Primary Orbital Melanoma Associated With Orbital Melanocytosis Charles D. Rice, MD, Harry H. Brown, MD
\s=b\ We report a case of primary orbital melanoma in a 17-year-old girl. The patient presented with painless proptosis during the first trimester of pregnancy. Computed tomography demonstrated a well-circumscribed mass located infratemporally in the right orbit. The tumor
was
bluish-black, grossly encapsulated,
and associated with orbital blue nevi. Histologic examination of the mass revealed a pigmented spindle-cell neoplasm. On electron microscopy, the presence of premelanosomes and the absence of basal lamina supported the diagnosis of melanoma. Malignant transformation of a preexisting nevus is postulated since perineural foci of benign dendritic melanocytes were seen within the melanoma. There has been no recurrence or metastasis in a 2-year follow-up. Of 30 primary orbital melanomas reviewed, 12 (40%) were associated with periorbital pigmentary disorders, such as oculodermal melanocytosis, blue nevus, and ocular melanocytosis. Our case is unique since the pigmentary lesions were limited to the orbital tissues. (Arch Ophthalmol. 1990 ;108:1130-
1134)
cutaneous
lanocyte,
melanomas.1 The orbital mea neural crest derivative,
may be found along ciliary nerves, scierai emissarial vessels, or optic nerve leptomeninges.1'2 Tumors may also originate from anomalous deposits associated with periorbital pigmentary
disorders.1"4 Nearly
one
half of the
pri¬
mary orbital melanomas have been as¬ sociated with pigmentary disorders, such as oculodermal melanocytosis (ne¬ vus of Ota), ocular melanocytosis, and blue nevi.1·3"11 In most cases associated with pigmentary lesions, ocular or cu¬ taneous pigmentation was visible pre¬
operatively. We describe our case as orbital melanocytosis since the abnor¬ mal pigmentation was confined to the
orbit and not distributed in ocular or cutaneous tissue.1 Additional notewor¬ thy findings include encapsulation of the tumor and its development during pregnancy. The clinical, roentgenographic, and histologie features are discussed. REPORT OF A CASE
17-year-old girl with a 3-month history right-sided proptosis presented to the University of Arkansas Ophthalmology Clinic, Little Rock (Fig 1). She denied any pain, decrease in vision, or diplopia. Her medical history was significant for pregnan¬ cy, with an estimated gestational age of 3 months. The patient's visual acuity was A
of
\ rbital melanomas
occur as primary secondary tumors. Primary le¬ sions arising from orbital melanocytes are less common than secondary tu¬ mors, which develop from ocular or or
Accepted for publication April 30, 1990. From the Departments of Ophthalmology (Drs Rice and Brown) and Pathology (Dr Brown), University of Arkansas for Medical Sciences, Lit-
tle Rock.
Reprint requests to the Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 W Markham, Mail Slot 523, Little Rock, AR 72205 (Dr Rice).
20/20 OD with 0 + 0.75x90° and 20/20 OS without correction. Lids, sclera, and con¬ junctiva were without hyperpigmentation. Ocular motility, pupillary reactions, slitlamp examination results, and fundus ex¬ amination results were normal. Two milli¬ meters of axial proptosis and 4 mm of upward displacement of the right globe were
present.
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An orbital
computed tomographic (CT)
demonstrated a well-circumscribed mass located infratemporally in the right orbit (Figs 2 and 3). No calcification or bony erosion was present and the tumor was enhanced slightly with contrast material. At surgery, focal areas of pigmentation remote from the main tumor were visible along the periorbita (Fig 4). The tumor was freed from the orbital tissues without diffi¬ culty but was firmly adherent along the orbital floor. The bluish-black encapsulated tumor measured 2.0x2.0x1.8 cm (Fig 5). Inspection of the excised tumor revealed a disruption of the capsule at its point of bony attachment. The tumor was diagnosed as a
scan
A thorough physical examination demonstrated the absence of cutaneous or mucous membrane melanoma. A complete blood cell count and results of liver enzyme studies, chest roentgenography, and a urinalysis were normal. Com¬ puted tomographic scans of the head and body were normal as well. A repeated surgery was performed due to the possibility of residual tumor. Biopsy specimens of pigmented areas along the orbital floor were histologically blue nevi and demonstrated the absence of melano¬ ma. Postoperatively, the patient's visual acuity was 20/20 in the right eye, with normal extraocular motility and 2 mm of right enophthalmos. The patient delivered a healthy girl 5 months after the initial sur¬ gery. There was no evidence of recurrence or metastasis after a 2-year follow-up.
spindle-cell melanoma.
