Sebaceous Gland Carcinoma Research Articles

MiRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma

BackgroundMicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally...

Immunohistochemical expression of X-linked inhibitor of apoptosis in eyelid sebaceous gland carcinoma predicts a worse prognosis.

Purpose:Overexpression of the inhibitors of apoptosis proteins have been demonstrated in a variety and of solid tumors including melanomas and nonmelanomas skin cancers. X-linked inhibitor of apoptosis protein (XIAP) is an inhibitor of apoptosis which prevents apoptosis by inhibiting caspases 9, 7, and 3. The prognostic value of XIAP in sebaceous gland carcinoma (SGC) remains unexplored.Methods:The immunohistochemical expression of XIAP was evaluated in 29 SGC cases.Results:The cytoplasmic overexpression of XIAP was detected in 62% SGC cases. XIAP expression was found to be significantly associated with advanced age, large tumor size, and with reduced disease-free survival (P = 0.0174). XIAP expression and advance tumor Grade III emerged as significant risk factors on univariate analysis. On stepwise multivariate analysis, both increased cytoplasmic XIAP expression and high tumor grade were found to be significantly associated with recurrence. Patients with low XIAP immunoexpression had a longer disease-specific survival than those with high expression in the 5-year follow-up.Conclusion:The present study demonstrates at the immunohistochemical level that XIAP is overexpressed in SGC and that high expression could be of biological significance in the development of eyelid SGC. Our finding suggests that up-regulation of XIAP may aggravate tumor metastasis in SGC.

Therapy options for malignant eyelid tumors

Basal cell carcinomas are the most common malignant tumors of the eyelids. Patient history, clinical symptoms and signs, inspection, palpation and slit-lamp examination usually allow aworking diagnosis; however, the clinical diagnosis requires histopathological confirmation and determination of the histopathological type. Squamous cell carcinomas, sebaceous gland carcinomas, melanomas and Merkel cell carcinomas can metastasize usually via the lymph vessels into the regional lymph nodes. Microscopically controlled excision of the primary tumor into healthy tissue is most commonly the first goal. Palpation and ultrasonography of the regional lymph nodes and also computed tomography (CT) with contrast enhancement and magnetic resonance imaging (MRI) for tumors with perineural sheath cell invasion are necessary to define the TNM stage. Non-surgical treatment options are becoming more popular in the further management of malignant eyelid tumors.

Orbital exenteration for advanced periorbital non-melanoma skin cancer: prognostic factors and survival.

PurposeTo describe prognostic factors and survival outcomes in patients who underwent orbital exenteration for periocular non-melanoma cutaneous malignancies.MethodsThe authors performed an institutional review board-approved retrospective review of all patients who underwent orbital exenteration for non-melanoma periocular cutaneous malignancies at a tertiary care hospital system over a 10-year period. Patient demographics, tumor, and treatment data were recorded. Survival outcomes included disease-free survival (DFS) and overall survival (OS). Log-rank tests were used to test for difference in survival curves among various potential prognostic indicators, and multivariate analysis was performed using Cox's proportional hazards model.ResultsForty-nine patients with an average age of 70.3 years were followed with a median follow-up of 17.5 months. At 2 years the OS was 78% while the DFS was 61%. The mean DFS for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and sebaceous gland carcinoma (SGC) were 52.6, 39.2 and 28.1 months, respectively. Multivariate analysis demonstrated that only positive final surgical margin was predictive of worse outcome (P=0.002). Recurrences were most frequent in the first 2 years.ConclusionsDespite the relatively more aggressive nature of periocular malignancies that have invaded the orbit, orbital exenteration offers an overall 2-year DFS of ~60%. BCC had the greatest mean survival time, however this was not statistically significant. We found worse prognosis with positive final surgical margins and recommend a multidisciplinary surgical approach to achieve complete resection when indicated.

