untitled


troretinography and antiretinal antibody testing were not
performed. Previous cases of vitelliform retinopathy have
had some clinical findings consistent with MAR,1,2,4,6 while
others have not.4,5 None of these reports had clinical evi-
dence of choroidal involvement. The vitelliform lesions
have been postulated to represent a new paraneoplastic
clinical manifestation. The pathologic results in this case
argue against a paraneoplastic entity but may suggest a
local metastatic cause with subclinical choroidal involve-
ment. Another explanation is that choroidal involve-
ment occurred after the vitelliform lesions with the dis-
semination of the metastatic melanoma. Further studies
are needed to determine the etiology of these vitelliform
lesions in metastatic melanoma.

Author Affiliations: Department of Ophthalmology, Uni-
versity of California, San Francisco (Dr Khurana), and
Northern California Retina Vitreous Associates, Moun-
tain View (Drs Khurana, Wieland, and Boldrey); and De-
partment of Ophthalmology and Visual Sciences, Uni-
versity of Wisconsin, Madison (Drs Lewis and Albert).
Correspondence: Dr Khurana, Northern California Retina
Vitreous Associates, 2485 Hospital Dr, Ste 200, Moun-
tain View, CA 94040 (rnkhurana@gmail.com).
Financial Disclosure: None reported.

1. Zacks DN, Pinnolis MK, Berson EL, Gragoudas ES. Melanoma-associated reti-
nopathy and recurrent exudative retinal detachments in a patient with cho-
roidal melanoma. Am J Ophthalmol. 2001;132(4):578-581.

2. Palmowski AM, Haus AH, Pföhler C, et al. Bilateral multifocal chorioreti-
nopathy in a woman with cutaneous malignant melanoma. Arch Ophthalmol.
2002;120(12):1756-1761.

3. Jampol LM, Kim HH, Bryar PJ, Shankle JB, Lee RT, Johnston RL. Multiple

serous retinal detachments and subretinal deposits as the presenting signs of
metastatic melanoma. Retina. 2004;24(2):320-322.

4. Sotodeh M, Paridaens D, Keunen J, van Schooneveld M, Adamus G, Baarsma
S. Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal
melanoma and metastases. Klin Monbl Augenheilkd. 2005;222(11):910-914.

5. Nieuwendijk TJ, Hooymans JM. Paraneoplastic vitelliform retinopathy asso-
ciated with metastatic choroidal melanoma. Eye (Lond). 2007;21(11):1436-
1437.

6. Javaheri M, Khurana RN, Bhatti RA, Lim JI. Optical coherence tomography
findings in paraneoplastic pseudovitelliform lesions in melanoma-associated
retinopathy. Clin Ophthalmol. 2008;2(2):461-463.

7. Eksandh L, Adamus G, Mosgrove L, Andréasson S. Autoantibodies against be-
strophin in a patient with vitelliform paraneoplastic retinopathy and a meta-
static choroidal malignant melanoma. Arch Ophthalmol. 2008;126(3):432-435.

Cutaneous Halo Nevi Following Plaque
Radiotherapy for Uveal Melanoma

H alo nevi have been described in both dermatol-ogy and ophthalmology.1,2 Cutaneous halo neviare found more often in children than adults and
are believed to result from an immune response.3 Cho-
roidal halo nevus represents 5% of all choroidal nevi and
displays low risk for transformation to melanoma.4 The
development of cutaneous halo nevi or vitiligo in adult-
hood can occur following treatment of cutaneous mela-
noma and correlates with decreased morbidity, presum-
ably due to activation of a systemic immune response.5

There have been rare reports of vitiligo and/or cutane-
ous halo nevi development following enucleation for uveal
melanoma.6,7 A comprehensive study on choroidal halo
nevi found a statistical association with history of skin
melanoma.2 Herein, we describe a young woman with
uveal melanoma who developed a halo ring around nu-
merous pigmented cutaneous nevi following plaque ra-
diotherapy for uveal melanoma.

Report of a Case. A 28-year-old woman with photopsia
in the left eye was diagnosed as having choroidal mela-

A B

Figure 2. Histopathologic findings. A, Just posterior to the equator, a relatively flat, pigmented, cellular infiltrate is seen within the choroid. The tumor is 500 mm
thick and tapers at the ends (hematoxylin-eosin, original magnification �2). B, The infiltrate displays a dense population of spindle-shaped and epithelioid
melanoma cells with pale cytoplasm that demonstrates marked cellular and nuclear pleomorphism. Several small retinal pigment epithelial detachments are seen
overlying the tumor (arrows). The retina is artifactually detached and not visible (hematoxylin-eosin, original magnification �20).

