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NCI CANCERLIT® Search: Intraocular Melanoma - October 2001
National Cancer Institute®
Last Modified: November 21, 2001
Table of Contents
1
UI - 20329341
AU - Singh AD; Shields CL; Shields JA; Sternberg P Jr
TI -
Occurrence of retinoblastoma and uveal melanoma in the same patient.
SO - Retina 2000;20(3):305-6
AD - Oncology Service, Wills Eye Hospital, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA. arunsighn@eyetumors.com
2
UI - 21085769
AU - Gamel J
TI -
Occurrence of retinoblastoma and uveal melanoma in the same period.
SO - Retina 2001;21(1):94-5
3
UI - 21396163
AU - Lee HM; Kang HJ; Choi G; Chae SW; Kim CH; Hwang SJ; Lee SH
TI -
Two cases of primary malignant melanoma of the lacrimal sac.
SO - Head Neck 2001 Sep;23(9):809-13
AD - Department of Otorhinolaryngology--Head and Neck Surgery, Korea
University College of Medicine, Guro Hospital, 80 Guro-dong, Guro-gu,
Seoul 152-703, South Korea. hmlee91@hotmail.com
BACKGROUND: Malignancy of the lacrimal sac is rare, and primary
malignant melanoma in this region is extremely rare. METHODS: We report
two cases of malignant melanoma of the lacrimal sac presented with
epiphora and a palpable mass in the medial canthal area. We performed
radical surgery and radiation therapy. RESULTS: The light microscopic,
immunohistochemical, and electron microscopic studies confirmed the
diagnosis. One of the patients, a 65-year-old-woman, has no evidence of
recurrence or distant metastasis 3 years after surgery and radiotherapy,
whereas another patient, a 56-year-old man, died of distant metastasis 6
months after surgery and radiotherapy. CONCLUSIONS: We present two cases
of malignant melanoma of the lacrimal sac that masqueraded as chronic
dacryocystitis. Head and neck surgeons should be aware of this disease
entity when encountered with patients with epiphora and mass in the
medial canthal area. Copyright 2001 John Wiley & Sons, Inc.
4
UI - 21268051
AU - Sulkowski S; Sulkowska M; Famulski W; Chyczewski L; Bakunowicz-Lazarczyk
TI -
A
Expression of P53 protein in primary uveal melanoma.
SO - Folia Histochem Cytobiol 2001;39(2):159-60
AD - Department of Pathological Anatomy, Medical Academy, Bialystok, Poland.
sulek@amb.ac.bialystok.pl
Malignant melanomas are the commonest intraocular tumours. The aim of
the present study was the immunohistochemical analysis of P53 protein
expression in 39 primary ocular melanomas treated surgically in the
years 1983-1997. Expression of P53 was estimated semiquantitatively with
the use of a light microscope at a magnification of x 400. At least 200
neoplastic cells per sample were analysed. The expression of P53 in 3%
of melanoma cells was considered the threshold of positive reaction. The
results were subjected to statistical analysis with exact Fischer's
test. No statistically significant correlations were found between P53
expression and anatomoclinical properties of tumours, although increased
P53 expression was observed in epithelioid-cellular melanomas and in
tumours growing in women. A lack of statistically significant
relationship between P53 protein level and the parameters examined, and
morphological specificity of ocular melanomas hindering
immunohistochemical analysis, indicate the necessity for studies on a
wider group of tumours or/and use of molecular biology techniques to
establish possible relations between P53 gene mutation and ocular
melanoma biology.
5
UI - 21373757
AU - Burnier Pereira F; Burnier MN Jr; Shibata H; Wang B; Carey W
TI -
Cytomorphometric parameters and the metastatic potential of cutaneous
and uveal melanoma: a comparison with prognostic factors.
SO - Am J Dermatopathol 2001 Aug;23(4):304-7
AD - Henry C. Witelson Eye Pathology Laboratory, Department of Ophthalmology,
The Royal Victoria Hospital, McGill University, Montreal, Quebec,
Canada.
