Congenital uveal malignant melanoma: a case report Maristela A. Palazzi,* MD; Michael D. Ober,† MD; Helio F.H. Abreu,* MD; Izilda A. Cardinalli,* MD; Cassiano R. Isaac,* MD; Alexandre N. Odashiro,‡ MD; Miguel N. Burnier, Jr.,‡ MD, PhD ABSTRACT • RÉSUMÉ Case report: We present a case of congenital choroidal mass in a male infant with multiple cutaneous pigmented lesions. Enucleation performed in the first weeks of life confirmed the diagnosis of diffuse uveal malignant melanoma with extraocular extension. The patient was also treated with 5 cycles of chemotherapy. He subsequently developed cutaneous and ocular pigmented lesions, including 2 choroidal nevi located within the posterior pole and a benign conjunctival lesion in the opposite eye, in addition to malignant melanoma of the skin. Comments: At 10 years follow-up, the child is clinically well with no evidence of further malignancy.We believe this represents the fourth case ever reported in the literature and the longest follow-up of a congenital malignant melanoma originating within the eye. Observation : Nous présentons un cas marqué par la présence d’une masse choroïdienne congénitale chez un enfant male ayant de multiples lésions pigmentées cutanées. L’énucléation, effectuée dans les premières semaines de vie, a confirmé le diagnostic de mélanome malin diffus de l’uvée avec extension extraoculaire. Le patient a aussi reçu 5 cycles de chimiothérapie. Il développa ensuite des lésions pigmentées cutanées et oculaires, y compris 2 nævus de la choroïde situés dans le pole postérieur et une lésion bénigne de la conjonctive dans l’œil opposé, en plus d’un mélanome malin de la peau. Commentaires : Après dix ans de suivi, l’enfant était cliniquement bien et ne présentait pas de signe d’autre malignité. Nous croyons qu’il s’agit du quatrième cas jamais signalé et du plus long suivi d’un mélanome malin congénital ayant eu son origine dans l’œil.
From * the Boldrini Children Center, Campinas, Brazil, †the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear & Throat Hospital, New York, N.Y., and ‡the Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Que. Originally received Feb. 19, 2004 Accepted for publication Mar. 7, 2005 Correspondence to: Dr. Maristela A. Palazzi, Boldrini Children Center, Ophthalmology, rua Gabriel Porto 1270, Campinas 13083-210 Brazil–SP;
[email protected] This article has been peer-reviewed. Can J Ophthalmol 2005;40:611–5
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REPORT
A
boy was born at 38 weeks gestation with proptosis, 360º perilimbal pigmentation, corneal edema, elevated intraocular pressure, and extraocular extension of a pigmented tumor in the right eye. Funduscopy was not elucidative because of severe opacity of the ocular lens. In addition, there were multiple pigmented cutaneous lesions on face and body. An enlarged right globe measuring 3.4 × 2.6 × 2.6 cm (left eye was 1.6 × 1.5 × 1.5 cm) had been identified
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A
C
B Fig. 1—A: Digital photomicrograph showing diffuse uveal melanoma localized underneath ciliary process (×40). B: Choroidal uveal melanoma comprising predominantly spindle cells in this field (×200). C: Detail showing large atypical epithelioid tumor cells, with delicate nucleolar chromatin, evident nucleolus, and frequent mitosis (arrows) (×400) (hematoxylin–eosin stain; original magnifications).
by obstetric ultrasonography at 36 weeks gestation. There was no family history of cutaneous or ocular malignant melanoma. Enucleation was performed in the first weeks of life. The histopathologic examination showed a diffuse malignant melanoma involving the choroid and ciliary body and infiltrating the sclera, optic nerve, and extraocular muscles. The patient was then treated with 5 cycles of vincristine, dactinomycin, and cyclophosphamide because of extension of the tumor beyond surgical margins. When he was 1 year old, 2 cutaneous lesions growing on his abdomen were resected; histopathologic analysis confirmed the diagnosis of cutaneous malignant melanoma for both lesions. The metastatic examination was once again negative and no further treatment was recommended. At age 7, 2 nonelevated pigmented choroidal lesions, each measuring 2 mm in largest diameter, were detected
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in the left eye. They have been followed closely and remain unchanged. A flat and densely pigmented lesion appeared in the conjunctiva at age 8, involving the inferior lacrimal punctum. An excisional biopsy showed the lesion to be an accumulation of melanin containing macrophages. The patient is currently 10 years old, developing normally, and remains free from metastatic disease. Histopathology
Histopathologic examination of the eye showed a diffuse malignant melanoma involving the choroid and ciliary body (Fig. 1). The tumor was a mixed cell type comprising epithelioid and spindle cells. Most of the cells presented a large hyperchromatic nucleus, conspicuous eosinophilic nucleolus, and frequent mitotic figures. The tumor was not multicentric, but it had invaded the optic nerve (Fig. 2A and 2B). The abdominal cutaneous specimens showed a melanocytic lesion localized in the dermis, displaying malignant features such as pleomorphism, large hyperchromatic nuclei, and conspicuous eosinophilic nucleoli, consistent with the diagnosis of melanoma (Fig. 2C and 2D). All cutaneous lesions had the same histopathologic picture.
