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PubMed2004

BRAF mutations in conjunctival melanoma.

PURPOSE: An activating mutation in exon 15 of the BRAF gene has been found in a high proportion of cutaneous melanomas and cutaneous nevi but not in uveal melanoma. Conjunctival melanoma shows greater clinical similarity to cutaneous melanoma than does uveal melanoma. The purpose of this study was to determine whether the T1799A BRAF mutation found in cutaneous melanoma is also present in conjunctival melanoma. METHODS: DNA was extracted from paraffin sections obtained from glutaraldehyde or formalin-fixed, paraffin-embedded conjunctival melanomas. Forty-two specimens were identified from 25 patients. Seminested PCR was used to amplify exon 15 of the BRAF gene, and the resultant PCR product was purified and directly sequenced. Sequences from conjunctival melanomas were compared with the wild-type sequence of the BRAF gene. The presence or absence of the BRAF mutation was compared with the clinicopathological features. RESULTS: The T1799A (V600E) mutation was detected by sequencing in melanomas from 5 of 22 patients as well as in the positive control, a cutaneous melanoma cell line. In this small series, no statistically significant associations between the presence of the BRAF mutation and clinicopathological characteristics were detected, although tumors with this mutation tended to have a larger diameter and greater depth of invasion and to contain epithelioid cells. CONCLUSIONS: Others have demonstrated a BRAF T1799A-activating mutation in cutaneous but not uveal melanoma. In this study, this BRAF mutation was demonstrated in some conjunctival melanoma tissue samples, suggesting that some conjunctival melanomas may share biological features in common with cutaneous melanoma.

Adult↗
PubMed2005

Conjunctival melanoma in the Netherlands: a nationwide study.

PURPOSE: To evaluate risk factors for local recurrence, regional and distant metastases, and mortality associated with conjunctival melanoma. METHODS: This was a retrospective study of 194 patients with histologically confirmed conjunctival melanoma diagnosed between 1950 and 2002 in the Netherlands. Data were collected from all university centers and many nontertiary hospitals, using the National Pathology and the Leiden Oncologic Registration Systems. Based on the number of incidences, this study included 70% of the conjunctival melanomas in The Netherlands. Clinical and histopathological data for conjunctival tumors were reviewed and compared with data reported in the literature. Risk factors for local, regional, and distant metastases and survival were analyzed using the Kaplan-Meier and Cox regression analyses. RESULTS: Of 194 patients with conjunctival melanoma, 112 had a local recurrence (median, 1; range, 1-9) during follow-up (median, 6.8 years; range, 0.1-51.5). Location was the most important risk factor for development of local recurrence, and significantly more occurred with nonepibulbar (log rank, P=0.044) tumors. Significantly fewer local recurrences occurred with tumors initially treated with excision and adjuvant brachytherapy rather than with excision only (log rank, P=0.008) or with excision and cryotherapy (log rank, P <0.038). Forty-one (21%) patients had regional lymph node metastases, mostly to the parotid or preauricular lymph nodes (n=26; 13%). Risk factors for regional metastases were tumor thickness (log rank, P <0.001) and tumor diameter (log rank, P=0.010). Forty-nine (25%) patients (mean, 4.37 years) had development of distant metastases, mainly in the lung, liver, skin, and brain. Tumor-related survival was 86.3% (95% confidence interval [CI], 81.0-91.6) at 5 years, 72% (95% CI, 79.7-64.4) at 10 years, and 67% (95% CI, 58.9-76.1) at 15 years. The main mortality risk factors were nonepibulbar location (log rank, P <0.0001) and tumor thickness (log rank, P=0.0004). CONCLUSIONS: Nonepibulbar tumors more often recur locally and are associated with a shorter survival independent of other risk factors. Tumor thickness is also an important predictor of regional and distant metastases, as well as survival. A prospective study is needed to compare the effect of excision with radiotherapy and excision with cryotherapy on the number of local recurrences, exenteration rate, and survival.

Conjunctival Neoplasms↗
PubMed2005

T1799A BRAF mutations in conjunctival melanocytic lesions.

