Invasive Squamous Cell Carcinoma of the Conjunctiva W. Jackson
Iliff, MD;
Roberto
Marback, MD; W. Richard Green, MD
In 27 cases of invasive conjunctival squamous cell carcinoma, three cases of deep corneal invasion and two cases of intraocular extension were found. Four cases showed orbital invasion, and one patient died of generalized metastases 18 months after diagnosis. The relatively low-grade nature of these lesions and their potential for local treatment is noted, but it is emphasized that careful clinical examination and close cooperation with the pathologist to ensure adequate evaluation of excised tissue are essential.
lesions is not well known. Recent acquisition of several inter¬ esting cases of squamous cell carci¬ noma of the conjunctiva, including with intraocular extension, one prompted the present study and this brief description of Wilmer Institute cases of invasive squamous cell carci¬ noma of the conjunctiva with in¬ traocular extension. Materials and Methods All cases squamous cell
coded
as
carcinoma,
epithelioma,
squamous carcinoma of the conjunctiva is uncommon, and intraocular extension of squamous cell carcinoma is very rare.1 François, et al,2 in 1967, collected only 49 cases from the literature and described an additional one. Greer,3 Stokes,4 and Dollfus5 have each described an addi¬ tional case, and Duke-Elder6 makes reference to several. Irvine7 reported 104 cases of "dyskeratotic epibulbar tumors," and in that series there was only one case of intraocular extension in 20 cases of squamous cell carci¬ noma. These various authors stress the rarity of this condition. The inci¬ dence and biologic behavior of these
carcinoma in situ of the cornea and conjunctiva on file in the eye pathology laboratory of the Wil¬ mer Institute of the Johns Hopkins Hospi¬ tal were examined. A total of 65 cases was encountered and analyzed for age, sex,
Submitted for publication Oct 24, 1973. From the Eye Pathology Laboratory, The WilInstitute, and the Department of Pathology, The Johns Hopkins Medical Institutions, Balti-
atypical papillomata (2), pseudoepitheliomatous hyperplasia (2), and ma¬ lignant melanoma (1). Of the 50 cases remaining, the 27 invasive cases are the subject of this report. The major incidence of inva-
Invasive
mer
more.
Reprint requests to Eye Pathology Laboratory, Johns Hopkins Hospital, 601 N Broadway, MD 21205 (Dr. Green).
race, tumor
and
or
location, duration, treatment,
follow-up when
available.
Results
Of the 65 cases, 27 proved to be in¬ were in situ, and 15 were excluded from the study for a variety of reasons that included insufficient material for review (4), secondary in¬ volvement from a lid tumor (2), and reclassification as benign or a nonsquamous lesion (9). The nine reclassified cases included dysplasia (4),
vasive, 23
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sive squamous carcinoma was in the sixth decade. The age range was 4 to 77 years, that includes two unusual cases arising in children ages 4 and 12. By decade, occurrence was as fol¬ lows: 0-10,1 case; 11-20,1; 21-30,1; 3140, 1; 41-50, 3; 51-60, 12; 61-70, 4; and 71 and up, 4. There were 17 male sub¬ jects and ten female subjects with in¬ vasive tumor. Although race was un¬ known in four of the 27 cases, it was white in all but two of the remainder. One patient was a Pakistani man and one was an Indian woman from Bra¬ zil. In the 27 invasive cases, the limbus was the most commonly involved re¬ gion (17: 4 temporal, 3 nasal, and 10 not specified), although the palpebrai (3) and forniceal (3) conjunctivae were also occasionally the primary site. The bulbar conjunctiva was the site in two patients, and the tumor was diffuse, in two other patients. Treatment in this series consisted of local excision (with and without ir¬
radiation), enucleation,
or
exentera-
tion. A breakdown of the treatment was as follows: excisional biopsy, 10; excisional biopsy plus irradiation, 4; biopsy and irradiation, 3; exenteration, 6; and enucleation, 4. Several cases showed definitely incomplete lo¬ cal excision but all but one of these were cases of biopsy for diagnosis only. In this one subject, there was no recurrence eight years later. Of the six cases treated with exenteration,
Fig 3 (EP 31055).—Raised white lesion straddling limbus with dilated vessels tem¬ porally and lipid in the cornea nasally.
