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.

Eyelid carcinoma: An experience from a tertiary cancer center.

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.

Prognostic Factors, Treatment, and Survival in Primary Cutaneous Mucinous Carcinoma: A SEER Database Analysis.

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.

Evaluation of PD-L1 and PD-1 expression in aggressive eyelid sebaceous gland carcinoma and its clinical significance.

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.

Eyelid sebaceous carcinoma: Validation of the 8th edition of the American Joint Committee on cancer T staging system and the prognostic factors for local recurrence, nodal metastasis, and survival.

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.

Radiotherapy in Periocular Cutaneous Malignancies: A Retrospective Study.

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.

Mohs micrographic surgery for eyelid sebaceous carcinoma: A multicenter cohort of 360 patients.

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.

Palpebral cutaneous melanomas: a review of 17 cases from a tertiary center.

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.

Prognostic factors for local recurrence, metastasis and survival for sebaceous carcinoma of the eyelid: observations in 100 patients.

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.

Impact of clinicopathologic factors on survival in patients with sebaceous carcinoma of the eyelid - a population-based analysis.

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.

14-year case series of eyelid sebaceous gland carcinoma in Chinese patients and review of management.

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.

Orbital invasive squamous cell carcinoma with adnexal involvement clinically mimicking feline restrictive orbital myofibroblastic sarcoma: 19 cases (1990-2016).

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.

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.

Treatment of Metastatic Eyelid Carcinoma.

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.

Prognosis of eyelid sebaceous gland carcinoma based on the tumor (T) category of the American Joint Committee on Cancer (AJCC) classification.

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.

Third eyelid gland neoplasms of dogs and cats: a retrospective histopathologic study of 145 cases.

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.

Comparison of the Clinical Characteristics and Outcome of Benign and Malignant Eyelid Tumors: An Analysis of 4521 Eyelid Tumors in a Tertiary Medical Center.

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.

ZEB2/SIP1 as novel prognostic indicator in eyelid sebaceous gland carcinoma.

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.