Muir-Torre Syndrome: A Case Report and a Literature Review of Genetic Insights and Cancer Surveillance.

Muir-Torre syndrome (MTS) is a rare autosomal dominant genetic disorder that manifests through the co-occurrence of sebaceous skin tumors and internal malignancies, primarily due to mutations in mismatch repair (MMR) genes such as MSH2, MLH1, and MSH6. This paper presents a detailed case report of a 57-year-old female diagnosed with MTS, highlighting her extensive medical history and the critical role of genetic testing and multidisciplinary management. The patient's dermatological and oncological assessments revealed multiple sebaceous carcinomas and recurrent urothelial carcinoma, confirmed by a pathogenic MSH2 mutation. Through comprehensive preventive surgeries and rigorous follow-up, this case underscores the necessity of proactive cancer surveillance. The discussion integrates findings from key genetic studies and emphasizes the importance of immunohistochemistry in diagnosis. Recommendations for clinical practice include routine genetic testing, stringent surveillance, and multidisciplinary management, underscoring the need for ongoing research to understand better and manage this complex syndrome.

Minimally Invasive Plasma Device Management of Multiple Benign Skin Cancers Associated with Rare Genodermatoses-Case Series and Review of the Therapeutic Methods.

Background: Non-melanocytic benign skin tumours encompass a diverse group of lesions, classified based on their cellular origin, such as epidermal, vascular, fibrous, neural, muscle, and adnexal tumours. Though they often reveal solitary lesions, multiple skin tumours focus on genodermatoses. Each syndrome exhibits distinct clinical characteristics and potential complications, including cutaneous and extra-cutaneous malignancies, some of which are potentially life-threatening. Diagnosing genetic syndromes is complex and requires numerous histopathological and immunohistochemistry tests due to similarities between the adnexal tumours and basal cell carcinoma upon pathology. Methods: To illustrate the clinical practice, we conducted a retrospective case study that included eleven patients with genodermatoses referred to a tertiary dermatology clinic from September 2018 to April 2024. We have also conducted a research study on available treatment modalities in this setting. Results: Five patients with excellent aesthetic results were treated using a recently approved FDA plasma device. After searching SCOPUS and PubMed database records, we assessed 96 original articles to present current knowledge regarding the dermato-surgical approach. Conclusions: Multiple skin tumours, especially on the face, may significantly affect patients' quality of life and have psychological consequences. An appropriate treatment selection tailored to the patient's needs should be provided. There is no standardised treatment for multiple benign tumours in genodermatoses, and selected methods with varying efficacy are employed. We presented the utility of a new plasma device in these settings.

A case of Muir-Torre syndrome on [18F]FDG PET/CT.

Muir-Torre syndrome (MTS) is a rare genetic disorder, considered a subtype of Lynch syndrome, that causes sebaceous cutaneous tumors and increases the risk of internal visceral tumors. We present a case of a 63-year-old male with a history of MTS with sebaceous tumors, colorectal, and urothelial cancers who underwent fluorine-18-deoxyglucose positron emission tomography/ computed tomography [18F]FDG PET/CT to follow-up on multiple [18F]FDG avid skin lesions and right pelvic lymph nodes. Although few reports are available detailing the utility of [18F]FDG PET/CT in this rare disease, this modality appears useful, and superior, to computed tomography in the diagnosis and follow-up of MTS.

Multiple Keratoacanthoma-like Syndromes: Case Report and Literature Review.

Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson-Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir-Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions' undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson-Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented.

Sebaceous carcinoma in a 54-year-old Black African man after cancer chemotherapy: a case report.