PURPOSE: To gain a better understanding of the molecular events leading to the development of conjunctival melanocytic lesions and conjunctival melanoma, this study was conducted to investigate the presence of T1799A BRAF oncogenic mutation in these lesions. METHODS: Forty-eight surgically excised conjunctival melanocytic lesions from 48 patients were examined for the presence of the BRAF T1799A mutation. Twenty-eight lesions were conjunctival nevi, of which 20 were excised from children younger than 18 years. Fifteen lesions were conjunctival primary acquired melanosis (PAM; 11 without atypia and 4 with atypia) and five were conjunctival melanomas. To detect the BRAF T1799A mutation, both a newly developed kit (Mutector; TrimGen, Sparks, MD) and direct DNA sequence analysis of exon 15 after PCR amplification were used. RESULTS: The T1799A BRAF mutation was identified in 14 of 28 (50%) conjunctival nevi analyzed, but in none of the 15 conjunctival PAMs, with and without atypia. The T1799A BRAF mutation was identified in two of the five (40%) conjunctival melanomas. There was no difference in the BRAF mutation detected in conjunctival nevi in children or adults, as the BRAF mutation was detected in 50%. CONCLUSIONS: The results showed that conjunctival nevi, similar to skin nevi, have a high frequency of oncogenic BRAF mutations. Furthermore, the results suggest that the oncogenic event leading to BRAF mutations affect only conjunctival nevi and not conjunctival PAM. The clinical significance of these observations remains to be determined.

Adolescent↗
PubMedDate not supplied

Reconstruction of conjunctiva with amniotic membrane after excision of large conjunctival melanoma: a long-term study.

PURPOSE: To evaluate, on a long- term basis, the role of amniotic membrane in the reconstruction of large conjunctival defects after excision of large conjunctival melanoma. METHODS: Four consecutive patients with diffuse conjunctival melanoma involving both bulbar and palpebral conjunctiva were studied. Conjunctival melanoma was completely excised (with wide clinically disease-free margins) and amniotic membrane immediately sutured to the surrounding conjunctiva and sclera to cover the conjunctival defect. Minimum follow-up was 48 months. RESULTS: Successful conjunctival surface reconstruction and physiologic fornical depth were achieved in all patients within 6 weeks. No recurrence of primary melanoma was observed during long-term follow-up. CONCLUSIONS: Amniotic membrane transplantation is an effective alternative in ocular surface repairing surgery after removal of large conjunctival tumors.

Aged↗
PubMedDate not supplied

Conjunctival papilloma and human papillomavirus: identification of HPV types by PCR.

PURPOSE: To report the identification of human papillomavirus types in four cases of conjunctival papillomas and to review the literature regarding human conjunctival papillomavirus (HPV). METHODS: Specimens from conjunctival papillomas of four patients were analyzed for the presence of HPV by polymerase chain reaction and subsequent filter hybridization. HPV types 6, 11, 16, 18, 31, and 33 were investigated. Histologic sections were analyzed for the presence of koilocytosis. RESULTS: Histologic examination confirmed HPV infection in all cases. HPV type 11 was detected in all specimens. CONCLUSIONS: HPV is frequently implicated in the pathogenesis of proliferative squamous lesions. HPV type 11 was the most frequently found in benign conjunctival lesion in this study.

Adolescent↗
PubMedDate not supplied

Malignant conjunctival epibulbar fibrous histiocytoma with orbital invasion.

The Authors report on a rare case of malignant conjunctival epibulbar fibrous histiocytoma with orbital invasion. Fibrous histiocytoma is a tumour of mesenchymal origin, which, although among the most common adult age soft tumours, appears very rarely at the conjunctival level. In fact the most frequent site is the orbit. So far only 15 cases concerning conjunctiva have been described in the Literature only 4 of those have been reported as malignant. We observed a male patient, who 6 years ago, at the age of 53, noticed a neoformation on the temporal portion of the bulbar conjunctiva. In June 1988, after three successive operations, with a histological diagnosis of inflammatory granuloma, he came to our Clinic, where, because of the characteristics of the orbit infiltrations, only a partial excision was carried out for a biopsy. The histological examination, associated with immunohistochemical techniques, gave the result of malignant fibrous histiocytoma. Consequently in, July 1988, the patient underwent an exenteratio orbitae. To date, the patient enjoys good health without a trace of recurrence. Besides the clinical presentation of the case, histopathological and immunohistochemical findings concerning this type of lesion are presented and discussed, with a comparison of our findings with those reported in the literature.

Conjunctival Neoplasms↗
PubMedDate not supplied

Gastric adenocarcinoma presenting as an eyelid and conjunctival mass.

A 50-year-old white man complained of "inflammation" of his right eyelid since January 1989. In June 1990, he had undergone a gastrectomy for an adenocarcinoma of the stomach. In August 1990, his right eye showed a painless, firm infiltration of the upper and lower lid, ulceration and loss of eyelashes of the upper lid and a reddish, subepithelial thickening of the medial bulbar conjunctiva. Biopsies of the right upper lid and nasal bulbar conjunctiva disclosed a metastatic, poorly differentiated adenocarcinoma of the stomach (signet ring cell carcinoma) both in the lid and conjunctival biopsies. Carcinoembryonic antigen (CEA) was detected in the tumor cells. Electron microscopic examination revealed tumor cells with signs of secretory activity. Although metastases to the eyelids and conjunctiva are rare, they may precede the clinical manifestation of the primary tumor for months or even years. In patients with chronic, recalcitrant lesions of eyelids or conjunctiva, especially if accompanied by loss of eyelashes, a primary or secondary malignancy should be excluded by early biopsies and histopathological examination.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Interferon alpha in the therapy of conjunctival lymphoma in an HIV+ patient.

