W. RICHARDGREEN MD
A 27-year-old woman developed malignant orbitoconjunctival melanoma
in her left eye 21 years after treatment of a left orbital embryonal sarcoma
with systemic chemotherapy and radiation therapy to the orbit. The coexistence
of these 2 malignancies in the same orbit is very rare. It may be coincidental,
but a genetic predisposition or late adverse effects of childhood cancer treatments
cannot be excluded.
Second malignant tumors can occur in patients treated for retinoblastoma
during childhood,1 but other multiple ophthalmic
malignancies in the same patient are a very rare occurrence. We report the
case of a patient who had 2 distinct tumors involving her left orbit. A childhood
sarcoma was followed 21 years later by a malignant melanoma.
In 1971, a 6-year-old girl developed a tumor in her left orbit. A specimen
from an incisional biopsy of the mass showed evidence of embryonal sarcoma
(Figure 1 A and B). The patient
received multidrug systemic chemotherapy (including dactinomycin) and radiation
therapy to the orbit. Radiation therapy consisted of an exclusive anterior
beam with a delivered dose of 5000 rad (50 Gy; 330 rad [3.3 Gy] per fraction)
with good local tumor control. During follow-up, the patient developed cataract
and strabismus and underwent uneventful surgical treatment for cataract. Her
final visual acuity was 20/200 because of macular retinal alterations that
were probably secondary to radiation retinopathy. A surgical procedure to
correct strabismus was then performed in 1982, and regular follow-up was performed
by her ophthalmologist.
A and B, Biopsy specimen of an
orbital lesion, embryonal sarcoma, shows syncytial arrangement of poorly differentiated
embryonic mesenchymal cells dispersed in edematous or fibrous stroma (hematein-eosin
saffron, original magnification ×10 [A] and ×40 [B]). C and D,
Orbital exenteration because of malignant melanoma shows highly cellular proliferation
of fusiform malignant cells with atypical nuclei and prominent nucleoli (hematein-eosin
saffron, original magnification ×10 [A] and ×40 [B]).
In July 1992, at age 27 years, the patient developed a slowly growing,
painless, temporal conjunctival mass of the left eye. The patient was then
referred to our clinic in September 1992. At that time, she had a slightly
pigmented bulbar conjunctival mass in the temporal area (Figure 2) with posterior extension on computed tomography (Figure 3). There were no palpable preauricular
or submandibular nodes. Systemic workup ruled out metastasis. A biopsy specimen
of the lesion revealed a conjunctival malignant melanoma, and the patient
underwent orbital exenteration in October 1992. Histological examination of
the biopsy specimen showed proliferation of malignant pleomorphic cells whose
morphologic features and immunophenotype were compatible with the diagnosis
of malignant amelanotic melanoma (tumor cells were positive for S100 protein
and negative for vimentin, desmin, actin, myoglobin, and cytokeratin). The
pathological characteristics of the exenteration specimen confirmed the diagnosis
of melanoma (Figure 1C and D). The
mass was located in the lower conjunctival fornix and extended inferiorly
to involve theorbicularis muscle and bulbar conjunctiva as far as the limbus.
The surgical margins were free of tumor.
Slightly pigmented mass adjacent
to the temporal region of the left eye.
Computed tomographic scan of the
left orbit shows posterior extension of the mass.
The patient was then fitted with transcutaneous implants and a magnetic
retained prosthesis with satisfactory aesthetic results. Regular systemic
and ophthalmologic follow-up was uneventful until January 1999, at which time
the patient complained of persistent nasal obstruction. Examination revealed
a mass in the left nasal fossa and maxillary sinus (Figure 4). Surgical treatment consisted of maxillectomy with immediate
reconstruction with latissimus dorsi free-flap, and pathological examination
confirmed the presence of malignant melanoma (Figure 5A and B).
Computed tomographic image shows
recurrent malignant melanoma involving the orbital apex, left ethmoidal and
maxillary sinuses, and nasal fossa.
A and B, Maxillary recurrence
of malignant melanoma shows proliferation of large epithelioid cells (hematein-eosin
saffron, original magnification ×10 [A] and ×40 [B]). C, Sinus
relapse of malignant melanoma shows epithelioid-type cells (hematein-eosin
saffron, original magnification ×20). D, Significant expression of a
melanoma-related antigen (HMB 45, ×20).
One year later, a sinus relapse was observed on a follow-up computed
tomographic scan. The patient underwent a salvage operation, and pathological
examination confirmed the presence of melanoma (Figure 5C and D). Disseminated hepatic and bone metastases appeared
in August 2000. The patient is currently receiving systemic chemotherapy with
interferon and temozolomide.
The association of embryonal sarcoma and melanoma in the same orbit
is a very rare occurrence; to the best of our knowledge, the literature reports
only 1 other case of orbital melanoma 45 years after successful treatment
of rhabdomyosarcoma.2 The appearance of
second tumors after treatment of rhabdomyosarcoma is also a very rare event.
In their series describing long-term follow-up of children treated for orbital
rhabdomyosarcoma, Oberlin et al3 did not
describe any patient with a second neoplasm (median follow-up, 8 years). Paulino
et al,4 in a smaller series but with a longer
follow-up, described a mucoepidermoid carcinoma of the parotid gland occurring
at the border of the radiation field after radiotherapy of the supraglottic
larynx. An epidermoid carcinoma was described 9 years after chemotherapy and
radiation therapy for rhabdomyosarcoma, and this lesion was attributed to
radiation therapy.5 However, the various
second malignant neoplasms described after treatment of rhabdomyosarcoma do
not include malignant melanoma.4,5
In a recent study on children with soft-tissue sarcomas, the incidence of
second malignant neoplasms was estimated to be 7.5%, but these authors reported
only 1 case of melanoma.6
The metachronous appearance of 2 primary malignancies may be due to
several causes. It could be an incidental occurrence, or it may be related
to a genetic predisposition. The role of previous cancer treatments (chemotherapy
and radiation therapy) cannot be excluded.
The possibility of a radioinduced tumor is supported by the preexisting
homolateral lesion treated by a combination of radiation therapy and chemotherapy;
the lesion also occurred in the radiation field several years after initial
treatment. However, the possibility of a genetic predisposition cannot be
excluded in our patient, despite the absence of a family history of cancer.
This case report describes and documents the very rare occurrence of
2 distinct orbital malignancies (rhabdomyosarcoma and malignant melanoma)
occurring in the same patient at an interval of 20 years; it further emphasizes
the current concern about childhood cancer treatments that might cause severe
late effects, especially second cancers.
Corresponding author and reprints: Livia Lumbroso, MD, Institut Curie,
26 Rue d'Ulm, 75005 Paris, France (e-mail: firstname.lastname@example.org).
Lumbroso L, Sigal-Zafrani B, Jouffroy T, Levy C, Rodriguez J, Desjardins L. Late Malignant Melanoma After Treatment of Rhabdomyosarcoma of the Orbit During Childhood. Arch Ophthalmol. 2002;120(8):1087-1090. doi: