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Melanocytic Nevi of the Palpebral Conjunctiva
Melanocytic Nevi of the Palpebral Conjunctiva An Extremely Rare Location Usually Signifying Melanoma GILA BUCKMAN, MD,t FREDERICK A. JAKOBIEC, MD,t ROBERT FOLBERG, MD,2 LOIS M. McNALLY, MDt
Abstract: Nevi of the conjunctiva generally develop during the first 2 decades of life, and are almost entirely restricted ot the epibulbar surface, the plica, the caruncle, and the lid margin. Therefore, any elevated pigmented lesion of the forniceal or tarsal conjunctiva acquired later in life must be regarded with suspicion as a melanoma or melanoma precursor, and a biopsy should be done routinely. This report is, to the best of the authors' knowledge, the first histopathologic documentation of nevi located in the palpebral conjunctiva. One nevus was acquired and the other was probably congenital. [Key words: conjunctiva, melanoma, nevus, palpebral conjunctiva, tarsus.] Ophthalmology
95: 1053-1 057, 1988
Encountering a partially pigmented conjunctival mass acquired later in life should immediately lead to the suspicion of a malignant melanoma, because most conjunctival nevi make their appearance in the first 2 decades of life. Furthermore, any thickened, pigmented lesion of the tarsal or fomiceal conjunctiva should be immediately excised, since a histopathologically documented case of a benign melanocytic nevus has never been reported in these sites, and the overwhelming majority of elevated pigmented nodules in these areas are malignant melanomas. We report two exceptional cases of benign palpebral nevi: one congenital and the other probably arising in adult life. Besides the unusuallocation of these lesions, the fact that both had pigmentary Originally received: November 23, 1987. Revision accepted: March 7, 1988. Departments of Ophthalmology and Pathology, Manhattan Eye, Ear & Throat Hospital, New York. 2 Departments of Ophthalmology and Pathology, University of Iowa Hospitals and Clinics, Iowa City.
1
Supported in part by a grant from the Zelda Radow Weintraub Foundation, Inc, New York, New York. Reprint requests to Frederick A. Jakobiec, MD, Manhattan Eye, Ear & Throat Hospital, 210 East 64th St, New York, NY 10021.
changes raised the possibility of malignant melanoma. Excisional biopsy, however, demonstrated in both cases the features of a benign nevus with scattered melanophages that may have been partly responsible for some of the pigmentary alterations detected clinically.
CASE REPORTS Case 1. A 60-year-old white man was referred for evaluation of an asymptomatic pigmented lesion of the palpebral conjunctiva of the right lower eyelid. The lesion had not been noted on previous ophthalmic examinations and was believed to be of recent onset. The patient denied a history of foreign body, injury, or neoplastic disease, and was unaware of the presence of the lesion. Best-corrected visual acuity was 20/20 in both eyes. Results of ocular examination were remarkable for a darkly pigmented 8 X 4-mm placoid lesion located in the inferomedial palpebral conjunctiva (Fig I). Results of slitlamp biomicroscopy showed the lesion to be minimally elevated with finely peppered pigmentation overlying its surface (Fig 2). In view of the suspicious location of the lesion, an excisional biopsy was done. Results of histopathologic examination showed a lesion consisting of well-circumscribed nests of bland nevus cells beneath the conjunctival epithelium in the substantia propria (Fig 3). The benign cytologic nature of these cuboidal nevus cells was indicated by their low nuclear:cytoplasmic ratio, the
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Fig 1. Case I. Top left. pigmented placoid lesion in the inferomedial tarsal conjunctiva. Fig 2. Top right. biomicroscopic photograph demonstrating moderate thickening of lesion with finely peppered surface pigmentation. Fig 3. Center left. nests of nevus cells in the substantia propria of conjunctiva. Cystic changes are the result of invaginations of surface epithelium (hematoxylin-eosin; original magnification, X40). Fig 4. Center right. high-power view demonstrating typical cytologic features of nevus cells, including low nuclear:cytoplasmic ratio, intranuclear vacuoles, and focal melanin production. Mitotic figures are notably absent (hematoxylin-eosin; original magnification, X220). Fig S. Bottom. nevus cells in deepest area of substantia propria, showing epithelial inclusion cysts and maturation into smalllymphocytoid cells (hematoxylin-eosin; original magnification, X80).
