Conjunctival Melanoma in Chinese Patients: Local Recurrence, Metastasis, Mortality, and Comparisons With Caucasian Patients.

Purpose: To evaluate the prognosis in Chinese patients with conjunctival melanoma and determine its predictors. Further, to explore the racial differences in clinical characteristics and outcomes between Chinese and Caucasian patients. Methods: This cohort study included 57 eyes of 57 consecutive patients with pathologically verified conjunctival melanoma between 1996 and 2016. Medical records were reviewed for factors associated with the local recurrence, metastasis, and tumor-related mortality. All eligible patients were followed up for these three outcome measures. The demographic data, clinical characteristics, and outcomes were compared between Chinese and Caucasian patients. Results: The mean follow-up period was 52.2 ± 49.4 months. Among the total 57 patients, 29 (51%) patients experienced local recurrence. The 1-, 5-, and 10-year recurrence rate was 31.0%, 59.7%, and 66.4%, respectively. Treatment complications detected in the follow-up included dry eye (32, 56.1%), irregular eyelid margin (25, 43.9%), eyelid retraction (18, 31.6%), blepharoptosis (9, 15.8%), mixed pigmentation of the tarsus reconstructed by mucosal membrane graft, corneal opacities (6, 10.5%), and symblepharon (2, 3.5%). Twenty (35%) patients developed metastasis. The 1-, 5-, and 10-year metastasis rate was 16.7%, 38.7%, and 50.9%, respectively. Fourteen (25%) patients died of conjunctival melanoma, with a median survival time of 24 months. The 1-, 5-, and 10-year tumor-related mortality was 3.8%, 30.5%, and 37.4%, respectively. Tumor hemorrhage is an independent risk factor for tumor-related death (hazard ratio [HR]: 18.81, P = 0.01) and metastasis (HR: 4.57, P = 0.02). Significant differences were noted between Chinese and Caucasians patients from America, Germany, and England in demographics, clinical characteristics, and outcomes. Compared to Caucasians, Chinese patients tended to have more male cases (P < 0.01) and to be younger (P = 0.03). At initial presentation, more Chinese patients had de novo tumor origin (P < 0.01), epithelioid cell type (P < 0.01), nonbulbar tumor location (P < 0.01), greater basal diameter (P = 0.04), multifocal tumor (P < 0.01), feeder vessels (P < 0.01), eyelid (P < 0.01) and orbit involvement (P < 0.01), and advanced T stages (P < 0.01). Over a similar follow-up period with Caucasians patients (52.2 vs. 52 months, P = 0.97), a significantly larger proportion of Chinese patients exhibited eyelid invasion (P = 0.04) and orbital invasion (P < 0.01) at follow-up, local recurrence (P < 0.01), metastasis (P < 0.01), and tumor-related death (P < 0.01). Conclusions: Conjunctival melanoma is a rare malignancy with great potential for mortality in Chinese. Special attention should be paid to patients with tumor hemorrhage. Compared to Caucasians, Chinese patients exhibit more aggressive clinical signs with compromised prognosis.

Prognostic factors for conjunctival melanoma: a study in ethnic Chinese patients.

BACKGROUND/OBJECTIVE: In patients with conjunctival melanomas, surgery is the first choice of treatment, but no standard adjuvant therapy has been established. In this study, we evaluated prognostic factors for conjunctival melanoma in ethnic Chinese patients. METHODS: Demographic data, known (published) prognostic factors, BRAF and KIT gene mutations, treatment strategies and outcomes were reviewed in 53 patients with pathologically confirmed conjunctival melanomas. Univariate and multivariate analyses of factors associated with survival were performed by the Kaplan-Meier method and a Cox proportional hazard model, respectively. RESULTS: Univariate analyses for 50 patients in whom data were available showed that a higher T stage (p=0.041), greater tumour thickness (p=0.006), local resection (p=0.033) and no adjuvant therapy (p=0.006) were associated with a worse recurrence-free survival (RFS) and metastasis-free survival (MFS). Patients with more involved quadrants also had worse MFS (p=0.039), while a higher T stage (p<0.001), local resection (p=0.008), and no adjuvant therapy (p=0.028) were associated with worse overall survival (OS). However, BRAF or KIT mutations showed no correlations with RFS, MFS or OS. Patients who received high-dose interferon (HDI) adjuvant therapy had a better RFS (p=0.004), MFS (p=0.001) and OS (p=0.005) than those who did not. Multivariate analysis showed that adjuvant therapy and tumour thickness were significant predictive factors for RFS, and the T stage was a significant predictive factor for OS. CONCLUSIONS: Adjuvant therapy and tumour thickness are significantly associated with RFS and T stage is a significant predictor of OS in Chinese patients with conjunctival melanomas. Patients may benefit from adjuvant therapy with HDI.

