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Purpose: To evaluate the prognosis of eyelid sebaceous carcinoma (SeC) in patients with disease stage worse than IIA., Methods: This retrospective, single-center study included 78 SeC patients. For stage II patients, 1:3 propensity score matching (PSM) was applied between those undergoing orbital exenteration and those receiving eye-sparing treatments. Risk factors in the eye-sparing group were analyzed using Cox regression, and Kaplan-Meier survival analysis assessed metastasis-free survival (MFS), recurrence-free survival (RFS), disease-specific survival (DSS), and progression-free survival (PFS)., Results: Seventy-eight patients treated at Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January 2010 to July 2024, were followed for a median of 40.5 months. Of these, 60 patients (76.9%) had stage II disease, 13 patients (16.7%) had stage III, and five patients (6.4%) had stage IV. After PSM, patients with an advanced clinical T (cT) category (cT4 vs. cT3) or equatorial region involvement were more likely to require orbital exenteration and had poorer MFS following eye-sparing surgery. For stage II patients who died of tumor-related causes, the average survival was 144.3 months. For stage III patients with distant metastasis, survival post-metastasis averaged 12.5 months; for stage IV patients, the time from diagnosis to tumor-specific death averaged 49.0 months., Conclusions: In stage II SeC, eye-sparing treatment offered comparable outcomes to orbital exenteration. Orbital exenteration is recommended for tumor involved with the equatorial region. Systemic therapy may be beneficial for patients with distant metastases, although further research is needed to optimize adjuvant treatment.

Purpose: To analyze the outcomes of eyelid and periocular sebaceous gland carcinoma (SGC) based on prognostic stage of the 8th edition of American Joint Committee on Cancer (AJCC) classification., Design: Retrospective study METHODS: Study of 500 eyes with SGC RESULTS: Based on the 8th edition of AJCC classification, tumors belonged to Stage 0 (n=13, 3%), I (n=158, 32%), II (n=269, 54%), III (n=48, 9%), and IV (n=12, 2%). The 5-year Kaplan-Meier estimates of regional lymph node metastasis, systemic metastasis, and metastasis-related death were higher for stage II (12%, 11%, and 12%, respectively), III (69%, 25%, and 42%, respectively) and IV (70%, 100%, and 100%, respectively) compared to stage I (0%, 6%, and 6%, respectively). Cox proportional analysis revealed a greater hazard ratio (HR) for lymph node metastasis in stage II (HR, 3.498; 95% CI, 0.200 to 10.200; p<0.022), III (HR, 95% CI, 24.836; 8.733 to 70.631; p<0.001), and IV (HR, 53.731; 95% CI, 15.418 to 187.253; p<0.001), systemic metastasis in stage III (HR. 13.895; 95% CI, 3.871 to 49.874; p<0.001) and IV (HR, 81.465; 95% CI, 22.267 to 298.051; p<0.001) and for disease-related death in stage III (HR, 9.182; 95% CI, 2.743 to 30.728; p<0.001) and IV (HR, 85.237; 95% CI, 25.331 to 287.422; p<0.001), compared to stage I., Conclusion: The prognostic staging of the 8th edition AJCC classification predicts the prognosis of patients with eyelid and periocular SGC, which worsens with the advancing stage. The high incidence of lymph node and systemic metastasis accounts for mortality in these patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Merkel cell carcinoma of the eyelid (MCCE) is a rare yet aggressive neuroendocrine tumour associated with significant morbidity and mortality. This study aimed to investigate survival trends and demographic factors related to MCCE, 2000-2019, using the Surveillance, Epidemiology, and End Results (SEER) Program., Methods: Cases were analysed by demographic parameters, disease properties, and survival. Statistical analyses were performed via a dedicated computerized software package., Results: A total 349 cases of MCCE were identified, accounting for 2% of all MCC cases in the United States during that time. Of note, the incidence of MCCE remained stable over the study period ( p  = .35). Female patients accounted for 56% of the cases, and males for 44%. White patients accounted for 90.8% of the the cases, and Black patients for 2.9%. MCCE incidence increased with age, with the majority of patients age 85+ ( p  < .05). Incidence was greatest in metropolitan areas and among those with median incomes >$75,000/year. Income correlated with likelihood of MCCE diagnosis ( p  < .05). Analysis of 5-year survival data showed 20% of the patients died due to MCCE within 5 years of diagnosis. Of these, the majority died within one year of diagnosis., Conclusions: Consistent with previous reports, most patients were white, female, and age 85+.Incidence correlated with metropolitan environments and median income. While most patients did not die from MCCE, majority of recorded deaths occurred within one year of diagnosis.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Eyelid carcinoma is rare tumors of the head and neck. They are rarely lethal but can be associated with significant morbidity if not treated early and appropriately. There are limited data available from world over and in particular the Indian subcontinent regarding eyelid carcinoma and its prognostic factors influencing treatment outcomes. Setting and Design:Retrospective study of patients treated in a tertiary cancer center between 2005 and 2016., Methodology: In this study, 51 patients with eyelid carcinoma treated at single tertiary cancer center were included. The demographic, clinical data, which includes the treatment received, histopathology report and follow-up, were recorded. All the relevant variables influencing disease-free survival (DFS) were analyzed., Results: Sebaceous carcinoma was the most common eyelid carcinoma followed by squamous cell carcinoma and basal cell carcinoma in descending order in this series. Lower eyelid was involved most often. The incidence of nodal metastasis was low (14%). Multivariate analysis revealed that margin status influenced the DFS (P= 0.001) (hazard ratios = 15.9 [95% confidence interval: 1.8-135.2]). The 5 years' DFS was 70%., Conclusion: Eyelid tumors are less common cancer with good prognosis if treated appropriately. The morbidity associated with treatment can be reduced if treated early., Competing Interests: None

Background: Limited information exists on the demographics, tumor characteristics, and treatment in primary cutaneous mucinous carcinoma (PCMC)., Objective: The authors sought to describe prognostic factors, incidence rates, and the subsequent primary malignancy (SPM) risk in patients with PCMC., Methods: Primary cutaneous mucinous carcinoma cases in the National Cancer Institute's Surveillance, Epidemiology, and End Results data (1972-2013) were analyzed to provide demographic, cancer-related, and treatment information and to calculate incidence and mortality. Patients were stratified by stage (local, regional, distant disease) for comparison. The risk of developing an SPM was calculated., Results: Four hundred eleven PCMC cases were identified. The age-adjusted incidence was 0.04 cases per 100,000-person years. Blacks were disproportionately affected by PCMC (0.048; 95% confidence interval, 0.034-0.065; p < .001). Approximately 67.4% of patients had local disease, 10.5% had regional disease, and 5.8% had distant disease. Primary cutaneous mucinous carcinoma-specific mortality was independent of sex, age, race, primary site, histologic tumor grade, tumor size, tumor stage, or treatment. The overall frequency of developing a second primary malignancy was not increased in patients with PCMC., Conclusion: Although PCMC occurs with equally in both sexes, it may be more common in African Americans than previously recognized. Although eyelid PCMC may have a higher rate of distant metastasis, all patients need close follow-up.

Purpose: Eyelid sebaceous gland carcinoma (SGC) is an aggressive but rare malignancy of ocular region. Over-expression of PD-L1 and PD-1 has been demonstrated in a variety of solid tumors including conjunctival melanoma. PD-L1 is an immunoinhibitory molecule that suppresses the effective T cells response against tumor antigen leading to the progression of tumors. Inhibitors of the interaction of PD-L1 and PD-1 are associated with good clinical response various carcinomas. The prognostic value of the PD-1/PD-L1 axis in SGC remains unexplored. The purpose of this study was to evaluate expressions of PD-1 and its ligand PD-L1 in SGC and correlate its expression with clinicopathological features and patients survival., Methods: The immunohistochemical expression of PD-L1 and PD-1 was evaluated in 30 SGC cases., Results: PD-L1 immunopositivity was detected in 41.9% of the SGC cases. PD-1 expression in tumor infiltrative lymphocytes (TILs) was observed in 53.3% samples. Tumor PD-L1 positivity, PD-1 expression in TILs and tumor size (>10 mm) was associated with reduced disease-free survival. On multivariate analysis only tumor size (>10 mm) and a combined positivity of PD-L1 in tumor cells and PD-1 in TILs with an odds ratio of 5.212 (95% confidence interval 1.449-18.737) continued to be significantly associated with SGC recurrence., Conclusion: PD-L1 is overexpressed in 50% of SGC cases. The combined tumor PD-L1 positivity and TILs showing PD-1 expression within the same SGC patient's samples predict high-risk SGC, suggesting that the up-regulation of PD-L1 in tumor cells and PD-1 positivity within the same SGC patient may aggravate tumor recurrence., Competing Interests: None

Purpose: To evaluate prognostic factors and survival of patients with sebaceous carcinoma of the eyelid through a population-based analysis. Methods: A total of 940 patients with primary sebaceous carcinoma of the eyelid were derived from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 1973 to 2013. Kaplan-Meier univariate analysis and Cox Regression multivariate analysis were performed to examine prognostic factors in overall survival (OS). 5- and 10-year survival rates, median survival, and prognostic variables with statistical significance were measured. Results: Kaplan-Meier analysis showed that OS is 66% and 44% at 5 years and 10 years respectively. Median OS is 9.4 years. Multivariate Cox regression analysis demonstrated that independent prognostic factors for OS are age at diagnosis (HR = 4.61 [95% CI 1.93-11.0], P = 0.001), surgical treatment (HR = 0.196 [95% CI 0.07-0.55], P = 0.002), combined surgical and radiation treatment (HR = 0.227 [95% CI 0.06-0.81], P = 0.023), and greater tumor size at diagnosis (HR = 3.381, [95% CI 1.77-6.45], P < 0.001). Conclusion: We report the largest population study to date to evaluate prognostic factors of patients with sebaceous carcinoma of the eyelid. Multivariate analysis shows that older age, and greater tumor size correlate with decreased overall survival, whereas surgical treatment or combined surgical and radiation treatment correlate with increased overall survival. Interestingly, tumor grade, lymph node involvement, and distant extent of tumor have not demonstrated to be independent prognostic factors for overall survival.

Background/aims: To validate the predictive value of the American Joint Committee on Cancer (AJCC) 8th-edition classification for local recurrence, metastasis and survival in patients with eyelid sebaceous carcinoma., Methods: We performed a retrospective review of 100 consecutive patients with eyelid sebaceous carcinoma. Eyelid carcinomas were staged according to the AJCC 7th-edition and 8th-edition criteria. Associations between T and N categories and disease-related outcomes including local recurrence, lymph node metastasis, distant metastasis and survival were evaluated., Results: 60 women and 40 men had a median age of 67 years (range, 41-94 years). The proportions of patients who experienced local recurrence, lymph node metastasis, distant metastasis and death from disease were 6%, 21%, 7% and 6%, respectively. Two-year and 5-year disease-specific survival (DSS) rates were 93.8% and 92.0%, respectively. There were significant correlations between (1) T2c or worse category and lymph node metastasis (p=0.04) and distant metastasis (p=0.01), (2) T3b or worse category and local recurrence (p=0.01) and death from disease (p=0.01) and (3) N1 category at presentation and distant metastasis (p<0.01) and death from disease (p<0.01). The AJCC 8th-edition classification showed a better homogeneity of the T-category distribution (p<0.01) and a slightly higher discrimination ability for lymph node metastasis (C=0.734 vs C=0.728) than the 7th-edition., Conclusions: T and N categories per AJCC 8th-edition classification are predictive of local recurrence, metastasis and DSS outcomes for eyelid sebaceous carcinoma. Surgeons should perform strict surveillance testing for nodal and systemic metastases in patients with T2c or worse T category and/or N1 disease at presentation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The decision to perform Mohs micrographic surgery (MMS) or wide local excision (WLE) for eyelid sebaceous carcinoma (SC) is controversial., Objective: To compare local recurrence, metastasis, and tumor-related mortality of patients with eyelid SC who were initially treated with MMS versus with WLE., Methods: A multicenter cohort study. Medical records were reviewed for factors associated with recurrence, metastasis, and tumor-related mortality. All eligible patients were followed up. The impact of initial surgical modality on the prognoses were determined by Cox analyses after control for all confounders., Results: Of the 360 patients included in this cohort, 115 (31.9%) underwent MMS as primary resection, whereas 245 (68.1%) underwent WLE. After a median follow-up period of 60.0 months, local recurrence was observed in 18 patients (15.7%) in the MMS group and 97 patients (39.6%) in the WLE group. Metastasis occurred in 9 patients (7.8%) who underwent MMS and 38 (15.5%) who underwent WLE. In all, 6 patients in the MMS group (5.2%) and 21 in the WLE group (8.6%) died of metastatic SC. Multivariable Cox regression indicated that compared with the WLE group, the MMS group exhibited more favorable local recurrence control (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.24-0.73; P = .002) but a comparable metastasis rate (HR, 1.38; 95% CI, 0.60-3.18; P = .453) and comparable tumor-related mortality (HR, 1.70; 95% CI, 0.59-4.93; P = .329). However, this beneficial effect became nonremarkable for patients with pagetoid intraepithelial neoplasia (HR, 1.73; 95% CI, 0.37-8.21; P = .488)., Limitations: Retrospective nature of the study., Conclusion: MMS should be proposed for eyelid SC without orbital involvement to achieve recurrence control; however, this surgical procedure did not change the long-term outcomes in terms of metastasis or tumor-related mortality. Patients with pagetoid intraepithelial neoplasia may require adjuvant measures., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the clinicopathological features and prognostic factors for eyelid sebaceous gland carcinoma (SGC) in an ethnic Chinese population and to validate the performance of the T category of the 8th edition AJCC staging systems, with the aim of providing information for refinements., Methods: Sixty-three patients with pathological diagnosis of SGC were enroled retrospectively. The clinicopathological features, treatments, and outcomes were collected. Prognostic factors associated with the outcome of local recurrence, regional lymph node metastasis, and tumour-related death were analysed. The performance analysis was performed by comparing the predictive value for survival and the monotonicity of gradients between the 7th and 8th staging systems., Results: The distribution of T1:T2:T3:T4 tumours according to the 7th and 8th edition was 6:40:16:1 and 23:26:5:9, respectively. Positive surgical margin was a poor prognostic factor. Local recurrence was associated with more aggressive histopathological features and surrounding structure invasions. Regional lymph node metastasis was associated with larger tumours. The T category of 8th edition showed better predictability for local recurrence and regional lymph node metastasis, while the T category of 7th edition had better monotonicity of gradients. Tumours classified as T2c or worse had higher risk of regional lymph node metastasis, while tumours T3b or worse in the 8th edition had more tumour-related death., Conclusions: Patients with higher T category are at risk of regional lymph node metastasis and tumour-related death. Further refinement of the T category of AJCC staging system can focus on the predictability for local recurrence and the monotonicity of gradients.