absence of both nucleoli and mitotic figures, and the frequent presence of intranuclear vacuoles (Fig 4). The deeper nevus cells focally appeared lymphocytoid (Fig 5). There was spotty junctional activity composed of small nests. Melanophages were present at all levels of the lesion. Invaginations of the surface conjunctival epithelium into the underlying connective tissue were seen. These findings were consistent with the diagnosis of a benign conjunctiVal nevus. Case 2. A 49-year-old white man was found on routine ophthalmologic examination to harbor a partially pigmented thickened lesion of the palpebral conjunctiva of the left lower eyelid. Visual acuity was 20/20 in both eyes, and results of anterior segment and fundus examinations were normal in
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both eyes. Because of the unusual location of the lesion, an excisional wedge resection of the eyelid was performed. Microscopically, the specimen consisted of a full-thickness eyelid resection with numerous nests of benign ovoid and spindled nevus cells (Fig 6). The nevus cells were seen in the subepithelial layer of the tarsal conjunctiva (Fig 7), infiltrating the tarsus (Figs 8, 9), interdigitating between bundles of orbicularis skeletal muscle fibers, and enveloping the shafts of the cilia (Fig 10). The nevus cells formed nests, had a benign appearance with small nuclei, indistinct nucleoli, a low nuclear:cytoplasmic ratio, and many intranuclear cytoplasmic invaginations. Occasional cells had large nuclei (Fig I I), and some collections of the nevus cells displayed a lymphocytoid
Fig 6. Case 2. Top left. full-thickness lid resection ofa pigmented lesion of the left lower lid. Notice that pigmented cells have extended through the tarsus to the orbicularis muscle and abut a cilium on the cutaneous aspect toward the right (hematoxylin-eosin; original magnification, X4). Fig 7. Top right. a portion of the tarsal conjunctiva shows nests of bland melanocytes along with scattered melanophages in the superficial tarsal connective tissues (hematoxylin-eosin; original magnification, XSO). Fig 8. Center left. a few superficial pseudoglandular invaginations of the surface epithelium are present on the top, but there is no conspicuous cyst formation within this lesion. Notice the permeation of nevus cells among the meibomian gland units in the tarsus (hematoxylin-eosin; original magnification, X60). Fig 9. Center right. smalllymphocytoid nevus cells envelop portions of the meibomian gland (hematoxylin-eosin; original magnification, X 160). Fig 10. Bottom left. nevus cells and scattered melanophages dissect among elements of the orbicularis muscle. A cilium is shown below (hematoxylin-eosin; original magnification, X60). Fig 11. Bottom right. occasional nevus cells are larger than the others, and many have intranuclear vacuoles of herniated cytoplasm. The heavily pigmented cells are melanophages (hematoxylin-eosin; original magnification, x220).
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character (Fig 9). The deeply pigmented cells primarily appeared to be melanophages (Fig 7), some of them present in the walls of shallow epithelial invaginations. Minimal junctional activity was present, which did not extend beyond the main body of the lesion in the substantia propria. There were no deep epithelial inclusion cysts. The microscopic findings were suggestive of a congenital nevus, in view of the penetration of the nevus cells into the tarsus and orbicularis muscle and the absence of epithelial inclusion cysts.