The authors evaluated the efficacy of interferon-alpha used intralesionally in the therapy of low-grade conjunctival non-Hodgkin lymphoma in an HIV-positive patient. The patient received one intralesional injection of 1,000,000 U of interferon-alpha three times a week for a total of twelve doses. The remission of conjunctival involvement was seen three months from the end of therapy. The intralesional use of interferon-alpha can be considered an efficacious therapy for low-grade conjunctival non-Hodgkin lymphoma.

Conjunctival Neoplasms↗
PubMedDate not supplied

Predictors of survival in malignant melanoma of the conjunctiva: a clinico-pathological and follow-up study.

The study comprised 61 patients with histologically diagnosed malignant melanoma of the conjunctiva (MMC) who were treated and followed up in the Department of Ophthalmology, Clinical Center of Serbia, Belgrade, over a period of 24 years (1970-1993). Data on 15 clinical and 10 histopathological characteristics of MMC were related to the outcome of the disease. Tumour thickness on the histological section was the most important single predictor of survival in MMC. Other predictors of survival in MMC were the number of mitoses, the histologically assessed degree of tumour pigmentation and the intensity of inflammation at the tumour site. The variables entered into the model comprised as much as 85.3% of all predictors of survival in MMC.

Adolescent↗
PubMed2005

Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci.

Non-Hodgkin lymphomas are among the most common primary tumors occurring in the ocular adnexa. Herein, we present a 14-year single-institution experience in 62 patients with primary ocular adnexal lymphomas (OALs). Association with Chlamydia psittaci infection is examined in 57 tumor specimens. Extranodal marginal zone lymphoma (EMZL) was the most frequent histologic subtype (89%). The majority of patients with EMZL (84%) presented with stage E-extranodal (IE), however only 16% had an advanced stage. All stage IE patients were treated with local radiotherapy, whereas patients with disseminated disease received systemic therapy with or without local irradiation. All but 1 patient with EMZL achieved complete remission (CR). During a median follow-up of 52 months (range, 3-153 months), the estimated 5-year overall survival (OS) and freedom from progression (FFP) were 96% and 79%, respectively. During the follow-up, 22% of patients relapsed, mainly in extranodal sites, and 4% transformed to diffuse large B-cell lymphoma. None of the patients exhibited local orbital failure in the radiation field. None of the OAL specimens harbored C psittaci DNA. Our study demonstrates that EMZLs, accounting for the majority of primary OALs, are characterized by an indolent natural history with frequent, continuous extranodal relapses. In South Florida, OALs are not associated with C psittaci infections.

Adult↗
PubMed2003

Evaluation of apoptosis markers in conjunctival and eyelid benign and malignant tumors.

The balance between cell proliferation and programmed cell death plays a crucial role in malignant development. Bcl-2 family proteins, including proapoptosis protein Bak and antiapoptosis protein Bcl-2, regulate the apoptotic process. Mutation of the p53 gene, which results in P53 protein accumulation, was observed in many types of human cancer. The aim of our study was to evaluate immunohistochemical Bcl-2, Bak, and P53 protein expression and the relation between these proteins in conjunctival and eyelid benign and malignant tumors. We examined a series of 42 papillomas (CEP), 12 squamous cell cancers (SCC), and 19 cases of basal cell cancer (BCC). The age in the CEP group ranged from 18-94 years, and in the SCC and BCC groups from 42-87 years. Staining patterns were correlated with sex, age, and tumor localization. P53 protein-positive immunostaining was observed in 71% of cases, Bcl-2 in 83.9%, and Bak in 74.2 cases in the SCC and BCC groups. In the CEP group, P53 overexpression was observed in 90.5% of cases, Bcl-2 in 71.4%, and Bak in 76.2%. No statistically significant correlation was found between examined protein expression and sex, age, and tumor localization. An inverse correlation was observed between P53 and Bak protein expression in the CEP group. No statistically significance correlation was noted between Bcl-2 and P53 and Bcl-2 and Bak protein expression in both examined groups. The obtained data suggests that P53 and Bcl-2 protein expression coupled with decreasing Bak expression are associated with apoptosis and proliferation as well as malignant progression in conjunctival and eyelid tumors.

Adult↗