Risk Factors for Local Recurrence or Metastasis of Eyelid Sebaceous Gland Carcinoma After Wide Excision With Paraffin Section Control

To identify risk factors for local recurrence and metastasis of sebaceous gland carcinoma (SGC) after wide excision with paraffin section control. Retrospective, observational case-control study. Setting: Single institution. Thirty-four patients with SGC who had undergone excision with 5-mm surgical margins and paraffin section pathologic analysis. Observational Procedures: The following were considered potential risk factors forlocal recurrence/metastasis of SGC: patient's sex, patient's age, initial diagnosis at other clinics, topical treatments at other clinics, interval between appearance of symptoms and referral to our institution, tumor location, tumor origin, tumor presentation pattern, T category, tumor size, presence/or absence of pagetoid spread, tumor differentiation, mitosis grade, growth pattern. Logistic regression analysis was performed to identify the actual risk factors. Risk factors for local recurrence or metastasis of SGC after wide excision with paraffin section control. Involvement of both upper and lower eyelids, topical treatments at other clinics, multicentric origin, diffuse pattern, stage T3a, large tumor size, and a nonlobular pattern significantly influenced local recurrence/metastasis (P < .050). Pagetoid spread tended to affect local recurrence/metastasis (P= .052). The other items did not significantly influence local recurrence/metastasis (P > .050). This study identified risk factors for local recurrence or metastasis of SGC after wide excision with paraffin section pathologic analysis. The results ofthis study will be helpful to surgeons when planning additional management, such as map biopsy or adjuvanttreatment.

Zymbal Gland (Auditory Sebaceous Gland) Carcinoma Presenting as Otitis Externa in a Pet Rat (Rattus norvegicus)

A 1-year-old sexually intact male fancy rat (Rattus norvegicus) was presented for unilateral purulent otitis externa and weight loss. A small amount of bloody discharge was noted at the ostium of the left ear canal. The canal and the surrounding tissue were firm to the touch. Mild left-sided enophthalmos and facial nerve paralysis were noted. Otoscopic examination demonstrated caseous debris, and a swab of the external ear canal demonstrated a mixed population of rods and cocci on cytological evaluation. Bacterial culture of the external ear canal grew Escherichia coli. The rat was initially placed on oral and topical antimicrobial therapy. Despite treatment, the condition of the affected ear deteriorated and the rat continued to lose weight. Other clinical signs observed at this time included a worsening of the facial nerve paralysis, head tilt, and circling. A biopsy sample of the swollen tissue surrounding the left ear canal was collected; however, the rat died the day following the biopsy procedure. Histopathology of the biopsied tissue revealed an invasive neoplasm consistent with a Zymbal gland (auditory sebaceous gland) carcinoma. Zymbal glands are modified sebaceous glands surrounding the ear canal of rodents. Although chemically induced neoplasia of these glands is frequently observed, spontaneous tumor formation is much less common. Tumors of the Zymbal gland should be considered as underlying causes for unilateral otitis externa in rats.

Clinical relevance of cyclooxygenase 2 and peroxisome proliferator-activated receptor γ in eyelid sebaceous gland carcinoma.

Sebaceous gland carcinoma (SGC) is a malignancy associated with the pilosebaceous unit, and occurs at ocular or non-ocular sites. Cyclooxygenases (COXs) are enzymes that are crucial for lipid metabolism. COX-2 is overexpressed in various cancers, and its inhibition by non-steroidal anti-inflammatory drugs is known to reduce the risk of many cancers. Peroxisome proliferator-activated receptor (PPAR)-γ is a transcription factor involved in adipogenesis. PPAR-γ is a potential therapeutic target for the treatment of malignant tumours, including colon carcinoma. The aim of this study was to explore the status of COX-2 and PPAR-γ as prognostic markers in human eyelid SGC. The immunohistochemical expression of COX-2 and PPAR-γ was evaluated in 31 SGC cases. Cytoplasmic expression of COX-2 was detected in 80% of the SGC cases, and nuclear expression of PPAR-γ in 87%. There were significant correlations of PPAR-γ expression with well-differentiated SGC [19/21 (90%)] and of COX-2 overexpression with reduced disease-free survival (P = 0.0441, log rank analysis). COX-2 expression [odds ratio (OR) 3.82, 95% confidence interval (CI) 1.02-14.33, P = 0.046] and lymph node metastasis (OR 0.17, 95% CI 0.04-0.65, P = 0.009) emerged as significant risk factors in the univariate analysis. However, COX-2 expression did not emerge as a significant independent prognostic factor in multivariate analysis. COX-2 is a potential marker for identifying high-risk SGC patients. Expression of PPAR-γ in eyelid SGC cases reflects terminal sebaceous differentiation. Inhibitors of COX-2 signalling and PPAR-γ agonists are both prospective novel therapeutic targets in the management of eyelid SGC patients.

