- Email: [email protected]
Ocular Surface Squamous Neoplasia in an Anophthalmic Socket 60 Years after Enucleation
SURVEY OF OPHTHALMOLOGY
VOLUME 56 NUMBER 6 NOVEMBER–DECEMBER 2011
CLINICAL PATHOLOGIC REVIEWS STEFAN SEREGARD AND MILTON BONIUK, EDITORS
Ocular Surface Squamous Neoplasia in an Anophthalmic Socket 60 Years after Enucleation Edgar M. Espana, MD,1 Mark Levine, MD,2 Lynn Schoenfield, MD,3 and Arun D. Singh, MD4,5 1
Department of Cornea, External Disease and Refractive Surgery; 2Cleveland Clinic Lorain Eye Institute; 3Department of Pathology; 4Ophthalmic Oncology; and 5The Cole Eye Institute and Taussig Cancer Center, The Cleveland Clinic, Cleveland, Ohio, USA
Abstract. Ocular surface squamous cell neoplasia in an anophthalmic socket is an exceptionally rare occurrence. We report a 62-year-old white man who had his left eye enucleated at age 2 and developed an invasive squamous cell carcinoma 60 years later. He received multiple treatments, including excisional biopsy, topical mitomycin C chemotherapy, cryotherapy, and finally exenteration. We review the literature to evaluate the clinical characteristics, time of onset following enucleation, treatment, and outcome of previously reported cases. Our case emphasizes the importance of a thorough examination of the anophthalmic socket, including upper and lower lid eversion. (Surv Ophthalmol 56:539--543, 2011. Ó 2011 Elsevier Inc. All rights reserved.) Key words.
neoplasia
anophthalmic socket
ocular surface
rate of 4%, an exenteration rate of 0.8%,11 regional and distant metastasis in 1.2%,11 and a mortality rate of 0.8%.11 A precise diagnosis requires histological evaluation to differentiate benign lesions from carcinoma in situ and invasive squamous cell carcinomas.6 Suspected risk factors for OSSN include ultraviolet light exposure,12 radiation,12 infection by human papillomavirus (HPV) types 16 and 18,14 human immunodeficiency virus infection,8,9 and chronic inflammatory diseases of the ocular surface such as mucous membrane pemphigoid, chronic blepharoconjunctivits, and atopic eczema.7 Herein, we present a case of OSSN developing in the anophthalmic socket 60 years after enucleation.
Ocular surface squamous cell neoplasia (OSSN) is a rare tumor with an incidence of 0.3 cases per million in the United States.16 Frequently, OSSN arises in the limbal region where the corneal epithelial stem cells are believed to reside. This area is also a transition zone between the conjunctival epithelium and the stratified squamous corneal epithelium. Clinically, the diagnosis is suspected by the appearance of epithelial changes. Slit lamp examination shows gelatinous, leukoplakic, or papilliform lesions on the ocular surface. Typically, OSSN is a slow-growing tumor; intraocular and orbital invasion and metastasis may occur, however. Analysis of published data from the United States5,11 and Australia11 reveals intraocular and orbital extension 539 Ó 2011 by Elsevier Inc. All rights reserved.
0039-6257/$ - see front matter doi:10.1016/j.survophthal.2011.06.005
540
Surv Ophthalmol 56 (6) November--December 2011
Fig. 1. A: Recurrent squamous cell carcinoma in the superior nasal aspect of tarsal conjunctiva of the upper lid in anophthalmic socket. B: Poorly differentiated invasive carcinoma without keratinization, which was associated with an overlying squamous carcinoma in situ. Although some areas were suggestive of sebaceous differentiation, oil red O and immunostaining for androgen receptor were both negative (40 magnification, hematoxylin and eosin).