Fig 1 (EP 21007).—Limbal toxylin-eosin, X140).
area
showing deep corneal
and intraocular invasion
(hema¬
Fig 4 (EP 31055).—Gross appearance of thickened limbal zone temporally after re¬ moval of superior cap. years in six subjects, five to nine years in six, and ten years or more in five—with two being followed 30 years without evidence of recurrent
Fig 2 (EP 21007).—Higher power of angle structures showing tumor Invasion of out¬ flow channels, Schlemm's canal, and trabecular meshwork (hematoxylin-eosin, 140). orbital invasion was observed in three, intraocular extension in one, and lid involvement in two. In the four enucleation specimens, there was deep corneal invasion in three and in¬ traocular invasion in one. In cases with adequate follow-up, there were recurrences in eight of 22 cases (36%) with all but one of the eight after local treatment (three af¬ ter local excision, four after excision or biopsy with irradiation, and one af¬ ter exenteration). Two recurrences were seen in two patients. Recur¬ rences were treated by re-excision (13) or re-excision with irradiation (1), exenteration (2), or radical neck dissection (2). Follow-up data are available in all but the two earliest cases and the
three most recent ones. Of the 22 pa¬ tients with follow-up, four had less than one year follow-up but all were free of tumor when last seen. One of these four died of unrelated causes eight months after excision. The other cases (18) had from two
thirty years follow-up. Of these, two developed metastasis (treated by excision and radical neck years
to
dissection) and one of these two died of
malignancy 18 months after initial treatment. The other developed an adenocarcinoma of the bowel eight years after the conjunctival tumor and has since died from her bowel malignant neoplasm without evi¬ dence of recurrent conjunctival tu¬ mor. Thus 17 subjects were free of tu¬ mor with a follow-up of two to four
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disease. Several unusual features were ob¬ served as follows: occurrence in young individuals (2), intraocular extension (2), deep corneal invasion (3), and re¬ gional métastases (2). These nine cases with unusual features are pre¬ sented briefly.
Report of Cases Case 1 EP 25790.-A 4-year-old white girl developed a lesion in the inferior pal¬ pebrai conjunctiva one year after stra¬ bismus surgery. The patient was treated with local excision and is free of tumor at follow-up five years after surgery. Diag¬ nosis was invasive squamous cell carci¬ noma. No evidence of foreign bodies was seen.
Case 2 EP 9735.-The patient was a 12year-old white girl who developed a lesion involving the limbus and cornea. The patient was known to have xeroderma pigmentosum and was treated by local exci¬ sion. Diagnosis was squamous cell car¬ cinoma of conjunctiva with superficial invasion of the cornea. Although vision is poor in the involved eye, there is no evi¬ dence of recurrence 25 years after removal
Fig
Fig 5 (EP 31055).—An
be
seen
island of tumor in
in scierai canal to
X110).
supraciliary space (long arrows). Tumor can right (short arrow) and in sclera above (hematoxylin-eosin,
of tumor. Case 3 EP 21007.-A 63-year-old white man had a tumor in the temporal limbus of the left eye. A biopsy was performed in 1959, 15 months prior to admission. A diagnosis of squamous cell carcinoma of the conjunctiva was made. The patient was not treated further and was lost to followup until early 1961 when he presented again; a recurrent tumor with probable in¬ traocular invasion was found. Exentera¬ tion was performed, which showed deep corneal stromal invasion (Fig 1) and tumor infiltration of Schlemm canal and trabecu¬ lar meshwork (Fig 2). The patient died four years later of sepsis following a pro¬ cedure for transitional-cell carcinoma of the bladder. There was no evidence of re¬ current
conjunctival
tumor.