Light Microscopic Findings The main tumor was composed of densely cells surrounding vascular spaces and clefts containing degenerating tumor cells and hemosiderin-laden microphages. A fibrous capsule incompletely en¬ veloped the tumor (Fig 6). Individual tumor cells displayed mild pleomorphism with elongated nuclei and inconspicuous but cen¬ trally placed nucleoli (Fig 7). The cytoplasm was weakly eosinophilic and occasionally
packed spindle
contained fine granular brown pigment. The pigmented material within the spindle cells reacted strongly with the FontanaMasson stain. Clusters of heavily pig¬ mented melanophages were scattered throughout the tumor. Mitotic figures were rarely identified. Areas of fibrinoid necrosis were present and individual cell death was observed within cystic spaces. The clinically observed pigmented areas remote from the main tumor were com¬ posed of heavily pigmented dendritic mela¬ nocytes. They were interspersed within fibroadipose connective tissue rather than forming a discrete mass. These lesions were diagnosed as blue nevi. A nerve within the main tumor demonstrated identical pig¬ mented dendritic cells infiltrating the peri¬ neural sheath (Fig 8). The three biopsy specimens obtained on reexploration of the orbit demonstrated two blue nevi and a cellular blue nevus. The cellular blue nevus showed a biphasic pat¬ tern with small, nonpigmented, spindle cells and pigmented dendritic melanocytes
(Fig 9).
Electron Microscopic
Tumor cells
were
ally separated by
Findings
closely packed a
but usu¬ discrete intercellular
space (Fig 10). Blunt-cell processes were noted to intercalate between polygonal cell bodies. No intercellular adaptations in the form of gap junctions or desmosome attach¬ ments were identified. No external laminae were seen investing individual cells. Tumor cells had irregularly shaped oval to elon¬ gated nuclei with peripherally clumped heterochromatin and occasionally with irregu¬ larly shaped nucleoli. The cytoplasm contained melanosomes in various stages of maturation, ranging from stage II to fully mçlanized stage IV (Fig 11). Occasional melanosomes exhibited irregular shapes and granular pigmentation. Mitochondria were slightly enlarged and demonstrated some disruption of the cristae. Rough, endoplasmic reticulum was present, but not abundant.
COMMENT
Primary orbital melanomas account for less than 1% of primary orbital neoplasms.212 Of 30 documented cases, 23 (77%) presented in adults and 7 (23%) developed in children or adoles¬ cents.1,3"11,13"27 Painless proptosis from a diffuse orbital mass is the most com¬ mon presentation. The duration of
Fig 1 .—Clinical photograph demonstrating proptosis and upward displacement of the right eye.
Figs 2 and 3.—Computed tomography infratemporally in the right orbit.
of orbits. Axial
(Fig 2)
and coronal
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(Fig 3)
symptoms is variable, with
progressing slowly during
some
several
others present rapidly months.6,7,1 16 They occur
years,3"5,17 while during
1 to 3
without sexual predilection and are found mainly in whites (only two cases have been reported in blacks to our
knowledge8,13). In
our
case, the circumscribed ap¬
scan suggested an encapsulated tumor, such as cavernous hemangioma, schwannoma, or fibrous histiocytoma. Operative findings, which were unusual for these diag¬ noses, included the discovery of focal pigmented lesions along the periorbita,
pearance
a
on
CT
bluish-black appearance of the main
tumor, and fixation along the orbital
floor. Of the 30 documented primary orbital melanomas, only 4 were encap¬ sulated and treatable by primary re¬ section.3,4,7,19 The degree of encapsula¬ tion did not correlate with the histologie cell types: epithelioid cell types were found in encapsulated tu¬ mors, and spindle-cell types were dem¬ onstrated in diffuse tumors. One feature that may aid the clini¬ cian in suspecting a primary orbital melanoma is its frequent association with pigmentary disorders. Associated ocular, cutaneous, or orbital pigmen¬ tary lesions were present in 12 (40%) of 30 primary orbital melanomas.1,3"11 These 12 pigmentary disorders in¬ cluded oculodermal melanocytosis (6 cases),3"6,9 blue nevi (4 cases),1,7'1" and ocular melanocytosis (2 cases)8,11 (Ta¬ ble). They represent arrested migra¬ tion of melanocytes with variable pig¬ mentation of the skin, eye, or orbit. In oculodermal melanocytosis, pigmenta¬ tion within the orbit has been reported along extraocular muscles, orbital fat, periorbita, and orbital bones.34 In most orbital melanomas associated with pig¬ mentary disorders, the ocular or cuta¬ neous pigmentation was visible preop-
scans show
circumscribed
mass
eratively. Our case is unique since the associated pigmentation was detected only intraorbitally at the time of surgery. The melanocytic lesions within the orbit were clinically and histologically separable as blue nevi, cellular blue nevus, and malignant melanoma. Clini¬ cally, the blue nevi were brownish-
Fig 4. —Focal the periorbita.
pigmented
lesions
(arrow)
on
Fig 5.—Surgical specimen demonstrates
thin capsule.
a
black, irregular lesions distributed along the periorbita (Fig 4), and the cellular blue nevus was a small, bluishblack, circumscribed lesion adherent to the orbital floor. Histologically, the blue nevi were composed of dendritic melanocytes interspersed within fi¬ brous tissue, whereas the cellular blue nevus
demonstrated
a
discrete nodule
Fig 6.—Spindle-cell neoplasm contains heavily pigmented areas, a cleavage planes, and irregular spaces (hematoxylineosin, original magnification 40).
