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Diffuse Epibulbar Squamous-Cell Epithelioma
D I F F U S E EPIBULBAR SQUAMOUS-CELL E P I T H E L I O M A A. RAY IRVINE, JR.,
M.D.
Los Angeles, California I n 1963, I reported on 104 dyskeratotic epibulbar tumors received at the Estelle Doheny E y e Foundation. 1 O n e of these, Case 102, was, to me, unique. T h e clinical picture was that of diffuse inflammation of the bul bar and palpebral conjunctivas of the right eye, without tumefaction. Dyskeratotic cells were present in the conjunctival scrapings treated by Papanicolaou stain. These findings were substantiated by multiple conjunctival biopsies. Because the lesions were diffuse, irradiation, rather than surgery, constituted the definitive therapy. O n e year later there was no evidence of recurrence. Since that report, however, the patient experienced a recurrence of squamous-cell carcinoma with tumefaction of the bulbar conjunctiva and subsequent metastasis to regional lymph nodes. I have also had the opportunity to observe two other such cases of diffuse epibulbar squamous-cell epithe lioma. Because of the unusual clinical char acteristics and poor response to therapy in these cases, it was felt that a detailed report would be instructive.
Fig. 1 (Irvine). Case 1. Appearance of eye. hyperchromatism, pleomorphism, abnormal polari ty, lack of cohesiveness and abnormal mitoses (fig. 2). There was also a marked inflammatory reaction, which posed a possibility of pseudoepitheliomatous hyperplasia. Minute focal areas were present where the basement membrane was not apparent and these were thought to represent local invasion. The changes in the epithelium re mained consistent with squamous-cell epithelioma. The diffuse nature of the lesion and the absence of tumefaction, however, were regarded as unusu al for epibulbar squamous-cell cancer. Because of the widespread involvement of ocu lar and adnexal epithelium, the lesion was irradi-
C A S E REPORTS CASE 1
The patient, a 65-year-old white man, ex hibited injection of the palpebral and bulbar con junctivas of the right eye for a year. The gener al treatments for conjunctivitis were unsuccessful, and the intensity of the injection and infiltration gradually increased. Finally, he developed small, gelatinous, vascularized limbal infiltrates (fig. 1). There was some mucous discharge but no indu ration or foreshortening of the fornices. Scrap ings from the corneal, bulbar and palpebral epi thelium suggested squamous-cell epithelioma, a diagnosis substantiated by multiple conjunctival biopsies taken over the ensuing three years. Histologically, the epithelium was not general ly increased in its number of cell layers and, in places, was reduced in thickness. The cells, how ever, were dyskeratotic, as evidenced by marked From the Estelle Doheny Eye Foundation.
Fig. 2 (Irvine). Section of bulbar conjuctiva, showing dyskeratotic epithelium. (Reduced from
xioo.)
SSO/32
SQUAMOUS-CELL EPITHELIOMA ated; during the following four months, the lids and bulbar conjunctiva received a dosage of ap proximately 3,000 r. This resulted in some irrita tion of the external eye and epilation of the lash es. There was, however, a rapid clearing of the conjunctival infiltration. The patient remained clini cally free of neoplasm for a year and was thought to be cured. Fourteen months later, recurrence of inflamma tion and gelatinous infiltration of the bulbar and limbal conjunctivas inferiorly was noted. Papanicolaou stain of conjunctival scrapings and subse quent biopsy confirmed the recurrence of intraepithelial epithelioma. A single irradiation dose of 750 r resulted in marked clinical improvement. However, eight months later, in May, 1964, a clinical recurrence appeared. In addition to the previous findings a thickened, white tumor developed in the region of the caruncle. Two months later this tumor was excised and histologically revealed invasive squamous-cell epithelioma (fig. 3). Two months later, he received 3,500 r of irradiation. By March, 1965, he had received a total of 4,100 r. The bulbar conjunctiva remained slightly in jected, the corneal epithelium stained diffusely and the eye became painful. A superior pannus was noted and the lens became cataractous. In March, 1965, a preauricular tender lymph node became palpable. The eye then became glaucomatous and painful, the iris was vascularized and in May, 1965, a spontaneous hyphema occurred. In August, 1965, the eye was enucleated. The preau ricular node was removed and found to be diffusely infiltrated with squamous-cell carcinoma (fig. 4). Histologically the eye showed changes thought to be secondary to irradiation. There was no evi dence of dyskeratosis but the epithelium was somewhat acanthotic. A fibrotic inflamed pannus was seen above. The corneal stroma was thinned and scarred. There were broad peripheral anterior synechiae and neovascularization of the iris, pro ducing ectropion uveae. There was proliferation from vascular endothelium, forming capillary
Fig. 3 (Irvine). Invasive squamous-cell carcinoma, showing tumefaction. (Reduced from XlOO.)