The Mean of the Ten Largest Nuclei (MTLN1) is one of the most important
prognostic factors in uveal malignant melanoma. This study was performed
to investigate the applicability of nuclear and nucleolar measurements
as a prognostic factor for cutaneous melanoma. A routine light
microscope (Carl Zeiss: Axiophot EL-Einnsatz; #451888) at 640 times
magnification with a Micrometer Eye Piece (Carl Zeiss: #444034) was used
to evaluate the correlation of MTLN1 and Mean of Ten Largest Nuclei
(MTLN) with the occurrence of metastasis in 58 primary cutaneous
melanoma. For uveal melanoma, cytologic classification was used for
comparison. Prognostic value was determined by univariate and
multivariate linear regression analysis. MTLN1 was the only significant
factor for uveal melanoma (p = 0.05). For cutaneous melanoma, all
factors were significantly associated with disease progression. MTLN1
was the only one to remain significant (p + 0.027) in multivariate
linear regression analysis. Nuclear and nucleolar morphometry are
significant prognostic factors for uveal and cutaneous melanoma.
6
UI - 21411328
AU - Albert D; Syed N; Cancer Committee, College of American Pathologists
TI -
Protocol for the examination of specimens from patients with uveal
melanoma: a basis for checklists.
SO - Arch Pathol Lab Med 2001 Sep;125(9):1177-82
AD - Department of Ophthalmology, University of Wisconsin Hospital, Madison,
USA.
7
UI - 21468543
AU - Brandberg Y; Kock E; Oskar K; af Trampe E; Seregard S
TI -
Psychological reactions and quality of life in patients with posterior
uveal melanoma treated with ruthenium plaque therapy or enucleation: a
one year follow-up study.
SO - Eye 2000 Dec;14(Pt 6):839-46
AD - Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
yvonne.brandberg@ce.ks.se
PURPOSE: To investigate psychological reactions and quality of life
among patients with posterior uveal melanoma. METHODS: Consecutive
patients with uveal malignant melanoma (99/106), referred to St Erik's
Eye Hospital 1995-1996, treated with rutheniuim plaque radiotherapy (n =
50) or enucleation (n = 49), were included in this non-randomised
prospective comparative study. Questionnaires were completed before
treatment (Hospital Anxiety and Depression Scale, HAD scale) and 2 and
12 months after diagnosis including the HAD scale, the Impact of Event
Scale and the EORTC QLQ-C30. A disease-specific questionnaire was
included 12 months after diagnosis. Between-group differences were
analysed by chi-square, Student's t-test and ANOVA. RESULTS: A majority
of the patients reported reduced 'Quality of Life' (72-85%), 'Emotional
functioning' (60-74%) and 'Cognitive functioning' (51-61%). 'Fatigue'
was the most frequently reported symptom (61-72%) followed by 'Insomnia'
(43-58%). Anxiety and depressive symptoms were relatively frequent up to
1 year after treatment, but the levels of anxiety decreased during the
first year after treatment. Disease and treatment-related problems were
reported in both treatment groups 1 year after diagnosis. Enucleated
patients had more problems with appearance and judging distances,
whereas those treated with radiotherapy reported vision impairment to a
higher extent. CONCLUSIONS: Enucleated patients reported high levels of
emotional distress, problems with appearance and judging distances
during the first year after treatment. Patients treated with
radiotherapy reported similar levels of quality of life and emotional
problems, but more problems with visual impairment. These differences in
impact on disease-related functioning should be taken into account when
treatment options are discussed.
8
UI - 21462582
AU - The Collaborative Ocular Melanoma Study Group
TI -
Sociodemographic and clinical predictors of participation in two
randomized trials: findings from the Collaborative Ocular Melanoma Study
COMS report no. 7.