Case 4 EP 31055.-A 54-year-old Indian woman had noted a lesion in the temporal limbus of the right eye for two years and an increase in size in the three months pre¬ ceding examination (Fig 3). Because of clinical suspicion of intraocular invasion, an enucleation was performed. Gross ex¬ amination of the enucleated eye revealed an eye normal in all respects except for the presence of a 10x7x1.5 mm lesion at the temporal limbus from 7 to 11 o'clock, and after opening the eye, the tumor seemed to have invaded the cornea and deep struc¬ tures (Fig 4). Microscopical examination revealed tumor on the outer surface and infiltrating deeply to invade a preformed scierai canal anteriorly and gain access to the supraciliary space posteriorly (Fig 5). Histologically, the tumor showed a typical squamous pattern with loss of normal ma-
6
(EP 31055).-Typical histologie
pattern of invasive squamous cell carci¬ noma (hematoxylin-eosin, X340).
turation, pearl formation, premature ma¬ turation, hyperkeratosis, large pleomorphic cells with prominent nucleoli (Fig 6), and several mitotic figures in every high-
power field. No evidence of recurrent tu¬ mor was found at follow-up seven months later. The patient has since been lost to fol¬
low-up.
465.-Unfortunately, no his¬ follow-up information is available for this 48-year-old man. The enucleation specimen shows deep corneal invasion by tumor (Fig 7). Case 6 EP 3282.-A 50-year-old man gave a two-year history of a whitish growth of the temporal bulbar conjunctiva Case 5 EP
tory
or
of the left eye. It had been cauterized else¬ where and subsequently spread to involve the cornea. Vision was decreased to light perception in the involved eye. Examina¬ tion revealed a white elevated growth tem¬ porally at 3 to 4 mm from the limbus. There was superficial and deep vascularization of the cornea. No fundus details could be seen. The eye was enucleated. Mi¬ croscopic examination revealed diffuse deep stromal infiltration of the cornea by tumor (Fig 8). There was no evidence of re¬ currence at the time of death about 30 years later. Case 7 EP 36792.-A 60-year-old Paki¬ stani man had a large fungating corneal lesion of five months' duration. He re¬ quested enucleation because of pain. The specimen showed deep corneal invasion. No follow-up information is available on this recent case. Case 8 EP 17251.-A 51-year-old white woman had a mass of five months' dura-
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Fig 7 (EP 465).—Deep corneal invasion by large squamous cell carcinoma (hema¬ toxylin-eosin, x18). tion in the inferior fornix of the right eye. A biopsy was done that revealed carci¬ noma, and an exenteration was performed. One year later nodules were noted in the neck and a radical neck dissection was car¬ ried out that showed metastatic squamous cell carcinoma. The patient died six months later of generalized métastases. Case 9 EP 24473.-A 65-year-old woman had a three-year history of redness and ir¬ ritation superiorly in the left eye. Biopsy was recommended but was refused for near¬ ly a year, at which time several pieces of biopsy tissue from the superior cul-de-sac revealed poorly-differentiated squamous cell carcinoma. This was treated with irra¬ diation. Repeat biopsy two years later
showed
only chronic inflammation. How¬ diagnosis
a recurrence in the orbit was found and cised. Four months later, a radical left
ex¬ su¬
perficial parotidectomy was performed for metastatic squamous cell carcinoma. Four years after this operation, the patient de¬ veloped an adenocarcinoma of the bowel, which was partially resected. The patient died shortly thereafter of her bowel dis¬ ease. There was no further evidence of residual conjunctival tumor.
