Volume 21 Number 6 / December 2017 Walters et al 501

tomography a predictor of visual acuity? Ophthalmology 2011;

118:1653-60.
6. Maldonado RS, O’Connell RV, Sarin N, et al. Dynamics of human
foveal development after premature birth. Ophthalmology 2011;118:
2315-25.
7. Vinekar A, Avadhani K, Sivakumar M, et al. Understanding clinically
undetected macular changes in early retinopathy of prematurity on
spectral domain optical coherence tomography. Invest Ophthalmol
Vis Sci 2011;52:5183-8.
8. Vajzovic L, Rothman AL, Tran-Viet D, Cabrera MT, Freedman SF,
Toth CA. Delay in retinal photoreceptor development in very preterm
compared to term infants. Invest Ophthalmol Vis Sci 2015;56:908-13.

Malignant melanoma
presenting as amelanotic
caruncular lesion in a child
Alexander R. Walters, BS,a Katie M. Keck, MD,a
Oliver Simmons, MD,b Sarah G. Williams, MD,c
Stephen Cross, MD,a and Rakesh M. Patel, MDa
Conjunctival melanoma is a rare malignant neoplasm that can pre-
sent in childhood in any part of the conjunctiva. The infrequency
with which conjunctival melanoma is encountered in childhood car-
uncular lesions makes it a formidable but important aspect of the
differential diagnosis. We report the case of a 10-year-old boy
who presented with a left caruncular lesion. On histopathologic
analysis, the lesion was determined to be BRAF-negative invasive
melanoma arising in association with melanocytic nevus. The mel-
anoma was excised using no-touch technique and double freeze
thaw cryotherapy. A full systemic work-up revealed no metastasis
or abnormality.
Case Report
A 10-year-old boy of mixed white and African American
ethnicity presented at Palmetto Health, Richland, with a
flesh-colored lesion of his left caruncle (Figure 1). Accord-
ing to his family, the lesion had been present since birth;
however, it had enlarged over the previous 3 months. Un-
corrected distance visual acuity was 20/20 in both eyes, and
comprehensive ophthalmic examination was otherwise
normal. Two weeks after presentation, the lesion was
excised and sent for pathologic analysis (Figures 2 and 3).
FIG 1. Lesion in left caruncle at initial presentation. Pigmentation pre-
sent from the 7:00 to 8:00 o’clock position at the limbus.
Thickness of the lesion was estimated at 2.5 mm. It was
reviewed at two different institutions and reported to be
invasive melanoma arising in association with a
melanocytic nevus with positive margins of the biopsy.
Real-time polymerase chain reaction revealed no mutation
at codon 600 of BRAF.
The patient was referred to pediatric oncology for a full
systemic work-up. Magnetic resonance imaging of the
brain and orbits with and without contrast and computed
tomography of the neck, chest, abdomen, and pelvis with
contrast revealed no metastasis, intracranial abnormality,
or orbital extension.
A second operation was performed to maximally excise
the melanoma with conjunctival margins using a no-touch
technique and double freeze-thaw cryotherapy.1 After
removal of the lesion, the ocular surface was reconstructed
with an amniotic membrane graft. Sentinel nodes were
determined by lymphoscintigraphy1,2 and after biopsy
proved to be negative for malignancy. Pathology of the
lesion revealed residual melanoma in situ with pagetoid
spread extending to the margins. Given these findings, the

Author affiliations: Departments of aOphthalmology, bOtolaryngology, and cPathology,

Palmetto Health/University of South Carolina, Richland.
Submitted May 21, 2017.
Revision accepted June 22, 2017.
Published online November 7, 2017.
Correspondence: Katie M. Keck, MD, Palmetto Health/University of South Carolina
School of Medicine, 9 Medical Park, Suite 340, Columbia, SC 29203 (email: keckkt@gmail.
com).