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 >6months (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 10years, 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 10years, 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 10years, 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.

Pathology of eyelid tumors.

The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms.

A Modified Cutler-Beard Technique to manage Extensive Sebaceous Gland Carcinoma of Upper Eyelid

ABSTRACT Introduction Sebaceous gland carcinoma (SGC) is a rare tumor affecting the elderly, with a predisposition for females arising from the meibomian glands and occurring more commonly on the upper eyelid. Diagnosis is difficult because the tumor mimics chalazion or blepharitis. Sebaceous gland carcinoma has a mortality rate of about 5 to 10%. Aim To present a modified Cutler-Beard technique of lid reconstruction to manage a case of extensive SGC of upper lid. Materials and methods A 65-year-old male presented with a rapidly growing extensive mass of right upper eyelid (size 4.2 × 4 × 2.1 cm) causing mechanical ptosis. Histopathology confirmed the diagnosis as SGC. Wide excision of the lesion was performed sacrificing the whole upper eyelid. Lid reconstruction was done employing lower eyelid as per the bridged flap technique with the use of 4 mm silicon band to enhance lid stability. Patient achieved a satisfactory functional and cosmetic result following the second stage of the procedure. Conclusion Total loss of upper eyelid is often dealt with classical lid sharing technique of reconstruction first described by Cutler-Beard. For lid stability, use of tarsus from contralateral eye, ear cartilage has their attendant problems. A 4.0 silicon band was used to replace the sacrificed tarsus, achieving good results. How to cite this article Gupta P, Rizvi Y, Goyal E. A Modified Cutler-Beard Technique to manage Extensive Sebaceous Gland Carcinoma of Upper Eyelid. Int J Adv Integ Med Sci 2016;1(4):188-190.

Neoadjuvant Systemic Chemotherapy in the Management of Extensive Eyelid Sebaceous Gland Carcinoma: A study of 10 Cases.

To report the efficacy of neoadjuvant systemic chemotherapy in the management of eyelid sebaceous gland carcinoma (SGC). Retrospective study of 10 patients that received neoadjuvant systemic chemotherapy (Cisplatin/Carboplatin and 5-Fluorouracil) for eyelid SGC. The mean age at presentation of eyelid SGC was 58 years (median, 55 years; range, 45 to 72 years). There were 6 females and 4 males. The mean tumor basal diameter was 36 mm (median, 31 mm, range, 20 to 65 mm), with orbital tumor extension in 9 cases. On the basis of TNM Classification, the tumors were classified as T3 (n = 10), N1 (n = 6), and M1 (n = 2). The mean number of cycles of neoadjuvant systemic chemotherapy per patient was 3 (median, 3; range, 3 to 4). The mean percentage reduction of tumor basal diameter after neoadjuvant chemotherapy was 74% (median, 80%; range, 30% to 100%). None of them had any major systemic side-effects of neoadjuvant chemotherapy. Postchemotherapy, surgical treatment for residual tumor was performed in 7 cases. Five cases underwent excision biopsy and 2 cases with residual orbital component underwent eyelid-sparing orbital exenteration. No tumor recurrence was noted in any of the 7 cases at a mean follow-up period of 18 months (median, 14 months; range, 3 to 63 months). One patient died due to systemic metastasis. Neoadjuvant systemic chemotherapy is effective and safe in the management of eyelid sebaceous gland carcinoma.