Background: Due to the importance of function and cosmetics, periocular skin malignancies represent a therapeutic challenge., Objective: To evaluate the safety and efficacy of radiotherapy (RT) treating periocular skin tumors., Methods: Data of patients with periocular tumors treated with grenz or soft X-rays at the University Hospital Zurich, Switzerland, between 2009 and 2014 were reviewed. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with associated in situ lesions, cutaneous melanoma, lentigo maligna (LM), cutaneous lymphoma and Kaposi's sarcoma were included in the analysis., Results: We found 159 periocular lesions in 145 patients. Overall recurrence was highest for actinic keratosis and Bowen's disease (27%), melanoma (17%) and LM (15%), whereas SCC and BCC showed recurrence in 11 and 10%, respectively. 45% of all recurrences occurred within 12 months after treatment, with a median time to recurrence of 13 months (range 3-73)., Conclusion: RT, which provides a good therapeutic response with minimal adverse events, is a therapy option for periocular cutaneous malignancies., (© 2019 S. Karger AG, Basel.)

Background: Melanomas arising from eyelid skin are exceptionally rare, accounting for <1% of eyelid malignancies and all cutaneous melanomas. The aim of this study was to identify the histopathological features and clinical behaviors of the palpebral skin melanoma patients from a single tertiary institution., Patients and Methods: Seventeen Caucasian patients diagnosed with eyelid cutaneous melanoma were analyzed retrospectively., Results: The median age of patients was 59 years, and females were predominant (n = 11). The most frequent localization of the lesions was the lower eyelid (n = 8). Nodular (n = 4), lentigo maligna (n = 3), and the superficial spreading melanoma (n = 3) were the most common histopathological subtypes. Only three patients had in situ melanomas. Tumor infiltrating lymphocytes were present in most of the patients; however, only a few cases had lymphovascular invasion. Regional lymph node involvement was present in two patients, and distant metastasis was found in only one patient. Four patients (24%) had disease relapses during follow-up, all of which were locoregional. The median relapse-free survival (RFS) time and 5-year RFS rate were 26.3 months and 60.4%, respectively. Two patients (12%) died. Median OS time was 32.1 months, and 5-year OS rate was 84%. Being elderly (older than 60 years of age) (P = 0.05), lesion originating from canthus compared to eyelid (P = 0.03) and presence of recurrence in follow-up (P = 0.04) have been found as poor prognostic indicators for OS., Conclusion: Palpebral skin melanoma is associated with favorable clinical features, and it is correlated with better survival rates., (© 2018 The International Society of Dermatology.)

Aims: Sebaceous gland carcinoma (SGC) of the eyelid is a rare but potentially deadly cancer. The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) 7th Edition T category for SGC correlated with metastasis and survival in the Chinese population., Methods: This was a retrospective, single-centre cohort study. Patients with surgically resected eyelid SGC between January 2001 and May 2015 at the Hong Kong Eye Hospital were reviewed. Tumours were staged using the AJCC criteria. The main outcome measures included local recurrence, metastasis and death. Disease-free survival (DFS) was measured from the completion of treatment; overall survival was measured from the date of initial diagnosis., Results: The study included 22 Chinese patients with a mean age of 65.4 years. The majority presented as a nodular lesion (91%) with 12 eyes (54.5%) initially misdiagnosed and a mean presentation time of 1 year. It was found that those with AJCC stage T2b or higher were significantly associated with lymph node metastasis (P=0.002) when compared with those with stage T2a. Older age at diagnosis (P=0.035) and no misdiagnosis (P=0.025) were associated with shorter DFS. Those with stage 3a or higher were associated with shorter DFS (P=0.007) and overall survival (P=0.024)., Conclusion: Similar to previous reports, in this Chinese cohort, AJCC staging for SGC correlated with lymph node metastasis, DFS and overall survival. Those with stage 2b or higher on presentation will need closer surveillance for lymph node metastasis and may benefit from sentinel lymph node biopsy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To describe the clinical presentations of patients diagnosed with ocular adnexal or orbital squamous cell carcinoma (SCC), which possess features similar to feline restrictive orbital myofibroblastic sarcoma (FROMS)., Procedures: A retrospective review of adnexal and/or orbital SCC was performed. Cases were collected from the University of Georgia College of Veterinary Medicine and the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) (1990-2016). Data included signalment, ophthalmic clinical signs, nonophthalmic history and clinical signs, clinician suspicion of FROMS, advanced imaging results, and subsequent histopathologic diagnosis. FROMS cases from the COPLOW over the same time span were reviewed and compared statistically to the SCC cases with a significance threshold of 0.05., Results: Nineteen cases (20 eyes) were identified with adnexal SCC with features similar to FROMS, including keratitis and eyelid/third eyelid restriction and/or thickening. There were no statistically significant differences between clinical findings in the SCC cases and the identified and compared FROMS cases (57 cases; 67 eyes), except for exophthalmos and/or resistance to retropulsion, which was less common in SCC cases (20%) than in FROMS cases (47.8%) (P = 0.027); and clinical or imaged presence of an overt eyelid or orbital mass, which was more common in the SCC cases (30%) than in the FROMS cases (4.5%) (P = 0.0010)., Conclusions: SCC with adnexal involvement has many features similar to FROMS. In addition to FROMS, SCC should be considered a differential diagnosis in cats with restrictive adnexal or orbital signs and corneal changes., (© 2017 American College of Veterinary Ophthalmologists.)

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.

Purpose: The aim of this study was to report management and outcomes in patients affected by eyelids carcinomas involving regional lymph nodes., Methods: We have retrospectively analyzed the data of patients affected by eyelids carcinoma with nodal involvement. The clinical records of 10 patients with malignant eyelid carcinoma and regional nodal metastasis treated between September 2011 and March 2015 have been analyzed., Results: The study included 5 women and 5 men (median age 54,5 years; range 37-80 years). The most common tumor was the squamous cell carcinoma (4 cases) followed by sebaceous carcinoma (2 cases): 1 case of epidermoid carcinoma, 1 case of malignant melanoma, 1 case of Merkel carcinoma, and 1 case of basal cell carcinoma. All patients were treated by surgical resection; in 2 cases, orbital exenteration was required. The treatment of regional nodal metastasis consisted of parotidectomy and radical neck dissection followed by radiation therapy. None of the patients developed local recurrence. Three patients died: one, affected by Merkel cell carcinoma, died after 2 months because of metastatic dissemination to the lung; another one, affected by epidermoid carcinoma involving the orbit, died because of liver metastasis; the third one, affected by malignant melanoma, died because of other causes. The follow-up time ranged from 9 to 36 months (median 19.3 months)., Conclusions: Patients affected by advanced malignant eyelid carcinoma need to be strictly controlled because metastasis can develop at least 5 years after surgical treatment. Therapy may include a combination of local surgery, neck dissection, and radiation.

The purpose of this study was to evaluate the clinical features and prognosis of eyelid sebaceous gland carcinoma (SGC) based on the T category of the American Joint Committee on Cancer (AJCC) classification (7th edition). This is a retrospective interventional case series study. Based on the T category of the AJCC classification, 191 patients with eyelid sebaceous gland carcinoma were classified as T1 (n = 1, 1 %), T2 (n = 111, 58 %), T3 (n = 76, 40 %), and T4 (n = 3, 2 %). Based on multivariate analysis, the factors predictive of regional lymph node metastasis included duration of symptoms >6 months (p = 0.04) and orbital tumor extension (p < 0.001). The factors predictive of systemic metastasis included orbital tumor extension (p < 0.001) and perivascular invasion (p = 0.007). The factor predictive of death due to systemic metastasis included orbital tumor extension (p < 0.001). Kaplan-Meier estimates of regional lymph node metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 11 and 11 % for T2, 44 and 59 % for T3, and 100 and 100 % for T4 (p < 0.001). Kaplan-Meier estimates of systemic metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 6 and 6 % for T2, 35 and 35 % for T3, and 100 and 100 % for T4 (p < 0.001). Kaplan-Meier estimates of death due to metastasis at 5 and 10 years, respectively, were 0 and 0 % for T1, 3 and 3 % for T2, 30 and 50 % for T3, and 100 and 100 % for T4 (p < 0.001). Primary tumor (T) category of the AJCC classification predicts the prognosis of patients with eyelid SGC. The risk of systemic metastasis and death increases with increasing tumor category.