Case Report A 62-year-old white man who had his left eye enucleated at the age of 2 years for a perforating globe injury was referred to the Cole Eye Institute for oncologic evaluation of a recurrent lesion in his left anophthalmic socket. He was initially treated for a papilloma in the upper forniceal conjunctiva 2 years before. Histopathology at that time showed a benign squamous papilloma. Six months later excisonal biopsy of a recurrent lesion showed an invasive, poorly differentiated carcinoma that was considered to be of either squamous or sebaceous derivation. One month before presentation, a second recurrent papillomatous lesion was treated with an excisional biopsy and intraoperative topical application of mitomycin C for 2 minutes, followed by
ESPANA ET AL
Fig. 2. A: Ulcerated surface squamous epithelium with deeply invasive poorly differentiated carcinoma. There is no keratinization, but it appears similar to the patient’s previous invasive tumor, which had been associated with squamous dysplasia and squamous carcinoma in situ (4 magnification, hematoxylin and eosin). B: High power showing invasive tumor islands consisting of nonkeratinizing poorly differentiated cells with atypical mitosis. Surrounding stroma is inflamed. In the context of previous squamous cell carcinoma in situ, this is considered to be a squamous cell carcinoma, recurrent (40 magnification, hematoxylin and eosin).
5-fluorouracil (1%) four times a day for 4 weeks. Pathology showed severe squamous dysplasia/ squamous carcinoma in situ (OSSN3) without invasion and absence of obvious sebaceous differentiation. At the initial examination, he denied smoking and had no relevant medical history. He was wearing a prosthesis with no discharge from the anophthalmic socket. Preauricular and submandibular lymph nodes were not palpable. No evident lesions were noted in the socket. Lashes were intact, and lids were normal. Examination of the upper and lower tarsus was normal by inspection and palpation.
Summary of Published Cases of Ocular Surface Squamous Neoplasia in the Anophthalmic Socket Author (Year) Campanella (1998)
2
Number of Cases
Age/Sex
Prosthesis Use (years)
2
69/M
49
Right orbital exenteration
77/M
43
Right orbital exenteration
Treatment
Whittaker (2002)18
1
62/M
49
Excisional biopsy with lid and fornix reconstruction
Endo (2006)4
1
51/M
40
Chaudhry (2006)3
1
50/M
50
Nguyen (2008)15
2
58/M
51
Exenteration of the orbit, superficial parotidectomy, and modified neck dissection. Two cycles of systemic chemo (cisplastin/fluorouracil) and radiation Excisional biopsy and enucleation, radiotherapy Left orbital exenteration
56/M
44
Right orbital exenteration
Barrett (2010)1
1
58/M
32
Topical mitomycin-C
Current study (2010)
1
62/M
60
Summary data
9
60.3 (Average)
44.8 (Average)
Excisional biopsy, topical mitomycin-C, cryotherapy, exenteration Exenteration rate 67%
Location/Histopathology
Outcome
Superior tarsal conjunctiva, nonkeratinizing SCC with metastasis to the parotid gland Upper eyelid, superior fornix; diffuse nonkeratinizing SCC Medial one third of the right lower lid and palpebral conjunctiva. Infiltrating SCC of the skin and in situ of the conjunctiva Lower left inferior conjunctiva with tissue invasion, well-differentiated keratinizing SCC; metastasis to the submandibular lymph nodes
Not reported
Left socket, unspecified location; moderately differentiated SCC Left upper bulbar conjunctiva, invasive, poorly differentiated invasive conjunctival SCC Right bulbar conjunctiva; invasive conjunctival SCC Left diffuse superior fornix SCC in situ Left superior fornix SCC
Not reported Tumor-free at 7 months Tumor-free at 15 months
OCULAR SURFACE SQUAMOUS CELL NEOPLASIA
TABLE 1
Tumor-free at 36 months Tumor-free at 12 months Tumor-free at 2 years Tumor-free at 10 months follow-up Tumor-free at 1 month
Regional metastasis rate 22%
541
542
Surv Ophthalmol 56 (6) November--December 2011
Examination of the right eye was unremarkable. Due to the history of multiple recurrences, topical 0.04% mitomycin C for four cycles (one week on and one week off) was recommended. Four months after the fourth cycle, a recurrent lesion was noted in the superior nasal aspect of tarsal conjunctiva of the upper lid (Fig. 1A). In addition to excisional tarsal conjunctival biopsy of the recurrent lesion, which pathologically revealed invasive and in situ carcinoma (squamous type), double freeze/thaw cryotherapy was applied to the whole upper tarsal conjunctiva (Fig. 1B). Additional biopsies of adjacent, clinically uninvolved upper eyelid conjunctiva and tarsus were free of tumor. He did well for a approximately 9 months, but then developed deeper orbital recurrence that required exenteration. The margins were tumor-free (Fig. 2). Chromatographic in situ hybridization for low-risk and high-risk HPV types were both negative.