A study on meibomian gland carcinoma in a tertiary care hospital, Hyderabad

Background: Sebaceous gland tumour is the second commonest tumour of meibomian glands of eye. Presence of other similar ocular conditions of eye, the diagnosis of the disease is usually late. It is more common in old age and more common in women. In one third of the cases, the common site of origin is upper eye lid and may invade overlying epithelium. This condition is multicentric origin and hedge biopsy is needed to confirm the case. Pleomorphic cells with hyperchromatic nuclei and vacuolated nuclei were seen. Wedge biopsy of the lesion from multiple sites is diagnostic of the condition. Cytoplasm is foamy due to fat content. Objective: To study the incidence and clinical behaviour of meibomian gland carcinoma of the lid in patients attending outpatient department of sarojini devi eye hospital, Hyderabad Methods: The present study titled “meibomian gland carcinoma” was a prospective interventional case series study undertaken in patients who attended oculoplasty department , Sarojini devi eye hospital, Hyderabad, between December 2011 to October 2013. The study included 90 eyes of 90 consecutive patients presented with lid swelling who were diagnosed on the basis of history, clinical symptoms and signs, and by histopathological examination as eyelid malignancy. Among these 47 were meibomian gland carcinoma. Cases were treated surgically using standard protocol. Post operative results and follow up were recorded. Results were analysed using statistical parameters. Results: Total number of eyes studied 90 in consecutive cases and 80% of them in the age group of 50-70 years. 60% of the studied cases were females. In 55% of the eyes, left eye was involved. Upper lid was involved in 72% cases. Lower lid was involved in 25% of cases. Excision of tumor and lid constructive surgery was done in 92% of cases. In 52% of cases, the histopathological diagnosis was Meibomian Gland Carcinoma. Conclusion: Incidence of sebaceous gland carcinoma is more common in India compared to western literature. More aggressive biological behavour was observed in India with metastasis.

Scrape cytology in ophthalmology: Our experience with three cases

The aim was to describe the use of scrape cytology as a procedure for the preliminary diagnosis of suspicious lesions in case of three patients. The first patient was diagnosed with sebaceous gland carcinoma of the upper lid, second patient had squamous cell carcinoma (SCC) of the bulbar conjunctiva, and the third patient had SCC of the skin of medial canthus of eye. In this article, we have discussed the history of evolution of cytology briefly. Different types of cytology procedures as well as advantages and disadvantages of each procedure have also been discussed. We have described the procedure of taking scrape specimen and further processing in brief. The article emphasizes the role of scrape cytology in initial diagnosis, treatment plan, prognosis, and subsequent follow-ups in patients of ocular surface tumor.

Expression of retinoic acid-binding proteins and retinoic acid receptors in sebaceous cell carcinoma of the eyelids.

BackgroundSebaceous cell carcinoma of the eyelid is a malignant tumor. However, the pathoetiology of sebaceous cell carcinoma is not clear. Retinoic acid (RA) signaling is essential for skin epidermal differentiation including the eyelids. In this study, we investigate the expression of β-catenin, RA-binding proteins and RA receptors in sebaceous cell carcinoma of the eyelid and try to estimate their influence on its pathoetiology.MethodsRetrospective, noncomparative, consecutive interventional case series. Sixteen cases of eyelid sebaceous gland carcinoma who received tumor excision at our hospital between 2001 and 2011 were included. Immunohistochemical staining for β-catenin, cellular retinoic acid binding protein 1 (CRABP1), cellular retinoic acid binding protein 2 (CRABP2), fatty acid-binding protein 5 (FABP5), retinoic acid receptors (RAR-α, −β, −γ), and retinoid X receptors (RXR-α, −β, −γ) was performed on tissue samples obtained from tumor excision.ResultsOf the 16 sebaceous cell carcinoma cases reviewed, six were male and 10 female. The mean follow-up period was 6.7 ± 3.66 years (range, 0.3–13 years). Of these 16 cases, the expression of β-catenin was significantly increased in sebaceous cell carcinoma cases. CRABP1 was similarly expressed in the sebaceous cell carcinoma and control groups. CRABP2 and FABP5 were expressed in hair follicles of lid skin in both groups, whereas the CRABP2 and FABP5 were aberrantly expressed in the tumor cells of the sebaceous glands. Notably, the expression of retinoic acid receptor (RAR-β) and retinoid X receptors (RXR-β, −γ) was significantly upregulated in sebaceous cell carcinoma of the eyelids.ConclusionsOur findings indicate that retinoic acid signaling is related to the pathogenesis of sebaceous cell carcinoma of the eyelids.

