors for developing this tumor.
The average age at diagnosis in this series was 46 years,
while the average age at diagnosis in the COMS study
was 60 years17, which is 14 years older than the age at
diagnosis in our series and 10 years more than in patients
participating in a study performed in Saudi Arabia
reporting an average age at 50 years13. The reasons for
younger age of incidence in our patients are not known.
There was a slight, statistically insignificant, predominance
of females in our retrospective study, in contrary to most
reported studies that showed male predominance18-21.
This difference may be due to the low number of patients in
our series. However, no sex predilection was found in the
COMS randomized prospective study6.
In our review, a significant percentage (65%) of affected
eyes had a visual acuity of less than 0.1, which is worse than
the visual acuity for of patients studied in the COMS study
where only 33% had visual acuity of less than 0.19. This
finding might be explained by the delay in presentation after the onset of ocular complaints in developing poor
countries where health care could be unachievable because
of the high cost or of far distance to travel.
Most (70%) of our patients who underwent enucleation
had the mixed cell type melanoma, 20% had the epithelioid
cell type, and 10% had the spindle cell type, which is almost
similar to COMS findings where 86% were of the mixed cell
type22. This indicates that melanoma in our community
is pathologically similar to the west.
In the COMS study, the estimated melanoma-related
mortality was 1% at 5 years and was 4% at 8 years for
patients with small melanomas23. 5-year melanomarelated
mortality, based on histopathologically confirmed
metastasis, increased to 10% for patients with mediumsized
tumors, and to 28% for patients with large tumors24.
The delay in presentation to our institution likely played
a major role in finding a significant number of patients
(about 98%) with medium and large uveal melanomas.
Due to the short follow-up period available (median of
24 months), it was difficult to determine the survival
outcome among our patient population. Of the 5 patients
who had metastasis in this series, 3 patients had medium
sized tumors and 2 patients had large sized tumors. In the
COMS, the liver was the predominant site of metastasis,
which was reported in 89% of metastatic patients25. Our
study showed metastasis in only 11% of patients and in all
the liver was involved.
It can be concluded that the incidence of uveal melanomas
in our region is low compared to that in the West. A
significant number of Arabic patients, unfortunately,
present to ocular oncology clinics at a time where the tumor
reaches a large size or is associated with complications
that make it non-amenable for brachytherapy and end up
with enucleation. Therefore, awareness must be increased
and early detection improved with prompt referral by the
general ophthalmologist to save more eyes and to enhance
survival of affected patients. This study was retrospective,
so the follow-up was limited after treatment. It is
recommended to perform larger, multicenter and longer
term follow-up studies with more emphasis on accurate and
detailed gathering of information from the patients before
and after treatment in addition to comprehensive clinical
and investigational exams to determine the true incidence
and predisposing risk factors in addition to improving
statistical data on uveal melanomas in our region.
We acknowledge the support of the Eye Cancer Foundation
Inc. (New York, NY USA, http://eyecancerfoundation.net)
for Dr. Zewar for the Ocular Oncology Fellowship.
CONFLICT OF INTEREST
The authors declared no conflict of interest.
The authors declared no funding source was involved in
the creation of this manuscript.
1) Finger PT. Intraocular melanoma. In: Devita VT, Lawrence TS,
Rosenberg SA, editors. Cancer (principles & practice of oncology)
Ophthalmology. 10th ed. Philadelphia: LWW; 2011. 1770-9.
2) Shields CL, Kaliki S, Furuta M, Mashayekhi A, Shields JA.
Clinical spectrum and prognosis of uveal melanoma based on age
at presentation in 8,033 cases. Retina. 2012;32:1363-72.
3) Shields CL, Kaliki S, Shah SU, Luo W, Furuta M, Shields JA. Iris
melanoma: Features and prognosis in 317 children and adults. J
4) Oittinen HA, O'Shaughnessy M, Cullinane AB, Keohane C.
Malignant melanoma of the ciliary body presenting as extraocular
metastasis in the temporalis muscle. J Clin Pathol. 2007;60:834-5.