551/33
Fig. 4 (Irvine). Metastatic squamous-cell carcinoma in preauricular node. (χ400.) nodules within the pigment epithelium of the iris. Both iris leafs were fibrotic and markedly necrotic. There was a mature cataract and free blood was seen in the anterior chamber, cirumlental space, vitreous cavity, on the surface of the nervehead and within the retina. On the temporal side, the inner layers of the retina were thinned, suggesting a vascular occlusion. At the equator there was a diminution of neurosensory epithelium, destruction of parts of the ciliary epithelium and a necrotizing process in the anterior uvea comparable to the pathologic changes seen in the arterial infarct. Ganglion cells were ab sent and the nerve-fiber layer was thinned and atrophie. Nasally, the retina revealed the stigma of reti nal venous occlusion and hemorrhagic glaucoma, while the temporal retina showed the pathologic alterations of ciliary vessel obstruction. The socket remained clinically free of epithe lioma from the time of enucleation in October, 1965, until the time of the patient's death in April, 1966. There was a recurrence of squa mous-cell carcinoma in the preauricular region which was unsuccessfully treated with irradiation. Cervical adenopathy was present and the patient became anemic, experienced marked loss of appe tite and weight. He died at the age of 69 years, approximately six years after the onset of his original epibulbar tumor.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 5 (Irvine). Epibulbar injection and pannus.
SEPTEMBER, 1967
bar conjunctiva were similar, revealing acute inflammatory cells, lymphocytes, a few eosinophils and dyskeratotic epithelial cells. A coagulase-negative Micrococcus was cultured. Papani colaou stains of the superior bulbar and palpebral conjunctivas were interpreted as being either a Bowenoid type of dysplasia or very low grade carcinoma (fig. 6). Two months later, biopsies from the inferior and superior bulbar conjuncti vas and from the upper tarsus revealed diffuse intraepithelial epithelioma (fig. 7). From September to mid-December, 1963, the patient received 1,750 r of irradiation, following which Papanicolaou stains were normal for the bulbar conjunctiva but the corneal epithelium re mained dyskeratotic. The corneal epithelium was then removed and the patient remained clinically normal until March, 1964, when there was a re currence of inflammation and corneal edema above, which again, with appropriate laboratory studies revealed the cytology of in situ carcino ma. For five months she was treated radiologically and received a total of 2,350 r. While some clini cal improvement was noted, the cornea stained diffusely and there was injection of the bulbar conjunctiva. The external eye lesions disappeared but a posterior cortical cataract developed, and the vision became reduced to 20/200. In March, 1965, malignant cells in large num bers were found and in May, 1965, scrapings from numerous sites were taken in an attempt to map the area involved prior to considering exten sive surgery. It was of interest, however, that there was still no evidence of tumefaction or a gelatinous appearance usually characteristic of ep ibulbar carcinoma in situ. Further cytologie evaluation of bulbar and palpebral conjunctival scrapings indicated that the only area free of
Fig. 6 (Irvine). Conjunctival scrapings treated with Papanicolaou stain, showing dyskeratosis. (Re duced from XlOOO.) On autopsy, a metastatic tumor was found in the preauricular region only. Unfortunately, the cervical nodes were not examined. The anatomic diagnosis was pyelonephritis, pulmonary edema and uremia. CASE 2
This 66-year-old patient was seen in July, 1963. Her vision was correctible to 20/40 in the right eye and 20/20 in the left eye. She com plained of inflammation and a foreign-body type of pain in the right eye of two years' duration. The tarsal conjunctiva of the upper lid was in jected, infiltrated, scarred and studded with small vascular tufts. There was a superficial pannus in vading the upper one third of the cornea. This area stained with fluorescein (fig. 5). A conjunc tival scraping and culture were taken. The cy tologie findings of the upper tarsus and bul-
Fig. 7 (Irvine). Dyskeratotic epithelium. (χ400.)