J AAPOS 2017;21:501-503. FIG 2. Initial biopsy showing polypoid neoplasm composed of mela-
Copyright Ó 2017, American Association for Pediatric Ophthalmology and
Strabismus. Published by Elsevier Inc. All rights reserved.
nocytes that lack maturation with increasing depth. Numerous mitotic
1091-8531/$36.00 figures in submucosal melanocytes (hematoxylin and eosin, original
http://dx.doi.org/10.1016/j.jaapos.2017.06.025 magnification 40, inset 100).

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502 Walters et al
FIG 3. Initial biopsy with Mart-1/Ki-67 two-color immunostaining.
Mart-1 staining (pink) demonstrates atypical intramucosal spread of
melanocytes, poor circumscription, and large size supportive of malig-
nancy. Ki-67 staining (a proliferation marker/brown staining) demon-
strates increased proliferation within submucosal melanocytes, .5%.
Further staining demonstrated near loss of p16, and photohistone H3/
Melan-A staining demonstrated positive nuclei up to 5/mm2. FISH re-
vealed gain of chromosome 6p, loss of chromosome 6q, and homozy-
gous loss of chromosome 9p, with no aberration of chromosome 11
(original magnification 40).
patient was referred to ocular oncology at Wills Eye
Hospital for further evaluation and management.
Clinical examination at Wills Eye Hospital revealed a fle-
shy caruncular mass 6 mm at the base and 6 mm in thickness
and concerning for residual melanoma. The patient was also
noted to have pigmentation of the conjunctival limbus from
the 7:00 to 8:00 o’clock position measuring 5 mm in diam-
eter. The pigmentation was suspicious for primary acquired
melanosis and was felt to be a potential source of the mela-
noma. The patient underwent re-excision of the conjunctiva
and caruncle of the left eye. Pathology revealed exuberant
granulation tissue. No evidence of melanoma was found in
the deeper tissues. The conjunctival pigmentation noted
near the limbus was also biopsied and was determined to
be mild benign intraepithelial melanocytic hyperplasia of
the limbal epithelium. No further treatment was recom-
mended. The patient will undergo careful systemic moni-
toring for recurrence of melanoma.
Discussion
Conjunctival melanoma is a relatively rare malignant
neoplasm that comprises 2% of all ocular malignancies.3
The mean age at diagnosis is 60.4 years, with only 0.68%
occurring at ages younger than 14 years.4 The 10-year
mortality rate for conjunctival melanoma has been re-
ported as high as 23%-39%.3 Most pigmented conjunctival
lesions in children and adults do not represent melanoma
and very rarely lead to melanoma.4 Risk factors that suggest
melanoma in children include older age, increased basal
thickness, a lack of cysts, and hemorrhage.5,6 From 1965
to 2015, 29 cases of conjunctival melanoma in children
\15 years of age were reported in the literature.3 Only 9
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Volume 21 Number 6 / December 2017
of these 29 cases were reported in detail3; however, no pe-
diatric caruncle melanomas have been previously reported.
Conjunctival melanomas in children most commonly
arise from conjunctival nevi7; in adults, most commonly
from primary acquired melanosis,7 with most studies re-
porting between 14% and 35% of cases arising from preex-
isting nevi.4 Although the melanoma in our patient was
adjacent to pigmentation at the limbus, the family reported
that a lesion had been present in the caruncle since birth.
Diagnosis of the limbal pigmentation as benign melano-
cytic hyperplasia suggests that the source of the amelanotic
melanoma likely was melanocytic nevus.
Surgical technique appears to play an important role in the
morbidity and mortality of conjunctival melanoma patients.