BACKGROUND: Sebaceous carcinoma is a very rare malignant skin adnexal tumor that is occasionally aggressive. We have not seen a case of sebaceous carcinoma in our center in the last 10 years. It is extremely rare in Black Africans. CASE PRESENTATION: We described the case of a 55-year-old man African man who presented to our ophthalmologist with complaints of growth on the right upper eyelid for 8 months. He had surgery and chemotherapy for rectal carcinoma 6 years prior to presentation and received his last dose of chemotherapy 5 years before seeing our ophthalmologist. There was a history of spontaneous unprovoked bleeding from the lesion. He subsequently underwent surgical excision under general anesthesia. Histology of the mass showed an effaced architecture due to proliferating malignant epithelial cells disposed as trabecules, solid nests, and tongues. The microscopic features of widespread multivacuolated cytoplasm of the neoplastic cells led us to conclude that the tumor was a sebaceous carcinoma. The patient is alive and well. CONCLUSION: Sebaceous carcinoma is a rare malignant skin adnexal tumor in Black Africans. It can present as an eyelid mass with spontaneous bleeding. It can follow cancer chemotherapy either because of its association with other tumors in Muir-Torre syndrome or because of mutagenic effects of chemotherapeutic agents.

Recurrent colon cancer in a patient with Muir-Torre syndrome: a case report.

Muir-Torre syndrome (MTS) is a rare subtype of hereditary nonpolyposis colorectal cancer syndrome caused by a defect in DNA mismatch repair leading to microsatellite instability. It is characterized by the presence of at least one sebaceous gland tumor and one internal malignancy, most commonly colorectal and endometrial tumors. These patients have a high propensity for tumorigenesis, and while strict screening protocols are in place, there are only two cases that describe the management approach to recurrent colon cancer. Here, we present a case of recurrent colorectal cancer in a patient with MTS, and describe how it was managed at our facility by a multidisciplinary team.

Extra-Ocular Sebaceous Carcinoma in Situ of the Arm of an Elder Male: An Unusual Presentation in an Atypical Location.

Background. Sebaceous carcinoma in situ outside the ocular region is an exceedingly uncommon. It is an intraepidermal neoplasm originating from sebaceous glands limited to the epidermis with no invasion into the underlying dermis or beyond. Although sebaceous carcinoma in situ is predominantly observed in ocular regions, particularly the eyelids, instances of its occurrence in extraocular locations are infrequent, with only a limited number of examples reported in the literature. Case Presentation. A 63-year-old man presented with a left posterior arm lesion. Microscopic examination revealed a proliferation of poorly differentiated atypical neoplastic sebocytes confined to the epidermis with pleomorphic nuclei, prominent nucleoli, and clear cell changes. The neoplastic cells demonstrated positive staining for adipophilin, androgen receptor, epithelial membrane antigen, P63, BerEP4, and keratin 7. Microsatellite instability markers showed preserved nuclear staining for MLH1, PMS2, MSH2, and MSH6. A definitive diagnosis of sebaceous carcinoma in situ was rendered. Discussion. The distinctive histopathologic characteristics typically involve the presence of atypical sebaceous cells confined within the epidermis. Atypical cells often exhibit enlarged nuclei, increased mitotic activity, and prominent nucleoli. A panel of epithelial membrane antigen, adipophilin, and androgen receptors is essential for ensuring an accurate diagnosis. Conclusion. This report underscores the importance of considering sebaceous carcinoma in situ in diagnosis in atypical locations, emphasizing the need for a comprehensive histopathologic examination and immunohistochemical staining panel. This article aims to demonstrate the rarity of sebaceous carcinoma in situ in extraocular sites to broaden our understanding of its diverse clinical presentations.

Sebaceous Adenoma: A Dermoscopic Case Perspective.

This report focuses on sebaceous skin tumors, specifically sebaceous adenoma, sebaceoma, and sebaceous carcinoma, along with their association with Muir-Torre syndrome (MTS). A clinical case of a 25-year-old male with a suspected sebaceous neoplasm based on dermoscopy appearance is presented. The histopathological examination confirmed the diagnosis and surgical management resulted in successful treatment. The report highlights the importance of considering differential diagnoses and utilizing dermoscopy for accurate evaluation of these rare skin tumors.

HPV-associated vulvar carcinoma with sebaceous differentiation.

•Sebaceous carcinoma is rare on the vulva and uncommonly associated with HPV.•Pregnancy may play a role in onset or exacerbation of HPV-associated vulvar cancers.•Treatment of vulvar sebaceous carcinoma is local excision and sentinel lymph node dissection with close follow-up.

A locally advanced colon cancer patient with Muir-Torre syndrome obtains durable response to neoadjuvant and adjuvant immunotherapy.