5) Kujala E, Makitie T, Kivela T. Very long-term prognosis of
patients with malignant uveal melanoma. Invest Ophthalmol Vis
6) Diener-West M, Earle JD, Fine SL, Hawkins BS, Moy CS,
Reynolds SM, Schachat AP, Straatsma BR; Collaborative Ocular
Melanoma Study Group. The COMS randomized trial of iodine
125 brachytherapy for choroidal melanoma, III: Initial mortality
findings. COMS Report No. 18. Arch Ophthalmol. 2001;119:969-82.
7) Singh AD, Kalyani P, Topham A. Estimating the risk of
malignant transformation of a choroidal nevus. Ophthalmology.
8) Collaborative Ocular Melanoma Study Group. The COMS
randomized trial of iodine 125 brachytherapy for choroidal
melanoma: V. Twelve-year mortality rates and prognostic
factors: COMS report No. 28. Arch Ophthalmol. 2006;124:1684-93.
9) Singh AD, Kivelä T. The collaborative ocular melanoma study.
Ophthalmol Clin North Am. 2005;18:129-42.
10) Accuracy of diagnosis of choroidal melanomas in the
Collaborative Ocular Melanoma Study. COMS report no. 1. Arch
11) Albert DM, Ruzzo MA, McLaughlin MA, Robinson NL, Craft
JL, Epstein J. Establishment of cell lines of uveal melanoma.
Methodology and characteristics. Invest Ophthalmol Vis Sci.
12) The AJCC Ophthalmic Oncology Task Force. Malignant
melanoma of the uvea. In: Edge SE, Byrd DR, Carducci MA,
Compton CA, editors. AJCC cancer staging manual. 7th ed. New
York: Springer; 2009. 547-53.
13) Alsuhaibani AH. Uveal melanoma in the Saudi Arabian
population: Two decades of management at the King Khaled Eye
Specialist Hospital. Saudi J Ophthalmol. 2009;23:157-63.
14) Kuo PK, Puliafito CA, Wang KM, Liu HS, Wu BF. Uveal melanoma
in China. Int Ophthalmol Clin. 1982;22:57-71.
15) M anschot WA, van Strik R. Uveal melanoma: Therapeutic
consequences of doubling times and irradiation results. A review.
Int Ophthalmol. 1992;16:91-9.
16) Bergman L, Seregard S, Nilsson B, Ringborg U, Lundell G,
Ragnarsson-Olding B. Incidence of uveal melanoma in Sweden
from 1960 to 1998. Invest Ophthalmol Vis Sci. 2002;43:2579-83.
17) Diener-West M, Earle JD, Fine SL, Hawkins BS, Moy CS,
Reynolds SM, Schachat AP, Straatsma BR; Collaborative Ocular
Melanoma Study Group. The COMS randomized trial of iodine
125 brachytherapy for choroidal melanoma, II: Characteristics of
patients enrolled and not enrolled. COMS Report No. 17. Arch
18) M cLean IW. Uveal nevi and malignant melanoma. In: Spencer
WH, editor. Ophthalmic pathology: An atlas and textbook, 4th
ed. Philadelphia: Saunders; 1996. 2121-217.
19) Barr CC, McLean IW, Zimmerman LE. Uveal melanoma in
children and adolescents. Arch Ophthalmol. 1981;99:2133-6.
20) Scotto J, Fraumeni JF Jr, Lee JA. Melanomas of the eye and other
noncutaneous sites: Epidemiologic aspects. J Natl Cancer Inst.
21) Phillpotts BA, Sanders RJ, Shields JA, Griffiths JD, Augsburger JA,
Shields CL. Uveal melanomas in black patients: A cases series and
comparative review. J Natl Med Assoc. 1995;87:709-14.
22) M cLean IW, Foster WD, Zimmerman LE, Gamel JW.
Modifications of Callender's classification of uveal melanoma
at the Armed Forces Institute of Pathology. Am J Ophthalmol.
23) The Collaborative Ocular Melanoma Study Group. Mortality in
patients with small choroidal melanoma: COMS Report No. 4.
Arch Ophthalmol. 1997;115:886-93.
24) 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
25) Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R,
Cumming K, Earle JD, Green DL, Hawkins BS, Hayman J,
Jaiyesimi I, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM,
Thoma J; Collaborative Ocular Melanoma Study Group Report
23) Screening for metastasis from choroidal melanoma: The
Collaborative Ocular Melanoma Study Group Report No. 23. J
Clin Oncol. 2004;22:2438-44.