SO - Control Clin Trials 2001 Oct;22(5):526-37
Collecting sociodemographic and clinical data concerning patients who
choose not to enroll in a randomized clinical trial can be useful in
assessing the feasibility of attaining sample size goals during the
course of a trial. It can also aid in addressing the extent of
generalizability of trial findings after a trial has ended. The
Collaborative Ocular Melanoma Study (COMS) consists of two multicenter
randomized clinical trials to evaluate the effectiveness of radiotherapy
in comparison to standard enucleation (removal of the affected eye) in
prolonging survival of patients with choroidal melanoma. One trial is
for patients with large tumors and the other trial is for patients with
medium-sized tumors. The same baseline sociodemographic and clinical
data were collected for both enrolled patients and eligible patients who
did not enroll in the randomized trials during the first 3 years of
patient recruitment. Partial information on nonrandomized patients was
collected thereafter. Recruitment ended in the large tumor and medium
tumor trials on December 31, 1994, and July 31, 1998, respectively. From
were evaluated for the randomized trials, of whom 4191 (61%) were
eligible for enrollment. Logistic regression methods were used to
identify factors predictive of trial participation. Sociodemographic
factors that appeared to be associated (p < 0.15) with participation in
the univariable models in the medium tumor trial were age 60 years or
older, less than college education, nonmanagerial occupation, current
smoking, and residing in the same state as a COMS clinical center. In
the large tumor trial, males, individuals who were not college-educated,
and individuals residing in the same state as a COMS clinical center
were more likely to enroll. In both trials, clinical determinants of
participation were larger tumor dimensions and initial visual acuity
worse than 20/20 in the study eye. In multivariable regression models,
the variables that were significantly predictive of enrollment (p <
0.05) in at least one of the trials were older age, residence in the
same state, larger tumor basal diameter, and worse initial visual acuity
in the study eye. Knowledge of possible sociodemographic and clinical
predictors of differentials in patient participation for nonenrolled
patients may help to refine patient education and recruitment strategies
for future trials. Patient enrollment in clinical trials may be
increased by heightened physician awareness of such predictors,
strategies for addressing these differences, and enhanced communication
between physicians and patients.
9
UI - 21464706
AU - Makitie T; Carpen O; Vaheri A; Kivela T
TI -
Ezrin as a prognostic indicator and its relationship to tumor
characteristics in uveal malignant melanoma.
SO - Invest Ophthalmol Vis Sci 2001 Oct;42(11):2442-9
AD - Ophthalmic Pathology Laboratory, Department of Ophthalmology, Helsinki
University Central Hospital, Finland. teemu.makitie@hus.fi
PURPOSE: Immunohistochemistry was used to investigate whether uveal
malignant melanoma expresses ezrin, a protein involved in cell migration
and cell recognition by acting as a linker between the plasma membrane
and actin cytoskeleton. Also investigated was whether ezrin
immunoreactivity correlates with survival prognosis. METHODS: A
monoclonal antibody, 3C12, that reacts with the carboxyl-terminal part
of ezrin was used in retrospective analysis of a population-based cohort
of 167 consecutive choroidal and ciliary body melanomas in eyes
enucleated from 1972 through 1981, with a median follow-up of 22 years.
RESULTS: Ezrin immunoreactivity in tumor cells was graded negative in 47
(36%) melanomas, positive in 74 (57%), and strongly positive in 9 (7%).
The immunoreactivity tended to be homogenous throughout the tumor, with
focal concentrations along the cell surface. Positive reaction was
significantly associated with high microvascular density (P < 0.001) and
presence of macrophages (P < 0.001), but not with tumor size, cell type,
or microvascular loops and networks. The 10-year melanoma-specific
survival was significantly associated with ezrin immunoreactivity (P =
0.018). After adjustment by Cox regression for tumor size, cell type,
microvascular loops and networks, and microvascular density, a
clinically meaningful 0.15 difference in 10-year melanoma-specific
survival persisted. CONCLUSIONS: The presence of ezrin immunoreactivity
in uveal malignant melanoma is associated with higher mortality and with
two independent high-risk characteristics: microvascular density and
number of infiltrating macrophages. Further experimental studies on the
interrelationship of these three factors may shed light on the
progression of uveal melanoma and perhaps that of other cancers.