[Epidemiological and clinical characteristics of primary ocular cancers in blacks: our experience with 111 cases]. / Aspects épidémiologiques et cliniques des cancers oculaires primitifs du mélanoderme : notre expérience à propos de 111 cas.

INTRODUCTION: In this work, the authors aim to study clinical and epidemiological characteristics of ocular and orbital primary cancers in sub-Saharan African. PATIENTS AND METHODS: This is a retrospective study over a period of 21 years, from 1984 to 2004, including all cases of ocular cancer, histologically proven after surgery of the globe or the orbit. For each patient, we studied the following parameters: age, sex, reason(s) for consultation, the affected eye, and histological result of the operative specimen. These data were collected by studying the departmental surgical registry, patient medical records and the tumor registry of the anatomicopathology laboratory of a tertiary care hospital in sub-Saharan Africa. RESULTS: We collected data on 111 black patients, among whom 15 cases (13.5%) presented with bilateral involvement, for a total of 126 eyes. The sex ratio was 1.17. Presenting signs showed a predominance of leukocoria (30.2%) followed by proptosis (21.7%) and in third place, protruding conjunctival mass (10.8%). Retinoblastoma was found most frequently, representing 66.6% of the oculo-orbital tumors and 95.45% of the tumors of the globe; followed by epidermoid carcinoma, representing 15.08% of cases. Malignant melanoma was third most common, representing 4.76%, with 83% arising in the anterior uvea and 7% in the choroid. Basal cell carcinoma and rhabdomyosarcoma follow in fourth place. Basal cell carcinoma constituted half (50%) of the eyelid tumors. Rhabdomyosarcoma was the most common orbital tumor in our series (57%). Next were lymphomas with conjunctival localization (2.38%), acute leukemia with orbital localization (1.59%) and rare tumors, palpebral dermatofibrosarcoma (0.79%), an orbital angiosarcoma (0.79%), a glioblastoma of the globe (0.79%) and a malignant solitary fibrous tumor of the orbit (0.79%). CONCLUSION: Ocular and orbital primary cancers in blacks remain tumors of the young, equally distributed between the sexes. Retinoblastoma is the most frequent, followed by epidermoid carcinoma. The globe is the preferential localization of these cancers.

Clinical and pathological characteristics of ocular surface squamous neoplasia in an Asian population.

BACKGROUND: In order to evaluate clinical and pathological characteristics of ocular surface squamous neoplasia (OSSN) in Asian population. METHODS: Medical records were reviewed of 30 eyes of 30 Korean patients who underwent en-bloc excision and biopsy for tumors in the corneal and conjunctival epithelium in the suspicion of OSSN. RESULTS: Tumors developed predominantly in males (21/30 patients, 70%) at the mean age of 64.8 years (range: 39-82 years). Histologic examination revealed that 11 cases were squamous cell carcinoma (SCC), eight were conjunctival or corneal intraepithelial neoplasm (CIN) with dysplastic cells in the epithelium, eight simple hyperplasia, and three inflammatory lesions. The majority of SCC (9/11 eyes, 81.8%) involved the nasal conjunctiva and cornea, while one of eight eyes (12.5%) with CIN was located at the nasal side. Vascularization was combined in all eyes with SCC, in two of eight (25%) with CIN, in two of three with inflammation, and in none with hyperplasia. Both cornea and conjunctiva were involved in ten of 11 eyes (90.9%) with SCC, in six of eight (75%) with CIN, in two of eight (25%) with hyperplasia, and in two of three (66.7%) with inflammation. When classified based on clinical appearance, seven of 11 eyes (63.6%) with SCC were papilliform sessile masses, and four of eight (50 %) with CIN showed gelatinous growth onto the surface. All lesions were treated with en-bloc excision and cryotherapy. Recurrence occurred in seven out of 19 patients (36.8%) with SCC or CIN during the mean follow-up of 30.0 months-four patients with SCC and three with CIN. Hyperplasia or lesions with inflammation did not recur. The recurrence rate was not associated with histological diagnosis of a lesion. However, the use of the postoperative chemotherapy including topical mitomycin C or interferon α 2b had a significant negative correlation with the recurrence. CONCLUSIONS: In total, 36.7% of tumors in the corneal and conjunctival epithelium were SCC, and 26.7% were CIN. Recurrence occurred in 36.8% of patients with SCC or CIN after primary excision and cryotherapy. The use of postoperative chemotherapy was a significant factor negatively affecting the recurrence.

Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas.

PURPOSE: To investigate racial and ethnic differences in the incidence of conjunctival melanoma in a large population-based study. DESIGN: Observational cross-sectional study. METHODS: Using data from 1992 through 2003 provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of conjunctival melanoma in various racial and ethnic groups (Black, American Indian, Asian and Pacific Islander, Hispanic, and non-Hispanic White). In addition, we calculated the standard incidence ratios (risk ratios) and 95% confidence intervals to describe the differences within these racial and ethnic groups. RESULTS: From 1992 through 2003, there were a total of 168 conjunctival melanomas diagnosed in 13 SEER registries with known racial and ethnic groups. The annual age-adjusted incidence rates (per million population) of conjunctival melanoma was 0.18 (Blacks), 0.17 (American Indians), 0.15 (Asians), 0.33 (Hispanics), and 0.49 (non-Hispanic Whites). The difference in the incidence of conjunctival melanoma between Whites and Blacks or Asians was statistically significant, but was not significant between Blacks and Asians. CONCLUSIONS: The overall White-to-Black incidence ratio in conjunctival melanoma was 2.6:1, which is much less than that of uveal melanoma (18:1) and cutaneous melanoma (13:1 to 26:1), but is similar to that of mucosal melanoma (2.2:1 to 2.3:1). The cause and significance of this difference of racial and ethnic incidence in various melanomas are discussed.

Elevated risk for squamous cell carcinoma of the conjunctiva among adults with AIDS in the United States.

Squamous cell carcinoma of the conjunctiva (SCCC) has been associated with HIV infection in equatorial Africa, but the evidence for association with HIV in developed countries, where SCCC is rarer, is controversial. We investigated the risk for SCCC and other eye cancers in the updated U.S. HIV/AIDS Cancer Match Registry Study. We calculated standardized incidence ratios (SIRs) to estimate excess risk for SCCC, primary ocular lymphoma, ocular Kaposi sarcoma (KS) and other eye tumors among 491, 048 adults (aged > 15 years or older) with HIV/AIDS diagnosed from 1980 to 2004. We calculated relative proportions (per 10(5)) to gain insight into risk factors. We identified 73 eye cancers (15 SCCC, 35 primary ocular lymphoma, 17 ocular KS and 6 other). Overall SIRs were elevated for SCCC (SIR, 12.2, 95% CI 6.8-20.2), primary ocular lymphoma (21.7, 95% CI 15.1-30.2) and ocular KS (109, 95% CI 63.5-175). Risk for SCCC was elevated regardless of HIV acquisition category, CD4 lymphocyte count and time relative to AIDS-onset. Relative proportions of SCCC risk were highest with age >or=50 (8/10(5)), Hispanic ethnicity (7/10(5)) and residence in regions with high-solar ultraviolet radiation (10/10(5)). We show significantly increased incidence of SCCC among persons with HIV/AIDS in the U.S. The associations with age and geography are in accord with etiological role for ultraviolet radiation in SCCC.

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.

Advanced conjunctival melanoma.