Clinicopathological profile of orbital exenteration: 14 years of experience from a tertiary eye care center in South India.

This study aims to describe the clinicopathological features and outcomes of patients who underwent orbital exenteration at a tertiary eye care center in south India. Retrospective chart reviews were performed on all patients undergoing orbital exenteration from January 1999 to December 2012. Parameters recorded include demographic data, clinical presentations, past medical or surgical interventions, exenteration notes, histopathological diagnosis, adjunctive treatment, follow-up examination findings, recurrences, complications, and their management. Orbital exenteration was performed on 119 orbits of 119 patients over a 14-year period. The mean age was 48.9years (range 1-82years). The indications were malignancies in 90.7% (108/119), while 9.3% (11/119) of cases were exenterated for non-malignant indications. Among the malignancies, the commonest tissue of origin was conjunctiva, noted in 45.4% (49/108), followed by eyelids (25.9%, 28/108), orbit (19.4%, 21/108), and intraocular tissues (9.3%, 10/108). The commonest malignancies noted in this series were an extensive ocular surface squamous neoplasia (OSSN) (44.4%, 48/108) and sebaceous gland carcinoma of eyelids with an orbital involvement (18.5%, 20/108). Extensive fungal granuloma (mucormycosis-4, aspergillosis-4) was the commonest (81.8%, 9/11) indication among the non-malignant group. All complications were wound related, and none had a recurrence at a mean follow-up of 12.8months. Extensive orbital involvement with OSSN and SGC were the commonest indications for exenteration. There is a need of creating awareness among general ophthalmologists in specific geographical regions regarding early diagnosis, standardized protocols of management, and appropriate referral.

Increased gene copy number of HER2 and concordant protein overexpression found in a subset of eyelid sebaceous gland carcinoma indicate HER2 as a potential therapeutic target.

To identify crucial molecular alterations of receptor tyrosine kinases that can be used as potential therapeutic targets for eyelid sebaceous gland carcinoma (SbGC). The expression levels of HER2, EGFR, C-MET, and FGFR1 were determined by immunohistochemistry (IHC). The copy numbers of the HER2, EGFR, C-MET, and FGFR1 genes were assessed by fluorescence in situ hybridization. The IHC and molecular results were correlated with the clinical parameters. A total of 49 patients with eyelid SbGC were included in this study. HER2, EGFR, C-MET, and FGFR1 protein expression was detected in 8 of 44 (16.3 %), 8 of 45 (17.8 %), 3 of 35 (8.6 %), and 0 of 45 patient samples, respectively. Increased copy numbers of the HER2 gene were found in 5 of 42 patient samples (11.9 %), including two with amplification (4.7 %) and three with polysomy (7.2 %). EGFR amplification was found in 2 of 33 (6.1 %) and FGFR1 amplification in 4 of 33 patient samples (12.1 %; high-level amplification in one and low-level amplification in three). None of the samples examined exhibited C-MET amplification. Gene copy number of the HER2 gene was correlated with its protein expression (p < 0.0001), whereas copy number of EGFR, C-MET, or FGFR1 was not correlated with protein expression. However, samples with EGFR amplification also exhibited a high level of expression of this protein. Extra copies of the HER2, EGFR, and FGFR1 genes were identified in a 6-12 % of eyelid SbGCs. A high level of concordant HER2 expression detected by immunohistochemistry can be predictive of a copy number gain of the HER2 gene. Our data suggest that the therapeutic targeting of HER2 might benefit for a subset of patients with periocular SbGCs.

Tumors of the eye and ocular adnexa at the Philippine Eye Research Institute: a 10-year review.