Discussion OSSN in anophthalmic sockets is very rare. 1--4,15,18 A detailed review of the eight published cases revealed some interesting characteristics that could be distinctive of OSSN (Table 1). All patients were male, and the age at diagnosis ranged between 50 and 77 years (mean, 60.1 years). There was a long interval between enucleation and the OSSN diagnosis, from 32 to 60 years (mean, 44.8 years). Our case represents the longest interval postenucleation. The upper eyelid was the most common site. Compared to low rates of local invasion, exenteration, and regional metastasis,5,11 an alarming observation in patients with OSSN in an anophthalmic socket was the advanced stage of the tumor at diagnosis, with six of nine (including the current study) requiring orbital exenteration. Moreover, metastatic lymph node spread was noted in two of the nine, confirming the aggressive behavior or delayed diagnosis of OSSN in anophthalmic sockets. Perhaps presence of prosthesis-induced inflammation masked the signs and symptoms of OSSN that could have led to early diagnosis. The exact cause of OSSN in the anophthalmic socket in our patient is unknown, because there was no possibility of ultraviolet light exposure of the conjunctival surface, which had been covered by the ocular prosthesis since the age 2. This patient did not have other known risk factors for developing OSSN, such as human papillomavirus, human immunodeficiency virus infection, immunosuppression, or smoking. Moreover, limbal stem cells, presumed to be the cell of origin of
ESPANA ET AL
OSSN, are either absent or greatly diminished after enucleation. Chronic inflammation is increasingly implicated in a variety of cancers.10,13 For example, periodontis confers an increased risk of head and neck squamous cell carcinoma.17 Similarly, it is quite plausible that chronic inflammation created by the ocular prosthesis may be a risk factor for OSSN. The predominant involvement of the upper eyelid, which has the most excursion and contact over the prosthesis, supports this view. In conclusion, we present a case of OSSN of the upper palpebral conjunctival surface of an anophthalmic socket with multiple recurrences . Chronic inflammation induced by long-term use of prosthesis may be a risk factor for OSSN. Moreover, presence of prosthesis-induced inflammation may mask the signs and symptoms of OSSN, delaying the diagnosis. Ophthalmologists should be aware of this entity during the evaluation of any patient with an anophthalmic socket. The current case, which occurred 60 years after enucleation, emphasizes the importance of long-term clinical surveillance to monitor for the development of OSSN. Careful examination of the anophthalmic socket with upper and lower eyelid eversion should be part of the physical examination.