Purpose: To describe the various types of primary neoplasms affecting the third eyelid (TEL) gland of dogs and cats., Methods: A retrospective search of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Veterinary ophthalmologists, primary care veterinarians, and, when appropriate, owners were contacted for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence, metastasis, and length of follow-up., Results: A total of 127 canine and 18 feline cases met the inclusion criteria. The most common canine TEL gland tumor was adenocarcinoma (n = 108; 85.0%) followed by adenoma (n = 18; 14.2%) and squamous cell carcinoma (SCC) (n = 1; 0.8%). For canine cases with follow-up information available (n = 62), 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. The most common feline TEL gland tumor was adenocarcinoma (n = 15; 83.3%) followed by SCC (n = 3; 16.7%). For feline cases with follow-up information available (n = 9), 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease., Conclusions: This study determined that adenocarcinoma was the most common third eyelid gland tumor in both dogs and cats. The overall survival times were less, and metastatic occurrence and recurrence rates appeared to be higher for feline tumors as compared to those diagnosed in dogs. This is the first report of SCC originating from glandular ductular epithelium., (© 2015 American College of Veterinary Ophthalmologists.)

Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and metastasis in various malignancies. ZEB2/SIP1 is an important EMT regulator and down-regulates E-cadherin expression. The present study was planned to explore status of EMT-associated markers ZEB2/SIP1 and E-cadherin in eyelid sebaceous gland carcinoma (SGC) and to correlate with clinicopathological high-risk features. Expressions of ZEB2 and E-cadherin were evaluated by immunohistochemistry in 65 cases of histopathologically proven eyelid SGC. The results were correlated with clinicopathological high-risk features and survival of the patients to determine the prognostic significance of ZEB2, E-cadherin, and various high-risk features. Cytoplasmic overexpression of ZEB2 and membranous loss of E-cadherin were seen in 68% and 66% of cases of eyelid SGC, respectively. ZEB2 overexpression was significantly associated with E-cadherin loss (P = .002). Overexpression of ZEB2 also showed significant association with lymph node metastasis (P = .046), orbital invasion (P = .049), large tumor size (P = .018), and advanced tumor stages (P = .036). Survival analysis revealed that patients with ZEB2 overexpression had poor survival. ZEB2 overexpression and orbital invasion were found to be independent prognostic indicators (univariate analysis). However, multivariate analysis showed that ZEB2 (hazard ratio, 0.094; 95% confidence interval, 00.012-0.709; P = .022) was the best poor prognostic indicator of eyelid SGC. Our study demonstrates the role of both ZEB2 and E-cadherin in the promotion of EMT in eyelid SGC. The outcome of this study also points toward ZEB2 as an independent prognostic marker as well as a potential therapeutic target in eyelid SGC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We retrospectively reviewed the clinical features and outcome of benign and malignant eyelid tumors from 1995 to 2015 in a tertiary medical center. Among 4,521 histologically confirmed eyelid tumors, 4,294 (95.0%) were benign tumors and 227 (5.0%) were malignant tumors. The mean age at diagnosis was significantly higher in patients with malignant lid tumors than those with benign lid tumors (72.5 and 55.4 years, resp., p < 0.001). The most common benign eyelid tumors were intradermal nevus (21.1%), followed by seborrheic keratosis (12.6%) and xanthelasma (11.2%). The most common malignant eyelid tumors were basal cell carcinomas (57.8%), followed by sebaceous gland carcinomas (21.1%) and squamous cell carcinomas (10.1%). There was a relative male predominance (63.4% and 49.2%, resp., p < 0.001) and higher recurrence rate (11.9% and 4.4%, resp., p < 0.001) in malignant lid tumors as compared with those of benign lid tumors. Twenty-two patients (9.7%) received orbital exenteration/enucleation. Eight patients (3.5%) with malignant lid tumors died of disease. Patients with eyelid melanoma were associated with a high mortality rate (25.0%). It is important to differentiate between benign and malignant eyelid tumors, because they may cause cosmetic disfigurement and severe morbidity, especially in those with malignant eyelid tumors.

Purpose: To present the results of a 30-year prospective study in which eyelid basal cell carcinomas were treated with cryosurgery., Methods: Basal cell carcinomas with well-defined borders on the eyelids or medial canthus, diagnosed by punch biopsy, were included. Cryosurgery was performed using liquid nitrogen sprayed into a cone circumscribing the tumours. The tumours were treated in a double freeze-thaw cycles technique. The minimum thawing time of the frozen area outside the tumour margin was at least 60 seconds. During the first 20 years of the study, patients were re-examined for up to 10 years. In the last 10 years of the study, most patients were followed up for 1 year, and if there was no visible scarring in the treated area at the 1-year check-up, follow-ups were implemented at the patient's request following self-assessment., Results: In total, 781 tumours in 768 patients were treated. The median age of the patients at treatment was 73 years, mean 70.9 years (range 22-102 years). More women (58%) were treated than men. The median tumour size was 8 mm, mean 9.1 mm (range 2-25 mm). There were few side-effects requiring intervention. Twelve patients underwent surgery due to ektropion during follow-up. In 101 patients, treatment of the tumour resulted in conjunctival growth on the skin side, which required correcting operations in 28 patients. Three recurrences have occurred., Conclusion: Cryosurgery is an effective treatment modality for eyelid basal cell carcinomas, resulting in few recurrences and good cosmetic and functional outcomes at a low cost., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Merkel cell carcinoma is a rare but potentially deadly cancer of the eyelid. To date, no studies have reported on clinical parameters at initial presentation of the eyelid tumor that may correlate with disease-free survival (DFS). The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) T category for eyelid carcinoma correlates with metastasis and DFS in patients with Merkel cell carcinoma of the periocular region., Methods: This is a retrospective cohort study from a tertiary referral cancer center. All consecutive patients treated for eyelid or periocular Merkel cell carcinoma between November 1, 1998, and November 1, 2012, were reviewed. The main outcome measures included AJCC T category for eyelid carcinoma and Merkel cell carcinoma at presentation, nodal metastasis at presentation, metastasis during follow up, and DFS., Results: The study included 18 patients, 7 men and 11 women, with median age of 68.5 years. The AJCC T categories for both eyelid carcinoma and Merkel cell carcinoma were significantly correlated with DFS. Using the T categories for eyelid carcinoma, when TX and T2a were grouped into a single category and T2b and T3a into another category, the estimated DFS rate at 3 years was 100% for patients with TX or T2a lesions and 57% for patients with T2b or T3a lesions (p=0.0298). Four patients (22%) had lymph node metastasis at presentation. Presence of lymph node metastasis at presentation was the strongest single predictor of shorter DFS and an increased risk of metastasis during follow up (p=0.0222)., Conclusions: The AJCC eyelid carcinoma T at presentation correlates with DFS in patients with Merkel cell carcinoma of the periocular region. The DFS rate at 3 years was significantly worse for patients with T2b or more extensive tumors by eyelid carcinoma T category. Presence of lymph node metastasis at presentation was predictive of shorter DFS and an increased risk of metastasis during follow up.

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.