10
UI - 21464710
AU - Scholes AG; Liloglou T; Maloney P; Hagan S; Nunn J; Hiscott P; Damato
TI -
BE; Grierson I; Field JK
Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the
retinoblastoma locus, in uveal melanoma.
SO - Invest Ophthalmol Vis Sci 2001 Oct;42(11):2472-7
AD - Unit of Ophthalmology, Department of Medicine, The University of
Liverpool, United Kingdom. agms@liv.ac.uk
PURPOSE: To identify tumor-suppressor loci that may contribute to the
pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence
microsatellite assays were performed on 27 uveal melanomas using markers
at 3p25-p26, 3p14.2, 9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to
or within the von Hippel Lindau (VHL), fragile histidine triad (FHIT),
p16/cyclin-dependent kinase inhibitor 2 (CDKN2A), retinoblastoma (RB1),
breast cancer 2 (BRCA2), and p53 tumor suppressor loci, respectively.
Further markers on chromosomes 3 and 9 were analyzed individually.
RESULTS: Loss of heterozygosity (LOH) was identified in 63% of tumors,
most frequently on chromosome 3 (52%), in association with epithelioid
cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority
of cases, LOH on chromosome 3 was detected at all informative markers.
The second most common alteration was LOH at an RB1 intragenic marker
(21% tumors), with retention of a more centromeric 13q marker (near
BRCA2). The pattern of LOH on chromosome 9p was consistent with the
involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent.
CONCLUSIONS: In the majority of cases, chromosome 3 LOH involves an
entire chromosome homologue, which hampers identification of the
relevant suppressor loci. This LOH correlates with the presence of
microvascular loops and epithelioid cells, two of the recognized
histologic indicators of poor prognosis. Data for chromosomes 13 and 9
support a role for RB1 in the pathogenesis of uveal melanoma but also
raise the possibility of the involvement of additional loci close to RB1
and CDKN2A.
11
UI - 21465239
AU - Shields CL; Shields JA; Brady LW
TI -
Visual acuity results after plaque radiotherapy.
SO - Ophthalmology 2001 Oct;108(10):1716-7
12
UI - 21421664
AU - Lee H; Choi SS; Kim SS; Hong YJ
TI -
A case of glaucoma associated with Sturge-Weber syndrome and Nevus of
Ota.
SO - Korean J Ophthalmol 2001 Jun;15(1):48-53
AD - The Institute of Vision Research, Department of Ophthalmology, Yonsei
University College of Medicine, Seoul, Korea.
The Sturge-Weber syndrome consists of a unilateral port-wine hemangioma
of the skin along the trigeminal distribution and is accompanied by an
ipsilateral leptomeningeal angioma. Glaucoma is present in approximately
half of the cases. The Nevus of Ota is a melanocytic pigmentary
disorder, most commonly involving the area innervated by the trigeminal
nerve. Elevated intraocular pressure, with or without glaucomatous
damage, is observed in 10% of the cases. We report the first case of
glaucoma associated with Sturge-Weber syndrome and Nevus of Ota in
Korea.
13
UI - 21452830
AU - Pe'er J; Stefani FH; Seregard S; Kivela T; Lommatzsch P; Prause JU;
TI -
Sobottka B; Damato B; Chowers I
Cell proliferation activity in posterior uveal melanoma after Ru-106
brachytherapy: an EORTC ocular oncology group study.
SO - Br J Ophthalmol 2001 Oct;85(10):1208-12
AD - Department of Ophthalmology, Hadassah University Hospital, Jerusalem,
Israel. peer@md2.huji.ac.il
AIM: To evaluate the cell proliferation activity in posterior uveal
melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal
or ciliary body melanoma from seven ocular oncology centres, which were
enucleated after first being treated by Ru-106 brachytherapy and which
had enough melanoma tissue to enable histological assessment, were
included. The 57 eligible specimens were divided into a group of 44 eyes
that were enucleated because of tumour regrowth, and a non-recurrent
group of 13 eyes that were enucleated because of complications such as
neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma
served as a control group. All specimens underwent routine processing.