Method of Literature Search The references in our review were obtained using Medline and the National Library of Medicine PubMed database. Only articles published in the English language were reviewed. A total of six articles were found. Key words used included anophthalmic cavity, anophthalmic socket, orbital squamous cell carcinoma, ocular surface neoplasia and enucleation. Relevant references within these articles were also reviewed.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Barrett RV, Meyer DR, Carlson JA. Conjunctival squamous cell carcinoma in situ in the anophthalmic socket. Ophthal Plast Reconstr Surg. 2010;26:52--3 2. Campanella PC, Goldberg SH, Erlichman K, et al. Squamous cell tumors and ocular prostheses. Ophthal Plast Reconstr Surg. 1998;14:45--9
OCULAR SURFACE SQUAMOUS CELL NEOPLASIA 3. Chaudhry TA, Memon M, Ahmad K. Use of artificial eye and conjunctival squamous cell carcinoma. J Postgrad Med. 2006;52:234--5 4. Endo T, Hata J, Togashi S, et al. Conjunctival squamous cell carcinoma of the orbit 40 years after enucleation. Ophthal Plast Reconstr Surg. 2006;22:299--301 5. Erie JC, Campbell RJ, Liesegang TJ. Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology. 1986;93:176--83 6. Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea. 1987;6:78--116 7. Heinz C, Fanihagh F, Steuhl KP. Squamous cell carcinoma of the conjunctiva in patients with atopic eczema. Cornea. 2003;22:135--7 8. Karp CL, Scott IU, Chang TS, et al. Conjunctival intraepithelial neoplasia. A possible marker for human immunodeficiency virus infection? Arch Ophthalmol. 1996;114: 257--61 9. Kestelyn P, Stevens AM, Ndayambaje A, et al. HIV and conjunctival malignancies. Lancet. 1990;336:51--2 10. Lax AJ, Thomas W. How bacteria could cause cancer: one step at a time. Trends Microbiol. 2002;10:293--9 11. Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol. 1995;39:429--50
543 12. Lee GA, Williams G, Hirst LW, et al. Risk factors in the development of ocular surface epithelial dysplasia. Ophthalmology. 1994;101:360--4 13. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454:436--44 14. McDonnell JM, McDonnell PJ, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia. Arch Ophthalmol. 1986;104:1801--5 15. Nguyen J, Ivan D, Esmaeli B. Conjunctival squamous cell carcinoma in the anophthalmic socket. Ophthal Plast Reconstr Surg. 2008;4:98--101 16. Sun EC, Fears TR, Goedert JJ. Epidemiology of squamous cell conjunctival cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:73--7 17. Tezal M, Sullivan MA, Hyland A, et al. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2009;18:2406--12 18. Whittaker KW, Trivedi D, Bridger J, et al. Ocular surface squamous neoplasia: report of an unusual case and review of the literature. Orbit. 2002;21:209--15 Reprint address: Arun D. Singh, MD, Director of Ophthalmic Oncology, Cole Eye Institute and Taussig Cancer Center, Cleveland, OH 44195 USA. e-mail: [email protected].
VOLUME 56 NUMBER 6 NOVEMBER–DECEMBER 2011
CLINICAL PATHOLOGIC REVIEWS STEFAN SEREGARD AND MILTON BONIUK, EDITORS
Ocular Surface Squamous Neoplasia in an Anophthalmic Socket 60 Years after Enucleation Edgar M. Espana, MD,1 Mark Levine, MD,2 Lynn Schoenfield, MD,3 and Arun D. Singh, MD4,5 1
Department of Cornea, External Disease and Refractive Surgery; 2Cleveland Clinic Lorain Eye Institute; 3Department of Pathology; 4Ophthalmic Oncology; and 5The Cole Eye Institute and Taussig Cancer Center, The Cleveland Clinic, Cleveland, Ohio, USA
Abstract. Ocular surface squamous cell neoplasia in an anophthalmic socket is an exceptionally rare occurrence. We report a 62-year-old white man who had his left eye enucleated at age 2 and developed an invasive squamous cell carcinoma 60 years later. He received multiple treatments, including excisional biopsy, topical mitomycin C chemotherapy, cryotherapy, and finally exenteration. We review the literature to evaluate the clinical characteristics, time of onset following enucleation, treatment, and outcome of previously reported cases. Our case emphasizes the importance of a thorough examination of the anophthalmic socket, including upper and lower lid eversion. (Surv Ophthalmol 56:539--543, 2011. Ó 2011 Elsevier Inc. All rights reserved.) Key words.
neoplasia
anophthalmic socket
ocular surface
rate of 4%, an exenteration rate of 0.8%,11 regional and distant metastasis in 1.2%,11 and a mortality rate of 0.8%.11 A precise diagnosis requires histological evaluation to differentiate benign lesions from carcinoma in situ and invasive squamous cell carcinomas.6 Suspected risk factors for OSSN include ultraviolet light exposure,12 radiation,12 infection by human papillomavirus (HPV) types 16 and 18,14 human immunodeficiency virus infection,8,9 and chronic inflammatory diseases of the ocular surface such as mucous membrane pemphigoid, chronic blepharoconjunctivits, and atopic eczema.7 Herein, we present a case of OSSN developing in the anophthalmic socket 60 years after enucleation.
