Uveal melanoma is a
rare tumour, however, it is the most common primary intraocular
malignancy in adults. It
may arise from melanocytes in any part of
the eye.
- i) Location of
the tumour : Tumours of the posterior pole causes early symptoms.
- ii) Clinical
stages:
- Stages I and II represent the early stages. These may be asymptomatic
or with symptoms related to loss of vision.
-Stage III shows ocular symptoms such as increased intraocular pressure,
inflammation and pain.
-Stage IV shows symptoms of extraocular extension such as proptosis,
subconjunctival mass.
- iii) Tumour
size: It is classified according to the largest tumour
dimension ; Small tumours are discoid shaped and less than 10 mm in the
largest dimension ; Medium and large tumours show collar stud or
mushroom-shaped appearance ; Large tumours are over 15mm in size.
-iv) Other
clinical parameters:
- Spread of tumour to extrascleral
site.
-
Tumor margin located anterior to the equator of the eye.
The tumour is
classified into two main cell types: Spindle and epithelioid.
Spindle cells are
highly cohesive fusiform cells with small nuclei. Small tumours seen in
early stages of disease are composed of these well- differentiated
melanocytes.
Epithelioid cells
are large polyhedral cells with abundant cytoplasm and contain large
nuclei with round nucleoli.
Image Link
In some cases
multinucleated epithelioid type cells are present. These poorly
differentiated melanocytes indicate aggressive nature of the tumour.
Immunohistochemical profile:
HMB-45 (most
specific) ; S-100 protein ; Neuron-specific enolase (NSE).
Differential
Diagnosis:
Metastatic
carcinoma ; Schwannoma ; Neurofibroma
Radiology:
- Ultrasonography A
and B scans are the most accurate method for diagnosis and to determine
the tumour size .
- Computed
tomography and Magnetic resonance imaging are useful in the diagnostic
evaluation.
Prognostic
factors:
-
Tumour
size and location (most important prognostic factors)
- Extraocular
extension.
- Other clinical
parameters: (i) tumor margin anterior to the equator of the eye
(ii) older age (iii)male
( iv)tumour
induced glaucoma
Metastasis,
treatment and survival:
Uveal melanoma metastasize hematogenously and preferentially to the liver.
Metastasis can
occur any time up to 20 years after treatment.
Aside from hematogenous spread, uveal
melanomas disseminate by traversing the sclera to enter the orbital
tissues, usually at sites where blood vessels and nerves pass
through the sclera.
Unlike melanomas of the skin, those of the uvea
do not exhibit lymphatic spread, because the eye lacks lymphatics.
Intra-ocular melanomas secondarily
cause hemorrhage, cataract, glaucoma, retinal detachment, and
inflammation. Each of these manifestations may mask the basic
pathologic disorder.
Treatment
depends on the size of the tumour .
1. Small tumours:
If
no further growth is seen no treatment is undertaken ;
If the tumour
grows radiation is applied ; If the tumour continues growing
enucleation is performed.
2.Large
tumours: Follow up with liver function tests is performed to
ensure that there is no metastasis. Even with treatment there is no
significant change in survival.
Life expectancy is
2 to 7 months after detection of metastasis.
Surgical resection
of hepatic metastasis coupled with chemotherapy is the best method of
improving survival.
Choroidal Melanoma:
The
choroid is the most common site. Choroidal melanomas are usually
circumscribed and invade Bruch's membrane, causing a collar stud or
mushroom-shaped mass. By contrast, some are flat (diffuse melanoma)
and either cause a gradual visual deterioration over many years or
not become apparent until extra-ocular or distant dissemination has
occurred. Orange lipofuscin pigment is evident over the surface of
some choroids melanomas. Based on the microscopic appearance of
uveal melanomas, they have been subdivided into different types
spindle A, spindle B, fascicular, necrotic, mixed, and epithelioid
types).