Fig 7.—Tumor cells contain moderately pleomorphic, oval, vesicular nuclei with distinct, centrally placed nucleoli (hematoxylin-eosin, origi¬ nal magnification x400).
Fig 8. —A perineural focus (arrow) of pigmented dendritic melanocytes found within the melanoma (hematoxylin-eosin, original magnification
Fig 9.—Cellular blue nevus demonstrates biphasic pattern with pig¬ mented (arrow) and nonpigmented (arrow in black circle) melanocytes
fibrous capsule,
x100).
(hematoxylin-eosin, original magnification 40).
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Fig 10.—Closely packed tumor cells display irregular nuclear outlines, coarsely clumped chromatin, and prominent nucleoli (original magnifi¬ cation X2400).
Fig 11.—Melanosomes (original magnification
Pigmentary Disorders Associated With Primary Orbital Melanomas Type of Nevus Within
Associated
Pigmentary Source, y al,3
Dutton et 1984
Cell type Spindle
the Tumor Cellular blue
Disorder
Oculodermal
melanocytosis None
Oculodermal
melanocytosis Hagler and Brown,5 1966 Haim et al,'
melanocytosis Oculodermal
Cellular blue and blue
Spindle
None
Epithel ¡oid
Cellular blue
Spindle
Blue
Epithelioid
melanocytosis
1982
Speakman and
Phillips,9
Jay,"
Oculodermal
1973
Oculodermal
melanocytosis Oculodermal
1965
melanocytosis
Jakobiec et al,' 1974
Cutaneous blue
nevus
Cellular blue
Epithelioid
Loftier and
Cutaneous blue
nevus
Cellular blue
Mixed
Cutaneous blue Cutaneous blue Ocular
nevus
Cellular blue Cellular blue Cellular blue
Spindle Spindle Epithelioid
Blue
Epithelioid
Witsche!,'0 Shields' Wilkes et 1984
al,e
Verdaguer,' 1965
1989 nevus
melanocytosis Ocular
melanocytosis
of closely packed spindle cells without intervening stroma. The melanoma was a larger, bluish-black, encapsu¬ lated mass, separable from surround¬ ing orbital structures. The histologie features of malignancy included pleomorphism, enlargement of nuclei, ne¬ crosis, and the presence of mitotic figures. Malignant transformation of a preexisting nevus is postulated since perineural foci of dendritic pigmented melanocytes were seen within the
melanoma. Ten primary melanocytic tumors had a blue nevus or a cellular blue demonstrated histologically nevus within the tumor.1,3'"" One was re¬ ported as a malignant cellular blue nevus" and nine were described as ma-
lignant melanomas arising from nevi. Histologie cell types included epitheli¬
oid (4 cases), spindle (5 cases), and spindle and epithelioid (1 case). Only one
tumor was
encapsulated and treat¬
by primary resection.3 In two patients who died of metastatic dis¬ able
ease,
one
demonstrated
an
epithelioid-
cell tumor4 and the other a spindle-cell lesion.9 Although the number of cases is too small for statistical analysis, the prognosis of tumors associated with nevi appears similar to melanomas without associated nevi. On electron microscopy, the pres¬ ence of melanosomes and the absence of basal laminae or mesaxons support¬ ed the diagnosis of melanoma rather than melanotic schwannoma or cellular
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are
12
present
in various
stages of maturation
000).
blue nevus. Ultrastructural character¬ istics of melanosomes may be helpful in distinguishing benign blue nevi from melanoma.28 Blue nevi contain numer¬ ous melanin granules (stage IV mela¬ nosomes), whereas melanomas have poorly developed melanosomes with ir¬ regular shapes and disordered internal structures.28 Desmosomelike struc¬ tures have been reported in primary orbital melanomas but were not dem¬ onstrated in our case.'"1 The development of melanoma dur¬ ing pregnancy suggests a possible hor¬ monal influence. While melanomas are not generally regarded as hormonedependent neoplasms, circumstantial evidence suggests that endocrine hor¬ mones may influence their biologic be¬ havior. Exacerbation of cutaneous melanomas,29 development of choroidal melanomas,3031 and accelerated growth of nevi have been reported in pregnan¬ cy. Of 14 primary orbital melanomas reported in female patients, 3 were in childbearing age and were not associ¬ ated with pregnancy. In cutaneous melanomas associated with pregnancy, only patients with metastatic disease had a poorer prognosis.32 Another consideration related to pregnancy is the potential spread of melanoma to the fetus. Since our patient's child is 2 years of age and shows no evidence of melanoma, the development of ma¬ lignancy is unlikely. Most cases of ma¬ ternal melanoma with metastasis to the fetus develop in mothers with widespread disease.33 All infants with melanoma from transplacental metas¬ tasis have developed the disease by 8 months of age.3" The clinical course of primary orbital melanomas is difficult to predict due to tumor rarity and the lack of long-term follow-up. Only two patients have16,lshad In a follow-up of more than 2 years. 30 cases, treatment has included
exenteration (17 cases), excision alone (9 cases), exenteration plus radiation (1 case), and unreported treatment (3 cases). Primary resection, rather than aggressive surgery or adjuvant thera¬ py, is probably sufficient for encapsu¬ lated tumors. Henderson and Farrow1* reported the primary resection of an encapsulated tumor with an epithelioid
histologie cell type.
