Eyelid Sebaceous Gland Carcinoma Research Articles

Masqueraded sebaceous gland carcinoma of the lower eyelid in ayoung pregnant patient.

The purpose of this case report is to present misdiagnosed sebaceous gland carcinoma of the lower eyelid with rapid growth in ayoung woman during pregnancy. Eyelid sebaceous gland carcinoma is arelatively rare tumor and adisease primarily of older patients. It occurs more commonly in oriental populations and with apredilection for the upper eyelid. Early diagnosis and appropriate treatment may help improve disease control and patient survival.

Neoadjuvant Chemotherapy in Non-Metastatic Eyelid Sebaceous Gland Carcinoma: A Report in 10 Cases

Introduction: Eyelid sebaceous gland carcinoma (SGC) is an aggressive malignancy. Surgical excision is the standard treatment for non-metastatic eyelid SGC. This study aimed to evaluate treatment outcomes with use of neoadjuvant chemotherapy (NACT) and any change in ease/difficulty of surgical treatment in such cases. Methods: This was a prospective interventional study conducted over 24-month period. Histopathologically, confirmed cases without any systemic metastasis were included. Clinico-demographic details were collected for 30 patients. 10 patients received NACT using cisplatin and 5-FU. Tumour response was evaluated using RECIST criteria. An ease of surgery questionnaire was used to assess difficulty of surgical treatment before and after NACT. Results: Of the 30 patients evaluated for recruitment, 37% had recurrent SGC and 72% had advanced tumour stage. Ten patients were recruited for NACT. There was partial response in 80% and complete response in 10% cases. Tumour T category downstaging was seen in 50% of cases. While tumour dimensions/volume reduced substantially, surgical ease improved in only 40% cases. Conclusion: A significant proportion of SGC patients evaluated in our study presented with recurrent and/or advanced disease. NACT caused tumour regression in 90% of cases. However, surgical ease improvement was limited, pointing to a need for surgical modification in such cases. Corneal ulceration was noted in 2 cases with large tumours causing a complete mechanical ptosis. Overall, the study introduced an ease of surgery questionnaire and provided insights into benefits and challenges of using NACT for eyelid SGC management.

Prevalence of human papillomavirus in eyelid carcinoma among Koreans: a clinicopathological study

BackgroundHuman papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across studies. This study aimed to investigate the presence of HPV in eyelid SGC and SCC among Koreans and its correlation with clinicopathological characteristics.MethodsSurgically resected eyelid samples diagnosed as SGC or SCC from January 1999 to June 2011 were identified from the pathology database of three referral centres in Korea. Clinicopathological information including origin (skin vs. tarsal conjunctiva) and treatment outcomes were retrospectively reviewed. Immunohistochemistry (IHC) for p16, HPV DNA in situ hybridisation (ISH), and polymerase chain reaction-based DNA microarray were performed in paraffin-embedded tissue sections.ResultsOur cohort included 34 SGC and 12 SCC cases with Asian ethnicity. HPV was detected in 4 SGC and 6 SCC by DNA microarray, while 2 SCC (16.7%) showed positivity in ISH. SCC of tarsal conjunctival origin was significantly more common in HPV-positive SCC than in HPV-negative SCC (5 of 6 vs. 0 of 6, P = 0.015, Fisher’s exact test). Among samples showing positive staining in p16 IHC, HPV positivity rates were 0.0% (0/19) in SGC and 100% (3/3) in SCC. There was no significant difference in overall and local recurrence rate in eyelid SGC and SCC according to the HPV status (P > 0.99).ConclusionsHPV was found in a subset of eyelid SGC and SCC among Koreans and might be aetiologically related to SCC of tarsal conjunctival origin. Overexpression of p16 is considered to be inappropriate as an indicator of HPV infection in eyelid SGC. Further investigation is required to elucidate the transmission route and pathogenic roles of HPV.

Development and validation of a nomogram to predict the recurrence of eyelid sebaceous gland carcinoma.

Eyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment are extremely important. This study aimed to develop a nomogram to predict SGC recurrence based on potential risk factors. We conducted a retrospective study to train and test a nomogram based on the clinical data of 391 patients across our hospital (304) and other grass-roots hospitals (87). After Cox regression, predictors included in the nomogram were selected, and sensitivity, specificity, concordance index (C-index), etc., were calculated to test their discrimination ability. After a median follow-up period of 4.12 years, SGC recurred in 52 (17.11%) patients. The 1-, 2-, and 5-year recurrence-free survival rates were 88.3%, 85.4%, and 81.6%, respectively. We examined five risk factors, such as lymph node metastasis at initial diagnosis (hazard ratio [HR], 2.260; 95% confidence interval [CI], 1.021-5.007), Ki67 (HR, 1.036; 95% CI, 1.020-1.052), histology differentiation degree (HR, 2.274; 95% CI, 1.063-4.865), conjunctival pagetoid infiltration (HR, 2.100; 95% CI, 1.0058-4.167), and orbital involvement (HR, 4.764; 95% CI, 1.436-15.803). The model had good discrimination in both internal and external test sets. The model had good discrimination in both internal and external test sets. The sensitivity of the internal test and external test set were 0.722 and 0.806, respectively, and specificity of the internal test and external test set were 0.886 and 0.893, respectively. We examined the potential risk factors for eyelid SGC recurrence and constructed a nomogram, which complements the TNM system in terms of prediction, indicating that our nomogram has the potential to reach clinical significance. This nomogram has the potential to assist healthcare practitioners in promptly detecting patients who are at an elevated risk and in tailoring clinical interventions to meet their individualized needs.

Integrated Whole-Exome and Transcriptome Sequencing Indicated Dysregulation of Cholesterol Metabolism in Eyelid Sebaceous Gland Carcinoma.

To identify the molecular background of eyelid sebaceous gland carcinomas (SCs), we conducted the integrated whole-exome sequencing and transcriptome sequencing for eyelid SCs in this study. The genetic alterations were studied by whole-exome sequencing, and the messenger RNA expression was studied using Oxford Nanopore Technologies (ONT) in five paired fresh eyelid SC tissues and adjacent normal tissues. Integrated analysis of exome and transcriptomic information was conducted for filtering candidate driver genes. Protein-protein interaction (PPI) network of filtered candidate genes was analyzed by STRING. The protein expression was verified by immunohistochemistry in 29 eyelid SCs and 17 compared normal sebaceous gland tissues. The average numbers of pathogenic somatic single-nucleotide variants (SNVs) and indels in eyelid SCs were 75 and 28, respectively. Tumor protein p53 (TP53), zinc finger protein 750 (ZNF750), filaggrin 2 (FLG2), valosin-containing protein (VCP), and zinc finger protein 717 (ZNF717) were recurrent mutated genes. A mean of 844 differentially expressed genes (DEGs) were upregulated, and 1401 DEGs were downregulated in SC samples. The intersection of DEG-based pathways and mutation-based pathways was mainly involved in microbial infection and inflammation, immunodeficiency, cancer, lipid metabolism, and the other pathways. The intersection of DEGs and mutated genes consisted of 55 genes, of which 15 genes formed a PPI network with 4 clusters. The PPI cluster composed of scavenger receptor class B member 1 (SCARB1), peroxisome proliferator-activated receptor γ (PPARG), peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) was involved in cholesterol metabolism. The expression of SCARB1 protein was found to be increased, whereas that of PPARG protein was decreased in eyelid SCs compared to that in the normal sebaceous glands. Increased SCARB1 and decreased PPARG indicated that dysregulation of cholesterol metabolism might be involved in carcinogenesis of eyelid SCs. The malfunction in cholesterol metabolism might advance our knowledge of the carcinogenesis of eyelid SCs.

Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India.

This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. A retrospective study was undertaken over a period of 100 months. Ninety-nine histopathologically proven cases of eyelid SGC available for follow-up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery. Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High-risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI-1.65-5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96-17.19%, p < 0.01) and disease-free survival (HR 4.61, 95% CI 2.81-7.54). The Kaplan-Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour-related deaths (p < 0.01) and reduced disease-free survival (p=0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease-free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS. Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.

