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PubMed2005

Papillomavirus infection in the conjunctiva of individuals with and without AIDS: an autopsy series from Uganda.

HIV and genus beta human papillomavirus (HPV) types have been associated with squamous cell carcinoma of the conjunctiva (SCC). To determine whether conjunctival HPV infection is associated with AIDS, we analysed 136 lesion-free eye biopsies and tested for genera alpha, beta and gamma HPV types. Only infections with genera beta and gamma HPV types was found. After adjustment for age and gender, no excess of genera beta or gamma HPV infection was found in individuals who had died of or with AIDS compared to those who had died of other infectious diseases [relative risk (RR)=1.3; 95% confidence interval (CI): 0.4-4.8], or chronic diseases or trauma (RR=0.9; 95% CI: 0.3-2.9). Our findings suggest that infection with genera beta or gamma HPV types in lesion-free conjunctivas is common, but not greatly enhanced by the presence of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2005

TP53 codon 72 polymorphism and risk of conjunctival squamous cell carcinoma in Uganda.

BACKGROUND: The most common TP53 gene polymorphism, which alters the amino acid sequence of the oncosuppressor p53 protein, is located at the codon 72, resulting in either Pro72 or Arg72 p53 variant. Several studies have associated this polymorphism with different types of cancer. We have analyzed the distribution and the role of TP53 Arg72 and Pro72 alleles in conjunctival neoplasia. METHOD: The study included 41 invasive conjunctival squamous cell carcinoma (ICSCC), 33 conjunctival intraepithelial neoplasia of grade 3 (CIN3), 33 of moderate grade (CIN1 and CIN2), and 115 controls from Uganda, a sub-Saharan country with the highest incidence rate of conjunctival neoplasia in the World, particularly in the era of AIDS. The TP53 Arg/Arg codon 72 genotype was detected in 21.9% of ICSCC and in 18.2% of CIN3 but only in 6% of CIN1-2 and in 5.2% of controls (P<0.05). RESULTS: These data show an increased risk of ICSCC (odds ratio (OR)=6.2, 95% confidence interval (CI): 1.6-24.6) and CIN3 (OR=4.1, 95% CI: 1.0-18.0) associated with TP53 Arg homozygosity, not observed in CIN1-2 lesions (OR=0.8, 95% CI: 0.1-5.1). Moreover, the frequency of the Arg homozygosity was similar in HIV-positive and HIV-negative groups. We conclude that TP53 Arg/Arg codon 72 genotype is a relevant risk factor for invasive squamous cell carcinoma of the conjunctiva and for CIN3 in the Ugandan population. DISCUSSION: The absence of statistically significant difference in the distribution of TP53 Arg72 or Pro72 encoding alleles between HIV-positive and -negative subjects, affected by conjunctival neoplasia, suggests that HIV infection and/or the associated immunodeficiency represent further independent risk factors for ICSCC.

Adult↗
PubMed2005

Immunolocalization of the Epstein-Barr nuclear antigen-1 in conjunctival squamous carcinomas and dysplasias.

Epstein-Barr virus (EBV) has been linked etiologically to infectious mononucleosis, some non-Hodgkin as well as Hodgkin lymphomas, and lymphoepithelioma-like carcinomas. Moreover, various EBV antigens have been identified by a variety of techniques in a number of visceral carcinomas including breast, prostate, colon and lung primaries. We have now demonstrated by immunohistochemistry the presence of EBV nuclear antigen-1 (EBNA-1) in 4 of 15 cases of conjuntival squamous carcinomas and related dysplasias. At present, there is no significant evidence linking etiologically EVB to this type of tumor and dysplasia. However, our findings merit further investigation given the growing evidence that EBV may enhance proliferation and aggressiveness of tumor systems as well as the immortalization of non-neoplastic cells.

Aged↗
PubMed2005

Rituximab in primary conjunctiva lymphoma.

Our experience with a patient with a primary conjunctiva lymphoma who was treated with conventional dose of rituximab obtaining a complete response without acute and late local toxicity for the eye.

Adult↗
PubMed2005

Ocular surface squamous neoplasia.

This article discusses ocular surface squamous neoplasia, a spectrum of malignancy that includes intraepithelial dysplasia, carcinoma in situ of the conjunctiva and cornea, and invasive squamous cell carcinoma.

Carcinoma in Situ↗
PubMed2005

Melanocytic conjunctival tumors.

Melanocytic conjunctival tumors include a wide range of lesions that vary in their clinical and histopathologic features. Their management depends on numerous factors, including their location, focality, tumor dimensions (including depth), histopathologic characteristics, recurrences, growth, and the presence of metastasis.

