British Journal ofOphthalmology, 1992,76, 294-296

Pigmented epithelial tumours of the conjunctiva

Israel Kremer, Judith Sandbank, Dov Weinberger, Aryeh Rotem, Amiram Shapiro

AbstractTwo out of 60 conjunctival epithelial tumoursreviewed between 1973 and 1989 were found tobe pigmented. One tumour was a pigmentedpapilloma and the other a pigmented squa-mous cell carcinoma. The melanin pigmentwas found in epithelial tumour cells as weli asin macrophages, dendritic melanocytes, andLangerhans cells. The distinction between thelatter two types of cells was possible in one ofthe tumours only. Both tumours were foundin dark-skinned white patients without anyevidence of conjunctival acquired melanosis.

Both benign and malignant tumours of thecutaneous surface of the eyelid (for example,basal cell carcinoma, seborrhoeic keratosis, etc),at times become pigmented as a result ofmelaniningestion. '" However pigmented epithelialtumours of the conjunctiva, especially in whitepatients, are rarely encountered."' Thisfinding is attributed mainly to the paucity ofmelanocytes in the epibulbar conjunctiva.We present two cases of pigmented con-

junctival tumours found in dark-skinned whitepatients. These tumours represent 3-33% of allconjunctival tumours examined histologically inthe past 16 years in the Pathology Department ofthe Beilinson Medical Center.

Beilinson MedicalCenter, Petah Tiqva andTel Aviv UniversitySackler School ofMedicine, IsraelDepartment ofOphthalmologyI KremerD WeinbergerA Shapiro

Department ofPathologyJ SandbankA RotemCorrespondence to:Dr I Kremer,Cornea Service,Wills Eye Hospital,9th and Walnut Streets,Philadelphia, PA 19107, USA.Accepted for publication17 October 1991

Materials and methodsAll the conjunctival tumour biopsies performedin the Eye Department at the Beilinson MedicalCenter between the years 1973 and 1989 werereviewed by two pathologists and their haema-toxylin-eosin stained slides were re-examined.These epithelial tumours included those excisedfrom the bulbar, limbal, caruncular, forniceal,and palpebral conjunctiva and were eitherbenign or malignant. When melanin pigmentwas found in the tumour bleached sections wereexamined in order to confirm the true nature ofthe pigment. Additionally immunohistochemi-cally stained slides for S-100 protein werereviewed. Electron microscopic specimens wereexamined in one case only.

ResultsThe breakdown of the total series of 60 con-

Table I Conjunctival epithelial tumours (1973-89)

1 Papilloma 42 (70%)2 In situ SCC 3 (5%)3 Epithelial dysplasia 8 (13-33%)4 SCC 5 (8 33%)5 Pigmented 2 (3*33)

junctival epithelial tumours is presented in Table1. Among these epithelial tumours only two(3-33%) were found to be pigmented. Onetumour was a pigmented squamous papillomaand the other a pigmented squamous cellcarcinoma (SCC). The two cases are presented.

CASE 1A 65-year-old dark-skinned white male pre-sented with a pigmented conjunctival tumour inhis right eye increasing in size over a period of8 months. His visual acuity was 6/6 in botheyes and the intraocular pressure was normal.Slit-lamp examination revealed a dark-browncoloured, cauliflower-like, exophytic conjunc-tival tumour abutting the right limbus (Fig 1).There was no evidence of melanosis in the wholeconjunctival surface. The skin of both eyelidswas completely normal. The tumour was excisedand light microscopy revealed an exophyticconjunctival tumour consisting of epithelial cellswith marked atypia, pleomorphism, large pro-minent nucleoli, and melanin-filled dendriticcells (Fig 2). Many atypical keratinocytes con-tained large amounts of cytoplasmic melanin(Fig 3). According to the electron microscopicexamination melanin was also found in macro-phages as well as in Langerhans cells anddendritic melanocytes. The Langerhans cellswere identified by electron microscopy by thefinding of 'Birbeck' granules in their cytoplasm;they were also found to be S-100 positive as werethe melanocytes.

