Sentinel Node Biopsy for Conjunctival Melanoma; Single Centre Experience and Review of Current Literature.

PURPOSE: To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). STUDY DESIGN: Retrospective observational cohort study and literature review. SUBJECTS: Slovenian patients with CjM are included in the study. METHODS: Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. MAIN OUTCOME MEASURES: The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. RESULTS: From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77-224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. CONCLUSION: Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

Conjunctival melanoma treatment outcomes in 288 patients: a multicentre international data-sharing study.

BACKGROUND: To relate conjunctival melanoma characteristics to local control. METHODS: Retrospective, registry-based interventional study with data gathered from 10 ophthalmic oncology centres from 9 countries on 4 continents. Conjunctival melanoma patients diagnosed between January 2001 and December 2013 were enrolled in the study. Primary treatments included local excision, excision with cryotherapy and exenteration. Adjuvant treatments included topical chemotherapy, brachytherapy, proton and external beam radiotherapy (EBRT). Cumulative 5-year and 10-year Kaplan-Meier local recurrence rates were related to clinical and pathological T-categories of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: 288 patients had a mean initial age of 59.7±16.8 years. Clinical T-categories (cT) were cT1 (n=218,75.7%), cT2 (n=34, 11.8%), cT3 (n=15, 5.2%), cTx (n=21,7.3%) with no cT4. Primary treatment included local excision (n=161/288, 55.9%) followed by excision biopsy with cryotherapy (n=108/288, 37.5%) and exenteration (n=5/288, 1.7%). Adjuvant therapies included topical mitomycin (n=107/288, 37.1%), plaque-brachytherapy (n=55/288, 19.1%), proton-beam (n=36/288, 13.5%), topical interferon (n=20/288, 6.9%) and EBRT (n=15/288, 5.2%). Secondary exenteration was performed (n=11/283, 3.9%). Local recurrence was noted in 19.1% (median=3.6 years). Cumulative local recurrence was 5.4% (3.2-8.9%), 19.3% (14.4-25.5%) and 36.9% (26.5-49.9%) at 1, 5 and 10 years, respectively. cT3 and cT2 tumors were twice as likely to recur than cT1 tumours, but only cT3 had statistically significantly greater risk of local recurrence than T1 (p=0.013). Factors such as tumour ulceration, plica or caruncle involvement and tumour thickness were not significantly associated with an increased risk of local recurrence. CONCLUSION: This multicentre international study showed that eighth edition of AJCC tumour staging was related to the risk of local recurrence of conjunctival melanoma after treatment. The 10-year cumulative local recurrence remains high despite current management.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome.

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

Oncologic and visual outcomes after postoperative proton therapy of localized conjunctival melanomas.

INTRODUCTION: conjunctival melanomas have high local relapse rates. Oncologic and visual outcomes can be improved with proton therapy and no-touch surgery. MATERIAL AND METHODS: a monocentric retrospective study of consecutive patients treated with surgery and proton therapy for conjunctival melanoma was conducted. Proton therapy was performed to a total dose of 45 Grays physical dose delivered in eight fractions over two weeks. RESULTS: Ninety-two patients were included. The mean age was 63-year-old. 65.2% of patients had primary acquired melanosis. The mean tumor thickness and diameter was 2.5 mm and 7.0 mm respectively. The clinical stage was T1 in 71.6% of cases, with a quadrangular involvement of more than 90° in 69% of cases. Conjunctival melanomas were of epithelioid cell-type in 40% of cases. Mean follow-up was 4.7 years. Five-year local failure rate was 33.2%. Of 25 local recurrences, 14 were marginal/out-of-field, 4 in-field, others were undetermined. First surgery at expert center resulted in 24.3% of local failure at 5 years versus 38.7% if performed elsewhere (p = 0.41). Salvage exenteration was performed in 13 patients. Tumor stage and quadrangular involvement were significant factors for local failure. Five-year progression-free survival and cause-specific death rates were 61.5 and 3.6%. Stage and epithelioid type were associated with poorer progression-free survival. Trophic toxicity occurred in 22.9% of patients and was treated locally, with grafts in 7 patients. Glaucoma and cataract occurred in 13 and 22 patients respectively. Prognostic factors for visual deterioration were age, tumor extent (multifocality, quadrangular involvement > 180°) and cryotherapy. CONCLUSIONS: 5-year local failure rate after postoperative proton therapy for conjunctival melanoma was of 33.2%. Radiation-induced complications were overall manageable.

