Grand Rounds
Amir R. Hajrasouliha, M.D.
University of Louisville
Department of Ophthalmology and Visual Sciences
Friday, August 15th, 2014
Patient Presentation

HPI: 80 y/o white male is presenting for
yearly checkup s/p excisional biopsy of
conjunctival melanoma in his right eye 4 yrs
ago. He had no recurrence of disease for the
past two years on examination. No other
complaint.
Patient Presentation

POH:


PMH:



HTN
Meds:


Conjuctival melonoma arising from primary acquired melanosis
OD s/p resection 2009
ROS:
HCTZ

Negative (No headaches, weight loss or night sweats)

NKDA
Allergy:
Exam
BCVA cc
20/20
20/20
EOM: FULL OU
P
32mm
(-) RAPD
32mm
CVF: FULL OU
TTP
14
15
Exam
OD
OS
WNL
WNL
WNL
K
AC
WNL
WNL
pigmented nests
at superior limbus
Clear
Formed
Iris
Lens
WNL
1+NS
WNL
1+NS
Ext
L/L
Conj
Clear
Formed
Plan
Excisional biopsy
melanosis of
basal cell
Nest of cells
Atypical cells
Assessment

80 year old male with recurrent conjuctival
melanoma OD
Plan/Follow up


Excision with topical Mitomycin-C 0.04%
four times a day for 4 cycles of 7 days on
drop and 7 days off.
Systemic workup was negative (including
whole body CT-PET)
Conjuctival Melanoma


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Malignant melanoma of
the conjunctiva presents
as a raised, pigmented or
nonpigmented lesion that
appears most commonly
in white patients in their
early 50s.
May arise from acquired
nevi (2%), from PAM (5075%), or de novo(10%).
Accounts for only 2% of
all ocular malignancies.
Clinical Finding

Poor prognosis indicators





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Location in palpebral conjunctiva, caruncle or fornix
Invasion into deeper tissue
Thickness > 1.8mm
Pagetoid or full-thickness intraepithelial spread
Lymphatic invasion
Involvement of eyelid margin
Management



Excisional biopsy should be considered for any
suspicious pigmented epibulbar lesions.
Excision is recommended 4mm beyond clinically
apparent margins of the tumor along with thin
lamellar scleral flap beneath the tumor and
cryotherapy applied to the conjuctival margins.
Topical mitomycin has been used to treat
residual diseases.
Management

Orbital exentration is performed for advanced
disease when local excision or enucleation
would be insufficient.
JAMA Ophthalmol. 2014 May;132(5):622-9.Usefulness of a red chromagen in the
diagnosis of melanocytic lesions of the conjunctiva.
Sentinel Lymph Node Biopsy
The role of SLNB remains controversial.
 The frequency of regional lymph node
metastases is reported to be between 26%
and 40%.
 Two studies reported that 17/194 patients
(8.7%) and 7/27 patients (26%) presented
with distant metastases without prior or concurrent regional
lymph node involvement (skipping metastases).
 A few studies show supporting evidence for the use of SLNB
for tumors thicker than 2 mm, as well as for tumors greater
than 10 mm in diameter with increasing tumor diameter
associated with a higher risk of distant recurrence.

Conjunctival melanoma: a review of conceptual and treatment advances. Clin Ophthalmol. 2013; 7: 521–
Gene mutation and diagnosis
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The application of gene mutation analysis to conjunctival
melanomas (CMs) has also not been definitive in
classifying lesions. However, recent work using multiplex
ligation-dependent probe amplification identified a BRAF
V600E mutation in approximately 50% of a small cohort
of primary CMs, and more than 50% of metastatic
specimens, supporting results of earlier studies.
It has been proposed that the BRAF inhibitor PLX4023
(vemurafenib), specific for the V600E mutation, could be
used for the treatment of CM, similar to the situation for
cutaneous melanoma with BRAF V600E mutation.
Lake SL et al. Multiplex ligation-dependent probe amplification of conjunctival melanoma reveals common BRAF V600E
gene mutation and gene copy number changes. Invest Ophthalmol Vis Sci. 2011;52(8):5598–5604.
Diagnosis


There is every possibility that blood testing for the presence of
methylated DNA will become an integral part of the clinical follow-up
of patients with melanoma. The ability to identify patients with
subclinical (asymptomatic) metastatic melanoma, combined with
new, highly active targeted and immunomodulatory agents, may
lead to further improvements in outcomes for this patient population.
Built on Digital Sequencing, Guardant360 provides high-fidelity
tumor sequencing information at the single-molecule level. Digital
Sequencing is a proprietary method of capturing and genetically
profiling trace fragments of tumor DNA that are shed into the blood
stream (cell-free DNA).
Identification of multiple informative genomic mutations by deep sequencing of circulating cell-free
tumor DNA in plasma of metastatic melanoma patients. J Clin Oncol 32:5s, 2014 (suppl; abstr
9018
Thank You