SQUAMOUS-CELL EPITHELIOMA dysplasia was the inferior palpebral conjunctiva. The superior palpebral conjunctiva was markedly dyskeratotic, the bulbar conjunctiva less so. A few weeks later the patient was noted to have glaucoma and was treated unsuccessfully with miotics. On June 29, 1965, she was seen at the University of California at Los Angeles Eye Clinic. Vision in the right eye was reduced to light perception. The conjunctiva was described as injected, the lids edematous and the intraocular pressure 63 units by applanation tonometry. The anterior chamber was deep and showed a three-plus flare and cells and a gross hyphema. No obvious neovascularization of the iris was seen. The clinical diagnosis was probable hemorrhagic glaucoma following retinal venous occlu sion. In July, 196S, an intracapsular extraction, with full iridectomy, inferior sphincterotomy and exci sion of a pupillary membrane was performed. Five days later, the anterior chamber was irrigat ed because of recurrent hyphema. The intraocular pressure was within normal limits. The eye re mained blind and painful and the hyphema per sisted. The globe was enucleated August 19, 1965. There was no record of recurrent epithelial carci noma. Gross examination. The specimen was an aphakic right eyeball of normal size and shape. There was a hemorrhagic fibrinous membrane on the surface of the endothelium centrally against which the vitreous face impinged. The iris leafs were in apposition to the cornea. A fibrinous ma terial was seen on the posterior surface of the iris and over the surface of the ciliary body. Focal choroidal hemorrhages were seen equatorially and inferiorly. The vitreous body was hazy, stranded and contained fresh hemorrhage. It ap peared to be displaced forward from its base. There were pigment deposits on the pars plana, the ciliary processes and the posterior retina. The globe was soft and the optic nervehead appeared edematous. Histologie examination. Histologically, the corneal epithelium revealed focal thinning and atrophy, other areas were edematous and in creased in cell layers but were not dyskeratotic. A fibrinous exudate was seen on the corneal limbal surface. There was diffuse scarring and focal acellular necrosis of the stroma. Polymorphonuclear infiltrates were present. Corneal scars with incarcerated epithelium were seen peripherally on both sides. Blood was seen in the anterior cham ber and in some sections within the corneal stro ma posteriorly. The endothelium was absent and Descemet's membrane was coiled temporally. Marked necrosis of the iris, particularly in the pupillary portion was evident, and free blood was visible in the necrotic iris stroma below. There were large peripheral anterior synechiae that al most obliterated the anterior chamber. The trabeculae were compressed and contained pigment granules and acute and chronic inflammatory cells. Condensed vitreous containing red blood
SS3/3S
Fig. 8 (Irvine). Showing injection and infiltration of palpebral and bulbar conjunctivas. cells was seen adherent to the cornea centrally. Dense infiltrates of lymphocytes and plasma cells were seen in the iris and ciliary body. There was but little inflammation of the posterior segment. The retina was atrophie peripherally. The choroid was congested. Ganglion cells were reduced in number but the nerve-fiber layer was not grossly atrophie. The optic nervehead appeared edema tous. There was no evidence of central retinal vein occlusion. Opinion. Necrosis of iris secondary to irradia tion; secondary angle-closure glaucoma; recur rent hyphema secondary to necrosis of iris; sur gical aphakia. CASE 3