Ocular surface squamous cell neoplasia (OSSN) is a rare tumor with an incidence of 0.3 cases per million in the United States.16 Frequently, OSSN arises in the limbal region where the corneal epithelial stem cells are believed to reside. This area is also a transition zone between the conjunctival epithelium and the stratified squamous corneal epithelium. Clinically, the diagnosis is suspected by the appearance of epithelial changes. Slit lamp examination shows gelatinous, leukoplakic, or papilliform lesions on the ocular surface. Typically, OSSN is a slow-growing tumor; intraocular and orbital invasion and metastasis may occur, however. Analysis of published data from the United States5,11 and Australia11 reveals intraocular and orbital extension 539 Ó 2011 by Elsevier Inc. All rights reserved.
0039-6257/$ - see front matter doi:10.1016/j.survophthal.2011.06.005
540
Surv Ophthalmol 56 (6) November--December 2011
Fig. 1. A: Recurrent squamous cell carcinoma in the superior nasal aspect of tarsal conjunctiva of the upper lid in anophthalmic socket. B: Poorly differentiated invasive carcinoma without keratinization, which was associated with an overlying squamous carcinoma in situ. Although some areas were suggestive of sebaceous differentiation, oil red O and immunostaining for androgen receptor were both negative (40 magnification, hematoxylin and eosin).
Case Report A 62-year-old white man who had his left eye enucleated at the age of 2 years for a perforating globe injury was referred to the Cole Eye Institute for oncologic evaluation of a recurrent lesion in his left anophthalmic socket. He was initially treated for a papilloma in the upper forniceal conjunctiva 2 years before. Histopathology at that time showed a benign squamous papilloma. Six months later excisonal biopsy of a recurrent lesion showed an invasive, poorly differentiated carcinoma that was considered to be of either squamous or sebaceous derivation. One month before presentation, a second recurrent papillomatous lesion was treated with an excisional biopsy and intraoperative topical application of mitomycin C for 2 minutes, followed by
ESPANA ET AL
Fig. 2. A: Ulcerated surface squamous epithelium with deeply invasive poorly differentiated carcinoma. There is no keratinization, but it appears similar to the patient’s previous invasive tumor, which had been associated with squamous dysplasia and squamous carcinoma in situ (4 magnification, hematoxylin and eosin). B: High power showing invasive tumor islands consisting of nonkeratinizing poorly differentiated cells with atypical mitosis. Surrounding stroma is inflamed. In the context of previous squamous cell carcinoma in situ, this is considered to be a squamous cell carcinoma, recurrent (40 magnification, hematoxylin and eosin).
5-fluorouracil (1%) four times a day for 4 weeks. Pathology showed severe squamous dysplasia/ squamous carcinoma in situ (OSSN3) without invasion and absence of obvious sebaceous differentiation. At the initial examination, he denied smoking and had no relevant medical history. He was wearing a prosthesis with no discharge from the anophthalmic socket. Preauricular and submandibular lymph nodes were not palpable. No evident lesions were noted in the socket. Lashes were intact, and lids were normal. Examination of the upper and lower tarsus was normal by inspection and palpation.