Comment Most authors indicate that local ex¬ cision with or without irradiation is the treatment of choice of these tu¬ mors. It would appear that this is ade¬ quate initial therapy if begun early. In our cases, recurrences, other than the fatal case, were treated success¬ fully either by repeated local excision and irradiation or by exenteration when location or extent precluded lo¬ cal excision. However, there was deep corneal invasion in three subjects and intraocular invasion in two additional subjects in this series. In these in¬ stances, superficial local excision would be inadequate. More extensive procedures, such as deep lamellar keratoplasty and scleroplasty, as advo¬ cated by Zimmerman,1-8 might be used to remove all the tumor and yet preserve the globe. When these proce¬ dures are feasible they may be ac¬ ceptable, but attention must be paid to the possibility of deep corneal, in¬ traocular, orbital, and lid involvement by the tumor. In these cases, enuclea¬ tion or orbital exenteration are the treatment of choice.7 Therefore, close cooperation between clinician and pa¬ thologist, and meticulous examina¬ tion of the deep as well as peripheral margins of locally excised tissue, are necessary to rule out the possibility of incomplete excision. It is interesting that in the cases in which duration is known, most are of six months' duration or more. In the fatal case, the duration prior to diag-
rather unlikely. Tumors in this age group are extremely rare, occur¬ ring most often on patients with xeroderma pigmentosum as in our other young patient (age 12). Zim¬ merman1 has noted the occurrence of squamous cell carcinoma in children and young adults from outside the United States. There was no evidence of xeroderma pigmentosum in the 4year-old patient at the time of sur¬ gery or at follow-up five years later. It is noteworthy that in two of our 27 cases, second primary internal ma¬ lignant neoplasms developed that led directly or indirectly to the death of the patient. Though this is not a striking incidence, the possibility of an increased risk of the development of a second tumor should not be over¬ looked. seems
ever, four years after the initial
Fig 8 (EP 3282).-Cornea is infiltrated widely with small islands of tumor (hema¬ toxylin-eosin, 110). nosis
was five months. Métastases noted one year after exentera¬ tion in that subject and a radical neck dissection was performed. Death due to metastatic tumor occurred 18 months after exenteration. The easy accessibility, the low re¬ currence rate, the apparent slow growth and low-grade histologie ap¬ pearance all indicate that these le¬ sions, although often invasive, can best be treated by local excision and still have a good prognosis, especially with adequate examination of excised material. These factors, coupled with were
relatively simple treatment proce¬ dures and good follow-up of the tu¬
mor site would tend to make preser¬ vation of useful vision common and fatal outcomes rare. However, as demonstrated here, a relatively early diagnosis in conjunction with radical surgery is not always curative. We have no ready explanation for the tumor that appeared in the 4-
year-old girl. Perhaps some agent used during the strabismus surgery was carcinogenic to her, but this
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/04/2015
Charles E.
manuscript, assistance.
Iliff, MD, critically reviewed the and David Andrews gave editorial
References 1. Zimmerman LE: The Poklington memorial lecture: The cancerous, precancerous and pseudocancerous lesions of the cornea and conjunctiva, in Rycroft PV (ed): Corneo-Plastic Surgery. New York, Pergamon Press, 1969, pp 547-555. 2. Fran\l=c;\oisJ, Hanssens M, Germen M: liomas perforants du limbe et de la conjonctive bulbaire. Ann Oculist 200:505-521, 1967. 3. Greer CH: Limbal epithelioma with intraocular invasion. Br J Ophthalmol 46:306-307, 1962. 4. Stokes JJ: Intraocular extension of epibulbar squamous cell carcinoma of the limbus. Trans Am Acad Ophthalmol Otolaryngol 59:143\x=req-\ 146, 1955. 5. Dollfus MA: Un cas d'\l=e'\pith\l=e'\liomaperforant du limbe et consid\l=e'\rationscliniques et th\l=e'\rapeutiques sur les \l=e'\pith\l=e'\liomasde la conjonctive bulbaire observ\l=e'\sdepuis 30 ans \l=a`\la Fondation Curie \l=a`\Paris. Bull Soc Belge Ophthalmol 146:295\x=req-\ 301, 1967. 6. Duke-Elder S: System of Ophthalmology. London, Henry Kimpton, 1965, vol 8, pp 1165\x=req-\ 1175. 7. Irvine AR Jr: Dyskeratotic epibulbar tumors. Trans Am Ophthalmol Soc 61:243-273, 1963. 8. Zimmerman LE: Squamous cell carcinoma and related lesions of the bulbar conjunctiva, in Boniuk M (ed): Ocular and Adnexal Tumors. St. Louis, CV Mosby, 1964, pp 49-74.