Analysis of sebaceous gland carcinoma associated genes using network analysis to identify potentially actionable genes

Eyelid sebaceous gland carcinoma (SGC) is a rare but life-threatening condi-tion. However, there is limited computational research associated with un-derlying protein interactions specific to eyelid sebaceous gland carcinoma. The aim of our study is to identify and analyse the genes associated with eyelid sebaceous gland carcinoma using text mining and to develop a protein-protein interaction network to predict significant biological pathways using bioinformatics tool. Genes associated with eyelid sebaceous gland carcinoma were retrieved from the PubMed database using text mining with key terms ‘eyelid’, ‘sebaceous gland carcinoma’ and excluding the genes for ‘Muir-Torre Syndrome’. The interaction partners were identified using STRING. Cytoscape was used for visualization and analysis of the PPI network. Molec-ular complexes in the network were predicted using MCODE plug-in and ana-lyzed for gene ontology terms using DAVID. PubMed retrieval process identi-fied 79 genes related to eyelid sebaceous gland carcinoma. The PPI network associated with eyelid sebaceous gland carcinoma produced 79 nodes, 1768 edges. Network analysis using Cytoscape identified nine key genes and two molecular complexes to be enriched in the protein-protein interaction net-work. GO enrichment analysis identified biological processes cell fate com-mitment, Wnt signalling pathway, retinoic acid signalling and response to cytokines to be enriched in our network. Genes identified in the study might play a pivotal role in understanding the underlying molecular pathways in-volved in the development and progression of eyelid sebaceous gland carci-noma. Furthermore, it may aid in the identification of candidate biomarkers and therapeutic targets in the treatment of eyelid sebaceous gland carcino-ma.

Commentary: Cryotherapy and the sebaceous glands.

Sebaceous glands are exocrine epithelial glands secreting protective surface lipids via a holocrine mechanism in which the sebocytes undergo a programmed disintegration. Sebaceous glands are found in the eyelids as the tarsal meibomian glands and the glands of Zeis near eyelash hair follicles.[1] Pathologically, the ophthalmic sebaceous gland lesions range from benign cysts and chalazia to malignant sebaceous gland carcinoma (SGC), which happens to be the most common eyelid malignancy in the Indian population.[2] Cryotherapy has been extensively used in ophthalmology, dermatology, and surgical specialties as a primary or adjunctive treatment for lesions ranging from intraocular tumors, eyelid cysts, skin tags, warts, and acne vulgaris to cervical and hepatic cancers.[3] There are two mechanisms of cryotherapy: (a) freezing-related direct cellular injury and (b) vascular disruption of the lesion. Its role in the treatment of localized basal cell carcinomas of the eyelid has been documented in the literature with a low recurrence rate.[2] The prolonged healing time with secondary intention healing and depigmentation remains a concern with cryotherapy of the skin tumors. However, it helps in preserving the functionality of essential structures like eyelids and the surrounding lacrimal system. The in vivo biological effect of cryotherapy on normal sebaceous glands has been evaluated with the help of coherent anti-Stokes Raman scattering microscopy by Jung et al.[4] They demonstrated that the effect of lipid crystallization had a limited role in causing cellular disruption. Instead, sebocyte loss occurred at temperatures lower than those required for lipid crystallization. In addition, the cryo-treated sebaceous glands began recovering 1–2 weeks after treatment. Ray Jalian et al.[5] also investigated the role of controlled local skin cooling in causing preferential injury to sebaceous glands to understand its mechanism in treating acne vulgaris. They observed that cooling-induced damage led to a 20% reduction in sebum output for 2 weeks, with minimal collateral injury to surrounding tissues. A higher number of freeze–thaw cycles and slower thawing resulted in more significant tissue injury. Immunohistochemistry-based expression of Ki67 (a proliferative marker) and keratin 15 (a progenitor basal cell marker) was not disrupted by cooling. This led them to conclude that cooling-induced damage was temporary and occurred due to disruption of cellular architecture, enzymatic activity, and decreased lipid content. The sebum output recovered after 4 weeks. Though both these studies used a temperature higher than what is used in ophthalmic practice, they did conclusively demonstrate the limited level of cytotoxicity as well as the temporary duration of the effect of cryotherapy on sebaceous glands. The ophthalmic literature describes the use of cryotherapy as an adjunct in addressing the pagetoid spread seen in eyelid SGC.[6] Lisman (1989) first reported the use of cryotherapy to manage the map biopsy-proven sites of pagetoid spread in six cases of sebaceous gland carcinoma, thereby avoiding exenteration.[7] Shields et al.[6] advocated the application of triple freeze cryotherapy on conjunctival edges to eliminate residual tumor cells. On the contrary, Esmaeli et al.[8] reported satisfactory outcomes in 50 patients of SGC without the need for cryotherapy. A survey of practice patterns in Nordic countries revealed that only 27% of respondents offered cryotherapy as an adjunctive treatment for addressing the pagetoid spread in SGC.[9] Thus, the biological effect of cryotherapy on sebaceous glands is limited and reversible. The reassurance provided by triple freeze and slow thaw to the margins may not be reliable in clinical practice. This fact has been highlighted by Alam et al.[10] in the present issue of this journal. They performed a histopathological study on a portion of excised SGC tumor that was subjected to cryotherapy. Greater than 50% of viable tumor cells along with extensive areas of necrosis were observed on microscopy, and the authors concluded that the cell damage induced by cryotherapy is insufficient for achieving adequate tumor control. We believe that an early diagnosis and timely treatment using a wide (~3-mm margin) full-thickness excision, intraoperative frozen section control, and map biopsy for pagetoid spread remains the preferred practice pattern. The adjunctive use of cryotherapy remains doubtful in the SGC of eyelids. Close monitoring and regular follow-up to observe for recurrences are vital in the long-term management of patients.