There has been no metastasis after a 32year follow-up (oral communication with J. W. Henderson, MD, November 1988). Although the follow-up period in our case was short (2 years), the ab¬ sence of recurrence or metastasis sup¬ ports an initial conservative approach. The best treatment for diffuse lesions recurrence or
may be adjuvant therapy since aggres¬ sive surgery is unlikely to reduce the risk of future metastasis.9 Surgical re¬ section may be necessary in large or painful tumors. Adjuvant therapy (ra¬ diation therapy and chemotherapy) should be considered in incompletely excised, recurrent, or metastatic tumors.
References 1. Shields JA. Primary melanocytic tumors. In: Diagnosis and Management of Orbital Tumors. Philadelphia, Pa: WB Saunders Co; 1989:275-289. 2. Reese AB. Orbital neoplasms. In: Tumors of the Eye. 3rd ed. New York, NY: Harper & Row
Publishers Inc; 1976:189,438. 3. Dutton JJ, Anderson RL, Schelper RL, Purcell JJ, Tse DT. Orbital malignant melanoma and oculodermal melanocytosis: report of two new cases and review of the literature. Ophthalmology.
1984;91:497-507. 4.
case
Jay B. Malignant melanoma of the orbit in a of oculodermal melanosis. Br J Ophthalmol.
1965;49:359-363.
5. Hagler WS, Brown CC. Malignant melanoma of the orbit arising in the nevus oto. Trans Am Acad Ophthalmol Otolaryngol. 1966;70:817-822. 6. Haim T, Meyer E, Kerner H, Zonis S. Oculodermal melanocytosis (nevus of Ota) and orbital malignant melanoma. Ann Ophthalmol.
1982;14:1132-1136. 7. Jakobiec FA, Ellsworth R, Tannenbaum M.
Primary
orbital melanoma. Am J
Ophthalmol.
1974;78:24-39. 8. Wilkes TD, Uthman EO, Thornton CN, Cole
Malignant melanoma of the orbit in a black patient with ocular melanocytosis. Arch OphthalRE.
mol. 1984;102:904-906. 9. Speakman JS, Phillips MJ. Cellular and malignant blue nevus complicating oculodermal melanosis. Can J Ophthalmol. 1973;8:539-547. 10. Loffler KU, Witschel H. Primary malignant melanoma of the orbit arising in a cellular blue nevus. Br J Ophthalmol. 1989;73:388-393. 11. Verdaguer J. Prepubertal and pubertal melanomas in ophthalmology. Am J Ophthalmol.
1965;60:1002-1011.
12. Shields JS, Bakewell B, Augsburger JJ, Flanagan JC. Classification and incidence of space\x=req-\ occupying lesions of the orbit. Arch Ophthalmol.
1984;102:1606-1611. 13. Coppeto JR, Jaffe R, Gillies CG. Primary orbital melanoma. Arch Ophthalmol. 1978;96:2255\x=req-\
2258. 14. Drews RC. Primary malignant melanoma of the orbit in a negro. Arch Ophthalmol. 1975;93:335\x=req-\ 336. 15. Henderson JW. Malignant melanoma. In: Orbital Tumors. Philadelphia, Pa: WB Saunders Co; 1973:329-331. 16. Henderson JW, Farrow GM. Malignant melanoma primary in the orbit: report of a case. Trans Am Acad Ophthalmol Oto. 1972;76:1487-1490. 17. Rottino A, Kelly AS. Primary orbital melanoma: case report with review of the literature. Arch Ophthalmol. 1942;27:934-949. 18. Wolter JR, Bryson JM, Blackhurst RT. Primary orbital melanoma. Eye Ear Nose Throat
Monthly. 1966;45:64-66.
19. Foster J. An encapsulated orbital melanoma. Br J Ophthalmol. 1944;28:293-296. 20. Walter O. Ein Fall von primaren Melanosarkom der Orbita. Klin Monatsbl Augenheilkd.
1893;31:357-368.
21. Bonnet P. Sur
une
forme
clinique
rare
de
tumeur de l'orbite: la forme 'oculaire' des tumeurs
de l'orbite. Arch Ophtalmol. 1951;11:329-332. 22. Offret G. Tumeurs melaniques de l'orbite. In: Tumeurs de L'orbite. Paris, France: Masson; 1951:411-413. 23. Vannini A, Faraldi I, Gracis GP, D'Onofrio M, Fessia L. Rare tumors of the orbit during childhood. Ophthalmologica. 1976;173:463-485. 24. Motolese E, Esposti P, Menicacci F, Pannani
S, DePascalis F, Patacchini E. Primary malignant melanoma of the orbit A- and B-scan echographic characteristics.