DISCUSSION Although much attention is directed today toward the accurate and early diagnosis of conjunctival melanomas and their precursors, the nature and behavior of benign conjunctival nevi have yet to be fully understood. Sometimes embryonic in origin, conjunctival epithelial nevi almost always appear within the first 2 decades of life. I Approximately 70% of conjunctival nevi are pigmented; 30% are not. 2 Topographically, they display an affinity for the interpalpebral zone, occurring anywhere from the limbus across the epibulbar surface to the caruncle and plica; the lid margin may also be involved. As a rule, any pigmented lesions located in the fornices or palebral conjunctiva are regarded as melanomas or melanoma precursors until proven otherwise. 3 Histopathologically, the cells comprising conjunctival nevi are rounded or cuboidal. These cells appear smaller and more lymphocytoid in the deeper connective tissues of the substantia propria. With time, conjunctival nevi acquire thickness as junctional activity progresses to the formation of a compound nevus, during which phase initial intraepithelial nevus cells drop into the underlying substantia propria to form nests. A highly characteristic feature of conjunctival nevi is the formation of epithelial inclusion cysts, 4 which may occasionally contain mucus-secreting goblet cells in their walls. Such epithelial inclusion cysts are derived from the conjunctival epithelium. Pigmentation is variable because nevus cells are less efficient at manufacturing melanin than are intraepithelial dendritic melanocytes. 3 Pigmentation is also not present in the deepest nevus cells because they lose their tyrosinase activity, the enzyme essential for the production of melanin. Indeed, observing cytoplasmic melanin granules in the deepest cells of a conjunctival nevus should lead to the suspicion of a melanoma, 5 unless the patient is black or dark complexioned. The frequent association of nevi with diffuse atypical melanocytic hyperplasia and/or malignant melanoma is becoming increasingly apparent. 6 Primary acquired conjunctival melanosis is characterized by intraepithelial proliferative activity of melanocytes. Predominantly seen in white patients, it is unilateral and develops in the middle-aged and elderly. The pigmentation is not restricted to the interpalpebral area but may begin anywhere, and spreads in an irregular and sometimes insidious manner. At the more worrisome end of the spectrum, cytologic atypia is seen, leaving little doubt that one is dealing with a formal precursor of malignant melanoma. 3,7-1O 1056
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Conjunctival melanomas often develop from a radial intraepithelial growth phase, and elevated nodules are a manifestation of the vertical growth phase. II ,12 Alternatively, malignant transformation of an intraepithelial melanocyte may eventuate in a vertical growth phase early on without a radial growth phase-so-called nodular melanoma. Approximately 75% of conjunctival melanomas develop from acquired melanosis, and 25% arise de novo. An associated nevus is found in approximately 30% of melanomas, supporting the contention that this is more than just a chance occurrence.I,1O The neoplastic clone in these cases usually develops from persistently active junctional cells, rather than from the subepithelial nevus cells which are typically mitotically dormant. De novo melanomas and acquired melanosis without a pre-existent nevus are thought to arise from the neoplastic transformation of scattered dendritic melanocytes that normally reside in the conjunctival epithelium. 13 The conjunctival nevi in this report are remarkable for their unique location and their late detection. Jayl4 and Duke-Elder and Leigh, 15 in their respective series of conjunctival nevi, both observed that their usual location is at the limbus or on the bulbar conjunctiva, but it was not until Jakobiec 3 emphasized the extreme rarity of nevi in the forniceal and palpebral conjunctiva that the importance of their location was recognized. We previously have not seen a nevus of the palpebral conjunctiva and, to our knowledge, these two cases are the first histopathologically documented nevi at this site. In the first case, the suspicion of a melanoma or intraepithelial melanocytic hyperplasia was initially raised because of the dispersed pigmentation associated with the lesion. In retrospect, it was the uniformity of the distribution of the pigmentation which actually correlates with the benign nature of the lesion. It is probable that both nevi were present from early childhood, and escaped detection by the patients and their physicians because of their location in the palpebral conjunctiva. The progressive shift of pigment from melanocytes to macrophages could have altered the pigmentation of the lesions and brought them to clinical attention. We believe that the first case represents an acquired nevus with typical conjunctival epithelial inclusion cysts. The second case probably represents a congenital nevus, in view of the extensive penetration of the cells into the tarsus and among the orbicularis muscle fibers, and the absence of epithelial inclusion cystS. 16- 18
REFERENCES 1. Zimmerman LE. The histogenesis of conjunctival melanomas. The first Algenon B. Reese lecture. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 600-30. 2. Henkind P, Friedman AH. External ocular pigmentation. Int Ophthalmol Clin 1972; 11 :(3)87-111. 3. Jakobiec FA. The ultrastructure of conjunctival melanocytic tumors. Trans Am Ophthalmol Soc 1984; 82:599-752. 4. Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983; 90:1459-61.
