Review of recent advances in managing periocular skin malignancies.

Management of cutaneous malignancies can be particularly challenging when they are located in the periocular region. The standard of care for localized disease is complete surgical excision, but this may not be possible without significant disruption to visual structures and facial appearance. Definitive radiation may be an option for some patients who cannot or do not wish to undergo surgery. Advances in systemic treatment options for locally advanced and metastatic skin cancers in the past 10 years have prompted investigation into neoadjuvant treatment of periocular cancers. The use of chemotherapy, immune checkpoint inhibitors, and targeted therapies have all been reported with varying degrees of success. For many patients, targeted therapies or immune checkpoint inhibitors should be considered depending on the cancer type, symptoms, and goals with the input of a multidisciplinary cancer care team. In this article, we systematically review the latest updates in surgical, radiotherapeutic, and medical management of periocular malignancies.

Base-Excision Repair Mutational Signature in Two Sebaceous Carcinomas of the Eyelid.

Personalized medicine aims to develop tailored treatments for individual patients based on specific mutations present in the affected organ. This approach has proven paramount in cancer treatment, as each tumor carries distinct driver mutations that respond to targeted drugs and, in some cases, may confer resistance to other therapies. Particularly for rare conditions, personalized medicine has the potential to revolutionize treatment strategies. Rare cancers often lack extensive datasets of molecular and pathological information, large-scale trials for novel therapies, and established treatment guidelines. Consequently, surgery is frequently the only viable option for many rare tumors, when feasible, as traditional multimodal approaches employed for more common cancers often play a limited role. Sebaceous carcinoma of the eyelid is an exceptionally rare cancer affecting the eye's adnexal tissues, most frequently reported in Asia, but whose prevalence is significantly increasing even in Europe and the US. The sole established curative treatment is surgical excision, which can lead to significant disfigurement. In cases of metastatic sebaceous carcinoma, validated drug options are currently lacking. In this project, we set out to characterize the mutational landscape of two sebaceous carcinomas of the eyelid following surgical excision. Utilizing available bioinformatics tools, we demonstrated our ability to identify common features promptly and accurately in both tumors. These features included a Base-Excision Repair mutational signature, a notably high tumor mutational burden, and key driver mutations in somatic tissues. These findings had not been previously reported in similar studies. This report underscores how, in the case of rare tumors, it is possible to comprehensively characterize the mutational landscape of each individual case, potentially opening doors to targeted therapeutic options.

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

BACKGROUND: Human 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. METHODS: Surgically 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. RESULTS: Our 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). CONCLUSIONS: HPV 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.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prognostic risk factors and nomogram construction for sebaceous carcinoma: A population-based analysis.

Background: Sebaceous gland carcinoma (SGC) is a rare tumor for which there are currently no effective tools to predict patient outcomes. We analyzed the clinical and pathological prognostic risk factors of sebaceous carcinoma based on population data and created a nomogram of related risk factors, which can more accurately predict the 3-, 5-, and 10-year overall survival (OS) rates of patients. Methods: SGC patients between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to training and validation cohorts. Relevant risk factors were identified by univariate and multivariate COX hazards regression methods and combined to produce a correlation nomogram. The concordance index (C-index), the area under the receiver operating characteristic (AUC) curve, and calibration plots have demonstrated the predictive power of the nomogram. Decision curve analysis (DCA) was used to measure nomograms in clinical practice. Results: A total of 2844 eligible patients were randomly assigned to 70% of the training group (n=1990) and 30% of the validation group (n=854) in this study. The derived meaningful prognostic factors were applied to the establishment of the nomogram. The C-index for OS was 0.725 (95% CI: 0.706-0.741) in the training cohort and 0.710 (95% CI: 0.683-0.737) in the validation cohort. The AUC and calibration plots of 3-, 5-, and 10-year OS rates showed that the nomogram had good predictive power. DCA demonstrated that the nomogram constructed in this study could provide a clinical net benefit. Conclusion: We created a novel nomogram of prognostic factors for SGC, which more accurately and comprehensively predicted 3-, 5-, and 10-year OS in SGC patients. This can help clinicians identify high-risk patients as early as possible, carry out personalized treatment, follow-up, and monitoring, and improve the survival rate of SGC patients.

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

PURPOSE: This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Red Breast Syndrome: Complete Resolution Following Replacement of Acellular Dermal Matrices With Acellular Collagen Matrices.

What is red breast syndrome (RBS)?What causes RBS?How often do patients present with RBS?What are effective treatments for RBS?