Conjunctival Neoplasms↗
PubMed2004

Orbitotemporal neurofibromatosis. Clinical features and surgical management.

PURPOSE: To classify the periorbital deformities of adult orbitotemporal neurofibromatosis (NF) and describe new clinical findings, and to recommend guidelines for surgical treatment and management of surgical complications. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-three patients over age 16 with orbitotemporal NF. METHODS: Retrospective surgical case record and serial photographic review recording the laterality and the severity of periorbital involvement, the presence of complications from previous surgery, the surgical techniques undertaken, and the surgical outcome and complications. MAIN OUTCOME MEASURES: Comparison of preoperative and postoperative level of deformities. RESULTS: New classification of periorbital deformities: (1) brow ptosis, (2) upper lid infiltration with ptosis, (3) lower lid infiltration, (4) lateral canthal disinsertion, and (5) conjunctival and lacrimal gland infiltration. Two patients had bilateral and 31 patients (94%) had unilateral orbitotemporal NF. All patients had upper and 19 patients (58%) had lower lid involvement. Six (18%) patients had significant brow infiltration. Fourteen (42%) patients had a dropped lateral canthus requiring surgical reattachment, 28 (85%) required anterior levator resection for ptosis, and 28 (85%) had lid-debulking surgery. New findings included severe brow infiltration, lacrimal gland involvement, and functional nasolacrimal duct obstruction. Complications from previous surgery included residual ptosis, ptosis overcorrection, poor lid contour, dry eye, corneal exposure, and upper and lower lid entropion/ectropion. CONCLUSIONS: The periorbital appearance and comfort of patients with NF type 1 who have orbitotemporal NF can be significantly improved through oculoplastic surgery.

Adolescent↗
PubMed2004

Long-term follow-up results of observation or radiation for conjunctival malignant lymphoma.

PURPOSE: To elucidate the long-term prognosis of biopsy-proven malignant lymphoma of conjunctival origin after a treatment option of observation or radiation. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Thirteen patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) of conjunctival origin. METHODS: In the 11-year period from 1992 to 2002, 13 consecutive patients (7 female and 6 male) with ages ranging from 32 to 68 years (mean, 57) who showed malignant lymphoma of conjunctival origin were enrolled in the study. Histopathological and immunohistochemical studies of biopsy specimens of the conjunctival lesions proved extranodal marginal zone B-cell lymphoma of MALT in all patients. At the initial visit, magnetic resonance imaging (MRI) showed no orbital tumors, and gallium scintigraphy demonstrated no systemic involvement. The patients chose observation or radiation after the biopsy. MAIN OUTCOME MEASURES: Clinical disappearance of the conjunctival lymphoma lesions. RESULTS: Five patients chose 30-Gy radiation to the remaining conjunctival lesions after the biopsy, whereas the other 8 patients were simply observed without administration of any medication. During the follow-up, ranging from 1 to 11 years (mean, 5.4), 7 of these 8 patients without radiation showed spontaneous regression of the conjunctival lesions 1 to 5 years after the biopsy. Yearly MRI of the orbit and gallium scintigraphy disclosed no lesions in any of the patients. CONCLUSIONS: A large fraction of patients with MALT lymphoma of conjunctival origin had spontaneous regression after the biopsy. Follow-up without radiation is an option for patients with MALT lymphoma of conjunctival origin after the pathologic diagnosis by biopsy.

Adult↗
PubMed2004

Metastatic pattern and survival in disseminated conjunctival melanoma: implications for sentinel lymph node biopsy.

PURPOSE: To study the pattern of metastasis and overall survival in patients with disseminated conjunctival melanoma. DESIGN: Population-based, retrospective cross-sectional study. PARTICIPANTS: Eighty-five Caucasian patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000. METHODS: Data were collected from the Finnish Cancer and Population Registries and all involved hospitals. The pattern (regional or systemic) and site of first metastasis were recorded. The time to first metastasis and survival by pattern were estimated by cumulative incidence analysis, which takes competing risks into account, and by Kaplan-Meier analysis, respectively. MAIN OUTCOME MEASURES: Metastatic pattern, time to metastasis by pattern, overall survival. RESULTS: In 45% (95% confidence interval, 23%-68%) of 20 patients with metastasis, regional lymph node metastases were detected before systemic ones. Median times to initial regional and systemic metastasis were 2.3 and 3.4 years, respectively, and the median time from regional to systemic metastasis, 1.0 year. The 10-year cumulative incidence of initial regional metastasis was 0.11, and it tended to be higher for tumors more than 2 mm thick (0.18 vs. 0.05, P = 0.062). The corresponding incidence of initial systemic metastasis was 0.18, and it was higher for nonlimbal tumors (0.38 vs. 0.07, P = 0.00023) and for tumors more than 2 mm thick (0.28 vs. 0.06, P = 0.026). Overall survival was longer after initial regional metastasis than after systemic metastasis (30 vs. 8 months, P = 0.012). CONCLUSION: Initial regional lymph node metastasis was as common as systemic metastasis, but initial lymph node metastasis was associated with better prognosis. Metastasis, especially initial regional lymph node metastasis, from limbal tumors and tumors less than 2 mm thick was rare. These patients may have less benefit from sentinel lymph node biopsy, a method that is currently under evaluation regarding its potential to improve survival.