A 56-year-old woman was first seen in 1962, with a history of chronic epibulbar inflammation of the left eye since 1958. The inferior palpebral conjunctiva of the left eye was described as hav ing follicular hypertrophy and scarring. The bul bar conjunctiva was injected and minute, whitish nodules were seen on the caruncle (fig. 8). A Pa panicolaou stain was suggestive of squamous-cell carcinoma in situ. A biopsy of the conjunctiva was originally interpreted as chronic conjunctivi tis with pseudoepitheliomatous hyperplasia. The injection and infiltration have continued until the present time. A symblepharon has since developed inferiorly. A few isolated foci of epidermalization are seen on the bulbar conjunctiva. A solid, tender nodule was seen at the site of the previous biopsy. Papanicolaou stains of the inferior fornix and bulbar conjunctiva taken in July, 1966, were positive for carcinoma in situ. Review of the original biopsy is now interpreted as intraepithelial epithelioma. A biopsy of the nodule in the pal pebral conjunctiva taken in October, 1966, re vealed invasive squamous-cell carcinoma. DISCUSSION
Epibulbar squamous-cell epitheliomas de crease in malignancy with proximity to the
554/36
AMERICAN JOURNAL OF OPHTHALMOLOGY
cornea. They are usually characterized by gross tumefaction, with or without epidermalization, exophytic growth, sharply de fined borders and a marked tendency for local recurrences. Those at the limbus rare ly, if ever, metastasize. Infrequently, they invade the eye by direct extension. They are best treated by local excision, repeated as necessary. The three cases presented are unusual in their chronicity, diffuse distribution and ab sence of early tumefaction. The dramatic response to irradiation and the even more ominous recurrences are probably indicative of their unusual malignant potential, which is further attested to by the development of typical invasive squamous-cell cancer with regional métastases, as illustrated by Case 1. The first two cases illustrate the in effectiveness of irradiation and suggest that more radical surgery, either exenteration or early wide excision of the involved conjunctiva, is indicated. Papanicolaou stain ing might facilitate the accurate mapping of the abnormal epithelium. Although the sec ond case has not shown any clinical recur rence in the socket, it is obviously prema ture to state that a cure has been effected. This contradicts conclusions made regarding Case 1 in a previous publication1 in which irradiation was stated to be the most effec tive treatment. The possible role of irradiation in pro duction of glaucoma in Cases 1 and 2 is of some interest. Both patients developed uni lateral cataracts, spontaneous hyphema, in tense anterior segment inflammation and ne crosis. The second patient had undergone surgery for cataract, glaucoma and hyphe ma, thus making it difficult to evaluate the role of irradiation in the pathologic process. However, pathologic similarities in the two
SEPTEMBER, 1967
cases and the monocular involvement in each seem to lend some credence to the impression that the radiologie therapy may have been a factor contributing to the enucleation ultimately necessary. An interesting feature of these cases is the predominant role of inflammation, a finding noted clinically and pathologically. In each case the dyskeratotic process in creased with chronicity, which might relate to the persistence of the inflammatory pro cess. This apparently substantiates the opin ion that trauma and persistent inflammation frequently precede and may be factors in the pathogenesis of in situ epithelioma. SUMMARY
Three cases of epibulbar squamous-cell lesions are presented. They are unusual in their diffuse distribution without tumefac tion and the intense inflammation that clini cally obscured their dyskeratotic nature. One patient developed invasive carcinoma and metastasis to regional lymph nodes. Ir radiation, although effecting a temporary recession of the pathologic process, was not curative and probably was a major cause of the intraocular pathologic processes that ul timately led to enucleation. 272 South Lake Street (90057) ACKNOWLEDGMENTS
I am indebted to Raymond A. Allen, M.D., professor of pathology, University of California at Los Angeles, School of Medicine, for his assistance in the gross and microscopic descriptions in Case 2, and to Bradley R. Straatsma, M.D., chief of the Division of Surgery/Ophthalmology, University of California at Los Angeles, School of Medicine, and director of the Jules Stein Eye Institute, Los An geles, for his permission to summarize the clinical record in Case 2. REFERENCE
1. Irvine, A. R., Jr.: Dyskeratotic epibulbar tu mors. Tr. Am. Ophth. Soc. 61:243, 1963.
M.D.