Reconstruction of an Extensive Full-Layer Defect of the Upper Eyelid.

What are the zones of the eyelid and the characteristics of this defect?What are the eyelid defect reconstruction options?What are the major potential complications of the eyelid defect reconstruction?How can the complications be avoided?

Overexpression of miR-651-5p inhibits ultraviolet radiation-induced malignant biological behaviors of sebaceous gland carcinoma cells by targeting ZEB2.

Background: Ultraviolet (UV) exposure is the most essential etiological factor in sebaceous gland carcinoma (SGC). The abnormal expression of microRNAs (miRNAs) is also involved in SGC. However, the function of miRNAs in UV-induced SGC is still unclear. Methods: In this study, the expression levels of miR-651-5p and zinc finger E-box binding homeobox 2 (ZEB2) in SGC tissues and cells were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Then, the effects of miR-651-5p on the apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) of UV-induced SGC cells were determined. The interactions between miR-651-5p and ZEB2 were verified by a dual-luciferase reporter assay. An in vivo tumor growth assay was performed to assess tumorigenicity. Results: The results showed that there was abnormal expression of miR-651-5p and ZEB2 in SGC tissues and cells compared with the control tissues and cells. Overexpression of miR-651-5p and knockdown of ZEB2 inhibited the malignant biological behaviors of SGC cells. Moreover, ZEB2 is one of the target genes of miR-651-5p, and the expression of ZEB2 was negatively regulated by miR-651-5p in SGC cells. Further studies showed that overexpression of miR-651-5p promoted cell apoptosis and inhibited the cell invasion and migration ability and EMT of UV-induced SGC cells by downregulating the expression of ZEB2 in vitro and in vivo. Conclusions: This study revealed that overexpression of miR-651-5p inhibited UV-induced SGC growth and metastasis by suppressing ZEB2, which may be a potential target for SGC prevention and therapy.

Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.

Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.

Clinical and histopathological profile of primary caruncular lesions.

Purpose: To provide a retrospective analysis of lesions of the caruncle which have been very rarely reported in the literature. Methods: A retrospective review of all the caruncular lesions between January 2000 and January 2020 was done at a single tertiary eye care hospital. The lesions were classified as benign and malignant lesions. Clinicopathological correlation was done for the excised lesions. Results: A total of 87 caruncular lesions were included in the study. Males (59%) were affected more than females (41%). The mean age at presentation was 44 ± 20 years. The mean duration of complaint was 36 ± 62 months. A total of 36 patients underwent surgical excision whereas the rest opted for conservative management. Recurrence was noted in five patients. Fifteen different types of lesions were identified histopathologically. Benign lesions (78%) were far more common than malignant ones (22%). Epithelial inclusion cyst was the most common benign lesion and sebaceous gland carcinoma was the most common malignant lesion. Correct clinicopathological correlation was seen in 52.7% of the cases. Caruncular tuberculosis, oncocytoma, and basosquamous cell carcinoma were some of the rare lesions. Conclusion: Caruncular lesions are uncommon and very diverse, which makes clinical diagnosis challenging. Epithelial inclusion cyst and sebaceous gland carcinoma were the most common benign and malignant lesions respectively. Correct clinicopathological correlation was seen in more than half of the cases.

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.

MicroRNA-3907 promotes the proliferation and migration of sebaceous gland carcinoma of the eyelid by targeting thrombospondin 1.

MicroRNAs (miRNAs/miRs) play an important role in various types of carcinoma, including sebaceous gland carcinoma (SGC) of the eyelid. miR-3907 was found to be highly expressed in lung cancer; however, to the best of our knowledge, the biological role of miR-3907 in SGC has not previously been evaluated. The aim of the present study was to determine the role and mechanism of miR-3907 in the occurrence and development of SGC. miR-3907 was screened and identified as a novel upregulated miRNA in SGC tissues and cells, as determined using miRNA microarrays and reverse transcription-quantitative (RT-q) PCR analyses. Compared with the control group, cellular proliferation and migration were enhanced in the miR-3907 mimics group, and decreased in the miR-3907 inhibitor group. Moreover, miR-3907 negatively regulated thrombospondin 1 (THBS1) expression, as shown by bioinformatics prediction, RT-qPCR, western blotting and dual-luciferase reporter assays. In addition, compared with the control group, the small interfering (si) siRNA-THBS1 group exhibited enhanced proliferation and migration abilities, which were decreased in the THBS1 overexpression group. Furthermore, THBS1 overexpression was found to attenuate the stimulative effect of miR-3907 mimics, and THBS1-knockdown reversed the inhibitory effect of the miR-3907 inhibitor in SGC cells. Collectively, the results of the present study indicated that miR-3907 promoted the proliferation and migration of SGC by downregulating THBS1, and that this axis may be a potential target for the prognostic assessment and treatment of SGC.