\l=E'\pith\l=e'\-
Iliff, MD;
Roberto
Marback, MD; W. Richard Green, MD
In 27 cases of invasive conjunctival squamous cell carcinoma, three cases of deep corneal invasion and two cases of intraocular extension were found. Four cases showed orbital invasion, and one patient died of generalized metastases 18 months after diagnosis. The relatively low-grade nature of these lesions and their potential for local treatment is noted, but it is emphasized that careful clinical examination and close cooperation with the pathologist to ensure adequate evaluation of excised tissue are essential.
lesions is not well known. Recent acquisition of several inter¬ esting cases of squamous cell carci¬ noma of the conjunctiva, including with intraocular extension, one prompted the present study and this brief description of Wilmer Institute cases of invasive squamous cell carci¬ noma of the conjunctiva with in¬ traocular extension. Materials and Methods All cases squamous cell
coded
as
carcinoma,
epithelioma,
squamous carcinoma of the conjunctiva is uncommon, and intraocular extension of squamous cell carcinoma is very rare.1 François, et al,2 in 1967, collected only 49 cases from the literature and described an additional one. Greer,3 Stokes,4 and Dollfus5 have each described an addi¬ tional case, and Duke-Elder6 makes reference to several. Irvine7 reported 104 cases of "dyskeratotic epibulbar tumors," and in that series there was only one case of intraocular extension in 20 cases of squamous cell carci¬ noma. These various authors stress the rarity of this condition. The inci¬ dence and biologic behavior of these
carcinoma in situ of the cornea and conjunctiva on file in the eye pathology laboratory of the Wil¬ mer Institute of the Johns Hopkins Hospi¬ tal were examined. A total of 65 cases was encountered and analyzed for age, sex,
Submitted for publication Oct 24, 1973. From the Eye Pathology Laboratory, The WilInstitute, and the Department of Pathology, The Johns Hopkins Medical Institutions, Balti-
atypical papillomata (2), pseudoepitheliomatous hyperplasia (2), and ma¬ lignant melanoma (1). Of the 50 cases remaining, the 27 invasive cases are the subject of this report. The major incidence of inva-
Invasive
mer
more.
Reprint requests to Eye Pathology Laboratory, Johns Hopkins Hospital, 601 N Broadway, MD 21205 (Dr. Green).
race, tumor
and
or
location, duration, treatment,
follow-up when
available.
Results
Of the 65 cases, 27 proved to be in¬ were in situ, and 15 were excluded from the study for a variety of reasons that included insufficient material for review (4), secondary in¬ volvement from a lid tumor (2), and reclassification as benign or a nonsquamous lesion (9). The nine reclassified cases included dysplasia (4),
vasive, 23
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sive squamous carcinoma was in the sixth decade. The age range was 4 to 77 years, that includes two unusual cases arising in children ages 4 and 12. By decade, occurrence was as fol¬ lows: 0-10,1 case; 11-20,1; 21-30,1; 3140, 1; 41-50, 3; 51-60, 12; 61-70, 4; and 71 and up, 4. There were 17 male sub¬ jects and ten female subjects with in¬ vasive tumor. Although race was un¬ known in four of the 27 cases, it was white in all but two of the remainder. One patient was a Pakistani man and one was an Indian woman from Bra¬ zil. In the 27 invasive cases, the limbus was the most commonly involved re¬ gion (17: 4 temporal, 3 nasal, and 10 not specified), although the palpebrai (3) and forniceal (3) conjunctivae were also occasionally the primary site. The bulbar conjunctiva was the site in two patients, and the tumor was diffuse, in two other patients. Treatment in this series consisted of local excision (with and without ir¬
radiation), enucleation,
or
exentera-
tion. A breakdown of the treatment was as follows: excisional biopsy, 10; excisional biopsy plus irradiation, 4; biopsy and irradiation, 3; exenteration, 6; and enucleation, 4. Several cases showed definitely incomplete lo¬ cal excision but all but one of these were cases of biopsy for diagnosis only. In this one subject, there was no recurrence eight years later. Of the six cases treated with exenteration,
Fig 3 (EP 31055).—Raised white lesion straddling limbus with dilated vessels tem¬ porally and lipid in the cornea nasally.