The effect of direct cell injury inflicted by cryotherapy on eyelid sebaceous gland carcinoma cells: An ex-vivo experimental study.

Purpose:To evaluate the effect of direct cell injury of cryotherapy on eyelid sebaceous gland carcinoma cells by an ex vivo cryotherapy experiment.Methods:It was a prospective interventional case series. Six patients with biopsy-proven nodular sebaceous gland carcinoma were included. After excision of the mass, a thin slice of the mass resembling the thickness of the conjunctiva was shaved off and was oriented over the broad end of a tissue forceps. Cryotherapy was applied to both its anterior and posterior aspects by the triple freeze-thaw technique. The mass was then labeled and sent separately for histopathological evaluation by fixation and staining.Results:A total of six patients with a mean age of 58.2 ± 15.5 years were included. There were four females and two males. The mean duration of the lesion was 21.6 ± 17.51 months. All patients had involvement of the upper eyelid. The patients were clinically staged as T2b (n=2), T1a (n=2), T2c (n=1), and T3a (n=1) respectively. There was no regional lymphadenopathy or metastasis in any of the cases. The experimental cryo-tissue containing the cryo-treated lesion revealed the presence of viable tumor cells (>50%) in all six specimens.Conclusion:The direct cell injury caused by cryotherapy may not be sufficient to kill all the residual sebaceous gland carcinoma cells on the tumor bed.

Second primary tumors in retinoblastoma survivors: a study of 7 Asian Indian patients.