Los Angeles, California I n 1963, I reported on 104 dyskeratotic epibulbar tumors received at the Estelle Doheny E y e Foundation. 1 O n e of these, Case 102, was, to me, unique. T h e clinical picture was that of diffuse inflammation of the bul bar and palpebral conjunctivas of the right eye, without tumefaction. Dyskeratotic cells were present in the conjunctival scrapings treated by Papanicolaou stain. These findings were substantiated by multiple conjunctival biopsies. Because the lesions were diffuse, irradiation, rather than surgery, constituted the definitive therapy. O n e year later there was no evidence of recurrence. Since that report, however, the patient experienced a recurrence of squamous-cell carcinoma with tumefaction of the bulbar conjunctiva and subsequent metastasis to regional lymph nodes. I have also had the opportunity to observe two other such cases of diffuse epibulbar squamous-cell epithe lioma. Because of the unusual clinical char acteristics and poor response to therapy in these cases, it was felt that a detailed report would be instructive.
Fig. 1 (Irvine). Case 1. Appearance of eye. hyperchromatism, pleomorphism, abnormal polari ty, lack of cohesiveness and abnormal mitoses (fig. 2). There was also a marked inflammatory reaction, which posed a possibility of pseudoepitheliomatous hyperplasia. Minute focal areas were present where the basement membrane was not apparent and these were thought to represent local invasion. The changes in the epithelium re mained consistent with squamous-cell epithelioma. The diffuse nature of the lesion and the absence of tumefaction, however, were regarded as unusu al for epibulbar squamous-cell cancer. Because of the widespread involvement of ocu lar and adnexal epithelium, the lesion was irradi-
C A S E REPORTS CASE 1
The patient, a 65-year-old white man, ex hibited injection of the palpebral and bulbar con junctivas of the right eye for a year. The gener al treatments for conjunctivitis were unsuccessful, and the intensity of the injection and infiltration gradually increased. Finally, he developed small, gelatinous, vascularized limbal infiltrates (fig. 1). There was some mucous discharge but no indu ration or foreshortening of the fornices. Scrap ings from the corneal, bulbar and palpebral epi thelium suggested squamous-cell epithelioma, a diagnosis substantiated by multiple conjunctival biopsies taken over the ensuing three years. Histologically, the epithelium was not general ly increased in its number of cell layers and, in places, was reduced in thickness. The cells, how ever, were dyskeratotic, as evidenced by marked From the Estelle Doheny Eye Foundation.
Fig. 2 (Irvine). Section of bulbar conjuctiva, showing dyskeratotic epithelium. (Reduced from
xioo.)
SSO/32
SQUAMOUS-CELL EPITHELIOMA ated; during the following four months, the lids and bulbar conjunctiva received a dosage of ap proximately 3,000 r. This resulted in some irrita tion of the external eye and epilation of the lash es. There was, however, a rapid clearing of the conjunctival infiltration. The patient remained clini cally free of neoplasm for a year and was thought to be cured. Fourteen months later, recurrence of inflamma tion and gelatinous infiltration of the bulbar and limbal conjunctivas inferiorly was noted. Papanicolaou stain of conjunctival scrapings and subse quent biopsy confirmed the recurrence of intraepithelial epithelioma. A single irradiation dose of 750 r resulted in marked clinical improvement. However, eight months later, in May, 1964, a clinical recurrence appeared. In addition to the previous findings a thickened, white tumor developed in the region of the caruncle. Two months later this tumor was excised and histologically revealed invasive squamous-cell epithelioma (fig. 3). Two months later, he received 3,500 r of irradiation. By March, 1965, he had received a total of 4,100 r. The bulbar conjunctiva remained slightly in jected, the corneal epithelium stained diffusely and the eye became painful. A superior pannus was noted and the lens became cataractous. In March, 1965, a preauricular tender lymph node became palpable. The eye then became glaucomatous and painful, the iris was vascularized and in May, 1965, a spontaneous hyphema occurred. In August, 1965, the eye was enucleated. The preau ricular node was removed and found to be diffusely infiltrated with squamous-cell carcinoma (fig. 4). Histologically the eye showed changes thought to be secondary to irradiation. There was no evi dence of dyskeratosis but the epithelium was somewhat acanthotic. A fibrotic inflamed pannus was seen above. The corneal stroma was thinned and scarred. There were broad peripheral anterior synechiae and neovascularization of the iris, pro ducing ectropion uveae. There was proliferation from vascular endothelium, forming capillary
Fig. 3 (Irvine). Invasive squamous-cell carcinoma, showing tumefaction. (Reduced from XlOO.)