Summary of Published Cases of Ocular Surface Squamous Neoplasia in the Anophthalmic Socket Author (Year) Campanella (1998)
2
Number of Cases
Age/Sex
Prosthesis Use (years)
2
69/M
49
Right orbital exenteration
77/M
43
Right orbital exenteration
Treatment
Whittaker (2002)18
1
62/M
49
Excisional biopsy with lid and fornix reconstruction
Endo (2006)4
1
51/M
40
Chaudhry (2006)3
1
50/M
50
Nguyen (2008)15
2
58/M
51
Exenteration of the orbit, superficial parotidectomy, and modified neck dissection. Two cycles of systemic chemo (cisplastin/fluorouracil) and radiation Excisional biopsy and enucleation, radiotherapy Left orbital exenteration
56/M
44
Right orbital exenteration
Barrett (2010)1
1
58/M
32
Topical mitomycin-C
Current study (2010)
1
62/M
60
Summary data
9
60.3 (Average)
44.8 (Average)
Excisional biopsy, topical mitomycin-C, cryotherapy, exenteration Exenteration rate 67%
Location/Histopathology
Outcome
Superior tarsal conjunctiva, nonkeratinizing SCC with metastasis to the parotid gland Upper eyelid, superior fornix; diffuse nonkeratinizing SCC Medial one third of the right lower lid and palpebral conjunctiva. Infiltrating SCC of the skin and in situ of the conjunctiva Lower left inferior conjunctiva with tissue invasion, well-differentiated keratinizing SCC; metastasis to the submandibular lymph nodes
Not reported
Left socket, unspecified location; moderately differentiated SCC Left upper bulbar conjunctiva, invasive, poorly differentiated invasive conjunctival SCC Right bulbar conjunctiva; invasive conjunctival SCC Left diffuse superior fornix SCC in situ Left superior fornix SCC
Not reported Tumor-free at 7 months Tumor-free at 15 months
OCULAR SURFACE SQUAMOUS CELL NEOPLASIA
TABLE 1
Tumor-free at 36 months Tumor-free at 12 months Tumor-free at 2 years Tumor-free at 10 months follow-up Tumor-free at 1 month
Regional metastasis rate 22%
541
542
Surv Ophthalmol 56 (6) November--December 2011
Examination of the right eye was unremarkable. Due to the history of multiple recurrences, topical 0.04% mitomycin C for four cycles (one week on and one week off) was recommended. Four months after the fourth cycle, a recurrent lesion was noted in the superior nasal aspect of tarsal conjunctiva of the upper lid (Fig. 1A). In addition to excisional tarsal conjunctival biopsy of the recurrent lesion, which pathologically revealed invasive and in situ carcinoma (squamous type), double freeze/thaw cryotherapy was applied to the whole upper tarsal conjunctiva (Fig. 1B). Additional biopsies of adjacent, clinically uninvolved upper eyelid conjunctiva and tarsus were free of tumor. He did well for a approximately 9 months, but then developed deeper orbital recurrence that required exenteration. The margins were tumor-free (Fig. 2). Chromatographic in situ hybridization for low-risk and high-risk HPV types were both negative.
Discussion OSSN in anophthalmic sockets is very rare. 1--4,15,18 A detailed review of the eight published cases revealed some interesting characteristics that could be distinctive of OSSN (Table 1). All patients were male, and the age at diagnosis ranged between 50 and 77 years (mean, 60.1 years). There was a long interval between enucleation and the OSSN diagnosis, from 32 to 60 years (mean, 44.8 years). Our case represents the longest interval postenucleation. The upper eyelid was the most common site. Compared to low rates of local invasion, exenteration, and regional metastasis,5,11 an alarming observation in patients with OSSN in an anophthalmic socket was the advanced stage of the tumor at diagnosis, with six of nine (including the current study) requiring orbital exenteration. Moreover, metastatic lymph node spread was noted in two of the nine, confirming the aggressive behavior or delayed diagnosis of OSSN in anophthalmic sockets. Perhaps presence of prosthesis-induced inflammation masked the signs and symptoms of OSSN that could have led to early diagnosis. The exact cause of OSSN in the anophthalmic socket in our patient is unknown, because there was no possibility of ultraviolet light exposure of the conjunctival surface, which had been covered by the ocular prosthesis since the age 2. This patient did not have other known risk factors for developing OSSN, such as human papillomavirus, human immunodeficiency virus infection, immunosuppression, or smoking. Moreover, limbal stem cells, presumed to be the cell of origin of
ESPANA ET AL
OSSN, are either absent or greatly diminished after enucleation. Chronic inflammation is increasingly implicated in a variety of cancers.10,13 For example, periodontis confers an increased risk of head and neck squamous cell carcinoma.17 Similarly, it is quite plausible that chronic inflammation created by the ocular prosthesis may be a risk factor for OSSN. The predominant involvement of the upper eyelid, which has the most excursion and contact over the prosthesis, supports this view. In conclusion, we present a case of OSSN of the upper palpebral conjunctival surface of an anophthalmic socket with multiple recurrences . Chronic inflammation induced by long-term use of prosthesis may be a risk factor for OSSN. Moreover, presence of prosthesis-induced inflammation may mask the signs and symptoms of OSSN, delaying the diagnosis. Ophthalmologists should be aware of this entity during the evaluation of any patient with an anophthalmic socket. The current case, which occurred 60 years after enucleation, emphasizes the importance of long-term clinical surveillance to monitor for the development of OSSN. Careful examination of the anophthalmic socket with upper and lower eyelid eversion should be part of the physical examination.