To assess the incidence, types, and outcomes of second primary tumors (SPT) in cases of retinoblastoma (RB) from a referral Tertiary eye care center METHODS: Retrospective chart review of 7 cases RESULTS: All 7 (100%) cases had bilateral RB at presentation. The mean age at diagnosis of RB was 16months (median 7months; range 5-72months). Treatment of RB with intravenous chemotherapy was noted in 3 (43%) patients, 1 (14%) patient had received external beam radiotherapy (EBRT) to the orbit, 1 (14%) patient had received a combination of chemotherapy and orbital EBRT, while 4 (57%) patients had undergone primary enucleation of the worse eye and focal treatment of the better eye. The mean age at detection of SPT was 15years (median 8years; range 6-46years). The mean time interval between diagnosis of RB and SPT was 13years (median 7years; range 1-41years). The SPT's included osteosarcoma of long bone (n = 2), eyelid sebaceous gland carcinoma (n = 2), ventricular ependymoma (n = 1), orbital neuroblastoma (n = 1), and acute lymphoblastic leukemia (n = 1). All patients received treatment for the SPT with either surgical excision (n = 2), intravenous chemotherapy (n = 1), or a combination of surgery/chemotherapy/radiotherapy (n = 4). Over a mean follow-up period of 8years (median 8years; range 4-11years), one (14%) patient died, while other 6 (86%) patients are alive and well. Though the incidence of SPT's in cases of RB is rare, life-long follow-up is mandatory in at-risk patients.

Eyelid sebaceous gland carcinoma: An assessment of the T classification of the American Joint Committee of Cancer TNM staging system 8th versus 7th edition.

To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition. Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality. Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis (p = 0.037) using the 8th edition criteria but not with the 7th edition (p = 0.066). The 8th edition T categorization significantly correlated with eye survival (p = 0.022) while the 7th edition did not (p = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis (p = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death (p = 0.281, p = 0.737, p = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation (p = 0.001), and papillary histologic pattern (p = 0.024) but not with pagetoid spread (p = 0.056). The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Detection of Epstein-Barr Virus in 130 Cases of Eyelid Sebaceous Gland Carcinoma Using In Situ Hybridization.

Purpose In this study, we aimed to investigate the presence of Epstein–Barr virus (EBV) in the eyelid sebaceous gland carcinoma (SGC) and its association with the clinicopathologic features. Methods One hundred and thirty paraffin-embedded SGC specimens were retrieved from the Clinical Pathology Department of Zhongshan Ophthalmic Center. Epstein–Barr virus-encoded RNA (EBER) was detected with in situ hybridization (ISH) using the Leica BOND system autostainer. The age and gender distributions of all patients were analyzed and compared with earlier reports. Pearson's χ2 and Fisher's exact tests were used to determine the association between clinicopathological features such as age, gender, laterality eye, tumor basal dimension, degree of tumor differentiation, and EBER positivity. Likewise, the relationship between the grade and tumor basal dimension in EBER-positive SGC of the eyelid was analyzed. Results Thirty-four out of one hundred and thirty (26.2%) eyelid SGC specimens were positively stained for EBER. The age range of highest incidence was 46–75 years, and the female to male ratio was 1 : 0.9. No significant correlation was found between EBER-positivity and age (p = 0.5370), gender (p = 0.4758), and degree of tumor differentiation (p = 0.7787). However, EBV positivity was strongly correlated with the right eye (p = 0.0287), the tumor basal dimension (p = 0.0001). EBV positivity grade presented statistically associated with tumor size (p = 0.0329). Conclusion We conclude that ISH is a sensitive method to identify EBV in SGC of the eyelid. A possible causal association of EBV in SGC patients is suggested by high frequency of EBER-ISH positivity and its association with the clinicopathologic features.

Taming the masquerader – a rare case of sebaceous gland carcinoma

The purpose of the study was to bring in perspective a rare case of exophytic, solitary, lower eyelid sebaceous gland carcinoma in an elderly male. A 70-year-old male presented with complaints of painless, progressive mass on the left lower eyelid for the past 6 years which grew rapidly in the past 4 months. Full-thickness wide local resection of the mass was done and sent for histopathological examination. Histopathological examination confirmed the tumor to be a grade-1 sebaceous cell carcinoma. This case report highlights the successful management of rare lower eyelid sebaceous gland carcinoma which is often misdiagnosed or undiagnosed leading to lethal consequences.

CDKN2A, CDK1, and CCNE1 overexpression in sebaceous gland carcinoma of eyelid.