They were cut into 5 microm sections, and were stained with two main
cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The
stained sections were assessed, and the cells that were positive in the
immunostaining were counted in each section. The results were evaluated
by various statistical methods. RESULTS: The PC-10 score showed a
statistically significant difference across the three groups (p =
0.002). The control group showed the highest PC-10 score (median 31.0
PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The
lowest PC-10 scores were found in the non-recurrent tumours (median 0.05
PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was
similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the
MIB-1 score in the non-recurrent tumours was statistically significantly
lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in
tumours composed of either spindle cells or epithelioid cells in all
groups. CONCLUSIONS: The non-recurrent melanomas demonstrate
significantly lower cellular proliferation activity than melanomas that
showed regrowth or that were not irradiated at all. In our hands, PCNA
gave more meaningful information than Ki-67. Our findings strongly
support the need for treating regrowing posterior uveal melanoma either
by enucleation or re-treatment by brachytherapy. On the other hand, also
in the non-recurrent uveal melanomas there are viable cells with
potential for proliferation, although fewer in number, with unknown
capacity for metastatic spread. Therefore, the irradiated tumours should
be followed for many years, probably for life.
14
UI - 21452831
AU - Char DH; Miller T; Crawford JB
TI -
Uveal tumour resection.
SO - Br J Ophthalmol 2001 Oct;85(10):1213-9
AD - The Tumori Eye Foundation, CPMC Davies, Stanford University, CA 94114,
USA. devron@tumori.org
AIM: To review the ocular retention rates, visual results, and
metastases in uveal tumours managed with eye wall resection techniques.
METHODS: This was a retrospective analysis of consecutive local uveal
tumour resections performed by a single surgeon. All enucleation
specimens were reviewed by one author. Both parametric and
non-parametric analysis of data were performed. RESULTS: 138 eyes were
scheduled for eye wall resection surgery. The mean age was 52 years
(range 11-86 years). Tumours involved predominantly the iris in 14
cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and
in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary
body-choroid, or choroid). 125 eyes harboured melanomas; posterior
tumours were more likely to have epithelioid cells (p<0.05). The mean
follow up was 6 years. The mean clock hours in iris and iris-ciliary
body tumours was 3.5. In tumours that involved the choroid the mean
largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138
(76%) eyes were retained. Histological assessment of surgical margins
did not correlate evidence of tumour in enucleated eyes or metastatic
disease. Surgical margins of more anterior tumours were more likely to
be clear on histological evaluation (p<0.05). Approximately 53% of
retained eyes had a final visual acuity of > or =20/40; visual results
were significantly better in more anteriorly located tumours (p<0.05).
All retained iris tumour cases had > or =20/40 final visual acuity. In
tumours that involved the choroid nine of 31 retained eyes kept that
level of visual acuity. Eight patients developed metastases; all
metastatic events developed in patients with tumours that involved the
choroid, and seven of eight were mixed cell melanomas. CONCLUSIONS: 76%
of eyes were retained and 53% of these had a final visual acuity of > or
=20/40. Only 7% of uveal melanoma patients developed metastatic disease
with a mean follow up of 6 years. Survival did not appear to be
compromised with eye wall resection and in very thick, more posterior
melanomas it appeared that ocular retention and visual results were
better than with radiation alone.
15
UI - 21486090
AU - Wilson MW; Schelonka LP; Siegel D; Meininger A; Ross D
TI -
Immunohistochemical localization of NAD(P)H:quinone oxidoreductase in
conjunctival melanomas and primary acquired melanosis.
SO - Curr Eye Res 2001 May;22(5):348-52
AD - Department of Ophthalmology, University of Tennessee Health Science
Center, Memphis, TN 38163, USA. mwilson@mail.eye.utmem.edu
PURPOSE. Mitomycin C has been used in the treatment of primary acquired
melanosis and melanomas of the conjunctiva. Because there is increasing
evidence that NAD(P)H:quinone oxidoreductase (EC 1.6.99.2, NQO1) or
DT-diaphorase plays an important role in the bioactivation of mitomycin
C, we examined pathologic specimens of these tumors for NQO1 by
immunohistochemistry. METHODS. Formalin-fixed, paraffin-embedded
sections with histologic diagnoses of primary acquired melanosis or
conjunctival melanomas were obtained from the Eye Pathology Laboratory,
University of Colorado Health Sciences Center. Detection of NQO1 in
tissues was performed using standard immunohistochemical techniques with
monoclonal antibodies against NQO1 and immunoperoxidase staining.
