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PubMed2004

Expression of cell adhesion molecules and tumour infiltrating leucocytes in conjunctival melanoma.

AIM: Very little is known about the immunology of conjunctival melanoma. We investigated the expression of cell adhesion molecules and the grade of tumour infiltration with lymphocytes and macrophages as important members for the communication between tumour cells and the immune system. METHODS: Archival material from 35 conjunctival melanomas was used for immunohistochemical detection of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), neural cell adhesion molecule (NCAM), CD3 and CD68 using monoclonal antibodies. Histological and clinical data for these tumours were assessed. RESULTS: ICAM-1 was expressed in 34 of 35 tumours; in 20 cases, more than 50% of the cells stained ICAM-1 positive. VCAM-1 was expressed in 21 of 34 tumours; in 17 cases, only a small proportion (1-25%) stained VCAM-1 positive. NCAM was expressed in 14 of 34 tumours; in 11 cases, only a small proportion (1-25%) stained NCAM positive. CD3-positive leucocytes were found in 26 of 32 tumours, whereas CD68-positive leucocytes were present in 33 of 34 tumours. Cox regression analysis revealed that patients with NCAM-positive tumours had a 6.4-fold higher risk of dying from conjunctival melanoma (P = 0.02). NCAM-positive tumours were preferentially (P = 0.03) located in prognostically 'unfavourable' areas (i.e. fornices, palpebral, caruncle) and had no or only a weak CD3-positive infiltrate (P = 0.03). CONCLUSIONS: ICAM-1, VCAM-1 and NCAM are differentially expressed in conjunctival melanoma. Leucocytes were present in almost every tumour. The association between NCAM expression and prognosis may be related to the differential anatomical tumour location of NCAM-positive and NCAM-negative tumours, and should be considered a preliminary observation due to the limited statistical power of this study.

Adult↗

PubMed2004

BRAF mutations are detectable in conjunctival but not uveal melanomas.

Activating mutations in exon 15 of BRAF have been detected in a high proportion of cutaneous melanomas. To determine whether such mutations are a feature of conjunctival or uveal melanomas, we screened DNA from these tumours. Twenty-one conjunctival and 88 uveal tumours were included in the study. Mutation analysis of BRAF exons 11 and 15 was undertaken using a combination of conformationally sensitive gel electrophoresis and direct sequencing. Mutations in exon 15 were detected in three of the conjunctival tumours (two V599E and one E585 K). None of the uveal tumours possessed a BRAF mutation in either exon 15 or 11. We conclude that uveal melanomas arise independently of oncogenic BRAF mutations, but the development of a proportion of conjunctival tumours involves mutation of this gene.

Adult↗

PubMed2003

Embryonal rhabdomyosarcoma presenting as conjunctival tumor.

The authors report the case of a 10-year-old girl who presented with a focal conjunctival lesion of the right eye. Conjunctival biopsy was performed and revealed an embryonal rhabdomyosarcoma. She received chemotherapy alone according to the Malignant Mesenchymal Tumor 95 Study (stage II nonalveolar orbital tumors) and is still in complete remission 6 months after the completion of treatment. Rhabdomyosarcomas of the conjunctiva without orbital extension are rarely reported. The authors discuss the prognosis and differential diagnosis of these lesions.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Tumors of the cornea and conjunctiva.

This article reviews literature regarding corneal and conjunctival tumors and explores some of the causative factors, prognostic factors, and treatment options for melanocytic, neoplastic, and lymphoid tumors. A review of epibulbar choristomas and associated syndromes is also included. Newer treatments including excimer laser phototherapeutic keratectomy and topical mitomycin C for corneal intraepithelial neoplasia, microscopic control of tissue margins with sequential surgery for squamous cell carcinoma and cryotherapy for lymphoma are reviewed and compared with traditional therapy. Conjunctival mucosal-associated lymphoid tissue (MALT) lymphoma is probably more common than previously realized. Recent findings of MALT lymphoma and the origin of conjunctival MALT is discussed.

Carcinoma, Squamous Cell↗

PubMed1996

Tumors of the cornea and conjunctiva.