Neoadjuvant Systemic Chemotherapy in Sebaceous Gland Carcinoma of the Eyelid: A Retrospective Study.

There are sparse data on neoadjuvant systemic chemotherapy (NACT) in eyelid sebaceous gland carcinoma (SGC). The aim of this study was to evaluate efficacy and outcomes with NACT in eyelid SGC. We retrospectively analyzed 8 patients who received platinum-based NACT. The median number of cycles per patient was 4 (range, 3-5). The mean percentage reduction of tumor diameter after NACT was 71% (range, 30-100%). Two patients had a radiological complete response (CR). After NACT, surgical treatment for residual tumor was performed in 5 cases. One patient had a pathological CR and is recurrence free for 11 years. After a mean follow-up period of 44.5 months (range, 9-109), tumor recurrence occurred in 4 cases. Among these 4 cases, 3 were rechallenged with the same regimen and all responded. Systemic NACT has a role in eyelid SGC, downstages the tumor, and allows less aggressive and organ-sparing surgeries, warranting a prospective study.

Emerging therapies for rare cutaneous cancers: A systematic review.

BACKGROUND: Rare cutaneous cancers require early management given their aggressive nature; however, few therapeutic options exist for managing these rare cancers. OBJECTIVE: To identify emerging therapies for extramammary Paget's disease, Merkel cell carcinoma, sebaceous gland carcinoma, microcystic adnexal carcinoma, Kaposi sarcoma and cutaneous angiosarcoma. METHODS: A systematic review was conducted using PubMed database from October 2010 to October 2020. Published clinical trials and case reports/series were included if they involved primarily a targeted agent rather than classic cytotoxic chemotherapy or photosensitizing medication. Active clinical trials were evaluated using ClinicalTrials.gov, the Japanese University Hospitals Clinical Information Network, and the ISRCTN registry. Quality of evidence for each study was rated using the Oxford Centre for Evidence-Based Medicine Level of Evidence Rating Scale. RESULTS: There are several emerging therapies for rare cutaneous cancers with many clinical trials actively recruiting. PD-1 receptor inhibitors were the most investigated treatment, targeting several cancers. Merkel cell carcinoma and Kaposi sarcoma had the most clinical trials while microcystic adnexal carcinoma and sebaceous gland carcinoma had the least. The main limitation was a lack of key findings from clinical trials still in progress. CONCLUSIONS: Emerging therapies exist for rare cutaneous cancers; results of ongoing studies will provide more robust evidence in the future.

Clinicopathological Analysis and Demographic Features of Ocular Malignancies.

OBJECTIVE: This study aimed to evaluate the epidemiological and clinicopathological spectrum of ocular malignancies among patients presenting to a teaching hospital in Northern India. METHODS: A total of 246 histopathologically diagnosed patients with ocular malignancies were included in the study. Tumor type and size, primary origin and location of tumor, clinical staging, radiological findings, histopathological type, and treatment outcomes were assessed. RESULTS: Overall, males over 55 years of age were most commonly affected and the majority of cases were primary ocular or adnexal malignancies (n = 226; 91.87%). The eyelids and periocular structures (n = 92; 37.40%) were the most commonly involved site, followed by the orbit (n = 72; 29.27%), ocular surface (n = 46; 18.70%) and intraocular region (n = 36; 14.63%). The majority of the patients (n = 68; 27.64%) were managed by primary surgical excision and reconstruction. However, 46 patients (18.70%) with advanced lesions underwent neoadjuvant chemotherapy followed by surgical excision and more extensive orbital lesions were treated by exenteration followed by adjuvant chemotherapy (n=48; 19.51%), while patients with metastatic tumor were given palliative chemotherapy/external beam radiation therapy (n= 46; 18.70%). Overall, 45.12% of patients were cured completely, 15.45% showed a partial response to the treatment, 13.04% had progressive disease and 16.67% demonstrated disease recurrence. CONCLUSION: A clinicopathological analysis of ocular malignancies at a teaching hospital in Northern India indicated the preponderance of primary ocular malignancies, with eyelid sebaceous gland carcinomas being the most common pathological diagnosis. Most of our patients had advanced and extensive disease among them majority belonged to the rural background and poor socio-economic status.