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5. Jakobiec FA, Zuckerman B, Berlin J, et al. Unusual melanocytic nevi of the conjunctiva. Am J Ophthalmol1985; 100:100-13. 6. Spencer WH, Zimmerman LE. Conjunctiva. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook, 3rd ed. Vol. 1. Philadelphia: WB Saunders, 1985; 215. 7. Sagebiel R. Histopathology of borderline and early malignant melanomas. Am J Surg Patho11979; 3:5 43-52. 8. Ackerman AB, Su W. The histology of cutaneous malignant melanoma. In: Knopf A, Bart R, Rodriguez-Sains R, et ai, eds. Malignant Melanomas. New York : Masson, 1979; 25-147. 9. Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum PathoI1985; 16:129-35. 10. Folberg R, McLean IW, Zimmerman L. Malignant melanoma of the conjunctiva. Hum Patho11985; 16:136-43. 11 . Henkind P. Conjunctival melanocytic lesions: natural history. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 572-82.
MELANOCYTIC NEVI
12. Bernardino VG Jr, Naidoff MA, Clark WH Jr. Malignant melanomas of the conjunctiva. Am J Ophthalmol1976; 82:383-94. 13. Jakobiec FA. Conjunctival melanoma: unfinished business [Letter) Arch Ophthalmol 1980; 98:1378- 84. 14. Jay B. Naevi and melanomata on the conjunctiva. Br J Ophthalmol 1965; 49:169-204. 15. Duke,Elder S, ed. System of Ophthalmology. Vol. 8: Diseases of the Outer Eye; Part 2: Cornea and Sclera. St Louis: CV Mosby, 1965; 1210-9. 16. Mark GJ, Mihm MC, Liteplo MG, et aI. Congenital melanocytic nevi of the small and garment type. Clinical, histologic, and ultrastructural studies. Hum Patho11973; 4:3 95-418. 17. Lever WF, Schaumburg-Lever G. Histopathology of the Skin, 6th ed. Philadelphia: JB Lippincott, 1983; 693-4. 18. Margo CE, Habal MB. Large congenital melanocytic nevus: light and electron microscopic findings. Ophthalmology 1987; 94:960- 5.
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Abstract: Nevi of the conjunctiva generally develop during the first 2 decades of life, and are almost entirely restricted ot the epibulbar surface, the plica, the caruncle, and the lid margin. Therefore, any elevated pigmented lesion of the forniceal or tarsal conjunctiva acquired later in life must be regarded with suspicion as a melanoma or melanoma precursor, and a biopsy should be done routinely. This report is, to the best of the authors' knowledge, the first histopathologic documentation of nevi located in the palpebral conjunctiva. One nevus was acquired and the other was probably congenital. [Key words: conjunctiva, melanoma, nevus, palpebral conjunctiva, tarsus.] Ophthalmology
95: 1053-1 057, 1988
Encountering a partially pigmented conjunctival mass acquired later in life should immediately lead to the suspicion of a malignant melanoma, because most conjunctival nevi make their appearance in the first 2 decades of life. Furthermore, any thickened, pigmented lesion of the tarsal or fomiceal conjunctiva should be immediately excised, since a histopathologically documented case of a benign melanocytic nevus has never been reported in these sites, and the overwhelming majority of elevated pigmented nodules in these areas are malignant melanomas. We report two exceptional cases of benign palpebral nevi: one congenital and the other probably arising in adult life. Besides the unusuallocation of these lesions, the fact that both had pigmentary Originally received: November 23, 1987. Revision accepted: March 7, 1988. Departments of Ophthalmology and Pathology, Manhattan Eye, Ear & Throat Hospital, New York. 2 Departments of Ophthalmology and Pathology, University of Iowa Hospitals and Clinics, Iowa City.
1
Supported in part by a grant from the Zelda Radow Weintraub Foundation, Inc, New York, New York. Reprint requests to Frederick A. Jakobiec, MD, Manhattan Eye, Ear & Throat Hospital, 210 East 64th St, New York, NY 10021.
changes raised the possibility of malignant melanoma. Excisional biopsy, however, demonstrated in both cases the features of a benign nevus with scattered melanophages that may have been partly responsible for some of the pigmentary alterations detected clinically.