Histological study of choroidal malignant
melanoma treated by carbon ion radiotherapy.Jpn
J Ophthalmol. 2007 Mar-Apr;51(2):127-30.
PURPOSE: To
report, we believe for the first time, a histological study of
choroidal malignant melanoma treated by carbon ion beam
radiotherapy. METHODS: A 75-year-old Japanese man was diagnosed
as having a choroidal melanoma after undergoing magnetic
resonance imaging (MRI). Positron emission tomography (PET)
revealed a hot spot in the same location as the intraocular mass
seen in MRI. Carbon ion radiotherapy was performed with a total
dose of 77 Gy, and the hot spot seen by PET disappeared
completely. At 15 months after carbon ion therapy, the eye had
to be enucleated because of uncontrollable ocular hypertension.
It was examined histologically in serial sections. RESULTS: A
large tumor mass (15 x 12 mm) with high pigmentation was found
in the vitreous space. Almost all tumor cells showed necrosis in
every section. A small number of intact tumor cells were present
at the periphery. The overlying retina did not show any
necrosis, but showed mild to moderate gliosis. No intraretinal
hemorrhage, lipid deposit, or protein exudate was apparent.
CONCLUSIONS: Almost all tumor cells showed necrosis after
radiotherapy with a carbon ion beam. However, the effect on the
adjacent tissues was determined as minimal in histological
analysis.
Melanomas of the ciliary body and
iris:
Image Link
Melanomas of the ciliary body and
iris may extend circumferentially around the globe ("ring
melanoma"). Melanomas in the iris present clinically one or two
decades earlier than those in the choroids and ciliary body, perhaps
because they are more easily seen.Image
Link
Clinical signs and differential diagnosis of
iris melanoma.Magy
Onkol. 2005;49(2):153-5, 158-9.
Iris
melanoma is the rarest type of uveal melanomas. Only 4-5% of
uveal melanomas occur on the iris. Although the iris can be
easily examined due to its location, differentiation of
melanocytic malformations such as naevi or melanomas is
difficult for the examiner. According to publications by Rones
and Zimmermann, histological examinations showed 22% of tumors
to be malignant and 78% to be benign. This lead to iridectomy
and iridocyclectomy as therapeutic solutions to gain ground over
enucleation. Follow-up of the clinical signs, transillumination,
ultrasonic biomicroscopy, iris fluorescein angiography and
photo-documentation of the clinical signs can be of great help
in diagnosis of pigmented iris tumours. Growth of the tumour,
secondary glaucoma, hyphaema, significant vascularisation of the
tumour and increasing extent of pigmentation can be signs of
malignant behaviour.
Occasionally, one or more irregular
areas of pigmentation appears spontaneously in a non-pigmented
portion of the conjunctive of one eye at about 40 to 50 years of
age. This condition, designated primary acquired melanosis, is
analogous to the lentigo-maligna variety of melanoma in the skin and
may regress spontaneously or evolve into a malignant melanoma. Other
malignant melanomas of the conjunctive are preceded by a nevus, or
have no overt antecedent lesion. Some tumours represent an extension
of an intra-ocular melanoma.
Presence and phenotype of dendritic cells in uveal melanoma.Br
J Ophthalmol. 2007 Jul;91(7):971-6.
BACKGROUND: Uveal melanoma arises in an immune-privileged site and
can itself add to the immunosuppressive environment. Previous
studies on cutaneous melanoma have shown the presence of tolerogenic
dendritic cells (DCs), which could play an important role in the
progression of the tumour. AIM: To examine the presence and
functional status of DCs in a small series of uveal melanomas.
METHODS: 10 cases of uveal melanoma were examined for the expression
of FXIIIa, CD68, human leucocyte antigen (HLA)-DR, CD40, CD83,
transforming growth factor betaR1 and indolamine 2,3 dioxygenase by
immunohistochemical analysis on sections embedded in paraffin wax.