Rahul N. Khurana, MD
Mark R. Wieland, MD
Edwin E. Boldrey, MD
David A. Lewis, MD
Daniel M. Albert, MD

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noma. There was no history of cutaneous melanoma. Vi-
sual acuity was 20/20 OD and 20/25 OS. The melanoma
measured 14 mm in basal dimension and 7 mm in thick-
ness (Figure, A).

Iodine 125 plaque radiotherapy was performed. Two
months after therapy, the patient reported development of
a noninflammatory, painless, circumscribed halo around
numerous previously pigmented cutaneous nevi, and 1 ne-
vus lost nearly all pigmentation (Figure, B-E). At 4 months,
the uveal melanoma regressed to 3.7 mm in thickness. Meta-
static evaluation findings were negative.

Comment. Cutaneous melanoma can stimulate vitiligo
or halo nevi through immune mechanisms. The pro-
posed pathophysiology involves cytotoxic T-cell–
mediated immune reaction targeted against antigens
shared between normal melanocytes and melanoma cells

such as MART-1, tyrosinase, gp100, TYRP1, and TYRP2.1

Histopathologically, a lymphohistiocytic infiltrate pre-
dominated by CD4 and CD8 T cells has been observed
at the margin of such depigmented lesions.1 Immuno-
therapeutic strategies for cutaneous melanoma have been
attempted based on this observation.1

In 1968, Nirankari et al8 described a 57-year-old man
who underwent evisceration for panophthalmitis from
undetected uveal melanoma. He developed vitiligo at 9
years and orbital recurrence of uveal melanoma at 11 years,
for which orbital exenteration was performed. In 1982,
Albert et al6 described 2 patients with skin depigmenta-
tion following enucleation for melanoma. Case 1 was a
69-year-old man who developed vitiligo 5 years after
enucleation, and case 2 was a 36-year-old man who de-
veloped cutaneous halo nevi 1 year after enucleation. Al-
bert and colleagues speculated that this represented a
heightened host response and more favorable progno-
sis. In 2004, Duh et al7 described a 74-year-old woman
with a 12.8-mm-thick uveal melanoma who developed
vitiligo 6 years after enucleation. These reports suggest
a possible role of the immune system following therapy
of uveal melanoma, similar to cutaneous melanoma. We
are not aware of other cases of cutaneous halo nevi de-
veloping after plaque radiotherapy for uveal melanoma.

The association of cutaneous halo nevus or vitiligo with
treated uveal melanoma could be more frequent be-
cause these dermal findings can be subtle, as in our case.

Author Affiliations: Department of Ocular Oncology, Wills
Eye Institute, Thomas Jefferson University, Philadelphia,
Pennsylvania (Drs Sarici, Shah, C. L. Shields, and J. A.
Shields); and Department of Ophthalmology, Walter Reed
Army Medical Center, Washington, DC (Dr Birdsong).
Correspondence: Dr C. L. Shields, Department of Ocu-
lar Oncology, Wills Eye Institute, Thomas Jefferson Uni-
versity, 840 Walnut St, Ste 1440, Philadelphia, PA 19107
(carol.shields@shieldsoncology.com).
Financial Disclosure: None reported.
Funding/Support: This study was supported by the Eye
Tumor Research Foundation, Philadelphia, Pennsylvania.

1. Speeckaert R, van Geel N, Vermaelen KV, et al. Immune reactions in benign
and malignant melanocytic lesions: lessons for immunotherapy. Pigment Cell
Melanoma Res. 2011;24(2):334-344.

2. Shields CL, Maktabi AM, Jahnle E, Mashayekhi A, Lally SE, Shields JA. Halo
nevus of the choroid in 150 patients: the 2010 Henry van Dyke Lecture. Arch
Ophthalmol. 2010;128(7):859-864.

3. Rhodes A. Neoplasms: benign neoplasias, hyperplasias, and dysplasias of
melanocytes. In: Fitzpatrick TB, Eisen A, Wolff K, Freedberg I, Austen KF,
eds. Dermatology in General Medicine. New York, NY: McGraw-Hill; 1987:
877-918.

4. Shields CL, Furuta M, Berman EL, et al. Choroidal nevus transformation into
melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009;127
(8):981-987.