Additionally many dyskeratotic cells, mitoticfigures, and areas of marked acantholysis werenoted in light microscopy. In several areastumour cells were seen beyond the epithelialbasement membrane. The diagnosis of com-pletely excised conjunctival pigmented SCC wasmade. A 4-year follow-up showed no evidence ofmetastasis.

Figure I A brown coloured cauliflower-like conjunctivaltumour abutting the limbus.

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Pigmented epithelial tumours ofthe conjunctiva

Figure 2 An epithelial tumour consisting ofpleomorphic atypical cells with large nuclei andprominent nucleoli; several melanin-filled dendritic cells are noted (arrows) (haematoxylin andeosin, magnification x270).

Figure 3 Melanin pigment is noted within keratinocytes (arrow), macrophages, and dendriticcells (arrowhead), present among the epithelial tumour cells (haematoxylin and eosin,magnification x270).

Figure 5 Giant dendritic cellsfilled with melanin pigment (arrow) are seen among the tumourepithelial cells in which no melanin is found (haematoxylin and eosin, magnification x 270).

Figure 4 A dark-brown coloured caulifiower-likepedunculated conjunctival tumour protrudingfrom the inferiorfornix.

CASE 2A 22-year-old dark-skinned white male noticed adark-coloured mass in the inferior fornix of hisright eye increasing rapidly in size over the past 4months.

In addition his visual acuity was 6/6 and theintraocular pressure was normal in both eyes.The slit-lamp examination of the right eye re-vealed a cauliflower-like, darkly pigmented,pedunculated tumour protruding from the con-junctiva of the inferior fornix (Fig 4). There wasno evidence of melanosis in the whole conjunc-tival surface. The skin of both eyelids wascompletely normal. The anterior and posteriorsegments of both eyes were found to be normal.The tumour's pedicle was excised and light

microscopy revealed a conjunctival papillomaconsisting of basaloid non-keratinised squamousepithelial cells. Many melanin-filled dendriticcells, some of them being very large, were notedlying in between the tumour cells (Fig 5). Thesedendritic cells were found to be S-100 positivefollowing immunohistochemical staining (Fig6). However we could not differentiate betweenmelanocytes and Langerhans cells, either byelectron microscopy or by immunohistochemicalstaining for HLA-DR, as the whole tumouraltissue was primarily fixed in formalin.

It should be noted that there were no tumourcells containing melanin pigment. The diagnosisof completely excised pigmented squamouspapilloma of the conjunctiva was made.

DiscussionPigmented tumours of the conjunctivalepithelium are generally a rare finding.'5 Inblacks they are usually associated with racialconjunctival melanosis.73 SCC arising from theocular mucous membrane are well known inman and cattle."7 There are considerable geo-graphical variations in the incidence of SCC ofthe conjunctiva. This tumour appears to be morecommon in African countries than in other partsof the world.57 Most SCC of the conjunctiva andcornea are non-pigmented.57 Duke-Elder8 statesthat surface ulceration of SCC may lead tohaemorrhages which colour the tumour almostblack. This should be differentiated from pig-

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Kremer, Sandbank, Weinberger, Rotem, Shapiro

Figure 6 S-100 positive dendritic cells (arrows) are noted between the epithelial tumour celi(immunoperoxidase stainingfor S-100 protein; magnification x270).

mentation with melanin in a rare variant ofconjunctival SCC which he calls 'melano-carcinoma'.A pigmented variant of SCC was first

described by Noyes,6 but is apparently very rare

especially in white people. Except for its pig-mentation this tumour usually resembles themore common non-pigmented exophytic SCC.From the few cases67 9' that havebeen followedfor a long period it can be concluded that thereis no relationship between the degree of pig-mentation and degree of malignancy.9 10