BACKGROUND: Conjunctival melanoma is a rare neoplasm with an aggressive behaviour characterized by a high tendency to develop recurrences and metastases. The authors describe the clinicopathological features of four Mexican patients with advanced conjunctival melanoma. METHODS: Review of the cases of four patients with advanced conjunctival melanoma seen at an ophthalmologic referral centre in Mexico City. The clinical characteristics, gross findings and histopathological features were noted. RESULTS: The mean age of the patients (two women and two men) was 72 years (range 49 to 95 years). The left eye was affected in three cases and the right eye in one. Orbital exenteration was performed in two patients, enucleation in one and complete excision of the mass in one. One patient died 2 years after debulking surgery, and another patient is alive and free of disease 13 years after enucleation; the two other patients were lost to follow-up. The mean largest mass dimension of the tumours was 4 cm (range 3-5.4 cm). Histopathologically, all cases were associated with primary acquired melanosis with atypia. Two cases were composed of epithelioid cells, one of spindle cells, and one of a mixture of epithelioid and spindle cells. In three cases the number of mitotic figures ranged from 3 to 36/10 high-power fields; no mitotic activity could be demonstrated in one case. INTERPRETATION: The mean age of our patients at the time of diagnosis was older and their tumours were larger than those reported in other series. All the cases were associated with primary acquired melanosis with atypia. At the time of writing, one patient, who had a 3.3-cm tumour, had survived 13 years without clinically detectable disease.

Conjunctival nevi: clinical features and natural course in 410 consecutive patients.

OBJECTIVES: To describe the clinical features of a conjunctival nevus and to evaluate the lesion for changes in color and size over time. DESIGN: Retrospective, observational, noncomparative case series. PARTICIPANTS: Four hundred ten consecutive patients with conjunctival nevi. MAIN OUTCOME MEASURES: The 2 main outcome measures were changes in tumor color and size. RESULTS: Of the 410 patients, 365 (about 89%) were white, 23 (about 6%) were African American, 8 (2%) were Asian, 8 (2%) were Indian, and 6 (1%) were Hispanic. The iris color was brown in 55% (229/418), blue in 20% (85/418), green in 20% (83/418), and not indicated in 5% (21/418). The nevus was brown in 65%, tan in 19%, and completely nonpigmented in 16%. The anatomical location of the nevus was the bulbar conjunctiva (302 eyes, 72%), caruncle (61 eyes, 15%), plica semilunaris (44 eyes, 11%), fornix (6 eyes, 1%), tarsus (3 eyes, 1%), and cornea (2 eyes, <1%). The bulbar conjunctival lesions most commonly abutted the corneoscleral limbus. The nevus quadrant was temporal (190 eyes, 46%), nasal (184 eyes, 44%), superior (23 eyes, 6%), and inferior (21 eyes, 5%). Additional features included intralesional cysts (65%), feeder vessels (33%), and visible intrinsic vessels (38%). Cysts were clinically detected in 70% of histopathologically confirmed compound nevi, 58% of the subepithelial nevi, 40% of the junctional nevi, and 0% of the blue nevi. Of the 149 patients who returned for periodic observation for a mean of 11 years, the lesion color gradually became darker in 5% (7 patients), lighter in 8% (12 patients), and was stable in 87% (130 patients). The lesion size was larger in 7% (10 patients), appeared smaller in 1% (1 patient), and was stable in 92% (137 patients). There were 3 patients who developed malignant melanoma from a preexisting compound nevus (2 cases) or blue nevus (1 case) over a mean interval of 7 years. CONCLUSIONS: Conjunctival nevus is a benign tumor most often located at the nasal or temporal limbus and rarely in the fornix, tarsus, or cornea. Over time, a change in tumor color was detected in 13% (20/149) and a change in tumor size was detected in 8% (12/149).

Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites.