Several publications have cautioned against performing inci-
sional biopsies in order to decrease the risk of seeding.1,8
Studies have also reported a poorer prognosis in patients
treated through excision without adjuvant treatment.9 The
current surgical treatment for conjunctival melanoma usu-
ally consists of en bloc removal, utilizing the no-touch tech-
nique, with use of fresh sterile instruments at each step of the
procedure to decrease risk of seeding.2 Decreasing specimen
manipulation also helps ensure accuracy of histopathologic
assessment. Local recurrence is common and has been re-
ported to range from 36% to 62%. Double freeze-thaw
cryotherapy as an adjuvant therapy in combination with sur-
gical excision at initial treatment has been shown to signifi-
cantly decrease tumor recurrence rates compared to
excision alone, but has not shown benefit in preventing
metastasis. Other adjuvant therapies, including localized
alcohol corneal epitheliectomy, have also been recommen-
ded, despite risk of damage to underlying structures.2
Polymerase chain reaction testing of the initial biopsy in
this case report revealed no mutation in the 600 codon of
BRAF. Somatic activating mutations in BRAF can result
in constitutive activation of the MAPK signaling pathway.8
In one 2015 study, BRAF mutations were identified in 67%
of specimens arising from nevus.8 BRAF mutations were
more common in younger patients. However, BRAF muta-
tions were less common in lesions of the extrabulbar con-
junctiva. BRAF-mutated lesions developed metastasis
more frequently and showed decreased metastasis-free sur-
vival.8 The lack of BRAF mutation in our patient’s lesion
may suggest a better prognosis.
A poorer prognosis for patients diagnosed with conjunc-
tival melanoma has also been associated with involvement
of the eyelid margin, invasion of local tissue, tumors not
touching the limbus, and pathological tumor margins.8,10
Some studies have reported caruncular involvement as an
indicator of poor prognosis in conjunctival melanoma,
but this was not confirmed in a recent study.8
Literature Search
PubMed was searched without date restriction for English-
language publications on June 14, 2017, using the
following combination of search terms: melanoma, eye,
Journal of AAPOS
Volume 21 Number 6 / December 2017
conjunctiva, and children. Individual case reports and of chil-
dren and case series of conjunctival melanoma were
reviewed. Additional studies were identified from bibliog-
raphies of the reviewed articles.
References
1. Lim L, Madigan MC, Conway RM. Conjunctival melanoma: a review of
conceptual and treatment advances. Clin Ophthalmol 2013;6:521-31.
2. Yin VT, Merritt HA, Sniegowski M, Esmaeli B. Eyelid and ocular surface
carcinoma: diagnosis and management. Clin Dermatol 2015;33:159-69.
3. Vora GK, Demirci H, Marr B, Mruthyunjaya P. Advances in the man-
agement of conjunctival melanoma. Surv Ophthalmol 2016;62:26-42.
4. Taban M, Traboulsi EI. Malignant melanoma of the conjunctiva in
children: a review of the international literature. J Pediatr Ophthalmol
Strabismus 2007;44:277-82.
5. Shields CA, Alset AE, Boal NS, et al. Conjunctival tumors in 5002
cases: comparative analysis of benign vs malignant counterparts: the
2016 James D. Allen Lecture. Am J Ophthalmol 2017;173:106-33.
6. Shields CL, Sioufi K, Alset AE, et al. Clinical features differentiating
benign from malignant conjunctival tumors in children. JAMA Oph-
thalmol 2017;135:215-24.
7. Shields CL, Kels JG, Shields JA. Melanoma of the eye: revealing hid-
den secrets one at a time. Clin Dermatol 2015;33:183-96.
8. Larsen A, Dahmcke CM, Dahl C, et al. A retrospective review of
conjunctival melanoma presentation, treatment, and outcome and
an investigation of features associated with BRAF mutations. JAMA
Ophthalmol 2015;133:1295-303.
9. Shields CL, Shields JA, G€ und€uz K, et al. Conjunctival melanoma: risk
factors for recurrence, exenteration, metastasis, and death in 150
consecutive patients. Arch Ophthalmol 2000;118:1497-507.
10. Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma:
outcomes based on tumor origin in 382 consecutive cases. Ophthal-
mology 2011;118:389-95.