Usually in pigmented skin tumours, such as

basal cell carcinoma, SCC, and seborrhoeickeratosis, most of the pigment is present withinmelanocytes.4 5I Similar to our observation otherinvestigators'0 have found that the melanin pig-ment, present in pigmented conjunctival SCC, islocated within macrophages, Langerhans cells,and melanocytes in addtion to tumour epithelialcells. According to the latter authors45 '0 themature melanosomes noted in the neoplasticsquamous epithelial cells, without any evidenceof premelanosomes, suggest that the neoplasticepithelial cells obtain melanin granules frommelanocytes in a manner similar to the normalprocess of pigmentation of cutaneous squamous

epithelial cells.Papillomas of the conjunctiva are much more

common tumours compared with SCC.5 Fromthe aetiological point of view they may be eitherof viral nature or neoplastic.8 Histologically bothtypes are usually non-pigmented. We have foundonly two reports in the literature on pigmentedconjunctival papillomas: one by Grom" and theother by Streeten and coauthors.'2 The latterauthors'2 report on three cases of inverted con-

junctival papillomas one of which was partiallypigmented. This lesion was found to containmelanin in many tumour cells and in occasional

melanocytes. In contrast we could hardly findany tumour cells containing melanin pigment inour papilloma case; melanin was mainly foundin either dendritic melanocytes or Langerhanscells, which unfortunately could not be distin-guished from each other. The conclusion drawnfrom our study is that pigmented tumours of theconjunctiva rarely develop in whites, but theyare found in dark-skinned patients but are notassociated with conjunctival melanosis. Thesetumours may cause clinical diagnostic problemsas they can be confused with the more commonpigmented conjunctival lesions such asmalignant melanoma, naevocellular naevus, orprimary acquired melanosis undergoing malig-nant change.We wonder about the association between the

melanocytes, melanin-filled Langerhans cells,and these pigmented epithelial tumours asclinical evidence of melanosis surrounding thetumours was not found. We have no otherexplanation for this association other than thepre-existence of these two types of cells amongthe epithelial cells which are the progenitors ofthe tumour cells. The embryonal origin of thesecells is totally different; Langerhans cells arethought to be of bone marrow origin'6 andmelanocytes of neural crest origin,'7 while con-junctival epithelial cells are of ectodermal origin.The relationship between these two types ofdendritic cells and the epithelial tumour cells isyet to be studied.

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3 Wilson-Jones E. Pigmented nodular hidradenoma. ArchDermatol 1971; 104:117-21.

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5 Lever WF. Histopathology of the skin. 4th ed. Philadelphia:Lippincott, 1967: 486-91, 584-6.

6 Noyes HD. Report of a case of melanotic epithelioma upon thefront of the eye. Extirpation of the tumor and preservation ofthe globe and of sight. Arch Ophthalmol 1879; 8: 145-6.

7 Templeton AC. Tumors of the eye and adnexa in Africans ofUganda. Cancer 1967; 20: 1689-98.

8 Duke-Elder S. Disease of the outer eye and adnexa. In: Duke-Elder S, ed. Textbook of ophthalmology. London: Kimpton,1965: 1159-74.

9 Jauregui HO, Klinworth GK. Pigmented squamous cellcarcinoma of the cornea and conjunctiva. Cancer 1976; 38:778-88.

10 Salisbury JA, Szpak CA, Klintworth GK. Pigmentedsquamous cell carcinoma of the conjunctiva. Ophthalmology1983; 90: 1477-81.

11 Grom E. Epithelioma espinocellular de la conjunctiva ocular.ArchSoc OftalHispano-Am 1950; 10:1155-8.

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13 Adefule AO, Mordi VPN. Squamous cell carcinoma of thelimbal conjunctiva with corneal involvement and racialmelanosis in an adult Nigerian female. Am J Ophthalmol1983; 96:106-7.

14 Campbell RJ. Tumors of the eyelids, conjunctiva and cornea.In: Garner A, Klintworth GK, eds. Pathobiology of oculardisease. New York & Basel: Marcel Dekker, 1982; Part A,24:624.

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