551/33
Fig. 4 (Irvine). Metastatic squamous-cell carcinoma in preauricular node. (χ400.) nodules within the pigment epithelium of the iris. Both iris leafs were fibrotic and markedly necrotic. There was a mature cataract and free blood was seen in the anterior chamber, cirumlental space, vitreous cavity, on the surface of the nervehead and within the retina. On the temporal side, the inner layers of the retina were thinned, suggesting a vascular occlusion. At the equator there was a diminution of neurosensory epithelium, destruction of parts of the ciliary epithelium and a necrotizing process in the anterior uvea comparable to the pathologic changes seen in the arterial infarct. Ganglion cells were ab sent and the nerve-fiber layer was thinned and atrophie. Nasally, the retina revealed the stigma of reti nal venous occlusion and hemorrhagic glaucoma, while the temporal retina showed the pathologic alterations of ciliary vessel obstruction. The socket remained clinically free of epithe lioma from the time of enucleation in October, 1965, until the time of the patient's death in April, 1966. There was a recurrence of squa mous-cell carcinoma in the preauricular region which was unsuccessfully treated with irradiation. Cervical adenopathy was present and the patient became anemic, experienced marked loss of appe tite and weight. He died at the age of 69 years, approximately six years after the onset of his original epibulbar tumor.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 5 (Irvine). Epibulbar injection and pannus.
SEPTEMBER, 1967
bar conjunctiva were similar, revealing acute inflammatory cells, lymphocytes, a few eosinophils and dyskeratotic epithelial cells. A coagulase-negative Micrococcus was cultured. Papani colaou stains of the superior bulbar and palpebral conjunctivas were interpreted as being either a Bowenoid type of dysplasia or very low grade carcinoma (fig. 6). Two months later, biopsies from the inferior and superior bulbar conjuncti vas and from the upper tarsus revealed diffuse intraepithelial epithelioma (fig. 7). From September to mid-December, 1963, the patient received 1,750 r of irradiation, following which Papanicolaou stains were normal for the bulbar conjunctiva but the corneal epithelium re mained dyskeratotic. The corneal epithelium was then removed and the patient remained clinically normal until March, 1964, when there was a re currence of inflammation and corneal edema above, which again, with appropriate laboratory studies revealed the cytology of in situ carcino ma. For five months she was treated radiologically and received a total of 2,350 r. While some clini cal improvement was noted, the cornea stained diffusely and there was injection of the bulbar conjunctiva. The external eye lesions disappeared but a posterior cortical cataract developed, and the vision became reduced to 20/200. In March, 1965, malignant cells in large num bers were found and in May, 1965, scrapings from numerous sites were taken in an attempt to map the area involved prior to considering exten sive surgery. It was of interest, however, that there was still no evidence of tumefaction or a gelatinous appearance usually characteristic of ep ibulbar carcinoma in situ. Further cytologie evaluation of bulbar and palpebral conjunctival scrapings indicated that the only area free of
Fig. 6 (Irvine). Conjunctival scrapings treated with Papanicolaou stain, showing dyskeratosis. (Re duced from XlOOO.) On autopsy, a metastatic tumor was found in the preauricular region only. Unfortunately, the cervical nodes were not examined. The anatomic diagnosis was pyelonephritis, pulmonary edema and uremia. CASE 2
This 66-year-old patient was seen in July, 1963. Her vision was correctible to 20/40 in the right eye and 20/20 in the left eye. She com plained of inflammation and a foreign-body type of pain in the right eye of two years' duration. The tarsal conjunctiva of the upper lid was in jected, infiltrated, scarred and studded with small vascular tufts. There was a superficial pannus in vading the upper one third of the cornea. This area stained with fluorescein (fig. 5). A conjunc tival scraping and culture were taken. The cy tologie findings of the upper tarsus and bul-
Fig. 7 (Irvine). Dyskeratotic epithelium. (χ400.)