To investigate the overexpression of genes in sebaceous gland carcinoma (SGC) of the eyelid compared to sebaceous adenoma of the eyelid in order to elucidate the molecular mechanism underlying pathogenesis. We performed histopathological examination of eyelid tissues surgically removed from four patients diagnosed with SGC (cases 1-3) and sebaceous adenoma (case 4) of the eyelid. Next, we performed global gene expression analysis of surgical tissue samples using a GeneChip® system and the Ingenuity Pathways Knowledge Base. The results of the GeneChip® analysis were explored with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. In the SGC samples, we found that 211, 199, and 199 genes, respectively, showed ≥ 2.0-fold higher expression than those in the sebaceous adenoma sample (case 4); 194 genes were common to all three SGC samples. For the 194 genes with upregulated expression, functional category analysis showed that SGC of the eyelid employed a unique gene network, including cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 1 (CDK1), and cyclin E1 (CCNE1), which are related to cell cycle progression, incidence of tumor, and cell viability. Furthermore, qRT-PCR analysis showed that the expression levels of CDKN2A, CDK1, and CCNE1 were significantly upregulated in all SGC cases compared to those in the sebaceous adenoma case. These data were similar to the results of microarray analysis. Overexpression of cell cycle-related genes CDKN2A, CDK1, CCNE1, and their gene network may help elucidate the pathogenic pathway of SGC of the eyelid at the molecular level.

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.

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. 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. 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. 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.

Vimentin overexpression as a novel poor prognostic biomarker in eyelid sebaceous gland carcinoma

BackgroundVimentin is an intermediate-sized filament which is highly expressed in mesenchymal cells and is associated with epithelial–mesenchymal transition (EMT). EMT markers ZEB2 and Slug lead to Vimentin overexpression and E-cadherin...

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.

Contemporary Update of Overall Prognosis and Nomogram to Predict Individualized Survival for Chinese Patients with Eyelid Sebaceous Carcinoma

Background: The prognosis of Chinese patients with eyelid sebaceous gland carcinoma (SC) has not been updated for more than 3 decades. The predictors for the prognoses are multifactorial, there is no validated prognostic model for eyelid SC. Methods: The study included 238 consecutive patients with eyelid SC. All patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between nomogram and Tumor, Node, Metastasis (TNM) staging system. Findings: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of the metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rate was 88.1% and 77.9%, respectively. Prior radiation therapy (HR:5.63, p=0.003), tumor with orbital involvement (HR:4.64, p=0.001), greatest tumor basal diameter (HR:1.07, p<0.001), the presence of pagetoid spread (HR:3.12, p=0.012) were the independent risk factors for tumor-related death. Nomogram integrating these 4 factors was developed with a C-index of 0.875, which is significantly better than that of TNM staging system (p=0.038). The risk groups stratified by nomogram scores (p=0.042 (low vs intermediate risk); p<0.001 (intermediate vs high risk)) displayed better discrimination ability than TNM staging (T1vsT2: p=0.358; T2vsT3: p=0.171; T3vsT4: p<0.001) in patients at an early stage. Interpretation: The prognosis of Chinese patients of eyelid SC has been improved for the last 3 decades, and it is comparable to the patients from other countries. This nomogram provides more-accurate individualized estimates of survival for eyelid SC patients, and may guide clinicians in their therapeutic decisions. Funding Statement: This work was supported by the Scientific Research Program of the National Health and Family Planning Commission of China (201402014). Declaration of Interests: The authors declare no conflict of interest in this paper. Ethics Approval Statement: This study adhered to the tenets of the Declaration of Helsinki and was approved by the Shanghai Jiaotong University research ethics committee.

MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.

Immunohistochemical evaluation of stress-responsive protein sestrin2 and its correlation with p53 mutational status in eyelid sebaceous gland carcinoma

Backgroundp53 is a stress-activated tumour suppressor gene, and its mutation has been associated with solid tumours including non-melanoma skin cancers. Sestrin2 expression is associated with DNA damage and oxidative stress...