Boll
Ital
Biol
Sper.
172.
26. Constantantinides G, Dascotte JC, Dupont A. Primary orbital nevocarcinoma. Bull Soc Ophtalmol Fr. 1974;74:517-519. 27. Mortada A. Incidence of melanomata of ocular adnexa in U A R (Egypt). Bull Ophthalmol Soc
Egypt. 1969;62:321-328. 28. Ghadially FN. Blue naevus. In: Diagnostic Electron Microscopy of Tumours. 2nd ed. Stoneham, Mass: Butterworths; 1985:401-403. 29. Ariel IM. Theories regarding the etiology of malignant melanoma. In: Malignant Melanoma. New East Norwalk, Conn: Appleton & Lange; 1981:19-20. 30. Frenkel M, Klein HZ. Malignant melanoma of the choroid in pregnancy. Am J Ophthalmol.
1966;62:910-913. 31. Seddon JM, Maclaughlin DT, Albert DM, Gragoudas ES, Ference M. Uveal melanomas presenting during pregnancy and the investigation of oestrogen receptors in melanomas. Br J Ophthalmol. 1982;66:695-704. 32. Shiu MH, Schottenfeld D, Maclean B. Adverse
effect of pregnancy
1976;37:181-187.
on
melanoma. Cancer.
33. Anderson JF, Kent S, Machin GA. Maternal with placental metastasis: a case report with literature review. Pediatr Pathol.
malignant melanoma 1989;9:35-42.
Currently in Other AMA Journals ARCHIVES OF DERMATOLOGY
Treatment of Tattoos by Q-Switched Ruby Laser: A Dose-Response Study C. R. Taylor; R. W. Gange; J. S. Dover; T. J. Flotte; E. Gonzalez; N. Michaud; R. R. Anderson (Arch Dermatol. 1990;126:893-899) A Dermatopathologist Looks at Mohs Micrographie Surgery J. T. Headington (Arch Dermatol. 1990;126:950-951)
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Soc
1984;60:1239-1244. 25. Vikovia E, Preisovia J, Winklerovia S, Kumstat Z, Nemecek R. Malignant melanoma of the orbit: case reports. Cesk Oftalmol. 1985;41:166\x=req-\
\s=b\ We report a case of primary orbital melanoma in a 17-year-old girl. The patient presented with painless proptosis during the first trimester of pregnancy. Computed tomography demonstrated a well-circumscribed mass located infratemporally in the right orbit. The tumor
was
bluish-black, grossly encapsulated,
and associated with orbital blue nevi. Histologic examination of the mass revealed a pigmented spindle-cell neoplasm. On electron microscopy, the presence of premelanosomes and the absence of basal lamina supported the diagnosis of melanoma. Malignant transformation of a preexisting nevus is postulated since perineural foci of benign dendritic melanocytes were seen within the melanoma. There has been no recurrence or metastasis in a 2-year follow-up. Of 30 primary orbital melanomas reviewed, 12 (40%) were associated with periorbital pigmentary disorders, such as oculodermal melanocytosis, blue nevus, and ocular melanocytosis. Our case is unique since the pigmentary lesions were limited to the orbital tissues. (Arch Ophthalmol. 1990 ;108:1130-
1134)
cutaneous
lanocyte,
melanomas.1 The orbital mea neural crest derivative,
may be found along ciliary nerves, scierai emissarial vessels, or optic nerve leptomeninges.1'2 Tumors may also originate from anomalous deposits associated with periorbital pigmentary
disorders.1"4 Nearly
one
half of the
pri¬
mary orbital melanomas have been as¬ sociated with pigmentary disorders, such as oculodermal melanocytosis (ne¬ vus of Ota), ocular melanocytosis, and blue nevi.1·3"11 In most cases associated with pigmentary lesions, ocular or cu¬ taneous pigmentation was visible pre¬
operatively. We describe our case as orbital melanocytosis since the abnor¬ mal pigmentation was confined to the
orbit and not distributed in ocular or cutaneous tissue.1 Additional notewor¬ thy findings include encapsulation of the tumor and its development during pregnancy. The clinical, roentgenographic, and histologie features are discussed. REPORT OF A CASE
17-year-old girl with a 3-month history right-sided proptosis presented to the University of Arkansas Ophthalmology Clinic, Little Rock (Fig 1). She denied any pain, decrease in vision, or diplopia. Her medical history was significant for pregnan¬ cy, with an estimated gestational age of 3 months. The patient's visual acuity was A
of
\ rbital melanomas
occur as primary secondary tumors. Primary le¬ sions arising from orbital melanocytes are less common than secondary tu¬ mors, which develop from ocular or or
Accepted for publication April 30, 1990. From the Departments of Ophthalmology (Drs Rice and Brown) and Pathology (Dr Brown), University of Arkansas for Medical Sciences, Lit-
tle Rock.
Reprint requests to the Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 W Markham, Mail Slot 523, Little Rock, AR 72205 (Dr Rice).