CASE REPORTS Case 1. A 60-year-old white man was referred for evaluation of an asymptomatic pigmented lesion of the palpebral conjunctiva of the right lower eyelid. The lesion had not been noted on previous ophthalmic examinations and was believed to be of recent onset. The patient denied a history of foreign body, injury, or neoplastic disease, and was unaware of the presence of the lesion. Best-corrected visual acuity was 20/20 in both eyes. Results of ocular examination were remarkable for a darkly pigmented 8 X 4-mm placoid lesion located in the inferomedial palpebral conjunctiva (Fig I). Results of slitlamp biomicroscopy showed the lesion to be minimally elevated with finely peppered pigmentation overlying its surface (Fig 2). In view of the suspicious location of the lesion, an excisional biopsy was done. Results of histopathologic examination showed a lesion consisting of well-circumscribed nests of bland nevus cells beneath the conjunctival epithelium in the substantia propria (Fig 3). The benign cytologic nature of these cuboidal nevus cells was indicated by their low nuclear:cytoplasmic ratio, the
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Fig 1. Case I. Top left. pigmented placoid lesion in the inferomedial tarsal conjunctiva. Fig 2. Top right. biomicroscopic photograph demonstrating moderate thickening of lesion with finely peppered surface pigmentation. Fig 3. Center left. nests of nevus cells in the substantia propria of conjunctiva. Cystic changes are the result of invaginations of surface epithelium (hematoxylin-eosin; original magnification, X40). Fig 4. Center right. high-power view demonstrating typical cytologic features of nevus cells, including low nuclear:cytoplasmic ratio, intranuclear vacuoles, and focal melanin production. Mitotic figures are notably absent (hematoxylin-eosin; original magnification, X220). Fig S. Bottom. nevus cells in deepest area of substantia propria, showing epithelial inclusion cysts and maturation into smalllymphocytoid cells (hematoxylin-eosin; original magnification, X80).
absence of both nucleoli and mitotic figures, and the frequent presence of intranuclear vacuoles (Fig 4). The deeper nevus cells focally appeared lymphocytoid (Fig 5). There was spotty junctional activity composed of small nests. Melanophages were present at all levels of the lesion. Invaginations of the surface conjunctival epithelium into the underlying connective tissue were seen. These findings were consistent with the diagnosis of a benign conjunctiVal nevus. Case 2. A 49-year-old white man was found on routine ophthalmologic examination to harbor a partially pigmented thickened lesion of the palpebral conjunctiva of the left lower eyelid. Visual acuity was 20/20 in both eyes, and results of anterior segment and fundus examinations were normal in
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both eyes. Because of the unusual location of the lesion, an excisional wedge resection of the eyelid was performed. Microscopically, the specimen consisted of a full-thickness eyelid resection with numerous nests of benign ovoid and spindled nevus cells (Fig 6). The nevus cells were seen in the subepithelial layer of the tarsal conjunctiva (Fig 7), infiltrating the tarsus (Figs 8, 9), interdigitating between bundles of orbicularis skeletal muscle fibers, and enveloping the shafts of the cilia (Fig 10). The nevus cells formed nests, had a benign appearance with small nuclei, indistinct nucleoli, a low nuclear:cytoplasmic ratio, and many intranuclear cytoplasmic invaginations. Occasional cells had large nuclei (Fig I I), and some collections of the nevus cells displayed a lymphocytoid
Fig 6. Case 2. Top left. full-thickness lid resection ofa pigmented lesion of the left lower lid. Notice that pigmented cells have extended through the tarsus to the orbicularis muscle and abut a cilium on the cutaneous aspect toward the right (hematoxylin-eosin; original magnification, X4). Fig 7. Top right. a portion of the tarsal conjunctiva shows nests of bland melanocytes along with scattered melanophages in the superficial tarsal connective tissues (hematoxylin-eosin; original magnification, XSO). Fig 8. Center left. a few superficial pseudoglandular invaginations of the surface epithelium are present on the top, but there is no conspicuous cyst formation within this lesion. Notice the permeation of nevus cells among the meibomian gland units in the tarsus (hematoxylin-eosin; original magnification, X60). Fig 9. Center right. smalllymphocytoid nevus cells envelop portions of the meibomian gland (hematoxylin-eosin; original magnification, X 160). Fig 10. Bottom left. nevus cells and scattered melanophages dissect among elements of the orbicularis muscle. A cilium is shown below (hematoxylin-eosin; original magnification, X60). Fig 11. Bottom right. occasional nevus cells are larger than the others, and many have intranuclear vacuoles of herniated cytoplasm. The heavily pigmented cells are melanophages (hematoxylin-eosin; original magnification, x220).