RESULTS: CD68-positive macrophages were present in all of the
tumours and were evenly distributed throughout. DCs expressing
FXIIIa-positive were seen in 7 cases, and were often found
concentrated in foci within the tumour mass. These cells were
dendritic and expressed high levels of HLA-DR. The DCs did not
express the maturation markers CD83 or CD40. In one case,
concentration of DCs around the area of tumour necrosis was
observed, and some of these cells expressed CD83. CONCLUSION:
Numerous tolerising antigen-presenting cells may play a role in
melanoma-related immunosuppression in the eye, although activation
of DCs may be associated with tumour necrosis.
Optic nerve
invasion of uveal melanoma.APMIS.
2007 Jan;115(1):1-16.
The aim of the
study was to identify the histopathological characteristics
associated with the invasion of the optic nerve of uveal melanoma
and to evaluate the association between invasion of the optic nerve
and survival. In order to achieve this, all uveal melanomas with
optic nerve invasion in Denmark between 1942 and 2001 were reviewed
(n=157). Histopathological characteristics and depth of optic nerve
invasion were recorded. The material was compared with a control
material from the same period consisting of 85 cases randomly drawn
from all choroidal/ciliary body melanomas without optic nerve
invasion. Prelaminar/laminar optic nerve invasion was in
multivariate analysis associated with focal retinal invasion,
neovascularization of the chamber angle, and scleral invasion.
Postlaminar invasion was further associated with non-spindle cell
type and rupture of the inner limiting membrane of the retina. The
optic nerve was invaded in four different ways: 1) by tumor
extension from the neuroretina through the lamina cribrosa; 2) by
direct extension into the optic nerve head between Bruch's membrane
and the border tissue of Elschnig; 3) by direct invasion through the
border tissue of Elschnig; and 4) in one case a tumor spread along
the inner limiting membrane to the optic nerve through the lamina
cribrosa. Invasion of the optic nerve had no impact on all-cause
mortality or melanoma-related mortality in multivariate analyses.
The majority of melanomas invading the optic nerve are large
juxtapapillary tumors invading the optic nerve because of simple
proximity to the nerve. A neurotropic subtype invades the optic
nerve and retina in a diffuse fashion unrelated to tumor size or
location.
Bruch's
membrane abnormalities in dome-shaped and mushroom-shaped choroidal
melanomas.Ann
Acad Med Singapore. 2006
Feb;35(2):87-8.
INTRODUCTION: Mushroom-shaped choroidal melanoma is known to be
associated with breaks in Bruch's membrane and is more likely to
develop when Bruch's membrane is diseased. The study's goal is to
determine if diseases causing breaks in Bruch's membrane predispose
a choroidal melanoma to develop into a mushroom-shaped melanoma.
MATERIALS AND METHODS: A retrospective review of cases of choroidal
melanoma seen at our institution was carried out to determine if
mushroom-shaped melanomas are more common than dome-shaped tumours
in patients with macular abnormalities involving a loss of Bruch's
membrane integrity. Forty-nine eyes of 48 patients were included in
this retrospective study. A dome-shaped or mushroom-shaped
configuration was assigned to each tumour. Macular degeneration,
macular drusen, retinal pigment epithelial (RPE) stippling, macular
oedema, choroidal neovascularisation (CNV), angioid streaks,
disciform scars, lacquer cracks, and myopia greater than -3.00 D,
were considered to constitute evidence of potential Bruch's membrane
breaks and were determined in both eyes. A chi-square evaluation was
used to compare the proportion of eyes with macular abnormalities in
the 2 tumour configuration groups. RESULTS: The tumour was
dome-shaped in 40 eyes (82%) and mushroom-shaped in 9 eyes (18%).
Macular abnormalities, indicative of loss of Bruch's membrane
integrity, were seen in 21 (53%) of 40 eyes with dome-shaped
melanomas and 5 (56%) of 9 eyes with mushroom-shaped melanomas. The
proportion of eyes with macular abnormalities was not statistically
different between the dome-shaped and mushroom-shaped tumours, as
assessed by chi-square analysis (P = 0.87). CONCLUSIONS: Bruch's
membrane disease does not influence the differentiation of choroidal
melanoma into mushroom-shaped or dome-shaped tumour growth patterns.