Fig 1 (EP 21007).—Limbal toxylin-eosin, X140).
area
showing deep corneal
and intraocular invasion
(hema¬
Fig 4 (EP 31055).—Gross appearance of thickened limbal zone temporally after re¬ moval of superior cap. years in six subjects, five to nine years in six, and ten years or more in five—with two being followed 30 years without evidence of recurrent
Fig 2 (EP 21007).—Higher power of angle structures showing tumor Invasion of out¬ flow channels, Schlemm's canal, and trabecular meshwork (hematoxylin-eosin, 140). orbital invasion was observed in three, intraocular extension in one, and lid involvement in two. In the four enucleation specimens, there was deep corneal invasion in three and in¬ traocular invasion in one. In cases with adequate follow-up, there were recurrences in eight of 22 cases (36%) with all but one of the eight after local treatment (three af¬ ter local excision, four after excision or biopsy with irradiation, and one af¬ ter exenteration). Two recurrences were seen in two patients. Recur¬ rences were treated by re-excision (13) or re-excision with irradiation (1), exenteration (2), or radical neck dissection (2). Follow-up data are available in all but the two earliest cases and the
three most recent ones. Of the 22 pa¬ tients with follow-up, four had less than one year follow-up but all were free of tumor when last seen. One of these four died of unrelated causes eight months after excision. The other cases (18) had from two
thirty years follow-up. Of these, two developed metastasis (treated by excision and radical neck years
to
dissection) and one of these two died of
malignancy 18 months after initial treatment. The other developed an adenocarcinoma of the bowel eight years after the conjunctival tumor and has since died from her bowel malignant neoplasm without evi¬ dence of recurrent conjunctival tu¬ mor. Thus 17 subjects were free of tu¬ mor with a follow-up of two to four
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/04/2015
disease. Several unusual features were ob¬ served as follows: occurrence in young individuals (2), intraocular extension (2), deep corneal invasion (3), and re¬ gional métastases (2). These nine cases with unusual features are pre¬ sented briefly.
Report of Cases Case 1 EP 25790.-A 4-year-old white girl developed a lesion in the inferior pal¬ pebrai conjunctiva one year after stra¬ bismus surgery. The patient was treated with local excision and is free of tumor at follow-up five years after surgery. Diag¬ nosis was invasive squamous cell carci¬ noma. No evidence of foreign bodies was seen.
Case 2 EP 9735.-The patient was a 12year-old white girl who developed a lesion involving the limbus and cornea. The patient was known to have xeroderma pigmentosum and was treated by local exci¬ sion. Diagnosis was squamous cell car¬ cinoma of conjunctiva with superficial invasion of the cornea. Although vision is poor in the involved eye, there is no evi¬ dence of recurrence 25 years after removal
Fig
Fig 5 (EP 31055).—An
be
seen
island of tumor in
in scierai canal to
X110).
supraciliary space (long arrows). Tumor can right (short arrow) and in sclera above (hematoxylin-eosin,
of tumor. Case 3 EP 21007.-A 63-year-old white man had a tumor in the temporal limbus of the left eye. A biopsy was performed in 1959, 15 months prior to admission. A diagnosis of squamous cell carcinoma of the conjunctiva was made. The patient was not treated further and was lost to followup until early 1961 when he presented again; a recurrent tumor with probable in¬ traocular invasion was found. Exentera¬ tion was performed, which showed deep corneal stromal invasion (Fig 1) and tumor infiltration of Schlemm canal and trabecu¬ lar meshwork (Fig 2). The patient died four years later of sepsis following a pro¬ cedure for transitional-cell carcinoma of the bladder. There was no evidence of re¬ current
conjunctival
tumor.