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character (Fig 9). The deeply pigmented cells primarily appeared to be melanophages (Fig 7), some of them present in the walls of shallow epithelial invaginations. Minimal junctional activity was present, which did not extend beyond the main body of the lesion in the substantia propria. There were no deep epithelial inclusion cysts. The microscopic findings were suggestive of a congenital nevus, in view of the penetration of the nevus cells into the tarsus and orbicularis muscle and the absence of epithelial inclusion cysts.
DISCUSSION Although much attention is directed today toward the accurate and early diagnosis of conjunctival melanomas and their precursors, the nature and behavior of benign conjunctival nevi have yet to be fully understood. Sometimes embryonic in origin, conjunctival epithelial nevi almost always appear within the first 2 decades of life. I Approximately 70% of conjunctival nevi are pigmented; 30% are not. 2 Topographically, they display an affinity for the interpalpebral zone, occurring anywhere from the limbus across the epibulbar surface to the caruncle and plica; the lid margin may also be involved. As a rule, any pigmented lesions located in the fornices or palebral conjunctiva are regarded as melanomas or melanoma precursors until proven otherwise. 3 Histopathologically, the cells comprising conjunctival nevi are rounded or cuboidal. These cells appear smaller and more lymphocytoid in the deeper connective tissues of the substantia propria. With time, conjunctival nevi acquire thickness as junctional activity progresses to the formation of a compound nevus, during which phase initial intraepithelial nevus cells drop into the underlying substantia propria to form nests. A highly characteristic feature of conjunctival nevi is the formation of epithelial inclusion cysts, 4 which may occasionally contain mucus-secreting goblet cells in their walls. Such epithelial inclusion cysts are derived from the conjunctival epithelium. Pigmentation is variable because nevus cells are less efficient at manufacturing melanin than are intraepithelial dendritic melanocytes. 3 Pigmentation is also not present in the deepest nevus cells because they lose their tyrosinase activity, the enzyme essential for the production of melanin. Indeed, observing cytoplasmic melanin granules in the deepest cells of a conjunctival nevus should lead to the suspicion of a melanoma, 5 unless the patient is black or dark complexioned. The frequent association of nevi with diffuse atypical melanocytic hyperplasia and/or malignant melanoma is becoming increasingly apparent. 6 Primary acquired conjunctival melanosis is characterized by intraepithelial proliferative activity of melanocytes. Predominantly seen in white patients, it is unilateral and develops in the middle-aged and elderly. The pigmentation is not restricted to the interpalpebral area but may begin anywhere, and spreads in an irregular and sometimes insidious manner. At the more worrisome end of the spectrum, cytologic atypia is seen, leaving little doubt that one is dealing with a formal precursor of malignant melanoma. 3,7-1O 1056
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Conjunctival melanomas often develop from a radial intraepithelial growth phase, and elevated nodules are a manifestation of the vertical growth phase. II ,12 Alternatively, malignant transformation of an intraepithelial melanocyte may eventuate in a vertical growth phase early on without a radial growth phase-so-called nodular melanoma. Approximately 75% of conjunctival melanomas develop from acquired melanosis, and 25% arise de novo. An associated nevus is found in approximately 30% of melanomas, supporting the contention that this is more than just a chance occurrence.I,1O The neoplastic clone in these cases usually develops from persistently active junctional cells, rather than from the subepithelial nevus cells which are typically mitotically dormant. De novo melanomas and acquired melanosis without a pre-existent nevus are thought to arise from the neoplastic transformation of scattered dendritic melanocytes that normally reside in the conjunctival epithelium. 