INTRODUCTION: Muir-Torre syndrome, presenting with cutaneous tumors and visceral malignancies, is a variant of Lynch syndrome. The development of immune checkpoint inhibitors provided novel effective treatment options for metastatic colorectal cancer patients with microsatellite instability and deficient mismatch repair. However, the use of immune checkpoint inhibitors in neoadjuvant and adjuvant settings for patients with locally advanced colorectal cancer remains undefined because of limited follow-ups in current studies. CASE PRESENTATION: In the present study, we reported a 33-year-old Muri-Torre syndrome patient with stage ⅢC (c.T4N2M0) colorectal cancer and keratoacanthoma. Microsatellite instability / deficient mismatch repair, high tumor mutation burden, and MSH2 germline mutation were identified by next-generation sequencing. Pembrolizumab monotherapy was used as neoadjuvant treatment and the patient achieved a major pathological response. After surgical resection, pembrolizumab was continuously used in an adjuvant setting for 12 months. The patient remained disease-free with a durable disease-free survival for 44 months. To our knowledge, this is the first and longest follow-up study reporting pembrolizumab as a single-agent neoadjuvant therapy for locally advanced colon cancer. CONCLUSIONS: The results demonstrate promising performance in neoadjuvant and adjuvant settings. Further studies are needed to confirm its potential usefulness as an outcome measure in clinical practice.

Immunohistochemistry, Molecular Biology, and Clinical Scoring for the Detection of Muir-Torre Syndrome in Cutaneous Sebaceous Tumors: Which Strategy?

BACKGROUND: Sebaceous neoplasms (SNs) always raise the possibility of an association with Muir-Torre syndrome (MTS) and permit to screen internal malignancies, colorectal and endometrial carcinomas, before they become symptomatic. Immunohistochemistry (IHC), molecular biology, and clinical examination are different approaches for detection of MTS. We conducted a retrospective analysis of non-selected SNs in order to determine the optimal tools to implement for MTS screening. METHODS: Deficient MMR phenotype (dMMR) was determined by either IHC using antibodies directed to four mismatch repair (MMR) antigens on tissue microarray or molecular biology using pentaplex PCR. The Mayo Clinic risk score of MTS was calculated from medical records. Sensibility and specificity of each test for the detection of MTS were determined. RESULTS: We included 107 patients, 8 with multiple SNs, for a total of 123 SNs (43 sebaceous adenomas, 19 sebaceomas, and 61 sebaceous carcinomas (SC)). Loss of at least one MMR protein was observed in 70.7% of tumors, while 48% had a microsatellite instable phenotype. Concordance between both techniques was 92.9%, with a 0.85 Cohen's kappa coefficient. Nineteen patients (20.2%) had a ≥2 points Mayo Clinic risk score, one having a pMMR SC. Among the 13 patients with confirmed MTS, 2 had a low Mayo Clinic risk score (1 point). IHC had the highest sensitivity for MTS screening (100%) with a specificity of 34.1%, while a >2-point Mayo Clinic risk score had a lower sensitivity (92%) but a higher specificity (89%). CONCLUSION: To detect MTS in SN patients, the first-line Mayo Clinic risk score followed by IHC appears to be the most accurate strategy with lower cost for society. This strategy should be adapted to the medico-economic resources of each country.

Muir-Torre syndrome and recent updates on screening guidelines: The link between colorectal tumors and sebaceous adenomas in unusual locations.

