Variation of Monosomy 3 Status Within
Uveal Melanoma
Lynn Schoenfield, MD; James Pettay, BS, MT(ASCP); Raymond R. Tubbs, DO; Arun D. Singh, MD
● Context.—Determining the most significant prognostic terns, scleral or extrascleral spread and size. One case was
variables in uveal melanoma is important for stratifying pa- excluded because of necrosis.
tients for metastasis surveillance and possible initiation of Results.—Ten of the 17 remaining cases (59%) demon-
chemotherapy or immunotherapy. Monosomy 3, one such strated monosomy 3 (in either the base or both base and
variable, can be determined using fluorescence in situ hy- apex of the tumor) with 7 cases (41%) showing disomy.
bridization, either on enucleated samples, fine-needle as- Seven cases (70%) with monosomy 3 demonstrated this in
piration biopsy, or tumor sample obtained by vitrector. both the apex and the base locations, whereas 3 cases
Objective.—To evaluate possible regional discordance in (30%) showed monosomy in one location only (always at
chromosome 3 by sites likely to be sampled by different the base). Fourteen of the 17 cases (82%) revealed con-
biopsy methods. cordance in chromosome 3–monosomy 3 (7 of 14, 50%)
Design.—Eighteen consecutive patients with uveal mel- or chromosome 3–disomy 3 (7 of 14, 50%). All 3 discor-
anoma who underwent primary enucleation were studied.
dant cases demonstrated the monosomy 3 at the base with
Representative paraffin blocks were selected based on re-
view of hematoxylin-eosin stained sections, and the apex disomy at the apex. Lack of concordance between the base
and base of each tumor was demarcated. Unstained par- and apex did not correlate with melanoma cell type.
affin sections, 4 m in thickness, were prepared, and fluo- Conclusions.—Prognostic variables are important in
rescence in situ hybridization, looking for monosomy 3, management of neoplasms, and this study points out that
was performed. The chromosomal analysis was also cor- the site of tissue biopsy for prognostication in uveal mel-
related with histologic evaluation for melanoma cell type anoma could affect the results obtained, at least for the
(spindle vs epithelioid cell), ciliary body involvement, pres- presence of monosomy 3.
ence of positive periodic acid–Schiff vascular mimicry pat- (Arch Pathol Lab Med. 2009;133:1219–1222)
U veal malignant melanoma is the most common pri-
mary intraocular malignancy in the adult popula-
tion, with an annual incidence of approximately 4.3 cases
patterns), and ciliary body involvement have been noted
to correlate with poor prognosis.5–8 More recently, studies
have turned to cytogenetic and molecular genetic analy-
per million per year in the United States, a rate which has ses. Chromosomal changes of prognostic significance have
essentially been stable during the past 50 years.1 It com- been found and include monosomy 3 and alterations of
prises approximately 5% of all melanomas, and 85% of 8q and 6p.9–15 Studies16,17 have reported heterogeneity for
ocular melanomas are uveal in origin.2 Mortality, princi- monosomy 3 within uveal melanoma but did not look at
pally from liver metastasis, has historically been approx- it from a geographic point of view, which could have clin-
imately 50%; this has not changed significantly in recent ical relevance.
years despite advances in early diagnosis and local treat- Monosomy 3 can be determined using fluorescence in
ment.3 Determining the most significant prognostic vari- situ hybridization (FISH), either on enucleated samples,
ables has been elusive but important for stratifying pa- fine-needle aspiration biopsy, or tumor sample obtained
tients for metastasis surveillance and possible initiation of by vitrector.18 Our hypothesis was that, just as there is
chemotherapy or immunotherapy.4 histologic variability, there may also be variability in the
Traditionally, several features, such as large size, epi- genetic alterations within a given tumor. Therefore, we ex-
thelioid cell type, presence of positive periodic acid–Schiff amined enucleated globes with uveal melanoma for the
(PAS) vascular mimicry patterns (or extracellula