Greater Tumor Thickness, Ulceration, and Positive Sentinel Lymph Node Are Associated With Worse Prognosis in Patients With Conjunctival Melanoma: Implications for Future AJCC Classifications.

Identifying tumor characteristics that correlate with metastasis and survival in patients with conjunctival melanoma can potentially lead to better outcomes through a better selection of patients for adjuvant treatments including potentially life-saving new melanoma therapy. The objective of this study was to validate the conjunctival melanoma staging criteria in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) and explore the prognostic importance of tumor thickness, histologic ulceration, and sentinel lymph node biopsy (SLNB) findings in patients with conjunctival melanoma. This is a case series of 88 consecutive patients with conjunctival melanoma. Clinicopathologic characteristics were analyzed. Associations between pathologic characteristics and outcomes were studied using Kaplan-Meier survival analysis. Local recurrence, lymph node metastasis, distant metastasis, and disease-specific survival (DSS) were the main outcome measures. The study included 56 women and 32 men; the median age was 62 years. At presentation, 41 patients had T1 disease, 23 had T2 disease, 23 had T3, and 1 had T4 disease. Sixty-six patients had invasive conjunctival melanoma (median thickness, 1.56 mm), 17 had conjunctival melanoma in situ, and in 5 patients, tumor thickness could not be determined. Overall, 22 patients had ulceration. In total, 31 patients underwent SLNB, and 4 had a positive sentinel lymph node (SLN). The median follow-up time was 46.6 months. Overall, 12 patients had nodal metastasis at presentation or during follow-up, 19 patients had distant metastasis at last follow-up, and 14 patients died of the disease. Tumor thickness and ulceration were associated with increased risks of nodal metastasis, distant metastasis, and death from the disease. Overall, greater clinical T category at presentation was associated with increased risks of distant metastasis and disease-related death; however, the risks of distant metastasis and disease-related death did not differ between T1 (bulbar) and T2 (nonbulbar) tumors or between T2c,d (caruncular) and T1-T2a,b (noncaruncular) tumors. In patients who underwent SLNB, a positive SLN was associated with worse distant metastasis free survival and DSS. Consideration should be given to adding ulceration and emphasizing tumor thickness as the main determinants of pathologic T category for conjunctival melanoma in future AJCC classifications. The significant association between a positive SLN and worse DSS highlights the importance of SLNB for prognosis in patients with conjunctival melanoma and selecting high-risk patients for adjuvant drug treatment.

Prognostic factors and survival for malignant conjunctival melanoma and squamous cell carcinoma over four decades.

PURPOSE: To determine the epidemiology and survival of primary conjunctival malignant neoplasms. METHODS: Retrospective analysis of primary malignant conjunctival neoplasms using Surveillance, Epidemiology, and End Results database from 1973 to 2012. RESULTS: Of 1661 cases, the most common neoplasms are squamous cell carcinoma (SCC) at 54.8% and melanoma at 38.8%. Mean diagnostic age for melanoma was 62.1 compared to 65.5 years for SCC (p = 0.002). 52.2% of melanoma are male versus 77.4% of SCC (p < 0.001). For SCC only age (HR: 1.09, 95% CI:1.04-1.14) is a predictor of survival. For melanoma, age (HR: 1.07, 95% CI: 1.05-1.10), male sex (HR: 2.04, 95% CI: 1.16-3.60), T4 tumors (HR: 3.38, 95% CI: 1.17-9.80) and N1 status (HR: 8.69, 95% CI: 2.75-27.42) are all survival predictors. The 5 and 10-year overall survival (OS) estimates are not significantly different between SCC and melanoma, with 70% and 50% respectively for SCC, and 71% and 50% respectively for melanoma. Median survival time is worse for blacks (52 months) compared to whites (118 months) and Asians/Native Americans/Pacific Islanders (145 months), however race was not found to be a significant prognostic factor in multivariate analysis. Five-year survival are similar between decades 1973-1982 (66.2%), 1983-1992 (69.2%), 1993-2002 (71.3%) and 2003-2012 (70.2%). CONCLUSION: Age at diagnosis is a determinant of survival for both conjunctival SCC and melanoma. Male sex, T4 and N1 staging are also important prognostic factors for melanoma. With respect to overall survival, SCC and melanoma did not differ significantly.