ObjectiveWe aimed to identify and describe the clinicopathologic characteristics of tumors of the eye and ocular adnexa at the Philippine Eye Research Institute.MethodsThe pathology reports of specimens submitted to the Ocular Pathology Section of the Philippine Eye Research Institute over a 10-year period (2003–2012) were reviewed, and collected data was subjected to descriptive statistical tabulation and analysis.ResultsA total of 1,551 histologically confirmed tumors were included. Of these, 254 were from the conjunctiva (155 benign, 99 malignant), 530 from the eyelids (360 benign, 170 malignant), 394 were intraocular tumors (21 benign, 373 malignant), and 373 were from the orbit (231 benign, 142 malignant). Retinoblastoma was the most common tumor of the eye and ocular adnexa in the series, accounting for 43.2% of all malignancies. Squamous cell carcinoma was the most frequent cancer of the conjunctiva, while basal cell carcinoma and sebaceous gland carcinoma were the most common eyelid malignancies. Orbital malignancies had a bimodal age distribution, with rhabdomyosarcoma being most frequent in children, while in adults, lymphoma was most common, followed by lacrimal gland carcinomas.ConclusionThe majority of tumors of the conjunctiva, eyelids, and orbit were benign, while most intraocular tumors were malignant, with retinoblastoma being the most common.

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.

Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians.

To study the clinical and histopathological features of eyelid sebaceous gland carcinoma (SGC) and to evaluate the prognosis in the Asian-Indian population. This is a retrospective study of 191 patients with SGC. The mean age at presentation of eyelid SGC was 57 years (median, 56 years). The tumor epicenter was most commonly located in the upper eyelid (n=125, 65%). The mean tumor basal diameter was 15 mm (median, 10 mm). There was evidence of tumor extension into the orbit (n=30, 16%), paranasal sinuses (n=3, 2%), and brain (n=1, 1%). Wide excision biopsy (n=146, 78%) was the most common treatment modality. Tumor recurrence was noted in 42 (24%) patients over a mean follow-up period of 29 months (median, 20 months). On the basis of the Kaplan-Meier estimate, lymph node metastasis occurred in 18%, systemic metastasis was detected in 10%, and death occurred in 2% of patients at 10 years. On multivariate analysis, the factors predicting locoregional lymph node and systemic metastasis were medial canthal involvement (P=0.004; P=0.013), lateral canthal involvement (P=0.013; P=0.025), tumor basal diameter >10 mm (P=0.002; P=0.002), and perivascular invasion (P=0.043; P<0.001), respectively. The factors predicting death due to metastasis on multivariate analysis were medial canthal involvement (P=0.012) and tumor basal diameter >10 mm (P=0.001). Advanced eyelid SGC is a tumor associated with poor prognosis. In this study, canthal involvement, larger tumor diameter, and perivascular invasion were poor prognostic factors.

Cancer Stem Cell Markers in Eyelid Sebaceous Gland Carcinoma: High Expression of ALDH1, CD133, and ABCG2 Correlates With Poor Prognosis.

To investigate the expression of cancer stem cell (CSC) marker proteins in eyelid sebaceous gland carcinoma and evaluate the clinical significance. Archival tissue blocks from 50 cases of eyelid sebaceous gland carcinoma were tested via immunohistochemistry for 16 putative CSC markers. Levels of protein expression were analyzed alongside various clinicopathologic parameters such as metastasis-free survival time. Ten patients (20%) showed nodal or distant metastasis during the follow-up period (median, 35.2 months; range, 1-128 months) without any mortality in our series. Among the 16 markers, ALDH1, CD44, CD133, ABCG2, Sox4, Sox9, and slug were selected for candidates of CSC markers because they were frequently and predominantly found in the tumor cells compared with control tarsus cells, which showed negative or very low expression. Univariate analysis revealed that ALDH1, CD133, and ABCG2 were significantly associated with metastasis; patients with ALDH1- or CD133-positive tumors developed metastasis more frequently than patients with tumors that were negative for these markers (log-rank test, P = 0.014, P = 0.013, respectively), and diffuse expression of ABCG2 was associated with significantly shorter metastasis-free survival (log-rank test, P = 0.010). Multivariate Cox proportional hazard model revealed that ALDH1 (hazard ratio [HR] = 5.682, P = 0.038) was significantly associated with metastasis. Development of metastasis in eyelid sebaceous gland carcinoma might be attributed to increased number of CSCs or acquisition of dedifferentiated phenotype. Our findings suggest that CSCs are involved in the disease progression of eyelid sebaceous gland carcinoma, and in particular, expression of ALDH1 is a predictor of a poor outcome.