13 The conjunctival nevi in this report are remarkable for their unique location and their late detection. Jayl4 and Duke-Elder and Leigh, 15 in their respective series of conjunctival nevi, both observed that their usual location is at the limbus or on the bulbar conjunctiva, but it was not until Jakobiec 3 emphasized the extreme rarity of nevi in the forniceal and palpebral conjunctiva that the importance of their location was recognized. We previously have not seen a nevus of the palpebral conjunctiva and, to our knowledge, these two cases are the first histopathologically documented nevi at this site. In the first case, the suspicion of a melanoma or intraepithelial melanocytic hyperplasia was initially raised because of the dispersed pigmentation associated with the lesion. In retrospect, it was the uniformity of the distribution of the pigmentation which actually correlates with the benign nature of the lesion. It is probable that both nevi were present from early childhood, and escaped detection by the patients and their physicians because of their location in the palpebral conjunctiva. The progressive shift of pigment from melanocytes to macrophages could have altered the pigmentation of the lesions and brought them to clinical attention. We believe that the first case represents an acquired nevus with typical conjunctival epithelial inclusion cysts. The second case probably represents a congenital nevus, in view of the extensive penetration of the cells into the tarsus and among the orbicularis muscle fibers, and the absence of epithelial inclusion cystS. 16- 18
REFERENCES 1. Zimmerman LE. The histogenesis of conjunctival melanomas. The first Algenon B. Reese lecture. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 600-30. 2. Henkind P, Friedman AH. External ocular pigmentation. Int Ophthalmol Clin 1972; 11 :(3)87-111. 3. Jakobiec FA. The ultrastructure of conjunctival melanocytic tumors. Trans Am Ophthalmol Soc 1984; 82:599-752. 4. Rosenfeld SI, Smith ME. Benign cystic nevus of the conjunctiva. Ophthalmology 1983; 90:1459-61.
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5. Jakobiec FA, Zuckerman B, Berlin J, et al. Unusual melanocytic nevi of the conjunctiva. Am J Ophthalmol1985; 100:100-13. 6. Spencer WH, Zimmerman LE. Conjunctiva. In: Spencer WH, ed. Ophthalmic Pathology: An Atlas and Textbook, 3rd ed. Vol. 1. Philadelphia: WB Saunders, 1985; 215. 7. Sagebiel R. Histopathology of borderline and early malignant melanomas. Am J Surg Patho11979; 3:5 43-52. 8. Ackerman AB, Su W. The histology of cutaneous malignant melanoma. In: Knopf A, Bart R, Rodriguez-Sains R, et ai, eds. Malignant Melanomas. New York : Masson, 1979; 25-147. 9. Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum PathoI1985; 16:129-35. 10. Folberg R, McLean IW, Zimmerman L. Malignant melanoma of the conjunctiva. Hum Patho11985; 16:136-43. 11 . Henkind P. Conjunctival melanocytic lesions: natural history. In: Jakobiec FA, ed. Ocular and Adnexal Tumors. Birmingham: Aesculapius, 1978; 572-82.
MELANOCYTIC NEVI
12. Bernardino VG Jr, Naidoff MA, Clark WH Jr. Malignant melanomas of the conjunctiva. Am J Ophthalmol1976; 82:383-94. 13. Jakobiec FA. Conjunctival melanoma: unfinished business [Letter) Arch Ophthalmol 1980; 98:1378- 84. 14. Jay B. Naevi and melanomata on the conjunctiva. Br J Ophthalmol 1965; 49:169-204. 15. Duke,Elder S, ed. System of Ophthalmology. Vol. 8: Diseases of the Outer Eye; Part 2: Cornea and Sclera. St Louis: CV Mosby, 1965; 1210-9. 16. Mark GJ, Mihm MC, Liteplo MG, et aI. Congenital melanocytic nevi of the small and garment type. Clinical, histologic, and ultrastructural studies. Hum Patho11973; 4:3 95-418. 17. Lever WF, Schaumburg-Lever G. Histopathology of the Skin, 6th ed. Philadelphia: JB Lippincott, 1983; 693-4. 18. Margo CE, Habal MB. Large congenital melanocytic nevus: light and electron microscopic findings. Ophthalmology 1987; 94:960- 5.
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