Loss of pRB in Conjunctival Squamous Cell Carcinoma: A Predictor of Poor Prognosis.

Conjunctival squamous cell carcinoma (SCC) is the most common tumor of conjunctival epithelium. It is associated with risk of permanent visual impairment and has the capability to recur, metastasize, and cause death. Deregulation of cell cycle control has been reported in a number of malignancies. The aim of the present study was to assess expression of G1/S cell cycle regulatory proteins [retinoblastoma protein (pRb)/P16/cyclin D1] in conjunctival SCC. Forty-four prospective cases of conjunctival SCC from a tertiary eye care referral center in northern India were included in this study. American Joint Committee on Cancer (AJCC) staging was performed and patients were followed up for 46±3.2 months. pRb loss was seen in 87% and overexpression of p16 and cyclin D1 in 36% and 66%, respectively. Kaplan-Meier analysis revealed reduced disease-free survival in patients with pRb loss (P=0.006). On univariate analysis, pRb loss (P=0.02), orbital invasion (P=0.03), and AJCC stage ≥T3 (P=0.03) emerged as significant high-risk features. On multivariate analysis pRb loss emerged as the most significant poor prognostic indicator in conjunctival SCC cases. Our findings suggest pRb loss to be a useful indicator of aggressive behavior and is recommended for identifying high-risk conjunctival SCC patients.

Clinicopathological Features of Ocular Adnexal Mantle-Cell Lymphoma in an International Multicenter Cohort.

Importance: To our knowledge, the clinical features of ocular adnexal mantle-cell lymphoma (OA-MCL) have not previously been evaluated in a large multicenter cohort. Objective: To characterize the clinical features of OA-MCL. Design, Setting, and Participants: This retrospective multicenter study included patient data collected from January 1, 1980, through December 31, 2015, at 6 eye cancer centers in 4 countries. Medical records of 55 patients with OA-MCL were reviewed; the median length of follow-up was 33 months. Main Outcomes and Measures: Overall survival, disease-specific survival, and progression-free survival were the primary end points. Results: Fifty-five patients were included; ocular adnexal MCL was found to be most common in older individuals (mean age, 70 years) and men (n = 42 of 55; 76%). Patients with OA-MCL frequently presented with disseminated lymphoma (n = 34 of 55; 62%), and were likely to experience stage IVE disease (n = 35 of 55; 64%), with bilateral involvement (n = 27 of 55; 47%), tumor masses (n = 27 of 36; 75%), and involvement of the orbit (n = 32 of 55; 58%). Chemotherapy with or without external beam radiation therapy was the most frequently used treatment. Overall survival rates for the entire cohort were 65% at 3 years (95% CI, 52%-78%) and 34% at 5 years (95% CI, 21%-47%). Disease-specific survival after 5 years was 38% for the entire cohort (95% CI, 25%-51%); the disease-specific survival adjusted by eye cancer center was better in patients who had received rituximab in addition to the chemotherapy regimen (hazard ratio, 3.3; 95% CI, 1.0-14.7; P = .06). The median progression-free survival was 2.3 years (95% CI, 1.8-2.7 years) in patients who experienced recurrence after primary treatment, and 4.1 years (95% CI, 3.9-4.3 years) in patients who presented with a relapse of systemic lymphoma in the ocular adnexal region. Conclusions and Relevance: These results suggest that the distinctive features of OA-MCL are its appearance in older male individuals, advanced stage and bilateral manifestation at the time of diagnosis, and aggressive course. The prognosis of patients with OA-MCL might be improved by addition of rituximab to chemotherapy treatment.

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.

Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated With BRAF Mutations.

IMPORTANCE: Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES: To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included. MAIN OUTCOMES AND MEASURES: BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined. RESULTS: A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models. CONCLUSIONS AND RELEVANCE: Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.

Analysis of SDHD promoter mutations in various types of melanoma.