This article reviews literature regarding tumors and tumor-like lesions of the conjunctiva and cornea as published in 1995. Causative and prognostic factors, as well as treatment options, are discussed. Ocular surface squamous neoplasia has been suggested as an "umbrella" term for dysplastic and carcinomatous lesions of the cornea and conjunctiva. Squamous cell carcinoma shows a higher incidence in patients with AIDS. A high prevalence (36%) of primary acquired melanosis is reported in one article, and the need for biopsy of all these lesions is questioned. Reviews of conjunctival myxoma, corneal pyogenic granuloma, and limbal juvenile xanthogranuloma are also included. The pathogenesis and newer treatment options for pterygia are discussed. Simple excision or resection of the pterygium followed by conjunctival autografting or intraoperative or postoperative mitomycin C application seems to be equally effective in reducing the rate of recurrence.

Combined Modality Therapy↗

PubMed1997

Tumors of the cornea and conjunctiva.

This article reviews the literature published in 1996 regarding conjunctival and corneal tumors. There is an increased incidence of squamous cell carcinoma of the conjunctiva in patients with HIV infection, especially in young individuals and Africans. Presumed causative factors for conjunctival squamous cell carcinoma include ultraviolet light, HIV infection, human papillomavirus and other unknown factors. Metastatic tumors to the conjunctiva appear at an advanced stage of the disease, and metastases to the conjunctiva are a poor prognostic sign for survival. Reviews of premalignant lesions of the conjunctiva, including diagnosis, treatment, and recurrence, are discussed. Spindle cell and mucoepidermoid variants of squamous cell carcinoma of the conjunctiva have a worse prognosis for intraocular extension compared with usual conjunctival squamous cell carcinoma.

Conjunctival Neoplasms↗

PubMed2000

Ocular adnexal lymphoid tumors.

This year, advances in the management of ocular adnexal lymphoid tumors have been based on the distinction between MALT and non-MALT lymphomas. MALT lymphomas have a more indolent course than non-MALT lymphomas, and in the conjunctiva a more conservative approach can be taken than has been recommended previously. In the orbit the likelihood of progression to systemic disease seems high, even with MALT lymphomas, and treatment with radiation is still recommended in all cases. The REAL classification system has replaced the Rappaport and Lukes-Collins system for classifying ocular adnexal lymphomas. Most ocular adnexal lymphomas are composed of neoplastic B-lymphocytes. Additional cases of T-cell lymphoma involving the orbit and conjunctiva were reported in the literature this past year.

Conjunctival Neoplasms↗

PubMed2002

Sentinel node biopsy as a tool for accurate staging of eyelid and conjunctival malignancies.

Sentinel lymph node (SLN) biopsy has emerged as a technique for accurate staging of solid tumors. This technique permits the detection of microscopic metastases in clinically negative regional lymph nodes and may be indicated for malignancies that have a propensity for regional nodal metastasis. With the exception of basal cell carcinoma, almost all malignancies of the eyelid and conjunctiva metastasize to regional lymph nodes as the site of first metastasis. The histologic status of the SLNs has been shown to be the most significant prognostic factor with respect to recurrence and survival in patients with cutaneous melanoma. The indications for and the feasibility of SLN biopsy for eyelid and conjunctival tumors and our experience with this technique are reviewed.

Conjunctival Neoplasms↗

PubMed2005

Liquid nitrogen cryotherapy of a conjunctival vascular tumor.

PURPOSE: To report the successful use of liquid nitrogen cryotherapy in treating a conjunctival vascular tumor. METHODS: A Brymil unit with a "D" tip was used to apply a liquid nitrogen spray for cryotherapy, using a previously described double freeze-thaw technique. RESULTS: One year after treatment, the suspected hemangioma was markedly decreased in size and redness. CONCLUSION: Liquid nitrogen cryotherapy should be considered as an alternative to more frequently used methods of treatment of conjunctival vascular tumors.

Conjunctival Neoplasms↗

PubMed2005

Ocular surface squamous neoplasia: a standard of care survey.