Clinical time course of the neglected giant sebaceous gland carcinoma.

In this report, we discussed the progression from the initial presentation until surgical intervention, clinical course, and devastating outcome of a neglected giant sebaceous gland carcinoma of the eyelid in a poorly compliant elderly patient. A 79-year-old woman was referred for treatment of a giant ulcero-nodular lesion in the right upper eyelid. Nine months before, an orange lesion arising from the tarsal conjunctiva in the upper eyelid was observed in her examination undergone in the healthcare center where she initially presented, and the cornea appeared transparent. Surgical excision was recommended, which she declined. The examination three months before in the same center revealed that the lesion invaded the globe and anterior segment architecture could not be visualized. She was then recommended surgical removal of the eyeball, which she also refused. Radiological imaging demonstrated a 33x35 mm mass lesion in the superior lateral of orbit with exophytic growth and invasion of the globe and no systemic metastases were found. Total orbital exenteration surgery was immediately planned and performed. Histopathological examination revealed sebaceous gland carcinoma. Elderly patients with poor compliance should discuss their condition with a psychiatrist and should be managed by a multidisciplinary approach. This way, patients with eyelid malignancies can be encouraged to undergo surgery and receive early treatment, decreasing the need for exenteration, improving clinical outcomes, and reducing the risk of morbidity and mortality.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Orbital exenteration: A 20-year experience from a tertiary center in Taiwan.

PURPOSE: To describe the prognostic factors and survival outcomes in patients who underwent orbital exenteration surgery at a tertiary center over a 20-year period. METHODS: This institutional retrospective study reviewed all patients who underwent orbital exenteration between January 1999 and January 2019 at Department of Ophthalmology, National Taiwan University Hospital. Patient demographics, tumor site, histopathology, status of surgical margins, additional resection, local recurrence, metastases, survival, and treatment data were recorded. Log-rank tests were used to verify the difference in survival curves among various potential prognostic factors. RESULTS: Thirty patients (27 with malignancy, 1 with hybrid neurofibroma/schwannoma, and 2 with mucormycosis) were included. Malignant melanoma (n = 11) and sebaceous gland carcinoma (n = 8) were the most common indications for exenteration. Survival rates were 83% at 1 year, 42% at 3 years, and 33% at 5 years. Among patients with malignancies, 71% patients had clear margins after exenteration. All the incidences of local recurrence developed in the first 2 years postoperatively. Postoperative survival was significantly related to lymphovascular invasion (p = 0.018), but was independent from surgical margins, presence of metastasis, local recurrence, or perineural invasion. CONCLUSION: We found worse prognosis with positive lymphovascular invasion. Although not significant, malignant melanoma showed poorer survival times compared to sebaceous gland carcinoma. Close follow-up, especially in the first 2 years after orbital exenteration, is crucial to identify disease recurrence.

Bioinformatics analysis of the microRNA-mRNA network in sebaceous gland carcinoma of the eyelid.

Sebaceous gland carcinoma (SGC) of the eyelid is an uncommon aggressive tumor with a relatively high rate of local recurrence and a poor prognosis following metastasis. However, the molecular mechanisms underlying the pathogenesis of SGC remain unclear. The purpose of the present study was to clarify microRNA (miRNA) expression profiles in SGC and to explore novel miRNA­mRNA networks of SGC. A small RNA­sequencing analysis was performed to identify miRNAs differentially expressed between SGC and sebaceous adenoma control samples. Bioinformatics analyses were conducted to reveal biological functions, canonical pathways and molecular interaction networks using integrated miRNA­mRNA datasets, including mRNA expression profiles of SGC from our previous study. The present results demonstrated that 16 upregulated miRNAs and 516 downregulated mRNAs were associated with loss of lipid metabolism function and enriched in cholesterol biosynthesis pathways. By contrast, 29 downregulated miRNAs and 194 upregulated mRNAs were mainly associated with the promotion of cell survival and proliferation in addition to enrichment of DNA damage­induced cell cycle­regulation pathways. Furthermore, network analyses revealed that the upregulated miRNAs, miR­130a­3p and miR­939­5p, and the downregulated miRNAs, miR­146a­5p, miR­149­3p, miR­193a­3p, miR­195­5p and miR­4671­3p, could be upstream regulators related to these functional changes of SGC. These results improved the understanding of molecular mechanisms of SGC and may help to improve the diagnosis of SGC.