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Clinicopathologic Reports, Case Reports, and Small Case Series
August 2002

Late Malignant Melanoma After Treatment of Rhabdomyosarcoma of the Orbit During Childhood

Author Affiliations
 

W. RICHARDGREEN MD

Arch Ophthalmol. 2002;120(8):1087-1090. doi:

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.

Report of a Case

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.

Figure 1.
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]).

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.

Figure 2.
Slightly pigmented mass adjacent
to the temporal region of the left eye.

Slightly pigmented mass adjacent to the temporal region of the left eye.

Figure 3.
Computed tomographic scan of the
left orbit shows posterior extension of the mass.

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).

Figure 4.
Computed tomographic image shows
recurrent malignant melanoma involving the orbital apex, left ethmoidal and
maxillary sinuses, and nasal fossa.

Computed tomographic image shows recurrent malignant melanoma involving the orbital apex, left ethmoidal and maxillary sinuses, and nasal fossa.

Figure 5.
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).

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.

Comment

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: livia.lumbroso@curie.net).

References
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Paulino  ACSimon  JHZhen  WWen  BC Long-term effects in children treated with radiotherapy for head and neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2000;481489- 1495Article
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Raney  RBAnderson  JRKollath  J  et al.  Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: report from the Intergroup Rhabdomyosarcoma Study (IRS)–III, 1984-1991. Med Pediatr Oncol. 2000;34413- 420Article
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Merimsky  OKollender  YIssakov  J  et al.  Multiple primary malignancies in association with soft tissue sarcomas. Cancer. 2001;911363- 1371Article
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