Iris melanoma: a case report and review.Ophthalmic
Physiol Opt. 2006 Jan;26(1):120-6.
Iris
melanoma is a rare ocular tumour, which can be detected early in its
development. This tumour is almost always unilateral and arises
usually from a pre-existing naevus. Failure to detect it may be
associated with morbid ocular and systemic complications, yet there
are successful therapies to treat this condition, if detected early.
The patient presented to the eye clinic with symptoms of occasional,
brief loss of vision in his left eye for a few weeks prior to his
visit. Slit-lamp examination revealed a mass on the inferior part of
the iris of the left eye. Intra-ocular pressure measurements were RE
15 mmHg and LE 38 mmHg. It was found that a tumour had spread
throughout the iris stroma and invaded the anterior chamber angle.
Although enucleation would have been the treatment of choice in the
past, the trend today in the treatment of a growing, large
circumscribed iris tumour is to excise it. It was successfully
excised by irido-cyclo-trabeculectomy.
Multiple locations on chromosome 3 are the targets of specific
deletions in uveal melanoma.
Eye. 2006 Apr;20 (4):476-81.
PURPOSE: Loss of
chromosome 3 is a frequent event in uveal melanomas, which is
associated with hepatic metastases and a poor prognosis. The entire
copy of chromosome 3 is usually lost (monosomy 3); however, a small
subset of tumours demonstrate partial deletions of chromosome 3.
Analysis of these tumours may allow the identification of tumour
suppressor genes (TSGs) that are the molecular target of monosomy 3.
Therefore, the purpose of this investigation was to determine the
location of these partial deletions of chromosome 3 in uveal
melanomas. METHODS: Microsatellite analysis and restriction
fragment-length polymorphism analysis were performed on 52 primary
uveal melanomas using 19 markers located on both arms of chromosome
3. Cytogenetic analysis and fluorescence in situ hybridisation were
performed, where possible, to confirm molecular findings. RESULTS:
Of 52 tumours studied, five tumours (10%) demonstrated LOH at one or
more informative markers, but retention of heterozygosity was
observed at other loci on chromosome 3, consistent with the presence
of structural abnormalities to chromosome 3. Consistent with
previous findings, the pattern of LOH in these tumours indicates the
presence of deletions around 3p25-26 and on 3q, and that a new
target region at 3p11-14 is preferentially deleted. CONCLUSIONS:
These results indicate the presence of several tumour suppressor
loci on chromosome 3 and support the notion that the high rate of
monosomy 3 in uveal melanoma is driven by disruption of several TSGs
located on both arms of chromosome 3.
Since the eye lacks
lymphatic vessels, uveal melanomas primarily metastasize
hematogenously. Here we report the case of a patient with ciliary
body ring melanoma who developed lymph node metastases after a
fistulating glaucoma operation. A 40-year-old female Caucasian
patient presented with unilateral pigment dispersion. Pigment
dispersion glaucoma was diagnosed and since the intraocular pressure
could not be managed with topical medication, transscleral
cyclophotocoagulation and two trabeculectomies had to be performed.
Due to enlargement of the pigmented iris mass and cell deposits in
the chamber angle, a ciliary body ring melanoma was presumed and the
eye enucleated. Histology confirmed the diagnosis of "ciliary body
ring melanoma". Six months after enucleation the patient presented
multiple metastases including ipsilateral preauricular and
submandibular lymph node metastases. The patient died two months
later. Lymph node metastases arising from ciliary body melanomas are
very rare. Tumor seeding through the trabeculectomy site into the
bleb and then via conjunctival lymphatic vessels might be the
crucial factor for this pathway of metastases. Therefore, in cases
of unilateral pigment dispersion, malignancy should be excluded
before fistulating operations are performed.