Background/aims: Squamous cell carcinoma (SCC) of eyelid is the second most common cancer of the eyelid with the potential for nodal metastasis. The purpose of this report is to determine whether primary tumour size and 'T' designation in the American Joint Committee on Cancer (AJCC) staging system, 7th edition, correlate with the risk of regional nodal metastasis in patients with eyelid SCC., Methods: Sixty-five consecutive patients with eyelid SCC treated by one ophthalmologist from March 1999 through July 2011 were included in this retrospective cohort study. Disease was staged using the AJCC 7th edition criteria based on clinical, pathological and radiographical data. Main outcome measures included regional lymph node metastasis at presentation, local recurrence, distant metastasis and survival at last follow-up., Results: 40 men and 25 women had a median age of 67.0 years (range 41-89). TNM designations at presentation per the AJCC 7th edition were as follows: T1N0M0, 6 patients; T2aN0M0, 11 patients; T2bN0M0, 17 patients; T2bN1M0, 2 patients; T3aN0M0, 22 patients; T3bN0M0, 2 patients; T3bN1M0, 1 patient; T4N0M0, 3 patients; and T4N1M0, 1 patient. Median follow-up was 27 months (range 1-150). Four patients had nodal metastasis at presentation. Two of these four patients had T2bN1M0 disease, one had T3bN1M0 disease and one had T4N1M0 disease. Two patients, with T3aN0M0 and T4N0M0 tumours, respectively, at presentation, developed lymph node metastasis at 2 weeks and 8.4 months, respectively, after tumour excision. The four patients who had lymph node metastases at presentation and the two who developed lymph node metastases during follow-up had tumours ≥18 mm in greatest dimension or T2b or higher at presentation. Seven local recurrences were observed during follow-up. Two-year and 3-year recurrence-free survival rates were 93% (95% CI 80% to 98%) and 82% (95% CI 63% to 92%), respectively. No distant metastasis or tumour-related death was observed during follow-up. The 2-year and 3-year disease-free survival rates were 90% (95% CI 77% to 96%) and 79% (95% CI 61% to 89%), respectively., Conclusions: Regional nodal metastases were observed among patients who presented with tumours >T2b. Tumour size and the AJCC TNM designations correlate with metastasis and should be reported more often for eyelid SCCs to allow comparisons across centres.

Aims: To report the local control and complication rates of orthovoltage radiotherapy in the management of medial canthal basal cell carcinoma (BCC)., Methods: The medical records of all patients treated with medial canthal BCC between 1998 and 2010, with orthovoltage radiotherapy as primary treatment, adjuvant treatment after incomplete surgical excision, or for tumour recurrence following surgical excision, were retrospectively studied. The actuarial rates of tumour control and complications were calculated using Kaplan-Meier estimates. Main outcome measures were rates of tumour control and radiation complications., Results: 90 patients were included with a median follow-up of 80 months. Tumour control rate at 10 years for the entire cohort was 94% (95% CI 84% to 98%). Tumour control rates showed no statistically significant differences among different treatment intents or treatment radiation energies. Radiation-related complication rates included loss of eyelashes in 59% (95% CI 48% to 66%), epiphora 51% (95% CI 39% to 62%), dry eye 14% (95% CI 3% to 35%) and conjunctival scarring 11% (95% CI 1% to 33%). No patient developed long-term corneal complications., Conclusions: Orthovoltage radiotherapy can be a reliable therapeutic alternative for selected medial canthal BCCs, which can be contained within the prescribed radiation field, with anticipated radiation-related toxicities.

Purpose: To evaluate the prognostic utility of the American Joint Committee on Cancer (AJCC) staging system for ocular adnexal lymphoma (OAL).
, Methods: A multicenter, consecutive case series of patients with biopsy-proven conjunctival, orbit, eyelid, or lacrimal gland/sac lymphoma was performed. The electronic pathology and clinical records were reviewed for new or recurrent cases of ocular adnexal lymphoma. The main outcome measures included pathology and clinical staging (AJCC and Ann Arbor systems), treatment, and recurrence (local and systemic). Statistical analysis included demographic evaluations and the Kaplan-Meier survival probability method.
, Results: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue were the most common (n=60/83, 72%). The most common Ann Arbor clinical stages were IE (76%) followed by IIE (17%) and IIIE (7%). Pathology identified 13 cases (15%) that were upstaged to group IV (p=0.017). Similarly, AJCC clinical stages were cT1NOMO (21.7%), cT2NOMO (44.6%), cT3N0M0 (5%), and cT4NOMO (2.4%). Local control was achieved in 75% of treated patients. There were 19 local recurrences from which 14 (74%) belonged to the non-radiation treatment groups. Lower-risk groups (T1 and T2 without lymph node involvement or metastatic disease of AJCC and IE of Ann Arbor) had longer disease-free survival than the higher-risk groups (AJCC T1, T2 with nodal involvement or metastatic disease, T3, and T4 as well as Ann Arbor II, III, and IV). The overall mean follow-up was 43.3 months (range 6-274).
, Conclusions: Regardless of stage, recurrence and disease-free survival were more closely related to treatment and histopathology rather than tumor size or site-specific location.

Background: The purpose of this study was to describe the incidence of nodal disease in sebaceous carcinoma and its impact on survival., Methods: Data from the 17 registries of the Surveillance, Epidemiology, and End Results (SEER) database was retrospectively collected for sebaceous carcinoma from 1973 to 2007. Information on location, histologic grade, stage of disease, and survival was gathered., Results: One thousand eight hundred thirty-six sebaceous carcinomas were diagnosed during the time period: 633 (34.5%) in the eyelid and 786 (42.8%) in the extraocular head and neck skin. Eyelid sebaceous carcinomas had higher histologic grade compared with tumors in extraocular sites (p < .001). Ocular sebaceous carcinomas had a higher incidence of regional or distant metastases at presentation (4.4%) compared with extraocular head and neck sites (0.9%; p = .03). There was a high incidence of N+ disease in poorly differentiated ocular sebaceous carcinomas (15.2%)., Conclusion: The incidence of nodal disease was higher with eyelid tumors. Sentinel lymph node biopsy can be considered for eyelid tumors, but not for non-eyelid head and neck tumors., (Copyright © 2012 Wiley Periodicals, Inc.)

Background and Purpose: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma., Patients and Methods: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions)., Results: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater., Conclusion: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.