PURPOSE: To identify the clinical determinants of prognosis and the incidence of malignant conjunctival melanoma in whites. METHODS: A nationwide search identified 85 patients in whom primary conjunctival melanoma was diagnosed in Finland between 1967 and 2000, all of whom were enrolled. Data were collected from the Finnish Cancer and Population Registries and from patients' charts in all involved hospitals. The age-specific and age-adjusted incidences were calculated. Clinical characteristics of the tumors were recorded and time to local recurrence and melanoma-specific survival were analyzed by Kaplan-Meier analysis and univariate and multivariate extended Cox regression. RESULTS: The annual crude incidence of conjunctival melanoma in Finland was 0.51 per million inhabitants, and the age-adjusted incidence (mean, 0.54) increased from 0.4 to 0.8 during the 34-year study period. The median age at diagnosis was 60 years (range, 20-90). Clinically detectable primary acquired melanosis preceded or accompanied the primary tumor in 61% of patients. The 5-year cumulative proportion of cases with local recurrence was 0.36 (95% confidence interval [CI], 0.25-0.48). The melanoma-specific 5-and 10-year mortalities were 0.20 (95% CI, 0.12-0.32) and 0.38 (95% CI, 0.26-0.53), respectively. By multiple-event Cox regression, nonlimbal location of the primary tumor predicted a short time to local recurrence (hazard ratio [HR] 1.81, P = 0.024). Nonlimbal location of the primary tumor (HR 4.08, P = 0.023) and increasing tumor thickness (HR 1.19 for each millimeter change, P=0.063) were associated with increased mortality. Local recurrence, analyzed as a time-dependent covariate, also increased mortality (HR 1.39 for each recurrence, P = 0.014). CONCLUSIONS: The incidence of conjunctival melanoma in the white population of Finland increased analogous to cutaneous melanoma. Nonlimbal tumors recur more often and are associated with decreased survival, independent of their greater thickness. Local recurrence contributes to mortality, whereas primary acquired melanosis was not associated with either outcome.

Conjunctival melanotic lesions in Chinese: comparison with Caucasian series.

Conjunctival melanotic lesions in Chinese were studied and compared with those of Caucasians. These lesions were diagnosed in Chinese patients over a two-year period. They were excised under the clinical diagnoses of nevi, primary acquired melanosis (PAM) and malignant melanoma. For the cases included, the histology slides and clinical information were reviewed. Eighteen cases of nevi and nine non-nevoid lesions were identified. Among the non-nevoid lesions, there were eight cases of basal cell hyperpigmentation (one congenital, five acquired, two unknown) and one malignant melanoma. Benign or atypical melanocytic hyperplasias (MH) were not seen. This pattern is very different from that of Caucasian series. Acquired hyperpigmentation is almost only seen in Chinese and seldom in Caucasians. On the other hand, atypical MH is only seen in Caucasians, and not in Chinese. We conclude that conjunctival hyperpigmentation is associated with ethnicity and does not progress to MH, whether benign or atypical. It should be recognised as a distinct entity of no malignant potential that is part of the PAM clinical spectrum.

Conjunctival melanoma in the black population.

Melanoma of the conjunctiva is a rare, unilateral malignancy primarily affecting middle-aged whites; the annual average age-adjusted incidence rate is 0.012 per 100,000 population. Although conjunctival melanoma in the black population is extremely rare, cases have been reported. Melanoma of skin in blacks has a predilection for nonsun-exposed, nonpigmented sites such as mucous membranes, palms, and soles. Primary acquired melanosis may lead to the development of melanoma even in blacks. Primary acquired melanosis in the black population may be difficult to differentiate from racial melanosis clinically and histopathologically. Early diagnosis through awareness and education can help improve the survival of black patients with conjunctival melanoma.

Caruncular malignant melanoma in a black patient.

An 84-year-old black woman had a right caruncular lesion that had progressively enlarged over the past 3 months. Surgical excision and cryotherapy were performed. A biopsy confirmed the diagnosis of caruncular malignant melanoma, a rare lesion which, to our knowledge, has not been previously reported in a black patient.

Factors associated with conjunctival intraepithelial neoplasia: a case control study.

Familial and environmental factors may play a role in the development of conjunctival intraepithelial neoplasia (CIN). Nineteen patients with biopsy-proven CIN completed a questionnaire to evaluate possible predisposing factors. Nineteen age-matched and sex-matched controls completed questionnaires and received slit-lamp examinations. Factors associated with a relatively increased risk of developing CIN included exposure to petroleum products, heavy cigarette smoking, light hair and ocular pigmentation, and family origin in the British Isles, Austria or Switzerland. Non-office and nonprofessional workers were more likely to develop conjunctival intraepithelial neoplasia (p = .05), as were those who were not college graduates (p = .07).

Conjunctival melanoma in Africa.

Malignant melanoma of the eye and adnexa is rare in blacks. A highly unusual malignant melanoma of the tarsal conjunctiva in an adult Ethiopian female, believed to be the first reported in a black patient, is described. Factors that contribute to melanoma in blacks and rates of occurrence are reviewed and discussed.