20/20 OD with 0 + 0.75x90° and 20/20 OS without correction. Lids, sclera, and con¬ junctiva were without hyperpigmentation. Ocular motility, pupillary reactions, slitlamp examination results, and fundus ex¬ amination results were normal. Two milli¬ meters of axial proptosis and 4 mm of upward displacement of the right globe were
present.
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/17/2015
An orbital
computed tomographic (CT)
demonstrated a well-circumscribed mass located infratemporally in the right orbit (Figs 2 and 3). No calcification or bony erosion was present and the tumor was enhanced slightly with contrast material. At surgery, focal areas of pigmentation remote from the main tumor were visible along the periorbita (Fig 4). The tumor was freed from the orbital tissues without diffi¬ culty but was firmly adherent along the orbital floor. The bluish-black encapsulated tumor measured 2.0x2.0x1.8 cm (Fig 5). Inspection of the excised tumor revealed a disruption of the capsule at its point of bony attachment. The tumor was diagnosed as a
scan
A thorough physical examination demonstrated the absence of cutaneous or mucous membrane melanoma. A complete blood cell count and results of liver enzyme studies, chest roentgenography, and a urinalysis were normal. Com¬ puted tomographic scans of the head and body were normal as well. A repeated surgery was performed due to the possibility of residual tumor. Biopsy specimens of pigmented areas along the orbital floor were histologically blue nevi and demonstrated the absence of melano¬ ma. Postoperatively, the patient's visual acuity was 20/20 in the right eye, with normal extraocular motility and 2 mm of right enophthalmos. The patient delivered a healthy girl 5 months after the initial sur¬ gery. There was no evidence of recurrence or metastasis after a 2-year follow-up.
spindle-cell melanoma.
Light Microscopic Findings The main tumor was composed of densely cells surrounding vascular spaces and clefts containing degenerating tumor cells and hemosiderin-laden microphages. A fibrous capsule incompletely en¬ veloped the tumor (Fig 6). Individual tumor cells displayed mild pleomorphism with elongated nuclei and inconspicuous but cen¬ trally placed nucleoli (Fig 7). The cytoplasm was weakly eosinophilic and occasionally
packed spindle
contained fine granular brown pigment. The pigmented material within the spindle cells reacted strongly with the FontanaMasson stain. Clusters of heavily pig¬ mented melanophages were scattered throughout the tumor. Mitotic figures were rarely identified. Areas of fibrinoid necrosis were present and individual cell death was observed within cystic spaces. The clinically observed pigmented areas remote from the main tumor were com¬ posed of heavily pigmented dendritic mela¬ nocytes. They were interspersed within fibroadipose connective tissue rather than forming a discrete mass. These lesions were diagnosed as blue nevi. A nerve within the main tumor demonstrated identical pig¬ mented dendritic cells infiltrating the peri¬ neural sheath (Fig 8). The three biopsy specimens obtained on reexploration of the orbit demonstrated two blue nevi and a cellular blue nevus. The cellular blue nevus showed a biphasic pat¬ tern with small, nonpigmented, spindle cells and pigmented dendritic melanocytes
(Fig 9).
Electron Microscopic
Tumor cells
were
ally separated by
Findings
closely packed a
but usu¬ discrete intercellular
space (Fig 10). Blunt-cell processes were noted to intercalate between polygonal cell bodies. No intercellular adaptations in the form of gap junctions or desmosome attach¬ ments were identified. No external laminae were seen investing individual cells. Tumor cells had irregularly shaped oval to elon¬ gated nuclei with peripherally clumped heterochromatin and occasionally with irregu¬ larly shaped nucleoli. The cytoplasm contained melanosomes in various stages of maturation, ranging from stage II to fully mçlanized stage IV (Fig 11). Occasional melanosomes exhibited irregular shapes and granular pigmentation. Mitochondria were slightly enlarged and demonstrated some disruption of the cristae. Rough, endoplasmic reticulum was present, but not abundant.
COMMENT
Primary orbital melanomas account for less than 1% of primary orbital neoplasms.212 Of 30 documented cases, 23 (77%) presented in adults and 7 (23%) developed in children or adoles¬ cents.1,3"11,13"27 Painless proptosis from a diffuse orbital mass is the most com¬ mon presentation. The duration of
Fig 1 .—Clinical photograph demonstrating proptosis and upward displacement of the right eye.