Purpose: To determine whether T category of the American Joint Committee on Cancer (AJCC) TNM staging system for eyelid carcinoma, 7th edition, correlates with lymph node metastasis, distant metastasis, and survival in patients with sebaceous carcinoma of the eyelid., Design: Retrospective, cohort study., Participants: Fifty consecutive patients treated by 1 author (BE) for eyelid sebaceous carcinoma between May 1999 and August 2010., Methods: Each tumor was staged according to the AJCC 7th edition TNM criteria. The Kaplan-Meier method was used to determine associations between disease-specific survival and (1) T category at presentation, (2) lymph node metastasis, and (3) distant metastasis., Main Outcome Measures: T category at presentation, nodal metastasis, survival., Results: The study included 37 women and 13 men (median age, 68.5 years; range, 44-86 years). Forty-four patients were white, 5 were Hispanic, and 1 was Asian. TNM designations were TXN0M0, 7 patients; T1N0M0, 4 patients; T2aN0M0, 12 patients; T2bN0M0, 11 patients; T2bN1M0, 2 patients; T2bN1M1, 1 patient; T3aN0M0, 2 patients; T3aN1M0, 5 patients; T3bN0M0, 1 patient; T3bN1M0, 1 patient; T3bN0M1, 2 patients; T4N0M0, 1 patient; and T4N0M1, 1 patient. T category at presentation was significantly associated with lymph node metastasis (P = 0.0079). No tumors with T category better than T2b or smaller than 9 mm in greatest dimension were associated with nodal metastasis. Five patients (10%) died of disease during follow-up. Their TNM designations were T2bN1M1, 1 patient; T3bN0M1, 2 patients; T4N0M0, 1 patient; and T4N0M1, 1 patient. No tumors smaller than 12 mm in greatest dimension were associated with distant metastasis or death. T category was significantly associated with disease-specific survival (P = 0.0009). Disease-specific survival was poorer among patients with T category of T3a or worse (P = 0.035)., Conclusions: T category in the 7th edition of the AJCC TNM staging system for eyelid carcinoma correlates with outcomes in patients with sebaceous carcinoma of eyelid. On the basis of the present findings, it seems reasonable to recommend sentinel lymph node biopsy or at least strict regional lymph node surveillance for patients with eyelid sebaceous carcinoma with tumors of T category T2b or worse or 10 mm or more in greatest dimension., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the following risk factors: initial tumor site, pathologic features, and initial treatment., Design: Retrospective, comparative, interventional case series., Methods: Charts of all patients with BCC referred to Orbital Unit of the University of Naples "Federico II" between 1984 and 2003 were reviewed. Charts were reviewed for patient demographics, previous treatments, tumor site, clinical presentation, duration of symptoms, and histologic subtype. The main outcomes were recurrence rate, tumor-related deaths, orbital infiltration, and rate of exenteration., Results: Data (including follow-up) were available for 506 patients. Twenty-eight patients (5.5%) underwent orbital exenteration. For 8 patients (28.5%), orbital exenteration was the first procedure performed. In the exenterated group, the most common tumor site was the medial cantus, whereas in the overall group, it was the lower eyelid (P = .001). The proportion of patients initially treated without margin control was significantly higher in patients undergoing exenteration (P = .0001). Pathologic examination revealed a higher incidence of infiltrative subtype in the exenterated group (P = .00019)., Conclusions: The need for exenteration for BCC may be significantly higher when the lesion involves a medial canthal location, initial management does not include margin-controlled excision, or pathologic analysis reveals an infiltrative subtype. Margin-controlled excision for periocular BCC and close follow-up after excision for medial canthal BCC may be indicated., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: To report the outcome at 5-year follow-up of a defined series of patients with primary periocular basal cell carcinoma treated by cryotherapy using a nitrous oxide probe., Methods: A prospective, non-comparative, interventional case series. One hundred primary periocular basal cell carcinomas were treated with a double freeze-thaw cycle nitrous oxide contact cryotherapy probe. Inclusion criteria were clinically well-defined primary periocular basal cell carcinomas with maximum diameter of 8 mm. The main outcome measure was histologically proven recurrence rate at 5-year follow-up., Results: Kaplan-Meier survival analysis showed a 5-year recurrence rate of 8%. Cox regression analysis revealed no correlation between tumour site, tumour size, cryotherapy freeze time and recurrence (p=0.60, p=0.86 and p=0.71, respectively). Thirty-six per cent of patients were lost to follow-up at 5 years following treatment., Conclusion: The results of this series suggest that nitrous oxide probe cryotherapy for primary periocular basal cell carcinomas up to 8 mm diameter has a recurrence rate of ∼8%. Cryotherapy has certain advantages over surgical removal of tumours of this size in the periocular region, but careful follow-up is advisable.

Objective: To assess the influence of hepatitis C virus (HCV) infection on disease appearance and outcome of ocular adnexal non-Hodgkin lymphoma (ONHL)., Design: Retrospective comparative study (from January 1, 1992, through December 31, 2006)., Methods: The medical records of 129 patients with ONHL were retrospectively reviewed. All the patients were tested serologically for the presence of HCV infection. Patients were divided into 2 groups according to the presence or absence of HCV infection., Main Outcome Measures: Prevalence of HCV infection, staging to evaluate the extent of disease at the onset, and clinical outcome data on overall and disease-free survival., Results: The prevalence of HCV infection among the patients with ONHL was 17.8%. Seropositivity for HCV infection was significantly associated with extraorbital lymphoma at the onset (P = .006). High prevalence of mucosa-associated lymphoid tissue disease (79.8%) was registered. Protocol therapy included radiotherapy and chemotherapy, depending on the stage of the disease. Complete remission was achieved in 99 patients (76.7%). A total of 23.6% of patients with HCV-seronegative status and 21.7% of those with HCV-seropositive status experienced relapse of the lymphomatous disease. No significant differences in the 5-year overall survival and disease-free survival between the 2 groups were observed., Conclusions: Prevalence of HCV infection in patients with ONHL is a relevant issue, accounting for 17.8% of the examined patients. Infection with HCV may influence the initial appearance of ONHL because it is associated with more widespread disease at the onset. However, the overall and disease-free survival of the infected patients are not statistically different than that of patients who are not infected.

Objective: To determine the primary sites, clinical features, treatment, and outcome of 20 patients with cancer metastatic to the eyelids., Methods: Retrospective review of medical records., Results: The primary tumors included skin melanoma (4 [20%]), uveal melanoma (4 [20%]), breast carcinoma and conjunctival melanoma (3 [15%] each), renal cell carcinoma (2 [10%]), and medullary thyroid carcinoma, prostate carcinoma, lung carcinoma, and salivary gland carcinoma (1 [5%] each). Eyelid metastasis was the first sign of systemic cancer in 3 patients (15%). The most common clinical finding at the initial examination was a solitary nodule in 12 patients (60%), a flat pigmented lesion and diffuse eyelid swelling in 3 patients each (15%), and multiple nodules and epiphora in 1 patient (5%) each. Ten patients (50%) had concomitant ocular site metastasis. Primary treatment included excision alone in 6 patients (30%), external beam radiotherapy in 7 (35%), systemic chemotherapy in 4 (20%), and observation in 3 (15%). The metastatic tumors regressed in 10 patients (50%), remained stable in 7 (35%), and showed progression in 3 (15%). After a mean follow-up of 16 months, 9 patients (45%) were alive and 11 (55%) had died of systemic metastatic disease., Conclusions: Eyelid metastasis can display a variety of clinical features and should be considered in patients with known systemic cancer. These patients usually have multiple metastatic sites, ocular and nonocular. The systemic prognosis is poor.

Purpose: To investigate the clinical features, time to diagnosis, histopathology, treatment, and mortality rates of patients with sebaceous cell carcinoma., Methods: This was a retrospective, consecutive series of patients with sebaceous cell carcinoma at a tertiary referral medical center. Between January 1984 and January 2006, 31 patients with sebaceous cell carcinoma were evaluated at the Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics. The main outcome measures were clinical presentations, treatments, reconstructive procedures, and outcomes., Results: Thirty-one patients were diagnosed with sebaceous cell carcinoma of the ocular adnexa on histopathology. Twenty (65%) of the patients were women and 11 were men. The upper eyelid was involved in 18 patients, lower eyelid in 10, both upper and lower eyelids in 1, and caruncle in 2. Twenty-three patients had in situ disease, pagetoid disease, or both. Eight patients reported symptoms for <6 months and 22 had symptoms for < or = 12 months before the diagnosis of sebaceous cell carcinoma was made. Local surgical excision of the tumor as initial treatment was performed in 25 patients. Exenteration was the initial surgery performed in 4 patients. Two patients died from metastatic sebaceous cell carcinoma., Conclusions: Sebaceous cell carcinoma has varied presentations and is commonly misdiagnosed. Tumor-related deaths occurred in only 2 patients (6.7%), which is lower than previous reports and may be related to earlier detection or improved surgical excision techniques.

Purpose: To review the clinical and histopathologic features, treatment, and outcomes of eyelid basal cell carcinomas., Methods: The clinical records and histopathologic specimens of 311 patients with eyelid basal cell carcinomas were reviewed and analyzed retrospectively. The main outcome measures are patient demographics, clinical characteristics, lesion size, duration of lesion, histologic subtypes, presence of orbital and perineural invasion, severity of peritumorous inflammation, treatment modalities, recurrence rate, tumor-related death, and prognostic features., Results: Two-hundred ninety patients underwent surgery whereas others received radiotherapy or chemotherapy. The most common histologic subtypes were infiltrative, nodular, and basosquamous basal cell carcinomas. Nearly one-third (29.9%) of the patients were previously recurrent. Orbital and perineural invasion rates were 17.04% and 10.6%, respectively. Recurrent basal cell carcinomas were larger, with longer duration of lesion and a higher rate of orbital and perineural invasion. Basosquamous basal cell carcinomas were more likely to have prior recurrences, larger lesion size, and the highest rate of orbital invasion. Perineural invasion was most frequent in morpheaform and basosquamous subtypes. Peritumorous inflammation differed between subtypes and was highest in the superficial subtype. The recurrence rate was 7.39% in total. The death of 2 patients was tumor-related., Conclusions: In this large case series from a single center, the outcomes were worse than previously reported due to delay in treatment and previous inadequate treatments. Adverse prognostic factors associated with secondary orbital invasion are previous recurrences, aggressive histologic subtypes, longer duration of lesion, larger lesion size, and the presence of perineural invasion.