Method of Literature Search The references in our review were obtained using Medline and the National Library of Medicine PubMed database. Only articles published in the English language were reviewed. A total of six articles were found. Key words used included anophthalmic cavity, anophthalmic socket, orbital squamous cell carcinoma, ocular surface neoplasia and enucleation. Relevant references within these articles were also reviewed.
Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.
References 1. Barrett RV, Meyer DR, Carlson JA. Conjunctival squamous cell carcinoma in situ in the anophthalmic socket. Ophthal Plast Reconstr Surg. 2010;26:52--3 2. Campanella PC, Goldberg SH, Erlichman K, et al. Squamous cell tumors and ocular prostheses. Ophthal Plast Reconstr Surg. 1998;14:45--9
OCULAR SURFACE SQUAMOUS CELL NEOPLASIA 3. Chaudhry TA, Memon M, Ahmad K. Use of artificial eye and conjunctival squamous cell carcinoma. J Postgrad Med. 2006;52:234--5 4. Endo T, Hata J, Togashi S, et al. Conjunctival squamous cell carcinoma of the orbit 40 years after enucleation. Ophthal Plast Reconstr Surg. 2006;22:299--301 5. Erie JC, Campbell RJ, Liesegang TJ. Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology. 1986;93:176--83 6. Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea. 1987;6:78--116 7. Heinz C, Fanihagh F, Steuhl KP. Squamous cell carcinoma of the conjunctiva in patients with atopic eczema. Cornea. 2003;22:135--7 8. Karp CL, Scott IU, Chang TS, et al. Conjunctival intraepithelial neoplasia. A possible marker for human immunodeficiency virus infection? Arch Ophthalmol. 1996;114: 257--61 9. Kestelyn P, Stevens AM, Ndayambaje A, et al. HIV and conjunctival malignancies. Lancet. 1990;336:51--2 10. Lax AJ, Thomas W. How bacteria could cause cancer: one step at a time. Trends Microbiol. 2002;10:293--9 11. Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol. 1995;39:429--50
543 12. Lee GA, Williams G, Hirst LW, et al. Risk factors in the development of ocular surface epithelial dysplasia. Ophthalmology. 1994;101:360--4 13. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454:436--44 14. McDonnell JM, McDonnell PJ, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia. Arch Ophthalmol. 1986;104:1801--5 15. Nguyen J, Ivan D, Esmaeli B. Conjunctival squamous cell carcinoma in the anophthalmic socket. Ophthal Plast Reconstr Surg. 2008;4:98--101 16. Sun EC, Fears TR, Goedert JJ. Epidemiology of squamous cell conjunctival cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:73--7 17. Tezal M, Sullivan MA, Hyland A, et al. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2009;18:2406--12 18. Whittaker KW, Trivedi D, Bridger J, et al. Ocular surface squamous neoplasia: report of an unusual case and review of the literature. Orbit. 2002;21:209--15 Reprint address: Arun D. Singh, MD, Director of Ophthalmic Oncology, Cole Eye Institute and Taussig Cancer Center, Cleveland, OH 44195 USA. e-mail: [email protected].