Figs 2 and 3.—Computed tomography infratemporally in the right orbit.
of orbits. Axial
(Fig 2)
and coronal
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/17/2015
(Fig 3)
symptoms is variable, with
progressing slowly during
some
several
others present rapidly months.6,7,1 16 They occur
years,3"5,17 while during
1 to 3
without sexual predilection and are found mainly in whites (only two cases have been reported in blacks to our
knowledge8,13). In
our
case, the circumscribed ap¬
scan suggested an encapsulated tumor, such as cavernous hemangioma, schwannoma, or fibrous histiocytoma. Operative findings, which were unusual for these diag¬ noses, included the discovery of focal pigmented lesions along the periorbita,
pearance
a
on
CT
bluish-black appearance of the main
tumor, and fixation along the orbital
floor. Of the 30 documented primary orbital melanomas, only 4 were encap¬ sulated and treatable by primary re¬ section.3,4,7,19 The degree of encapsula¬ tion did not correlate with the histologie cell types: epithelioid cell types were found in encapsulated tu¬ mors, and spindle-cell types were dem¬ onstrated in diffuse tumors. One feature that may aid the clini¬ cian in suspecting a primary orbital melanoma is its frequent association with pigmentary disorders. Associated ocular, cutaneous, or orbital pigmen¬ tary lesions were present in 12 (40%) of 30 primary orbital melanomas.1,3"11 These 12 pigmentary disorders in¬ cluded oculodermal melanocytosis (6 cases),3"6,9 blue nevi (4 cases),1,7'1" and ocular melanocytosis (2 cases)8,11 (Ta¬ ble). They represent arrested migra¬ tion of melanocytes with variable pig¬ mentation of the skin, eye, or orbit. In oculodermal melanocytosis, pigmenta¬ tion within the orbit has been reported along extraocular muscles, orbital fat, periorbita, and orbital bones.34 In most orbital melanomas associated with pig¬ mentary disorders, the ocular or cuta¬ neous pigmentation was visible preop-
scans show
circumscribed
mass
eratively. Our case is unique since the associated pigmentation was detected only intraorbitally at the time of surgery. The melanocytic lesions within the orbit were clinically and histologically separable as blue nevi, cellular blue nevus, and malignant melanoma. Clini¬ cally, the blue nevi were brownish-
Fig 4. —Focal the periorbita.
pigmented
lesions
(arrow)
on
Fig 5.—Surgical specimen demonstrates
thin capsule.
a
black, irregular lesions distributed along the periorbita (Fig 4), and the cellular blue nevus was a small, bluishblack, circumscribed lesion adherent to the orbital floor. Histologically, the blue nevi were composed of dendritic melanocytes interspersed within fi¬ brous tissue, whereas the cellular blue nevus
demonstrated
a
discrete nodule
Fig 6.—Spindle-cell neoplasm contains heavily pigmented areas, a cleavage planes, and irregular spaces (hematoxylineosin, original magnification 40).
Fig 7.—Tumor cells contain moderately pleomorphic, oval, vesicular nuclei with distinct, centrally placed nucleoli (hematoxylin-eosin, origi¬ nal magnification x400).
Fig 8. —A perineural focus (arrow) of pigmented dendritic melanocytes found within the melanoma (hematoxylin-eosin, original magnification
Fig 9.—Cellular blue nevus demonstrates biphasic pattern with pig¬ mented (arrow) and nonpigmented (arrow in black circle) melanocytes
fibrous capsule,
x100).
(hematoxylin-eosin, original magnification 40).
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Fig 10.—Closely packed tumor cells display irregular nuclear outlines, coarsely clumped chromatin, and prominent nucleoli (original magnifi¬ cation X2400).
Fig 11.—Melanosomes (original magnification
Pigmentary Disorders Associated With Primary Orbital Melanomas Type of Nevus Within
Associated
Pigmentary Source, y al,3
Dutton et 1984
Cell type Spindle
the Tumor Cellular blue
Disorder
Oculodermal
melanocytosis None
Oculodermal
melanocytosis Hagler and Brown,5 1966 Haim et al,'
melanocytosis Oculodermal
Cellular blue and blue
Spindle
None
Epithel ¡oid
Cellular blue
Spindle
Blue
Epithelioid
melanocytosis
1982
Speakman and
Phillips,9
Jay,"
Oculodermal
1973
Oculodermal
melanocytosis Oculodermal
1965
melanocytosis
Jakobiec et al,' 1974
Cutaneous blue
nevus
Cellular blue
Epithelioid
Loftier and
Cutaneous blue
nevus
Cellular blue
Mixed
Cutaneous blue Cutaneous blue Ocular
nevus
Cellular blue Cellular blue Cellular blue
Spindle Spindle Epithelioid
Blue
Epithelioid
Witsche!,'0 Shields' Wilkes et 1984
al,e
Verdaguer,' 1965
1989 nevus
melanocytosis Ocular
melanocytosis
of closely packed spindle cells without intervening stroma. The melanoma was a larger, bluish-black, encapsu¬ lated mass, separable from surround¬ ing orbital structures. The histologie features of malignancy included pleomorphism, enlargement of nuclei, ne¬ crosis, and the presence of mitotic figures. Malignant transformation of a preexisting nevus is postulated since perineural foci of dendritic pigmented melanocytes were seen within the
melanoma. Ten primary melanocytic tumors had a blue nevus or a cellular blue demonstrated histologically nevus within the tumor.1,3'"" One was re¬ ported as a malignant cellular blue nevus" and nine were described as ma-
lignant melanomas arising from nevi. Histologie cell types included epitheli¬
oid (4 cases), spindle (5 cases), and spindle and epithelioid (1 case). Only one
tumor was
encapsulated and treat¬
by primary resection.3 In two patients who died of metastatic dis¬ able
ease,
one
demonstrated
an
epithelioid-
cell tumor4 and the other a spindle-cell lesion.9 Although the number of cases is too small for statistical analysis, the prognosis of tumors associated with nevi appears similar to melanomas without associated nevi. On electron microscopy, the pres¬ ence of melanosomes and the absence of basal laminae or mesaxons support¬ ed the diagnosis of melanoma rather than melanotic schwannoma or cellular
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/17/2015
are
12
present
in various
stages of maturation
000).