Background: Recent isolated case reports have suggested a potential role for neoadjuvant chemotherapy in patients with angiosarcoma. The goal of this report was to investigate the overall treatment outcomes and the neoadjuvant chemotherapy-specific outcomes in patients with cutaneous angiosarcoma of the face with periorbital involvement., Methods: Our tumor database was searched for patients with angiosarcoma and periorbital involvement seen at our institution between 1981 and 2005., Results: Twenty-one patients were identified,15 of whom had neoadjuvant chemotherapy and 6 of whom had a traditional approach of surgery followed by adjuvant therapy. Fourteen of 15 patients who had neoadjuvant chemotherapy had complete clinical response. Neoadjuvant chemotherapy made definitive surgery unnecessary for 9 patients. The median disease-free interval for the neoadjuvant chemotherapy group was 11.8 months (mean, 38.1 months; range, 2.4-239.6 months). Nine of the 15 patients had recurrences. The time from end of treatment to recurrence ranged from 2.6 to 24.5 months (median, 12.7 months). Five of the 6 patients who had primary surgical resection followed by adjuvant radiotherapy and/or chemotherapy had a complete clinical response, and the median disease-free interval was 31.8 months (mean, 35.9 months; range, 2.7-85 months). Two later developed recurrences, one at 2.7 months and the other at 31.8 months after the end of treatment., Conclusion: On the basis of this series, the authors conclude that neoadjuvant chemotherapy for periorbital angiosarcoma is a potentially attractive option and in some patients may obviate the need for major surgery, thereby preserving the eye and/or ocular adnexal structures. Given the propensity for recurrence and poor survival, the authors strongly recommend that these patients receive multidisciplinary evaluation and treatment at a major cancer center.

Purpose: To evaluate retrospectively the management and prognosis of Merkel cell carcinoma of the eyelid in Japanese patients., Subjects and Methods: Cases diagnosed as Merkel cell carcinoma of the eyelid from January 1993 to February 2005 in 111 institutions in Japan were included in this retrospective study. Management and prognosis were evaluated., Results: The total number of cases enrolled was 21(5 male and 16 female patients). Excision of the tumor was carried out in 18 cases. Two cases were treated with either irradiation or local injection of interferon after biopsy of the tumor. After initial treatment, there were recurrences in 3 cases; local recurrence in one case and nodal metastasis in two cases. No patient died because of Merkel cell carcinoma of the eyelid., Conclusions: Excision with wide surgical margins with irradiation is recommended as the first choice of treatment for Merkel cell carcinoma of the eyelid. Because the number of patients was only 21 and the duration of observation was short, further investigation is necessary to determine the optimal management and more accurate prognosis for Merkel cell carcinoma.

Squamous cell carcinoma (SCC) is the second most common eyelid malignancy and its incidence is increasing. Because of its variable clinical presentation, SCC may be difficult for even the experienced clinician to diagnose. Hence, all suspicious lesions warrant biopsy. As SCC behaviour may range widely in aggression, management should be individualized based on tumour (e.g. size, location, grade, histological subtype, previous recurrence, perineural invasion) and patient factors (e.g. age, health). Treatment of eyelid SCC should include margin control whenever possible for the highest cure rate in this high-risk area. Immediate histological monitoring of surgical margins with frozen sections or Mohs' micrographic surgery also allows for smaller margins of excision in an area where tissue conservation is important. Other special considerations in the periocular area include maintaining a high level of suspicion for perineural invasion as this may be associated with a poorer prognosis.

Purpose: To review the clinical, radiological, and histopathologic features in 8 patients with natural killer/T-cell lymphoma (NKTL) involving the orbit and/or ocular adnexa, and to describe the responses of these patients to various treatment regimens., Design: Retrospective observational case series., Participants: Eight patients (5 male, 3 female) with NKTL involving the orbit and/or ocular adnexa were identified from 1999 through 2005. The mean age at presentation was 45 years (range, 26-65)., Methods: We retrospectively identified patients with NKTL of the ocular adnexa treated in the authors' medical centers from 1999 through 2004 using computerized diagnostic index retrieval. The clinical records and radiologic studies were analyzed to define modes of presentation and progression, response to therapy, and areas of anatomic involvement. Histopathologic findings, including the presence of CD3, CD56, and Epstein-Barr virus-encoded mRNA in each patient, were reviewed., Main Outcome Measurements: Time of survival from presentation to last known follow-up and tumor-related death., Results: Four of the 8 patients (50%) with NKTL involving the orbit or ocular adnexa had systemic involvement at presentation. Five of the 8 patients (62.5%) had concurrent sinonasal involvement, whereas 3 (37.5%) had orbital involvement alone. All lesions demonstrated CD3, CD56, and/or Epstein-Barr virus positivity on immunopathology studies. Therapy consisted of various chemotherapeutic regimens typically employed in the treatment of non-Hodgkins lymphoma, steroids, surgical intervention, and radiation. Seven (87.5%) patients died 5 weeks to 13 months after presentation, and 1 (12.5%) is alive without disease (5-year follow-up)., Conclusions: Natural killer/T-cell orbital lymphoma is a rare Epstein-Barr virus-associated neoplasm that may occur with or without associated sinonasal involvement. Our series, the largest cohort reported to date, demonstrates the high lethality of this condition despite aggressive conventional therapy, suggesting that new treatment options should be considered early in the course of treatment of patients with this disorder.

Purpose: To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data., Methods: Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control., Results: Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival., Conclusions: The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Purpose: To review the clinicopathological features, management, and survival rates for patients with sebaceous gland carcinoma of the eyelid, and to analyse the reasons for improved survival., Methods: In the west of Scotland between 1975 and 2001, 32 cases were identified through the pathology index for sebaceous carcinoma. Pathology specimens were reviewed in all cases. The clinical data were obtained from hospital records and the database provided by the Regional Cancer Registry., Results: A total of 22 female and 10 male patients were identified. Follow-up ranged from 6 months to 15 years, median of 4.8 years. Primary treatment involved excisional techniques in 27 cases, exenteration in two cases, enucleation in two cases, and two cases required adjuvant radiotherapy. Intraepithelial spread and masquerade presentations delayed the diagnosis. Poorly differentiated tumours were associated with an unfavourable outcome. Three patients developed local tumour recurrence and one metastatic disease. In all, 10 patients died from nontumour-related causes and one died from metastatic sebaceous carcinoma. The overall tumour mortality rate in the west of Scotland was 3%., Conclusions: From this study, patients in the west of Scotland have a better prognosis than is indicated in the literature. Astute clinical suspicion and accurate histopathological diagnosis, together with radical and aggressive surgical approaches were key factors.