Adult↗
PubMed2004

Treatment of recurrent corneal and conjunctival intraepithelial neoplasia with topical interferon alfa 2b.

OBJECTIVE: To evaluate topical interferon alfa 2b (IFNalpha2b) as a single therapeutic agent in the treatment of presumed recurrent corneal and conjunctival intraepithelial neoplasia. DESIGN: Noncomparative, retrospective case series. PARTICIPANTS: Seven consecutive patients with recurrent corneal and conjunctival intraepithelial neoplasia diagnosed at the University of Minnesota from July 2000 to November 2003 were studied retrospectively. All patients had a history of histologically proven primary corneal and conjunctival intraepithelial neoplasia and were treated by surgery, cryotherapy, radiation, and/or topical mitomycin C before recurrence. INTERVENTION: Patients with a clinical diagnosis of recurrent corneal and conjunctival intraepithelial neoplasia were treated with recombinant topical IFNalpha2b drops (1 million IU/ml) 4 times daily until lesion resolution was noted. MAIN OUTCOME MEASURES: A review of medical records was performed to assess the duration of and response to treatment with topical IFNalpha2b, defined by clinical resolution of corneal and conjunctival intraepithelial neoplasia. RESULTS: The average age of the 7 patients at the initiation of topical IFNalpha2b treatment for presumed recurrent corneal and conjunctival intraepithelial neoplasia was 68.7 years (range, 54-88). Six of 7 patients had successful treatment of recurrent corneal and conjunctival intraepithelial neoplasia lesions with topical IFNalpha2b treatment. The average length of IFNalpha2b treatment to resolution of recurrent corneal and conjunctival intraepithelial neoplasia was 14.5 weeks (range, 5-24). After treatment with topical IFNalpha2b for recurrent corneal and conjunctival intraepithelial neoplasia, 2 patients had another recurrence of corneal and conjunctival intraepithelial neoplasia, noted at 1 year and 2 months, respectively. The average post-treatment follow-up was 11.7 months (range, 8-17) after the resolution of recurrent corneal and conjunctival intraepithelial neoplasia. No side effects of treatment were noted in any patient. CONCLUSIONS: Topical IFNalpha2b as a single therapeutic agent is an effective treatment of presumed recurrent corneal and conjunctival intraepithelial neoplasia. It offers the benefits of topical therapy and avoids the risks of surgical or other interventions-specifically, ocular surface toxicity, cicatricial conjunctival changes, and limbal stem cell deficiency. Larger controlled studies with longer follow-up periods are recommended to confirm the long-term efficacy and safety of this topical treatment.

Administration, Topical↗
PubMed2004

Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors.

OBJECTIVE: To report the spectrum and frequency of melanocytic and nonmelanocytic conjunctival tumors in an ocular oncology practice. DESIGN: Retrospective noninterventional case series. PARTICIPANTS: One thousand six hundred forty-three consecutive patients with a conjunctival mass evaluated at an ocular oncology department. METHODS: A chart review was conducted to obtain the clinical features of the patient and tumor and to tabulate and categorize the diagnoses. MAIN OUTCOME MEASURES: Tumor diagnosis overall and relative to patient age, race, and gender and relative to tumor location and laterality. RESULTS: In 1643 consecutive patients, the tumor was classified as melanocytic in 872 cases (53%) and nonmelanocytic in 771 cases (47%). The nonmelanocytic categories included congenital choristomatous (n = 40 [2%]), epithelial (n = 219 [13%]), vascular (n = 63 [4%]), fibrous (n = 7 [<1%]), neural (n = 1 [<1%]), xanthomatous (n = 1 [<1%]), myxomatous (n = 1 [<1%]), lipomatous (n = 23 [1%]), lacrimal gland origin (n = 12 [<1%]), lymphoid (n = 128 [8%]), leukemic (n = 3 [<1%]), metastatic (n = 13 [<1%]), secondary (n = 54 [3%]) tumors, and non-neoplastic lesions simulating a tumor (n = 206 [13%]). Of the 872 melanocytic lesions, the specific tumor diagnosis was nevus in 454 cases (52%), melanoma in 215 (25%), and primary acquired melanosis in 180 (21%). Patients with choristomatous, vascular, fibrous, xanthomatous, and myxomatous tumors presented at a mean age of <40 years, and those with malignant epithelial, lipomatous, leukemic, and secondary tumors presented at a mean age of >60. Of the 219 patients with epithelial tumors, 80% occurred in males, whereas the incidence of melanocytic lesions was equal in males and females. African-American patients represented only 7% of epithelial tumors, <1% of melanomas, and 8% of lymphoid tumors. CONCLUSION: Conjunctival tumors were of melanocytic origin in 53% of cases and nonmelanocytic origin in 47%. Overall, melanocytic tumors, epithelial tumors, and lymphoid tumors accounted for 74% of all cases. These tumors were far more common in Caucasian patients, and epithelial tumors were found more frequently in men.

