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Journal of the American Academy of... Dec 2023Sebaceous carcinomas (SC) may be associated with the cancer predisposition syndrome Muir-Torre/Lynch syndrome (MTS/LS), identifiable by SC mismatch repair (MMR)...
BACKGROUND
Sebaceous carcinomas (SC) may be associated with the cancer predisposition syndrome Muir-Torre/Lynch syndrome (MTS/LS), identifiable by SC mismatch repair (MMR) screening; however, there is limited data on MMR status of SC.
OBJECTIVE
To describe the epidemiology of SC, copresentation of other cancers, and population level frequency of MMR screening in SC.
METHODS
A population-based retrospective cohort study of SC patients in the National Cancer Registration and Analysis Service in England.
RESULTS
This study included 1077 SC cases (739 extraocular, 338 periocular). Age-standardized incidence rates (ASIR) were higher in men compared with women, 2.74 (95% CI, 2.52-9.69) per 1,000,000 person-years for men versus 1.47 person-years (95% CI, 1.4-1.62) for women. Of the patients, 19% (210/1077) developed at least one MTS/LS-associated malignancy. MMR immunohistochemical screening was performed in only 20% (220/1077) of SC tumors; of these, 32% (70/219) of tumors were MMR deficient.
LIMITATIONS
Retrospective design.
CONCLUSIONS
Incorporation of MMR screening into clinical practice guidelines for the management of SC will increase the opportunity for MTS/LS diagnoses, with implications for cancer surveillance, chemoprevention with aspirin, and immunotherapy treatment targeted to MTS/LS cancers.
Topics: Male; Humans; Female; Muir-Torre Syndrome; Retrospective Studies; Adenocarcinoma, Sebaceous; Sebaceous Gland Neoplasms; Colorectal Neoplasms; Neoplasms, Adnexal and Skin Appendage; Carcinoma, Basal Cell
PubMed: 37031776
DOI: 10.1016/j.jaad.2023.03.046 -
Cancer Medicine Jul 2023Eyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment...
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.
Topics: Humans; Nomograms; Retrospective Studies; Sebaceous Glands; Eyelid Neoplasms; Risk Factors; Carcinoma; Eyelids
PubMed: 37387455
DOI: 10.1002/cam4.6126 -
Investigative Ophthalmology & Visual... Dec 2023Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is...
PURPOSE
Eyelid sebaceous carcinoma (SeC) is the third most frequent eyelid malignancy worldwide and is relatively prevalent in Asian patients. An eyelid SeC cell line model is necessary for experimental research to explore the etiology and pathogenesis of eyelid SeC. This study established and characterized an eyelid SeC cell line with a TP53 mutation that might be useful for analyzing potential treatment options for eyelid SeC.
METHODS
The eyelid SeC cell line SHNPH-SeC was obtained from a patient with eyelid SeC at Shanghai Ninth People's Hospital (SHNPH), Shanghai JiaoTong University School of Medicine. Immunofluorescence staining was employed to detect the origination and proliferation activity. Short tandem repeat (STR) profiling was performed for verification. Chromosome analysis was implemented to investigate chromosome aberrations. Whole exome sequencing (WES) was used to discover genomic mutations. Cell proliferation assays were performed to identify sensitivity to mitomycin-C (MMC) and 5-fluorouracil (5-FU).
RESULTS
SHNPH-SeC cells were successively subcultured for more than 100 passages and demonstrated rapid proliferation and migration. Karyotype analysis revealed abundant chromosome aberrations, and WES revealed SeC-related mutations in TP53, KMT2C, and ERBB2. An in vivo tumor model was successfully established in NOD/SCID mice. Biomarkers of eyelid SeC, including cytokeratin 5 (CK5), epithelial membrane antigen (EMA), adipophilin, p53, and Ki-67, were detected in SHNPH-SeC cells, original tumors, and xenografts. MMC and 5-FU inhibited the proliferation and migration of SHNPH-SeC cells, and SHNPH-SeC cells presented a greater drug response than non-TP53-mutated SeC cells.
CONCLUSIONS
The newly established eyelid SeC cell line SHNPH-SeC demonstrates mutation in TP53, the most commonly mutated gene in SeC. It presents SeC properties and malignant characteristics that may facilitate the investigation of cellular behaviors and molecular mechanisms of SeC to explore promising therapeutic strategies.