SQUAMOUS-CELL EPITHELIOMA dysplasia was the inferior palpebral conjunctiva. The superior palpebral conjunctiva was markedly dyskeratotic, the bulbar conjunctiva less so. A few weeks later the patient was noted to have glaucoma and was treated unsuccessfully with miotics. On June 29, 1965, she was seen at the University of California at Los Angeles Eye Clinic. Vision in the right eye was reduced to light perception. The conjunctiva was described as injected, the lids edematous and the intraocular pressure 63 units by applanation tonometry. The anterior chamber was deep and showed a three-plus flare and cells and a gross hyphema. No obvious neovascularization of the iris was seen. The clinical diagnosis was probable hemorrhagic glaucoma following retinal venous occlu sion. In July, 196S, an intracapsular extraction, with full iridectomy, inferior sphincterotomy and exci sion of a pupillary membrane was performed. Five days later, the anterior chamber was irrigat ed because of recurrent hyphema. The intraocular pressure was within normal limits. The eye re mained blind and painful and the hyphema per sisted. The globe was enucleated August 19, 1965. There was no record of recurrent epithelial carci noma. Gross examination. The specimen was an aphakic right eyeball of normal size and shape. There was a hemorrhagic fibrinous membrane on the surface of the endothelium centrally against which the vitreous face impinged. The iris leafs were in apposition to the cornea. A fibrinous ma terial was seen on the posterior surface of the iris and over the surface of the ciliary body. Focal choroidal hemorrhages were seen equatorially and inferiorly. The vitreous body was hazy, stranded and contained fresh hemorrhage. It ap peared to be displaced forward from its base. There were pigment deposits on the pars plana, the ciliary processes and the posterior retina. The globe was soft and the optic nervehead appeared edematous. Histologie examination. Histologically, the corneal epithelium revealed focal thinning and atrophy, other areas were edematous and in creased in cell layers but were not dyskeratotic. A fibrinous exudate was seen on the corneal limbal surface. There was diffuse scarring and focal acellular necrosis of the stroma. Polymorphonuclear infiltrates were present. Corneal scars with incarcerated epithelium were seen peripherally on both sides. Blood was seen in the anterior cham ber and in some sections within the corneal stro ma posteriorly. The endothelium was absent and Descemet's membrane was coiled temporally. Marked necrosis of the iris, particularly in the pupillary portion was evident, and free blood was visible in the necrotic iris stroma below. There were large peripheral anterior synechiae that al most obliterated the anterior chamber. The trabeculae were compressed and contained pigment granules and acute and chronic inflammatory cells. Condensed vitreous containing red blood
SS3/3S
Fig. 8 (Irvine). Showing injection and infiltration of palpebral and bulbar conjunctivas. cells was seen adherent to the cornea centrally. Dense infiltrates of lymphocytes and plasma cells were seen in the iris and ciliary body. There was but little inflammation of the posterior segment. The retina was atrophie peripherally. The choroid was congested. Ganglion cells were reduced in number but the nerve-fiber layer was not grossly atrophie. The optic nervehead appeared edema tous. There was no evidence of central retinal vein occlusion. Opinion. Necrosis of iris secondary to irradia tion; secondary angle-closure glaucoma; recur rent hyphema secondary to necrosis of iris; sur gical aphakia. CASE 3