PURPOSE: To determine the current standard of care in the treatment of ocular surface squamous neoplasia (OSSN) with particular regard to topical chemotherapeutic agents including mitomycin C, 5-fluorouracil, and interferon-alpha2b. METHODS: A mail survey of the 325 physician members of the Ocular Microbiology and Immunology Group. RESULTS: The survey response rate was 38%, and the average number or cases of OSSN managed by respondents was 6.5 per year. A majority (54%) believed sufficient evidence existed to justify the use of mitomycin C in the treatment of OSSN, and fewer felt the published literature justified the use of 5-fluorouracil or interferon (11% and 21%, respectively). About one-half of responding physicians always perform a biopsy before institution of topical therapy. The reported use of topical chemotherapy as an adjunct to surgical excision increased with the size of the lesion; 45% of the respondents utilize topical therapy along with surgery for lesions greater than 8 mm in diameter. CONCLUSION: The standard of care for the treatment of ocular surface squamous neoplasia appears to have shifted from surgery toward the use of topical chemotherapeutic agents as adjuncts to surgery or even as sole therapy, despite a paucity of long-term studies in the published literature. Longer-term observational studies and prospective masked and controlled studies are indicated to determine the optimal treatment(s) for squamous neoplasia of the ocular surface.

Administration, Topical↗

PubMed2005

Conjunctival melanoma arising from diffuse primary acquired melanosis in a young black woman.

PURPOSE: To report a case of conjunctival melanoma arising from diffuse primary acquired melanosis (PAM) with atypia in a young black woman in the context of previously published cases of this lesion in blacks. METHODS: Retrospective case report with literature review. The number and percentage of conjunctival melanomas occurring in black patients were determined from case series in which race was specified, published from 1950 to the present. RESULTS: Nodular multifocal conjunctival melanoma in a 30-year-old black woman was treated using surgical excision and adjuvant cryotherapy. Extensive PAM with severe atypia, including areas of microinvasive melanoma, was treated using topical mitomycin C. Literature review revealed 35 cases of conjunctival melanoma occurring in black patients. No previous reports of mitomycin C use in black patients with melanoma or PAM were identified. CONCLUSIONS: Conjunctival melanoma is an exceedingly rare tumor in black patients. The current case brings the total of reported cases to 36. We successfully treated nodular melanoma and diffuse PAM in a young black woman using a combination of excision with cryotherapy and topical mitomycin C, suggesting that these lesions are amenable to the same types of therapy previously described for white patients.

Administration, Topical↗

PubMed2005

Human leukocyte class I antigen and beta2-microglobulin expression in conjunctival dysplasia, carcinoma in situ, and squamous cell carcinoma.

PURPOSE: Malignant transformation of cells is frequently associated with abnormalities in HLA expression. These abnormalities may play a significant role in the clinical course of the disease because the cellular immune response to tumors relies on concomitant recognition of tumor antigens with self-HLA molecules. Since HLA molecules mediate interactions of tumor cells with specific receptors on T and natural killer (NK) cells, tight control of expression of HLA molecules is critical for initiation and implementation of an effective cellular immune response. There is not much information on HLA class I antigens in conjunctival carcinomas. We studied the immunoexpression of HLA class I antigen and beta2-microglobulin (beta2-m) in conjunctival dysplasias and conjunctival squamous cell carcinomas. METHODS: HLA class I antigen and beta2-m expression were analyzed in 10 conjunctival dysplasias, 6 carcinomas in situ, and in 11 conjunctival carcinomas by immunoperoxidase staining with monoclonal antibodies to HLA class I antigen and beta2-m on the archival clinical samples. Immunoanalysis was done according to the International Histocompatibility Working Group Project Description. RESULTS: HLA class I antigen and beta2-m were heterogeneous in 10 conjunctival dysplasias, negative in 6 carcinomas in situ, and 11 conjunctival squamous cell carcinomas. The difference of immunoexpression for HLA class I and beta2-m among the 3 groups was statistically significant (P <0.001). CONCLUSIONS: HLA class I antigens and beta2-m are decreased in conjunctival dysplasias and negative in carcinomas in situ, and carcinomas. The findings support the role of cytotoxic T lymphocyte-mediated control of tumor growth in the clinical course of conjunctival squamous cell carcinomas.