blue nevus. Ultrastructural character¬ istics of melanosomes may be helpful in distinguishing benign blue nevi from melanoma.28 Blue nevi contain numer¬ ous melanin granules (stage IV mela¬ nosomes), whereas melanomas have poorly developed melanosomes with ir¬ regular shapes and disordered internal structures.28 Desmosomelike struc¬ tures have been reported in primary orbital melanomas but were not dem¬ onstrated in our case.'"1 The development of melanoma dur¬ ing pregnancy suggests a possible hor¬ monal influence. While melanomas are not generally regarded as hormonedependent neoplasms, circumstantial evidence suggests that endocrine hor¬ mones may influence their biologic be¬ havior. Exacerbation of cutaneous melanomas,29 development of choroidal melanomas,3031 and accelerated growth of nevi have been reported in pregnan¬ cy. Of 14 primary orbital melanomas reported in female patients, 3 were in childbearing age and were not associ¬ ated with pregnancy. In cutaneous melanomas associated with pregnancy, only patients with metastatic disease had a poorer prognosis.32 Another consideration related to pregnancy is the potential spread of melanoma to the fetus. Since our patient's child is 2 years of age and shows no evidence of melanoma, the development of ma¬ lignancy is unlikely. Most cases of ma¬ ternal melanoma with metastasis to the fetus develop in mothers with widespread disease.33 All infants with melanoma from transplacental metas¬ tasis have developed the disease by 8 months of age.3" The clinical course of primary orbital melanomas is difficult to predict due to tumor rarity and the lack of long-term follow-up. Only two patients have16,lshad In a follow-up of more than 2 years. 30 cases, treatment has included
exenteration (17 cases), excision alone (9 cases), exenteration plus radiation (1 case), and unreported treatment (3 cases). Primary resection, rather than aggressive surgery or adjuvant thera¬ py, is probably sufficient for encapsu¬ lated tumors. Henderson and Farrow1* reported the primary resection of an encapsulated tumor with an epithelioid
histologie cell type.
There has been no metastasis after a 32year follow-up (oral communication with J. W. Henderson, MD, November 1988). Although the follow-up period in our case was short (2 years), the ab¬ sence of recurrence or metastasis sup¬ ports an initial conservative approach. The best treatment for diffuse lesions recurrence or
may be adjuvant therapy since aggres¬ sive surgery is unlikely to reduce the risk of future metastasis.9 Surgical re¬ section may be necessary in large or painful tumors. Adjuvant therapy (ra¬ diation therapy and chemotherapy) should be considered in incompletely excised, recurrent, or metastatic tumors.
References 1. Shields JA. Primary melanocytic tumors. In: Diagnosis and Management of Orbital Tumors. Philadelphia, Pa: WB Saunders Co; 1989:275-289. 2. Reese AB. Orbital neoplasms. In: Tumors of the Eye. 3rd ed. New York, NY: Harper & Row
Publishers Inc; 1976:189,438. 3. Dutton JJ, Anderson RL, Schelper RL, Purcell JJ, Tse DT. Orbital malignant melanoma and oculodermal melanocytosis: report of two new cases and review of the literature. Ophthalmology.
1984;91:497-507. 4.
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Jay B. Malignant melanoma of the orbit in a of oculodermal melanosis. Br J Ophthalmol.
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une
forme
clinique
rare
de
tumeur de l'orbite: la forme 'oculaire' des tumeurs
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S, DePascalis F, Patacchini E. Primary malignant melanoma of the orbit A- and B-scan echographic characteristics.
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Egypt. 1969;62:321-328. 28. Ghadially FN. Blue naevus. In: Diagnostic Electron Microscopy of Tumours. 2nd ed. Stoneham, Mass: Butterworths; 1985:401-403. 29. Ariel IM. Theories regarding the etiology of malignant melanoma. In: Malignant Melanoma. New East Norwalk, Conn: Appleton & Lange; 1981:19-20. 30. Frenkel M, Klein HZ. Malignant melanoma of the choroid in pregnancy. Am J Ophthalmol.
1966;62:910-913. 31. Seddon JM, Maclaughlin DT, Albert DM, Gragoudas ES, Ference M. Uveal melanomas presenting during pregnancy and the investigation of oestrogen receptors in melanomas. Br J Ophthalmol. 1982;66:695-704. 32. Shiu MH, Schottenfeld D, Maclean B. Adverse
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Soc
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