Sebaceous carcinoma epidemiology, associated malignancies and Lynch/Muir-Torre syndrome screening in England from 2008 to 2018.

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.

Comparison of clinicopathologic features, survival, and demographics in sebaceous carcinoma patients with and without Muir-Torre syndrome.

BACKGROUND: Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated. OBJECTIVE: To investigate features and survival of SC patients with and without MTS. METHODS: Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000 to 2019 of patients with SC. Patients were classified as MTS or non-MTS cases based on a threshold score of 2 on the Mayo MTS risk score. RESULTS: We identified 105 (2.8%) MTS cases and 3677 (97.2%) non-MTS cases. On univariate analysis, MTS patients were younger, had a higher proportion of tumors outside the head/neck, and had fewer high-grade tumors. On Kaplan-Meier analysis, MTS patients trended toward having better SC-specific survival. On multivariate Cox proportional hazards analysis adjusting for other covariates, MTS status was an independent predictor of worse overall survival. However, there was no association between MTS status and SC-specific survival. LIMITATIONS: Given relatively high disease-specific survival in SC, our study may have been underpowered to detect a difference on Kaplan-Meier analysis. CONCLUSIONS: Our study suggests SC does not behave more aggressively in patients with MTS.

Sebaceous Carcinoma Incidence and Survival Among Solid Organ Transplant Recipients in the United States, 1987-2017.

Importance: Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective: To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants: This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures: Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results: A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P < .001), race/ethnicity (non-Hispanic Black vs non-Hispanic White, IRR, 0.28; 95% CI, 0.10-0.77; P = .01), older age (IRR, 7.85; 95% CI, 3.85-16.0; ≥65 vs 0-44 years; P < .001 for trend), use of thymoglobulin induction (IRR, 1.82; 95% CI, 1.16-2.86; P = .009), posttransplant cutaneous squamous cell carcinoma (IRR, 4.60; 95% CI, 2.67-7.94; P < .001), and longer time since transplant (IRR, 8.40; 95% CI, 3.94-17.90; ≥10 vs 0-1.9 years; P < .001 for trend). Muir-Torre syndrome-associated cancers were rare among both SOTRs and others with SC (3.3%-4.1%). Among patients with SC, prior transplantation was associated with increased overall mortality (adjusted hazard ratio, 2.09; 95% CI, 1.45-3.01), although few deaths were attributed to SC (4 of 92 SOTRs [4.3%]; 235 of 3585 non-SOTRs [6.6%]). Conclusions and Relevance: Among SOTRs, results of this large cohort study suggest that SC was associated with measures of immunosuppression, and overall survival was worse than for other patients with SC. Findings also suggest a possible role for UV radiation in carcinogenesis.

Cutaneous sebaceous tumours and Lynch syndrome: long-term follow-up of 60 patients.

BACKGROUND: Sebaceous neoplasms (SN) may appear sporadically in the general population but may also be part of the Muir-Torre variant of Lynch syndrome (MT-LS). There are few studies in southern Europe on the incidence of MT-LS in the population of patients with SN. AIM: To retrospectively review patients with SN and to analyse their clinical features and the incidence of MT-LS. METHODS: Patients with SN diagnosed between 1995 and 2015 were enrolled in the study. The diagnosis of MT-LS was made according to established clinical criteria and, whenever possible, was confirmed by germline mutation analysis. RESULTS: In 60 patients (32 men, 28 women, mean age 69.22 years), 96 SN were diagnosed: 65 adenomas (67.7%), 16 sebaceomas (16.7%) and 15 carcinomas (15.6%). Of the 60 patients, 50 (83.3%) had a single SN and 10 (16.7%) had multiple lesions. Patients diagnosed with MT-LS (12 patients, 20%) were younger (63.25 years vs. 70.71 years), and had a higher incidence of extrafacial SN (4/12 patients, 33.3%), and were significantly (P < 0.001) more likely to have multiple SNs (8/12, 75%) and keratoacanthomas (KAs) (6/12, 50%). CONCLUSION: Our study confirms that all patients with SN should be investigated, as 20% of our patients were diagnosed with MT-LS. The most specific features of SN associated with MT-LS in our study were the presence of multiple lesions and association with KAs.