Congenital uveal melanoma—Palazzi et al
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B
C
D
Fig. 2—A: Infiltration of optic nerve by melanoma tumor cells (×40). B: Higher magnification of Fig. 2A showing detail of neoplastic cells in optic nerve (×200). C:Abdominal cutaneous lesion showing dermal infiltration by neoplastic cells (×100). D: Higher magnification of Fig. 2C. Malignant cells display pleomorphism, hyperchromasia, and conspicuous nucleoli (×400) (hematoxylin–eosin stain; original magnifications).
COMMENTS
Although malignant melanoma presenting at birth is extremely rare, several cases have been published, including 3 originating within the eye.1–7 After an extensive review of the literature, we believe our patient represents the longest follow-up of a congenital malignant melanoma originating within the eye, and the fourth case ever reported. (Table 1) Pathological interpretation of this lesion was consistent with choroidal malignant melanoma. Diagnosis was made by morphologic features of the tumor cells and the pattern of immunohistochemical staining, which was strongly positive for the S-100 and
HMB-45 antigens. Although it was believed to be a primary choroidal melanoma, the possibility that this tumor represented a metastatic lesion was also initially considered, given the development of cutaneous melanomas at 1 year of age. However, the diffuse presentation of the lesion and the presence of 2 cell types characteristic of uveal melanoma favored the diagnosis of a primary tumor. Moreover, while metastasis of cutaneous malignant melanoma to the eye may occur in adults, it has never been reported in children.8–10 Transplacental metastasis of melanoma is also known to take place,11 but was excluded in our case as the patient’s mother had no clinical evidence or previous history of malignancy.
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Table 1—Comparison of reported cases of congenital ocular melanoma and its association with pigmented skin lesions Presentation / sex Greer 1966
birth / M
Broadway et al 1991
birth / M
Posnick et al 1993
birth / F
Palazzi et al (present case)
birth / M
Ocular tumor •
•
•
•
Skin lesions
anterior uvea
•
uveal tumor with orbital extension
•
orbital mass, extensive extraocular involvement
•
uveal tumor with extraocular involvement of muscles and optic nerve
•
Outcome
multiple melanocytic nevus
•
multiple melanocytic nevus
•
no reported
•
•
•
•
•
multiple melanocytic nevus 2 skin melanomas
•
no systemic disease alive at 2 y liver metastasis alive at 2 y 10 mo extension to maxilla alive over 2 y alive and well with no systemic disease at 10 y
Note: M = male; F = female; y = year; mo = month.
The first description of a congenital ocular melanoma was by Greer in 1966.6 He reported a boy born with an anterior uveal mass filling over 50% of the globe in conjunction with multiple pigmented skin lesions. Histopathology of the enucleated specimen revealed a mixed-cell malignant melanoma. The patient was alive and healthy at 2 years of age. Broadway et al reported a newborn boy with a large left ocular tumor with orbital extension, a liver mass, and multiple pigmented cutaneous lesions.4 Pathology showed an epithelioid melanoma infiltrating the extraocular muscles and orbital fat. Liver biopsy revealed metastatic melanoma with identical cell type, and multiple skin biopsies revealed congenital melanocytic nevus without malignant features. Despite the liver metastasis, the patient was well at 2 years and 10 months following tumor resection and chemotherapy. Posnick et al also reported a baby girl born with a large left orbital mass.5 No cutaneous lesions were described. This tumor filled the pterygopalatine fossa, infiltrated the maxilla, and effectively closed the left nasal passage. The exenteration specimen showed relatively undifferentiated cells, which were confirmed as melanoma by immunostaining and electron microscopy. The patient was also doing well over 2 years following tumor resection and chemotherapy. Colenbrander presented a brief report of a newborn with a cystic eye and a pigmented choroidal tumor; the description was inadequate, however, to definitely classify the tumor as a melanoma.7
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Although some conditions predispose patients to the development of multiple cutaneous melanomas, including the B-K mole syndrome, dysplastic nevus syndrome, and xeroderma pigmentosum,12–15 the simultaneous occurrence of cutaneous and ocular melanoma remains a rare event.14,15 Curious similarities among some of these cases are the orbital extension of the tumor, the relative longterm survival even despite extensive local disease, and the favorable response to chemotherapy that is not usually seen for metastatic uveal melanoma in adults. The survival time observed for most uveal melanoma that extended outside the eye, in adults, used to be brief, with death occurring within months or, exceptionally, a few years.15 It has been suggested that ocular melanomas in children respond more favorably to chemotherapy than do those in adults, however given the small sample size, it becomes impossible to draw accurate conclusions.5,18,19 Because little is known about the natural behavior of congenital melanoma of the eye, a close follow-up of these rare cases may contribute to better understand of this singular condition. The authors have no financial or proprietary interest in any of the materials or techniques used in this study.
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Key words: eye, malignant melanoma, uveal melanoma, congenital melanoma, congenital neoplasm
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