Positive ice test in a patient
with a lymphomatous
infiltration of the levator
palpebrae superioris
Hee Kyung Yang, MD,a,* Namju Kim, MD,a,*
Jae Hyoung Kim, MD,b and
Jeong-Min Hwang, MDa
Author affiliations: Departments of aOphthalmology and bRadiology, Seoul National
University College of Medicine, Seoul National University Bundang Hospital, Seongnam,
Korea
* These authors contributed equally to this work.
Submitted April 11, 2017.
Revision accepted July 11, 2017.
Published online November 7, 2017.
Correspondence: Jeong-Min Hwang, MD, Department of Ophthalmology, Seoul
National University College of Medicine, Seoul National University Bundang Hospital,
166, Gumiro, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea (email: hjm@snubh.
org).
J AAPOS 2017;21:503-505.
Copyright Ó 2017, American Association for Pediatric Ophthalmology and
Strabismus. Published by Elsevier Inc. All rights reserved.
1091-8531/$36.00
http://dx.doi.org/10.1016/j.jaapos.2017.07.210
Journal of AAPOS
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Yang et al 503
The ice test is known to be specific for the diagnosis of ocular myas-
thenia gravis in patients with ptosis, with reported specificities of
97%-100%. We report a patient with diffuse large B-cell lymphoma
who showed a positive result to the ice test. A 53-year-old woman
presented with left eyelid ptosis of 3 weeks’ duration. She had
finished chemotherapy and radiotherapy for diffuse large B-cell
lymphoma a year previously. On ophthalmological examination,
her best-corrected visual acuity was 20/20 in each eye. Marginal re-
flex distances were 14 in the right eye and 1 in the left eye. Leva-
tor palpebrae superioris functions were 11 mm in the right eye and
8 mm in the left eye. Ptosis improved after 5 minutes’ application of
ice to both eyelids, after which marginal reflex distances were 14 in
the right eye and 11 in the left eye. Thyroid function tests, anti-
acetylcholine receptor antibody test, and the repetitive nerve stim-
ulation test were all negative. Magnetic resonance imaging showed
fusiform masslike enlargement of the left superior rectus muscle
and left levator palpebrae superioris muscles, with enhancement
suggesting metastatic infiltration.
Case Report
A 53-year-old woman presented at Seoul National Univer-
sity Bundang Hospital with diplopia of 1 year’s duration
and left eyelid ptosis that became noticeable 3 weeks
before. A year prior to presentation she had completed
chemotherapy and radiotherapy for diffuse large B-cell
lymphoma involving the left nasal cavity and maxillary
and ethmoid sinus, with meningeal invasion. On ophthal-
mological examination, best-corrected visual acuity was
20/20 in each eye. Marginal reflex distances were 14 in
the right eye and 1 in the left eye. Levator palpebrae
superioris functions were 11 mm in the right eye and
8 mm in the left eye. Exophthalmometry measurements
were 15 mm on the right and 14.5 mm on the left. The pu-
pils of both eyes were isocoric and promptly reactive to
light. Alternate prism cover test revealed exotropia of 4D
and a left hypotropia of 10D at distance and intermittent
exotropia of 4D and intermittent left hypotropia of 6D at
near in the primary position. Left hypotropia increased
to 8D with left gaze compared to 6D with right gaze
and increased to 10D on right head tilt compared to 5D
on left head tilt. Ductions and versions showed mild under-
action of the right superior oblique muscle. Ptosis
improved after application of ice to both eyelids for 5
minutes (Figure 1A,B); marginal reflex distances after ice
application were 14 in the right eye and 11 in the left
eye. Thyroid function tests, anti-acetylcholine receptor
antibody test and the repetitive nerve stimulation test
were all negative.
Magnetic resonance imaging (MRI) showed fusiform
masslike enlargement of the left superior rectus muscle
and left levator palpebrae superioris muscles with contrast
enhancement (Figure 1C,D). On diffusion-weighted
MRI, this lesion had high signal intensity with low
apparent diffusion coefficient (0.7  10 3 mm2/sec),
suggesting metastatic lymphoma (Figure 1E,F). Whole