Case 4 EP 31055.-A 54-year-old Indian woman had noted a lesion in the temporal limbus of the right eye for two years and an increase in size in the three months pre¬ ceding examination (Fig 3). Because of clinical suspicion of intraocular invasion, an enucleation was performed. Gross ex¬ amination of the enucleated eye revealed an eye normal in all respects except for the presence of a 10x7x1.5 mm lesion at the temporal limbus from 7 to 11 o'clock, and after opening the eye, the tumor seemed to have invaded the cornea and deep struc¬ tures (Fig 4). Microscopical examination revealed tumor on the outer surface and infiltrating deeply to invade a preformed scierai canal anteriorly and gain access to the supraciliary space posteriorly (Fig 5). Histologically, the tumor showed a typical squamous pattern with loss of normal ma-
6
(EP 31055).-Typical histologie
pattern of invasive squamous cell carci¬ noma (hematoxylin-eosin, X340).
turation, pearl formation, premature ma¬ turation, hyperkeratosis, large pleomorphic cells with prominent nucleoli (Fig 6), and several mitotic figures in every high-
power field. No evidence of recurrent tu¬ mor was found at follow-up seven months later. The patient has since been lost to fol¬
low-up.
465.-Unfortunately, no his¬ follow-up information is available for this 48-year-old man. The enucleation specimen shows deep corneal invasion by tumor (Fig 7). Case 6 EP 3282.-A 50-year-old man gave a two-year history of a whitish growth of the temporal bulbar conjunctiva Case 5 EP
tory
or
of the left eye. It had been cauterized else¬ where and subsequently spread to involve the cornea. Vision was decreased to light perception in the involved eye. Examina¬ tion revealed a white elevated growth tem¬ porally at 3 to 4 mm from the limbus. There was superficial and deep vascularization of the cornea. No fundus details could be seen. The eye was enucleated. Mi¬ croscopic examination revealed diffuse deep stromal infiltration of the cornea by tumor (Fig 8). There was no evidence of re¬ currence at the time of death about 30 years later. Case 7 EP 36792.-A 60-year-old Paki¬ stani man had a large fungating corneal lesion of five months' duration. He re¬ quested enucleation because of pain. The specimen showed deep corneal invasion. No follow-up information is available on this recent case. Case 8 EP 17251.-A 51-year-old white woman had a mass of five months' dura-
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Fig 7 (EP 465).—Deep corneal invasion by large squamous cell carcinoma (hema¬ toxylin-eosin, x18). tion in the inferior fornix of the right eye. A biopsy was done that revealed carci¬ noma, and an exenteration was performed. One year later nodules were noted in the neck and a radical neck dissection was car¬ ried out that showed metastatic squamous cell carcinoma. The patient died six months later of generalized métastases. Case 9 EP 24473.-A 65-year-old woman had a three-year history of redness and ir¬ ritation superiorly in the left eye. Biopsy was recommended but was refused for near¬ ly a year, at which time several pieces of biopsy tissue from the superior cul-de-sac revealed poorly-differentiated squamous cell carcinoma. This was treated with irra¬ diation. Repeat biopsy two years later
showed
only chronic inflammation. How¬ diagnosis
a recurrence in the orbit was found and cised. Four months later, a radical left
ex¬ su¬
perficial parotidectomy was performed for metastatic squamous cell carcinoma. Four years after this operation, the patient de¬ veloped an adenocarcinoma of the bowel, which was partially resected. The patient died shortly thereafter of her bowel dis¬ ease. There was no further evidence of residual conjunctival tumor.