OBJECTIVES: Recently, recurrent mutations in regulatory DNA regions, such as promoter mutations in the TERT gene were identified in melanoma. Subsequently, Weinhold et al. reported SDHD promoter mutations occurring in 10% of melanomas and being associated with a lower overall survival rate. Our study analyzes the mutation rate and clinico-pathologic associations of SDHD promoter mutations in a large cohort of different melanoma subtypes. METHODS: 451 melanoma samples (incl. 223 non-acral cutaneous, 38 acral, 33 mucosal, 43 occult, 43 conjunctival and 51 uveal melanoma) were analyzed for the presence of SDHD promoter mutations by Sanger-sequencing. Statistical analysis was performed to screen for potential correlations of SDHD promoter mutation status with various clinico-pathologic criteria. RESULTS: The SDHD promoter was successfully sequenced in 451 tumor samples. ETS binding site changing SDHD promoter mutations were identified in 16 (4%) samples, of which 5 mutations had not been described previously. Additionally, 5 point mutations not located in ETS binding elements were identified. Mutations in UV-exposed tumors were frequently C>T. One germline C>A SDHD promoter mutation was identified. No statistically significant associations between SDHD promoter mutation status and various clinico-pathologic variables or overall patient survival were observed. CONCLUSIONS: Melanomas harbor recurrent SDHD promoter mutations, which occur primarily as C>T alterations in UV-exposed melanomas. In contrast to the initial report and promoter mutations in the TERT gene, our analysis suggests that SDHD promoter mutations are a relatively rare event in melanoma (4% of tumors) of unclear clinical and prognostic relevance.

Clinicopathologic features and prognostic factors in patients with non-cutaneous malignant melanoma: a single-center retrospective study of 71 cases.

OBJECTIVES: This retrospective study was carried out to define the clinical features and prognostic differences in non-cutaneous malignant melanoma (non-CMM) originating from different anatomic sites. METHODS: Clinical and follow-up data for 71 patients with non-CMM were collected and reviewed. RESULTS: Of the 71 non-CMM patients, 59 were diagnosed with mucosal malignant melanoma (MMM) and 12 with ocular malignant melanoma (OMM). In the 59 MMM patients, the nasal cavity was the most common anatomic site (n = 31, 43.7% of all non-CMM), followed by the oral cavity (n = 9, 12.7%), the genitourinary tract (n = 9, 12.7%), the anorectum (n = 8, 11.3%), and the gastrointestinal tract (n = 2, 2.8%). In the 12 patients with OMM, anatomic sites included the choroid (n = 8, 11.3% of all non-CMM) and the conjunctiva (n = 4, 5.6%). The survival outcome of patients with OMM was much better than that of patients with MMM (P < 0.001). In MMM patients, anorectal melanoma was associated with a worse survival outcome. Age of ≥ 70 years (P < 0.001) and tumor size of > 2 cm (P = 0.02) were significantly poor prognostic factors in MMM. Age (relative risk [RR] 1.068, 95% confidence interval [CI] 1.006-1.133; P = 0.03) and tumor size (RR 1.410, 95% CI 1.038-1.915; P = 0.028) were independent predictors for the postoperative survival of MMM patients. Patients with these two risk factors had a higher risk for recurrence or death (RR 3.107, 95% CI 1.627-5.595). CONCLUSIONS: Our findings demonstrate that prognoses differ in patients with different anatomic sites of primary non-CMM. Advanced age and larger tumor size are the main factors affecting prognosis. Patients with poor risk factors should be treated differently to improve their survival outcome.

Conjunctival melanoma: survival analysis in twenty-two Mexican patients.

PURPOSE: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). METHODS: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment. RESULTS: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. CONCLUSION: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy.

Conjunctival melanoma: survival analysis in twenty-two Mexican patients / Melanoma conjuntival: análise de sobrevivência em vinte e dois pacientes mexicanos

Purpose: To describe the cases of conjunctival melanoma (CM) and report the disease-free interval (DFI) and overall survival (OS). Methods: The charts of 22 patients who were admitted to two hospitals between 1985 and 2006 were reviewed for pertinent data, including demographics, site of involvement in the conjunctiva and sub-sites, surgical treatment, and adjuvant treatment. Results: There were 10 (45.45%) males and 12 (54.55%) females. Mean age was 52.3 years. In this group, 15 patients (68.1%) involved the bulbar conjunctiva, and 7 (31.9%) involved the palpebral conjunctiva. Of the 22 patients, 72.72% had a history of conjunctival melanosis. The average tumor size was 20.4 mm. Eight (36.36%) patients underwent orbital exenteration, 2 (9.06%) had enucleation, 5 (22.72%) had wide excision of the lesion followed by radiotherapy, 2 (9.06%) had orbital exenteration with neck dissection, and the remaining 5 patients (22.72%) were considered adequately treated only with wide excision. Eight (36.36%) patients received adjuvant treatment. Disease-free survival at 5 years was 51% and the overall survival at 5 and 10 years was 50% and 37%, respectively. Conclusion: Conjunctival melanoma is a rare entity. Tumor behavior is aggressive, and the optimal treatment is surgery with adjuvant therapy. .