Neoplasias de origen sebáceo asociadas a Síndrome de Muir-Torre. A propósito de un caso / Sebaceous neoplasias associated to Muir-Torre syndrome. A propos of a case

El Síndrome de Muir-Torre (SMT) descrito desde 1967, es una genodermatosis con herencia autosómica dominante y penetrancia variable, caracterizada por la presencia de neoplasias cutáneas de origen sebáceo manifestado en áreas seborreicas, como la cara y cuero cabelludo. Los adenomas son los tumores sebáceos más frecuentes. Se han descrito también hiperplasias, neoformaciones sebáceas quísticas, epiteliomas o carcinoma. Los mismos pueden presentarse de manera aislada o múltiple; en conjunto con al menos una neoplasia visceral maligna. Entre las descritas con frecuencia están las gastrointestinales. Se pueden asociar a otras neoplasias, como las renales, las de endometrio, útero y de laringe. El diagnóstico clínico está dado por la presencia y asociación de un tumor visceral primario y otro de origen sebáceo. El tratamiento de esta entidad se basa en la exéresis de los tumores y el seguimiento especializado según el sistema afectado. Se presentó el caso de un hombre de 62 años de edad, cuya afección cutánea demostró múltiples lesiones de origen sebáceo de siete años de evolución por lo que se le realizaron complementarios para identificar entidades asociadas (AU).

The Muir-Torre syndrome, described since 1967, is a genodermatosis with dominant autosomal inheritance and variable penetrance, characterized by the presence of sebaceous skin neoplasias manifested in seborrheic areas as the face and scalp. Adenomas are the most frequent sebaceous tumors. Hyperplasia, cystic sebaceous neoformations, epitheliomas or carcinomas have been also described. They could appear in an isolated or multiple way, in all with at least one malignant visceral neoplasia. The gastrointestinal ones are among those frequently described. They might be associated to other neoplasias, as the renal ones, or the ones of the endometrium, the uterus and the larynx. The clinical diagnosis is given by the presence and association of one primary visceral tumor and another of sebaceous origin. The treatment of this entity is based on the tumors resection and the specialized follow-up according to the affected system. The case of a man, aged 62 years, is presented; his cutaneous condition showed multiple sebaceous lesions of seven years of evolution. Complementary exams were carried out for identifying associated lesions (AU).

Neoplasias de origen sebáceo asociadas a Síndrome de Muir-Torre. A propósito de un caso / Sebaceous neoplasias associated to Muir-Torre syndrome. A propos of a case

El Síndrome de Muir-Torre (SMT) descrito desde 1967, es una genodermatosis con herencia autosómica dominante y penetrancia variable, caracterizada por la presencia de neoplasias cutáneas de origen sebáceo manifestado en áreas seborreicas, como la cara y cuero cabelludo. Los adenomas son los tumores sebáceos más frecuentes. Se han descrito también hiperplasias, neoformaciones sebáceas quísticas, epiteliomas o carcinoma. Los mismos pueden presentarse de manera aislada o múltiple; en conjunto con al menos una neoplasia visceral maligna. Entre las descritas con frecuencia están las gastrointestinales. Se pueden asociar a otras neoplasias, como las renales, las de endometrio, útero y de laringe. El diagnóstico clínico está dado por la presencia y asociación de un tumor visceral primario y otro de origen sebáceo. El tratamiento de esta entidad se basa en la exéresis de los tumores y el seguimiento especializado según el sistema afectado. Se presentó el caso de un hombre de 62 años de edad, cuya afección cutánea demostró múltiples lesiones de origen sebáceo de siete años de evolución por lo que se le realizaron complementarios para identificar entidades asociadas (AU).

The Muir-Torre syndrome, described since 1967, is a genodermatosis with dominant autosomal inheritance and variable penetrance, characterized by the presence of sebaceous skin neoplasias manifested in seborrheic areas as the face and scalp. Adenomas are the most frequent sebaceous tumors. Hyperplasia, cystic sebaceous neoformations, epitheliomas or carcinomas have been also described. They could appear in an isolated or multiple way, in all with at least one malignant visceral neoplasia. The gastrointestinal ones are among those frequently described. They might be associated to other neoplasias, as the renal ones, or the ones of the endometrium, the uterus and the larynx. The clinical diagnosis is given by the presence and association of one primary visceral tumor and another of sebaceous origin. The treatment of this entity is based on the tumors resection and the specialized follow-up according to the affected system. The case of a man, aged 62 years, is presented; his cutaneous condition showed multiple sebaceous lesions of seven years of evolution. Complementary exams were carried out for identifying associated lesions (AU).

Sebaceous adenomas of the eyelid and Muir-Torre Syndrome.