Comment Most authors indicate that local ex¬ cision with or without irradiation is the treatment of choice of these tu¬ mors. It would appear that this is ade¬ quate initial therapy if begun early. In our cases, recurrences, other than the fatal case, were treated success¬ fully either by repeated local excision and irradiation or by exenteration when location or extent precluded lo¬ cal excision. However, there was deep corneal invasion in three subjects and intraocular invasion in two additional subjects in this series. In these in¬ stances, superficial local excision would be inadequate. More extensive procedures, such as deep lamellar keratoplasty and scleroplasty, as advo¬ cated by Zimmerman,1-8 might be used to remove all the tumor and yet preserve the globe. When these proce¬ dures are feasible they may be ac¬ ceptable, but attention must be paid to the possibility of deep corneal, in¬ traocular, orbital, and lid involvement by the tumor. In these cases, enuclea¬ tion or orbital exenteration are the treatment of choice.7 Therefore, close cooperation between clinician and pa¬ thologist, and meticulous examina¬ tion of the deep as well as peripheral margins of locally excised tissue, are necessary to rule out the possibility of incomplete excision. It is interesting that in the cases in which duration is known, most are of six months' duration or more. In the fatal case, the duration prior to diag-
rather unlikely. Tumors in this age group are extremely rare, occur¬ ring most often on patients with xeroderma pigmentosum as in our other young patient (age 12). Zim¬ merman1 has noted the occurrence of squamous cell carcinoma in children and young adults from outside the United States. There was no evidence of xeroderma pigmentosum in the 4year-old patient at the time of sur¬ gery or at follow-up five years later. It is noteworthy that in two of our 27 cases, second primary internal ma¬ lignant neoplasms developed that led directly or indirectly to the death of the patient. Though this is not a striking incidence, the possibility of an increased risk of the development of a second tumor should not be over¬ looked. seems
ever, four years after the initial
Fig 8 (EP 3282).-Cornea is infiltrated widely with small islands of tumor (hema¬ toxylin-eosin, 110). nosis
was five months. Métastases noted one year after exentera¬ tion in that subject and a radical neck dissection was performed. Death due to metastatic tumor occurred 18 months after exenteration. The easy accessibility, the low re¬ currence rate, the apparent slow growth and low-grade histologie ap¬ pearance all indicate that these le¬ sions, although often invasive, can best be treated by local excision and still have a good prognosis, especially with adequate examination of excised material. These factors, coupled with were
relatively simple treatment proce¬ dures and good follow-up of the tu¬
mor site would tend to make preser¬ vation of useful vision common and fatal outcomes rare. However, as demonstrated here, a relatively early diagnosis in conjunction with radical surgery is not always curative. We have no ready explanation for the tumor that appeared in the 4-
year-old girl. Perhaps some agent used during the strabismus surgery was carcinogenic to her, but this
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/04/2015
Charles E.
manuscript, assistance.
Iliff, MD, critically reviewed the and David Andrews gave editorial
References 1. Zimmerman LE: The Poklington memorial lecture: The cancerous, precancerous and pseudocancerous lesions of the cornea and conjunctiva, in Rycroft PV (ed): Corneo-Plastic Surgery. New York, Pergamon Press, 1969, pp 547-555. 2. Fran\l=c;\oisJ, Hanssens M, Germen M: liomas perforants du limbe et de la conjonctive bulbaire. Ann Oculist 200:505-521, 1967. 3. Greer CH: Limbal epithelioma with intraocular invasion. Br J Ophthalmol 46:306-307, 1962. 4. Stokes JJ: Intraocular extension of epibulbar squamous cell carcinoma of the limbus. Trans Am Acad Ophthalmol Otolaryngol 59:143\x=req-\ 146, 1955. 5. Dollfus MA: Un cas d'\l=e'\pith\l=e'\liomaperforant du limbe et consid\l=e'\rationscliniques et th\l=e'\rapeutiques sur les \l=e'\pith\l=e'\liomasde la conjonctive bulbaire observ\l=e'\sdepuis 30 ans \l=a`\la Fondation Curie \l=a`\Paris. Bull Soc Belge Ophthalmol 146:295\x=req-\ 301, 1967. 6. Duke-Elder S: System of Ophthalmology. London, Henry Kimpton, 1965, vol 8, pp 1165\x=req-\ 1175. 7. Irvine AR Jr: Dyskeratotic epibulbar tumors. Trans Am Ophthalmol Soc 61:243-273, 1963. 8. Zimmerman LE: Squamous cell carcinoma and related lesions of the bulbar conjunctiva, in Boniuk M (ed): Ocular and Adnexal Tumors. St. Louis, CV Mosby, 1964, pp 49-74.
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