Objetivo: Descrever o intervalo livre de doença (DFI) e sobrevida global (OS) de pacientes com melanoma conjuntival (CM). Método: Prontuários de 22 pacientes que foram internados em dois hospitais entre 1985 e 2006 foram revisados para dados pertinentes, incluindo dados demográficos, local de envolvimento na conjuntiva e outros locais de acometimento, tratamento cirúrgico e tratamento adjuvante. Resultados: Dez (45,45%) homens e 12 (54,55%) mulheres foram selecionados. A média de idade foi de 52,3 anos. Em 15 pacientes (68,1%) CM envolveu a conjuntiva bulbar, e em 7 (31,9%) envolveu a conjuntiva palpebral. Dos 22 pacientes, 72,72% tinham história de melanose conjuntival. O tamanho médio do tumor foi de 20,4 mm. Oito (36,36%) pacientes foram submetidos à exenteração orbital, 2 (9,06% ) à enucleação, 5 (22,72%) à ampla excisão da lesão seguida de radioterapia, 2 (9,06%) à exenteração orbital com esvaziamento cervical e os restantes 5 pacientes (22,72%) foram considerados adequadamente tratados apenas com excisão ampla. Oito (36,36%) pacientes receberam tratamento adjuvante. Sobrevida livre de doença em 5 anos foi de 51% e sobrevida global em 5 e 10 anos foi de 50% e 37%, respectivamente. Conclusão: Melanoma conjuntival é uma entidade rara. Comportamento do tumor é agressivo, e o melhor tratamento é a cirurgia com terapia adjuvante. .

Ocular adnexal follicular lymphoma: a multicenter international study.

IMPORTANCE: The clinical features of the follicular subtype of ocular adnexal lymphoma (OAL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize the clinical features of follicular OAL. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective multicenter study that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific, and progression-free survivals were the primary end points. RESULTS: Ninety-eight eligible patients with follicular OAL were included; 60 (61%) were women. The median patient age was 63 years (range, 32-96 years). Sixty-nine patients (70%) had primary OAL, 19 (19%) had OAL in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma, and 31 (45%) had stage IIE lymphoma. Patients with disseminated lymphoma had stage IIIE (9 of 19 [47%]) and stage IV (10 of 19 [53%]) disease, whereas patients with a relapse of systemic lymphoma presented with stage IE (8 of 10 [80%]), stage IIE (1 of 10 [10%]), and stage IIIE (1 of 10 [10%]) disease. Patients with primary follicular lymphoma (n = 69) and those with isolated ocular relapse (n = 9) were treated with external beam radiation therapy (EBRT) (35 of 78 [45%]) or EBRT plus chemotherapy (22 of 78 [28%]). Patients presenting with stage IIIE-IV follicular lymphoma (n = 20) most frequently received chemotherapy (9 of 20 [45%]) or EBRT plus chemotherapy (4 of 20 [20%]). The 10-year overall survival for the entire study cohort was 60%. Primary patients treated with EBRT had a better disease-specific survival compared with patients receiving ERBT plus chemotherapy (10-year disease-specific survival, 94% vs 40%; P = .02 by log-rank test). CONCLUSIONS AND RELEVANCE: Follicular OAL was more commonly found in elderly female patients. These tumors were equally noted to involve the conjunctiva, lacrimal gland, and orbit. Patients with ocular adnexal follicular lymphoma primarily treated with EBRT had a more favorable long-term disease-specific survival.

Progesterone and estrogen receptors in conjunctival melanoma and nevi.

BACKGROUND: Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma. METHODS: Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients. RESULTS: Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1-4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort. CONCLUSIONS: We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.