Purpose: Although systemic or eyelid involvement by ocular adnexal lymphoma carries a worse prognosis, there have been few reports of the outcome in relation to clinical presentation. The outcome of malignant ocular adnexal lymphoma was, therefore, related to presenting clinical symptoms and signs., Design and Methods: A retrospective, noncomparative case-note review of 326 patients treated in the Orbital Clinic at Moorfields Eye Hospital. The associations between presenting symptoms or signs and three outcome measures (v.i.) were assessed by univariate and multiple variable regression together with Kaplan-Meier analysis., Main Outcome Measures: (i) Presence of extra-orbital disease at the time of presentation; (ii) development of systemic lymphoma after new presentation with solely ocular adnexal disease; and (iii) death attributable to widespread lymphoma., Results: Presentation with disseminated disease was rarer with over 1 year's ophthalmic symptoms (odds ratio (OR) 0.7; 95% CI 0.5-0.9) and much more frequent with bilateral adnexal disease (OR 5.8; 95% CI 3.0-11.2). With solely adnexal disease at presentation, subsequent extra-orbital lymphoma was more frequent and earlier with lacrimal gland disease (as compared to those without; hazard ratio (HR) 1.9; 95% CI 1.2-4.5) or with eyelid disease (compared to those without; HR 2.4; 95% CI 1.2-4.5), or with bilateral disease (compared to unilateral disease; HR 2.6; 95% CI 1.4-5.2). Prior or concurrent systemic disease was the most significant predictive factor for lymphoma-related death (HR 6.8; 95% CI 4.3-10.9), but tumour-related death was also commoner and earlier with bilateral disease (HR 2.4; 95% CI 1.4-4.0) or where a relative afferent papillary defect was present (HR 2.8; 95% CI 1.6-4.9). Similarly, the rate of tumour-related death was slightly less where symptoms had been present for more than a year (HR 0.8; 95% CI 0.7-1.0) and slightly greater in the elderly (HR 1.03; 95% CI 1.01-1.05). Conjunctival lymphoma had the lowest rate of extra-orbital spread and lymphoma-related death, the rate of these two events being sequentially greater for patients with predominantly deep orbital lymphoma, lacrimal gland lymphoma, or eyelid lymphoma., Conclusion: These data suggest that presenting symptoms and signs of patients with ocular adnexal lymphoma are significantly associated with the risk of systemic disease at orbital presentation, the rate of subsequent spread, and the rate of lymphoma-related death.

Aims: To describe the clinical characteristics of patients with eyelid cancers in Taiwan., Methods: Between 1980 and 2000, 127 (58 males and 69 females) patients (mean age 62.6; range 10-91 years) with histologically confirmed eyelid cancers were retrospectively evaluated at the National Taiwan University Hospital and Far Eastern Memorial Hospital in Taiwan. Clinical data of all patients were reviewed from medical records. The mean follow-up period was 62.4 months (range 3-240) for 113 patients., Results: The 127 eyelid cancers included 79 basal cell carcinomas (62.2%), 30 sebaceous gland carcinomas (23.6%), 11 squamous cell carcinomas (8.7%), five malignant melanomas (3.9%), one Kaposi's sarcoma (0.8%), and one metastatic cancer (0.8%). Tumours developed more commonly in the lower (37.0%) than the upper eyelid (33.9%). The clinical accuracy in predicting eyelid malignancy was 90.5%. Primary treatment modality was mainly surgical excision. The recurrence, metastasis, and mortality rates at 5 years were 15.2, 11.7, and 7.3%, respectively, for all eyelid malignancies. Rates of sebaceous gland carcinoma recurrence, metastasis, and mortality were significantly higher (P<0.05) than those of basal cell carcinoma. The mean interval of recurrence or metastasis after primary treatment was 26.3 months (range 4-112) for all eyelid cancers., Conclusions: Although basal cell carcinoma is the most common eyelid cancer in Taiwan, sebaceous gland carcinoma is also common. Of the two, basal cell carcinoma has a better prognosis and sebaceous gland carcinoma has a higher mortality and therefore should be treated much more aggressively. Long-term follow-up is needed after treatment of malignant eyelid tumours.

Background: This study involved 73 patients with lymphoproliferative lesions of the ocular adnexa. The lesions were categorized using the Revised European American Lymphoma classification of lymphoid tissues and analysed to determine the frequency and prognostic impact of tumour type, location, stage and patient's age and sex., Methods: The clinical, histopathological, immunohistochemical and phenotypic analysis by flow cytometry and follow-up data were studied., Results: The ocular adnexal lymphoproliferative lesions included 70 lymphomas and six reactive lymphoid hyperplasia. Seventy-nine per cent had stage IE disease, 4% stage II, 1.5% stage III and 15.5% stage IV. Five patients (7%) had a past history of systemic lymphoma. Major histological types were extranodal marginal zone lymphoma (MZL) in 44 (63%), follicular (FL) in 12 (17%), diffuse large B-cell (DLBCL) in eight (11%), mantle cell (MCL) in two (3%), B-cell chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma in two (3%), peripheral T-cell lymphoma (PTCL) one (1.5%) and natural killer cell lymphoma (NKCL) in one (1.5%). Longest survival was seen in those with low-grade lymphomas (MZL and FL) and worst in PTCL and NKCL. Lymphoma-related mortality was 2% for MZL, 33% for FL, 38% for DLBCL, and 100% for MCL, PTCL and NKCL. Systemic lymphoma was present prior to, at presentation or at subsequent follow up in 26/68 (39%) of all lymphoma patients, 17% for MZL, 38% for DLBCL, 83% for FL, and 100% for MCL, CLL, PTCL and NKCL., Conclusion: The majority of ocular adnexal lymphomas were low-grade B-cell lymphomas (MZL). Multivariate analysis showed that the only significant independent predictors of all causes of mortality were the histological type of lymphoma and the stage of disease at presentation.

Purpose: To review the clinical presentation, histopathologic analysis, management, and ocular and systemic outcome of rhabdomyosarcoma affecting the ocular region., Design: Retrospective, noncomparative, consecutive, interventional case series., Participants: Thirty-three consecutive patients with primary ophthalmic involvement of rhabdomyosarcoma from a single tertiary care center specializing in ocular oncology., Main Outcome Measures: Final visual acuity, treatment complications, local recurrence, and distant metastasis., Results: The mean age at presentation was 10 years (median, 7 years; range, 1 month-68 years). At presentation, 8 patients (24%) were older than age 10 years and 4 patients (12%) were older than 20 years. The rhabdomyosarcoma was primarily located in the orbit in 25 cases (76%), conjunctiva in 4 cases (12%), eyelid in 1 case (3%), and uveal tract in 3 cases (9%). Symptoms or signs related to the tumor were present for a mean of 5 weeks and included proptosis in 10 patients (30%), eyelid swelling in 7 patients (21%), and blepharoptosis in 6 patients (18%). The initial diagnosis before referral to us included rhabdomyosarcoma in 8 cases (24%), conjunctivitis in 5 cases (15%), orbital or preseptal cellulitis in 5 cases (15%), idiopathic orbital inflammatory pseudotumor in 4 cases (12%), and others. Using the Intergroup Rhabdomyosarcoma Study Group staging and treatment protocols, the tumor was classified as group I in 4 cases (12%), group II in 12 cases (36%), group III in 16 cases (48%), and group IV in 1 case (3%). Treatment included surgical debulking and various regimens of chemotherapy and radiotherapy for the periocular tumors and enucleation for the three intraocular tumors. Local tumor recurrence was detected in 6 patients (18%). Orbital exenteration was necessary for tumor recurrence in 2 cases (6%). Long-term visual outcome of the 28 patients who maintained their globe was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 patients (18%), and 20/200 to no light perception in 12 patients (43%). Regional lymph node metastasis was detected in 2 patients (6%), one at initial visit and one after therapy. Distant metastasis occurred in 2 patients (6%), one detected at initial visit and one after therapy. With mean follow-up of 8.3 years, tumor-related death occurred in 1 patient (3%)., Conclusions: Rhabdomyosarcoma can present in the orbit, eyelid, conjunctiva, and uveal tract. After treatment, local tumor recurrence occurs in 18%, metastasis in 6%, and death in 3%.

Purpose: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy., Patients and Methods: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT)., Results: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%., Conclusion: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.