A 56-year-old woman was first seen in 1962, with a history of chronic epibulbar inflammation of the left eye since 1958. The inferior palpebral conjunctiva of the left eye was described as hav ing follicular hypertrophy and scarring. The bul bar conjunctiva was injected and minute, whitish nodules were seen on the caruncle (fig. 8). A Pa panicolaou stain was suggestive of squamous-cell carcinoma in situ. A biopsy of the conjunctiva was originally interpreted as chronic conjunctivi tis with pseudoepitheliomatous hyperplasia. The injection and infiltration have continued until the present time. A symblepharon has since developed inferiorly. A few isolated foci of epidermalization are seen on the bulbar conjunctiva. A solid, tender nodule was seen at the site of the previous biopsy. Papanicolaou stains of the inferior fornix and bulbar conjunctiva taken in July, 1966, were positive for carcinoma in situ. Review of the original biopsy is now interpreted as intraepithelial epithelioma. A biopsy of the nodule in the pal pebral conjunctiva taken in October, 1966, re vealed invasive squamous-cell carcinoma. DISCUSSION
Epibulbar squamous-cell epitheliomas de crease in malignancy with proximity to the
554/36
AMERICAN JOURNAL OF OPHTHALMOLOGY
cornea. They are usually characterized by gross tumefaction, with or without epidermalization, exophytic growth, sharply de fined borders and a marked tendency for local recurrences. Those at the limbus rare ly, if ever, metastasize. Infrequently, they invade the eye by direct extension. They are best treated by local excision, repeated as necessary. The three cases presented are unusual in their chronicity, diffuse distribution and ab sence of early tumefaction. The dramatic response to irradiation and the even more ominous recurrences are probably indicative of their unusual malignant potential, which is further attested to by the development of typical invasive squamous-cell cancer with regional métastases, as illustrated by Case 1. The first two cases illustrate the in effectiveness of irradiation and suggest that more radical surgery, either exenteration or early wide excision of the involved conjunctiva, is indicated. Papanicolaou stain ing might facilitate the accurate mapping of the abnormal epithelium. Although the sec ond case has not shown any clinical recur rence in the socket, it is obviously prema ture to state that a cure has been effected. This contradicts conclusions made regarding Case 1 in a previous publication1 in which irradiation was stated to be the most effec tive treatment. The possible role of irradiation in pro duction of glaucoma in Cases 1 and 2 is of some interest. Both patients developed uni lateral cataracts, spontaneous hyphema, in tense anterior segment inflammation and ne crosis. The second patient had undergone surgery for cataract, glaucoma and hyphe ma, thus making it difficult to evaluate the role of irradiation in the pathologic process. However, pathologic similarities in the two
SEPTEMBER, 1967
cases and the monocular involvement in each seem to lend some credence to the impression that the radiologie therapy may have been a factor contributing to the enucleation ultimately necessary. An interesting feature of these cases is the predominant role of inflammation, a finding noted clinically and pathologically. In each case the dyskeratotic process in creased with chronicity, which might relate to the persistence of the inflammatory pro cess. This apparently substantiates the opin ion that trauma and persistent inflammation frequently precede and may be factors in the pathogenesis of in situ epithelioma. SUMMARY
Three cases of epibulbar squamous-cell lesions are presented. They are unusual in their diffuse distribution without tumefac tion and the intense inflammation that clini cally obscured their dyskeratotic nature. One patient developed invasive carcinoma and metastasis to regional lymph nodes. Ir radiation, although effecting a temporary recession of the pathologic process, was not curative and probably was a major cause of the intraocular pathologic processes that ul timately led to enucleation. 272 South Lake Street (90057) ACKNOWLEDGMENTS
I am indebted to Raymond A. Allen, M.D., professor of pathology, University of California at Los Angeles, School of Medicine, for his assistance in the gross and microscopic descriptions in Case 2, and to Bradley R. Straatsma, M.D., chief of the Division of Surgery/Ophthalmology, University of California at Los Angeles, School of Medicine, and director of the Jules Stein Eye Institute, Los An geles, for his permission to summarize the clinical record in Case 2. REFERENCE
1. Irvine, A. R., Jr.: Dyskeratotic epibulbar tu mors. Tr. Am. Ophth. Soc. 61:243, 1963.