Samples were examined by two independent reviewers and NQO1 staining was
graded from 0 (no staining) to 3+ (intense staining). RESULTS. Eleven of
11 melanomas (95% confidence interval, 72% to 100%) and three of three
lesions with primary acquired melanosis with atypia stained positively
for NQO1. In the melanomas, staining was relatively uniform, while in
primary acquired melanosis there was cell-to-cell variability in the
staining. CONCLUSIONS. NQO1 was detected by immunohistochemistry in
every examined section of primary acquired melanosis and melanoma of the
conjunctiva, suggesting that NQO1 may play a role in the bioactivation
of mitomycin C in these tumors.
16
UI - 94231652
AU - Marwick C
TI -
National Eye Institute study under investigation.
SO - JAMA 1994 May 18;271(19):1470-1
17
UI - 21473785
AU - Shields CL; Shields JA; Armstrong T
TI -
Management of conjunctival and corneal melanoma with surgical excision,
amniotic membrane allograft, and topical chemotherapy.
SO - Am J Ophthalmol 2001 Oct;132(4):576-8
AD - Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson
University, 900 Walnut St., Philadelphia, PA 19107, USA.
carol.shields@shieldsoncology.com
PURPOSE: To illustrate a novel method of management for extensive
conjunctival and corneal melanoma. METHODS: Interventional case report.
A 40-year-old Caucasian woman presented with a large, diffuse
conjunctival melanoma involving 6 clock hours of the limbus. The
remaining bulbar conjunctiva and the entire corneal epithelium were
affected by diffuse, flat melanosis. RESULTS: The conjunctival melanoma
was completely resected microsurgically in one piece without disrupting
the tumor. The conjunctival melanosis was treated with double
freeze-thaw cryotherapy. The extensive conjunctival defect, involving
one-half of the bulbar conjunctiva, was reconstructed with an amniotic
membrane allograft. The corneal melanosis was subsequently treated with
topical mitomycin C eyedrops. At 8 months follow-up, the conjunctiva and
the cornea were completely healed with resolution of all pigment and
20/20 visual acuity. CONCLUSION: Preliminary evidence suggests that
combined therapeutic approaches, consisting of extensive tumor removal,
cryotherapy, amniotic membrane allograft, and topical mitomyin C, can be
effective in the management of diffuse conjunctival and corneal melanoma
arising from primary acquired melanosis.
18
UI - 21473786
AU - Zacks DN; Pinnolis MK; Berson EL; Gragoudas ES
TI -
Melanoma-associated retinopathy and recurrent exudative retinal
detachments in a patient with choroidal melanoma.
SO - Am J Ophthalmol 2001 Oct;132(4):578-81
AD - Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street,
Boston, MA 02114, USA. David_Zacks@meei.harvard.edu
PURPOSE: To report a patient who presented with photopsias, night
blindness, exudative retinal detachments, and melanoma-associated
retinopathy in her right eye 23 years after the left eye was enucleated
for a choroidal melanoma. METHODS: Assessment of fundus findings,
fluorescein angiograms, and electroretinograms. RESULTS: The patient had
recurrent exudative detachments of the macula in her right eye and
electroretinogram responses consistent with the diagnosis of
melanoma-associated retinopathy. The abdominal computed tomography (CT)
scan was negative, but 13 months later, CT scanning revealed many masses
in her liver. Fine-needle biopsy confirmed the diagnosis of metastatic
melanoma. CONCLUSION: To our knowledge, this is the first report of
melanoma-associated retinopathy in a patient with a previous choroidal
melanoma.
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