Topics: Animals; Mice; Humans; Tumor Suppressor Protein p53; Biomarkers, Tumor; Mice, SCID; Mice, Inbred NOD; China; Adenocarcinoma, Sebaceous; Carcinoma; Chromosome Aberrations; Cell Line, Tumor; Eyelids; Eyelid Neoplasms; Skin Neoplasms; Sebaceous Gland Neoplasms; Fluorouracil
PubMed: 38095907
DOI: 10.1167/iovs.64.15.16 -
Japanese Journal of Clinical Oncology Jan 2024Eyelid squamous cell carcinoma is a major type of rare eyelid cancer, together with basal cell carcinoma and sebaceous gland carcinoma. It is a painless disease that...
Eyelid squamous cell carcinoma is a major type of rare eyelid cancer, together with basal cell carcinoma and sebaceous gland carcinoma. It is a painless disease that progresses slowly and is often detected by the appearance of nodules or plaques. Risk factors include exposure to ultraviolet light, fair skin, radiation and human papillomavirus infection. The standard treatment is surgical removal, and in cases of orbital invasion, orbital content removal is required. If sentinel node biopsy reveals a high risk of lymph node metastasis, adjuvant radiotherapy may be considered. Local chemotherapy, such as imiquimod and 5-fluorouracil, may be used for eyelid squamous cell carcinoma in situ. When surgery or radiotherapy is not recommended for distant metastases or locally advanced disease, drug therapy is often according to head and neck squamous cell carcinoma in Japan. The treatment often requires a multidisciplinary team to ensure the preservation of function and cosmetic appearance.
Topics: Humans; Carcinoma, Squamous Cell; Eyelid Neoplasms; Sentinel Lymph Node Biopsy; Skin Neoplasms; Head and Neck Neoplasms; Eyelids
PubMed: 37747408
DOI: 10.1093/jjco/hyad127 -
Frontiers in Oncology 2024Management of cutaneous malignancies can be particularly challenging when they are located in the periocular region. The standard of care for localized disease is... (Review)
Review
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.
PubMed: 38500654
DOI: 10.3389/fonc.2024.1275930 -
BMC Ophthalmology Sep 2023Human papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across...
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.
Topics: Humans; Eyelid Neoplasms; Human Papillomavirus Viruses; Papillomavirus Infections; Prevalence; East Asian People; Retrospective Studies; Skin Neoplasms; Carcinoma; Adenocarcinoma, Sebaceous; Sebaceous Gland Neoplasms
PubMed: 37752463
DOI: 10.1186/s12886-023-03131-9 -
Indian Journal of Pathology &... 2024Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from the sebaceous glands. Sebaceous carcinomas are divided into those occurring in ocular (75%)...
Sebaceous gland carcinoma is a rare and aggressive skin cancer derived from the sebaceous glands. Sebaceous carcinomas are divided into those occurring in ocular (75%) and extra-ocular locations. A 45-year-old female patient presented with rapidly growing swelling over the upper back region. It was provisionally diagnosed as an infected sebaceous cyst, and an excision biopsy was received in the pathology department. Histopathology was reported as sebaceous carcinoma, Grade II, Stage P T3 Nx. Immunohistochemistry was positive for epithelial membrane antigen. Sebaceous carcinoma accounts for 0.2-4.6% of all malignant cutaneous neoplasms, and the estimated rate of occurrence is only 1-2 per 1 million individuals per year. These tumors frequently present with a painless sub-cutaneous nodule, but they can also present as pedunculated lesions, irregular mass, or diffuse thickening of the skin. Hence, they are misinterpreted as other benign tumors or inflammatory conditions, thereby leading to delay in diagnosis, inappropriate treatment, increased morbidity, and mortality.
Topics: Female; Humans; Middle Aged; Adenocarcinoma, Sebaceous; Sebaceous Gland Neoplasms; Skin Neoplasms; Skin; Sebaceous Glands
PubMed: 38358213
DOI: 10.4103/ijpm.ijpm_860_21 -
Genes Nov 2023Personalized medicine aims to develop tailored treatments for individual patients based on specific mutations present in the affected organ. This approach has proven...
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.
Topics: Humans; Sebaceous Gland Neoplasms; Adenocarcinoma, Sebaceous; Eyelids; Carcinoma, Basal Cell; Skin Neoplasms; DNA Repair
PubMed: 38002998
DOI: 10.3390/genes14112055