5. Nordlund JJ, Kirkwood JM, Forget BM, Milton G, Albert DM, Lerner AB.
Vitiligo in patients with metastatic melanoma: a good prognostic sign. J Am
Acad Dermatol. 1983;9(5):689-696.

6. Albert DM, Todes-Taylor N, Wagoner M, Nordlund JJ, Lerner AB. Vitiligo or
halo nevi occurring in two patients with choroidal melanoma. Arch Dermatol.
1982;118(1):34-36.

7. Duh EJ, Schachat AP, Albert DM, Patel SM. Long-term survival in a patient

A

B

D E

C

Figure. Cutaneous halo nevi development following plaque radiotherapy for
uveal melanoma. A, Wide-angle fundus photograph of the left eye in a
28-year-old woman shows a ciliochoroidal melanoma. B-E, Four months
after treatment with iodine 125 plaque radiotherapy, halo (arrows) around
multiple cutaneous nevi involving the face, neck, upper chest, and back were
documented, with almost complete depigmentation of 1 of the nevi
(arrowhead) (B).

Ahmet M. Sarici, MD
Sanket U. Shah, MD
Carol L. Shields, MD
Richard H. Birdsong, MD
Jerry A. Shields, MD

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with uveal melanoma and liver metastasis. Arch Ophthalmol. 2004;122(2):
285-287.

8. Nirankari MS, Khanna KK, Mathur RP. Uveal malignant melanoma with
leucoderma. J All India Ophthalmol Soc. 1968;16(2):63-66.

Histopathologic, Immunohistochemical,
Ultrastructural, and Cytogenetic Analysis
of Oncocytic Uveal Melanoma

T he histological findings of malignant melanomamay be highly variable, and the tumor can mimicmany other neoplasms.1 Oncocytic change is de-
fined histologically by abundant, eosinophilic, finely granu-
lar cytoplasm due to densely packed mitochondria. Onco-
cytic change has rarely been described in dermal nevi,2

meningeal melanocytoma,3 cutaneous melanoma,4,5 or meta-
static melanoma.6 To our knowledge, we give the first de-
scription of exclusively oncocytic uveal melanoma.

Report of a Case. A 73-year-old man visited the outpa-
tient department of ophthalmology with signs of a para-
central scotoma, decreased vision, and metamorphop-
sia in his left eye for 1 month. Best-corrected visual acuity
was 40/40 OD and 20/40 OS. On dilated funduscopic and

ultrasonographic examination of the left eye, a mushroom-
shaped hypopigmented subretinal mass was seen supe-
rior and temporal to the fovea with a thickness of 7.1 mm,
a diameter of 11.4 mm, and medium to low internal re-
flectivity (Figure, A). No atypical cutaneous pig-
mented lesions were observed. Systemic radiologic evalu-
ation revealed no metastatic lesions. The patient opted
for enucleation. After a follow-up of 24 months, there
were no signs of metastases.

Sections of the eye confirmed a mushroom-shaped tu-
mor (Figure, B) exclusively composed of a trabecular ar-
rangement of epithelioid cells with abundant, finely granu-
lar, eosinophilic cytoplasm (Figure, C). Mitotic figures were
present at 2 per 10 high-power fields. Intracytoplasmic
brown pigment stained positive with Masson-Fontana stain.
The cytoplasm stained positive with periodic acid–Schiff
stain with resistance to diastase treatment. Vascular mim-
icry with a closed loop pattern was present. The tumor did
not show extrascleral extension. Tumor cells stained posi-
tive for Melan-A, HMB-45 (Figure, D), and tyrosinase, con-
firming melanocytic lineage. They stained negative for kera-
tin A1/A3, CD56, chromogranin, and synaptophysin,
excluding epithelial (neuroendocrine) metastasis.

Ultrastructural studies on formalin-fixed, paraffin-
embedded tumor tissue that was deparaffinized, postfix-

A B

C D

Figure. Ultrasonographic, whole-mount, histologic, and immunohistochemical appearance of the tumor. A B-scan of the tumor (A) and a whole-mount
hematoxylin-eosin–stained section (B) of the left eye show a mushroom-shaped subretinal mass in the posterior pole. C, The tumor was exclusively composed of
a nested and trabecular pattern of polygonal epithelioid cells with distinct borders and a granular eosinophilic cytoplasm that sometimes contained brown
pigment. The nests and trabeculae were surrounded by a delicate capillary network. Nuclei were enlarged with coarse open chromatin and prominent irregular
nucleoli (hematoxylin-eosin, original magnification �400). D, The cells stained positive for the melanocytic marker HMB-45 (original magnification �400).

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