BACKGROUND/AIMS: Sebaceous adenomas (SAs) are rare, benign sebaceous gland tumours of the eyelid. SAs may be associated with primary internal malignancies. This association is known as Muir-Torre Syndrome (MTS). The purpose of this study was to approximate the prevalence of SAs, to determine the reliability of the clinical diagnosis of SAs and to demonstrate immunohistochemical staining of DNA mismatch repair proteins mutL homologue 1 (MLH1) and mutS homologue 2 (MSH2) for a case of MTS. METHODS: We reviewed the histopathology reports from all eyelid specimens collected between 1993 and 2013 at the Henry C Witelson Ocular Pathology Laboratory to determine the proportion of SAs. For the SAs identified on histopathology, we looked at patient charts to see what diagnosis was originally suspected on clinical examination. Immunohistochemical staining for MLH1 and MSH2 was performed on all SAs to screen for MTS. RESULTS: Of the 5884 eyelid specimens collected, 9 were SAs (6 women, 3 men; 42-72 years old). The diagnosis of SA was suspected clinically in only one of the nine cases based on the gross appearance of the eyelid lesion. Immunohistochemistry revealed one SA case with positive MLH1 expression and negative MSH2 expression. These findings prompted systemic work-up and this patient was diagnosed with MTS after discovery of a colon adenocarcinoma T2M0N0. CONCLUSIONS: The diagnosis of eyelid SA is rare. The importance of this benign eyelid tumour stems from its association with internal malignancies in MTS. Immunohistochemical staining of mismatch repair proteins MLH1 and MSH2 is a valid and accessible strategy for investigating MTS in patients with SAs.

A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome.

PURPOSE: The Muir-Torre syndrome variant of Lynch syndrome is characterized by the presence of sebaceous neoplasms (adenoma, epithelioma/sebaceoma, carcinoma) and Lynch syndrome-associated cancers (colon, endometrial, and others). Several clinical scoring systems have been developed to identify patients with colon cancer at high risk of Lynch syndrome. However, no such system has been described for patients presenting with sebaceous neoplasms. METHODS: Based on logistic regression analysis, a scoring system was developed for patients with sebaceous neoplasm to identify those with the highest likelihood of having Muir-Torre syndrome. The final version of the scoring system included variables such as age at presentation of initial sebaceous neoplasm, total number of sebaceous neoplasms, personal history of a Lynch-related cancer, and family history of Lynch-related cancers. RESULTS: Patients with a score of 3 or more were more likely to have Muir-Torre syndrome (28 of 29 patients), those with a score of 2 had intermediate likelihood (12 of 20 patients), and no patient with a score of 0 or 1 was diagnosed with Muir-Torre syndrome. CONCLUSION: The Mayo Muir-Torre syndrome risk scoring system appears to identify whether patients who present with sebaceous neoplasms are in need of further Lynch syndrome evaluation using easily ascertained clinical information. Abnormal mismatch repair gene immunohistochemistry of a sebaceous neoplasm is a poor predictor in regard to diagnosing Lynch syndrome.

[Clinical follow-up and presence of visceral tumors in 12 patients with sebaceous gland tumors]. / Tumores sebáceos: seguimiento clínico y presencia de neoplasias en una serie de 12 pacientes.

BACKGROUND: Sebaceous gland tumors are a rare type of neoplasm. In some cases they have been associated with visceral tumors in patients with Muir-Torre syndrome, a hereditary form of nonpolyposis colorectal cancer. The aim of this study was to review the diagnosis and follow-up of a series of patients with sebaceous gland tumors to assess how many met the criteria for Muir-Torre syndrome. PATIENTS AND METHODS: A search was performed of records from 1990 to 2005 in the database of the Department of Dermatology of the Consorcio Hospital General Universitario de Valencia in Valencia, Spain, to identify patients with sebaceous gland tumors. The biopsy material was reviewed to confirm the diagnosis. We also searched the patient histories for information suggestive of a diagnosis of Muir-Torre syndrome; when the histories were incomplete, we contacted the patients by telephone. RESULTS: We identified 20 patients diagnosed with sebaceous gland tumors, but after reviewing the biopsy material diagnosis was only confirmed in 12. Two patients belonged to a family with a history of visceral tumors that met the clinical criteria for hereditary nonpolyposis colorectal cancer syndrome. Follow-up was not uniform in all patients and not all underwent the same tests. CONCLUSIONS: It is essential to rule out the presence of Muir-Torre syndrome in patients with sebaceous gland tumors. The use of new techniques such as immunohistochemistry or detection of microsatellite instability may help to identify families at increased risk of Muir-Torre syndrome.