Antibodies, Monoclonal↗

PubMed2005

Conjunctival mascaroma masquerading as melanoma.

PURPOSE: To describe a conjunctival mass composed of keratin with mascara deposition that clinically simulated a melanoma. METHODS: A 50-year-old woman, who used mascara for 20 years, was referred for a conjunctival mass that was suspected to be melanoma. Excisional biopsy was performed, and the lesion was studied histopathologically. RESULTS: The lesion consisted of conjunctival epithelium with a keratin plaque that contained multiple dark particles that exhibited birefringence with polarized light. The final diagnosis was conjunctival hyperkeratosis containing foreign bodies compatible with mascara deposition. The patient continues to use mascara, and there is no recurrence after 12 months. CONCLUSIONS: Deposition of mascara can assume tumorous proportions and simulate a conjunctival melanoma.

Conjunctival Diseases↗

PubMed2005

Topical 0.002% mitomycin C for the treatment of conjunctival-corneal intraepithelial neoplasia and squamous cell carcinoma.

PURPOSE: To demonstrate the efficacy of topical 0.002% mitomycin C (MMC) as an adjunctive and alternative treatment in primary and recurrent conjunctival-corneal intraepithelial neoplasia (CCIN) and squamous cell carcinoma (SCC). METHODS: The medical records of 7 patients with histopathologically confirmed CCIN and conjunctival SCC were retrospectively reviewed. All cases were treated with topical 0.002% MMC 4 times daily. The tumor size pre- and post-treatment, clinical response, and ocular complications were evaluated. RESULTS: The mean age of the patients was 56 +/- 13.4 years. The most common presenting symptom was foreign body sensation (57.1%) with a mean duration of 2.3 +/- 3.8 months. Six patients had pathologically proven CCIN (85.7%) and 1 had SCC (14.3%). Before MMC treatment, 6 eyes (85.7%) had recurrences after surgical excision. The tumor-free period ranged from 2 to 19 months. Two patients had multiple recurrences. MMC 0.002% 4 times daily was applied for a period of 5.4 +/- 4.4 weeks (range, 2-14). All had complete tumor regression as observed clinically and confirmed by impression cytology. Side effects of MMC therapy included ocular irritation, mild conjunctival hyperemia, and punctate keratopathy. There were no serious complications detected. The mean follow-up time was 30.7 +/- 15 months (range, 2-52) with no evidence of clinical recurrence in any case. CONCLUSIONS: Topical 0.002% MMC showed a favorable outcome as an adjunctive and alternative treatment of CCIN and SCC with regression of primary and recurrent tumors.

Administration, Topical↗

PubMed2005

Corneal topographic changes in a case of limbal conjunctival carcinoma.

PURPOSE: To describe topographic changes in a case of limbal conjunctival carcinoma. METHODS: Corneal topography was performed before and 3 months after excision. RESULTS: Preoperative topography revealed a localized flattening (37.1 diopters [D]) adjacent to the tumor and extending to the corneal apex, causing a 3-diopter asymmetric with-the-rule astigmatism. Preoperative corneal curvature was abnormally flat in all hemimeridians (average 40.8 D). During surgical excision, no corneal infiltration was found. Three months later, the astigmatism was 0.3 D, and corneal curvature had increased to normal values in all hemimeridians (45.5 D in the tumor area; average of all hemimeridians 45.5 D). Corneal steepening after tumor excision measured by topography almost doubled that observed in refraction. CONCLUSION: The similarity with the patterns induced by pterygia, the lack of corneal infiltration, and the complete reversal of astigmatism after excision support the theory that tear pooling at the tumor apex is responsible for secondary astigmatism and diffuse corneal flattening. However, the irregularity induced by the tumor may affect the precision of topographic measurements.

Aged, 80 and over↗

PubMed2006

Oral cimetidine adjuvant therapy for recalcitrant, diffuse conjunctival papillomatosis.