Adolescent↗
PubMed2004

Conjunctival metastasis as initial sign of disseminated cutaneous melanoma.

PURPOSE: To describe a patient with conjunctival metastasis as the initial manifestation of metastasis from a cutaneous melanoma. DESIGN: Single interventional case report. METHODS: A 48-year-old woman with a history of cutaneous axillary melanoma developed a rapidly growing conjunctival mass. Subsequent systemic evaluation disclosed asymptomatic liver metastasis. The conjunctival lesion was resected. RESULTS: Histopathologic evaluation of the conjunctival tumor disclosed an epithelioid cell melanoma located in the conjunctival stroma, without appreciable junctional activity, compatible with metastatic melanoma. CONCLUSIONS: Conjunctival metastasis from cutaneous melanoma can rarely be the initial manifestation of disseminated melanoma.

Conjunctival Neoplasms↗
PubMed2006

Conjunctival T-cell lymphoma: a clinicopathologic case report.

OBJECTIVE: To report a patient with conjunctival T-cell lymphoma, an extremely rare entity. DESIGN: Single case report. METHODS: Based on clinical examination, an excisional biopsy and immunostaining were performed on the conjunctival lesion. For management, we excised and performed triple freeze-thaw cryotherapy to the involved area, and we consulted the oncology service. MAIN OUTCOME MEASURES: T-cell and B-cell markers, and clinical examination of the lesion. RESULTS: Both examination and laboratory assessment revealed no evidence of systemic involvement. Conjunctival biopsy showed expansion of the substantia propria with an infiltrate of chronic inflammatory cells (including lymphocytes, plasma cells, and eosinophils), and prominent lymphocyte exocytosis with reactive epithelial changes. The CD-45 RO (T-cell marker) was strongly positive, whereas the CD-20 (B-cell marker) was negative. The T-cell receptor gene rearrangement was positive with beta clonality, confirming the diagnosis of T-cell lymphoma. CONCLUSIONS: T-cell lymphoma is a rare but possible diagnosis of gelatinous conjunctival lesions. The oncology consultants were reluctant to treat the patient with systemic chemotherapy or radiation because extraconjunctival extension could never be documented. The answer to the question of what is the most appropriate treatment for conjunctival T-cell lymphoma remains unknown.

Antigens, CD20↗
PubMed2006

Positron emission tomography in the detection and staging of ocular adnexal lymphoproliferative disease.

PURPOSE: To evaluate the role of fluorine 18 deoxyglucose positron emission tomography (FDG PET) in the initial staging of ocular adnexal lymphoma (OAL). DESIGN: Retrospective nonrandomized case series. PARTICIPANTS: Eleven patients with OAL who underwent FDG PET at initial staging. METHODS: Retrospective review of all the clinical and imaging records, including computed tomography (CT) and FDG PET. MAIN OUTCOME MEASURES: The ability of PET studies to detect OAL and distant disease was compared with CT. RESULTS: Eleven patients with OAL who underwent FDG PET at initial staging were retrospectively reviewed having full access to their clinical and imaging data. Fluorine 18 deoxyglucose PET found distant disease in 5 of 6 lymphoma patients with systemic disease; 4 of these patients (66%) were upstaged, changing the clinical management. Orbital lesions were demonstrated in 3 of 11 patients, giving PET a sensitivity of 27% in the orbit and 83% systemically for detection of lymphoma. CONCLUSION: The ability of FDG PET to find systemic extranodal lymphomatous sites not detected with conventional imaging provides valuable information in OAL patients, which may result in important changes in staging and management. The technique does have limitations in detecting OAL compared with conventional imaging, possibly owing to background physiologic activity in the extraocular muscles in the orbit and the small volume of some orbital deposits.

Adult↗