PURPOSE: To describe a case of recurrent, advanced conjunctival papillomatosis, treated by oral cimetidine (CIM) combined with secondary surgical intervention and an application of intraoperative mitomycin C. METHODS: Case report and literature review. RESULTS: A 9-year-old boy suffered from recurrent, progressive, diffuse multifocal conjunctival papillomatosis over the left upper and lower palpebral and the fornical conjunctiva. He underwent 3 separate surgeries; however, they did not prevent tumor recurrence. The recurrent lesions were more severe and extensive than before the surgeries. To avoid postoperative symblepharon, ankyloblepharon, dry eye, and possible corneal neovascularization after extensive lesion excision, oral CIM at a dosage of 200 mg 4 times daily was administered for 4 months before surgery. A debulking excision of the residual tumor with an intraoperative application of mitomycin C was performed as a secondary therapy after the main mass decreased in size. Postoperative oral CIM was continued for 6 months. The papillomatosis cleared without recurrence or symblepharon, ankyloblepharon, conjunctival scarring, or corneal neovascularization after 4 years of follow-up examinations. CONCLUSION: Oral CIM can be used as an initial, nonsurgical strategy for treating cases of massive, recalcitrant conjunctival papillomatosis. If there is tumor shrinkage, surgical debulking with applications of mitomycin C may be sufficient to eliminate any residual tumor tissue without inducing conjunctival scarring or corneal neovascularization.

Administration, Oral↗

PubMed2006

Multifocal squamous cell carcinoma of the conjunctiva with intraocular penetration in a patient with AIDS.

PURPOSE: To describe the clinical findings and to study the histopathology of conjunctival masses in a patient with HIV infection. METHODS: A case report. RESULTS: The histopathology from a 38-year-old Thai female patient who presented with visual loss on the left eye was studied. She had been diagnosed with AIDS 3 years before and was treated with highly active antiretroviral therapy and anti-tuberculous drugs for 1 year. The left eye was blind and showed 2 separate whitish masses on the bulbar conjunctiva in adjacent to the inferomedial limbus. Multiple nodules under the conjunctiva were seen inferiorly. Computerized tomography of the orbit revealed slight thickening of the left lower eyelid but could not show any globe involvement. The patient underwent orbital exenteration. Gross pathology showed multiple areas of the tumor. Histopathology revealed dysplastic squamous epithelium invading into the substantia propria of the conjunctiva with intraocular penetration. The anterior surface of the iris was filled with tumor cells containing keratin pearls. CONCLUSION: Squamous cell carcinoma can be multifocal and aggressive in HIV-infected patients. Rapid progression to intraocular penetration can be observed.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Conjunctival malignant melanoma-associated pseudomelanoma of the apposing tarsal conjunctiva.

PURPOSE: To describe a case of conjunctival malignant melanoma associated with pseudomelanomatous alteration of the apposing tarsal conjunctiva. METHODS: A 93-year-old woman presented with an elevated, pigmented mass on her superior bulbar conjunctiva. The tumor was associated with increased pigmentation of the apposing superior tarsal conjunctiva. An excisional biopsy of the epibulbar melanoma and pigmented tarsal conjunctiva was performed. RESULTS: Histopathologic evaluation of the epibulbar tumor revealed epithelioid melanocytes diagnostic of malignant melanoma. Histopathologic evaluation of the pigmented tarsal lesion showed large areas of ulceration and foci of granulation tissue composed of neovascular sprouts arising in the background of a loose connective tissue, with a moderate chronic inflammatory infiltrate. The infiltrate was composed of mature lymphocytes, plasma cells, and scattered histiocytes. Densely packed intracytoplasmic, brown pigment granules that stained positive with HMB 45 were found, attesting to adjacent melanocytes' releasing melanin-laden granules. There was no evidence of malignancy in the pigmented tarsal specimen. CONCLUSION: Noncontiguous pigmented conjunctival tumor can be found in apposition to an epibulbar melanoma. Although a limited biopsy could be considered, only a complete resection and histopathologic evaluation can determine whether the entire lesion is free of malignant melanoma.

Aged, 80 and over↗