BACKGROUND: Muir-Torre syndrome (MTS) is a rare genetic disorder that is caused by mismatch repair (MMR) protein mutations. MTS increases the risk of developing skin and gastrointestinal tumors such as sebaceous adenomas (SAs), sebaceous carcinomas, colorectal cancer, endometrial cancer, and ovarian cancer. The risk of developing these types of tumors varies depending on the involved mutation and the individual's family history risk. CASE PRESENTATION: A 47-year-old male presented with multiple skin lesions on the scalp, face, flank, and back. The examination revealed well-circumscribed, dome-shaped papules with a yellowish appearance with white oily material in the center. Histopathologic examination showed a well-circumscribed sebaceous neoplasm consistent with a mixture of basaloid cells and lobules of bland-appearing mature adipocytes that communicate directly to the surface epithelium. Focal cystic changes and peritumoral lymphocytic infiltrate were noted. Increased mitotic figures were seen in the basaloid cell component. The overall findings were consistent with the diagnosis of SAs. MMR staining showed preserved expression in MLH1 and PMS2 proteins, while MSH2 and MSH6 staining showed loss of protein expression. A screening colonoscopy showed numerous colon and rectal tumors, prompting concerns about the likelihood of MTS. Surgical intervention was pursued for complete resection. Histology revealed a diagnosis of mucinous adenocarcinoma/adenocarcinoma with mucinous features of the colon. The diagnosis of MTS was supported by molecular testing that revealed MSH2 germline mutation. The increased likelihood of MTS was attributed to the occurrence of SAs in unusual locations of the head and neck regions, unlike typical cases. CONCLUSION: MTS is a rare clinical condition that necessitates prompt thorough evaluation and periodic surveillance. When SA is encountered in atypical locations, it is important to consider additional testing supported by immunohistochemical staining, molecular testing, and regular screening to exclude the likelihood of MTS.

Looking beyond the surface: Muir Torre syndrome.

Muir-Torre Syndrome (MTS) is associated with multiple visceral malignancies. Initial presentation may be a benign skin tumor mimicking a sebaceous cyst. This case report highlights the importance of early diagnosis, genetic testing, and multidisciplinary screening. A 67-year-old man was diagnosed with MTS following excision of a skin lesion (sebaceoma). He was declined both screening colonoscopy and genetic testing. Subsequently, advanced colon cancer was found following presentation with iron deficiency anemia, which ultimately led to palliation despite successful surgery. MTS can present insidiously with skin lesions clinically diagnosed as sebaceous cysts. Once MTS is suspected on histology, genetic testing and screening for MTS-related cancers is warranted. Better understanding of the genetic variants for MTS can aid in earlier diagnosis thus not dismissing the need for screening for MTS-related cancers.

Sebaceous carcinoma in Western Australia: A registry-based study of site-related outcomes.

Sebaceous carcinoma is a rare cutaneous malignancy which is typically regarded as relatively aggressive and has traditionally been subdivided into periorbital or extraorbital tumours. We conducted a retrospective review of all cases of sebaceous carcinoma reported to the Western Australian Cancer Registry between 1987 and May 2019. The incidence of sebaceous carcinoma in Western Australia has increased over the last three decades, with extraorbital tumours being much more common than periorbital tumours. Very few sebaceous carcinomas have led directly to the death of patients; however, adverse outcomes were more likely with periorbital tumours, in particular local recurrence and the need for major surgical intervention.

Sebaceous Neoplasms.

Sebaceous neoplasms describe a group of tumors with sebaceous differentiation commonly seen in lesions located primarily in the face and neck. The majority of these lesions are benign, while malignant neoplasms with sebaceous differentiation are uncommon. Sebaceous tumors present a strong association with the Muir-Torre Syndrome. Patients suspected with this syndrome should undergo neoplasm excision, followed by histopathologic and additional immunohistochemistry and genetics examinations. Clinical and dermoscopic features of the sebaceous neoplasms, as well as management procedures collected from the literature analysis regarding sebaceous carcinoma, sebaceoma/sebaceous adenoma, and sebaceous hyperplasia are described in the current review. A special note is made for describing the Muir-Torre Syndrome in patients presenting multiple sebaceous tumors.

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.

A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.

Routine screening of tumors for DNA mismatch repair (MMR) deficiency (dMMR) in colorectal (CRC), endometrial (EC) and sebaceous skin (SST) tumors leads to a significant proportion of unresolved cases classified as suspected Lynch syndrome (SLS). SLS cases (n = 135) were recruited from Family Cancer Clinics across Australia and New Zealand. Targeted panel sequencing was performed on tumor (n = 137; 80×CRCs, 33×ECs and 24xSSTs) and matched blood-derived DNA to assess for microsatellite instability status, tumor mutation burden, COSMIC tumor mutational signatures and to identify germline and somatic MMR gene variants. MMR immunohistochemistry (IHC) and MLH1 promoter methylation were repeated. In total, 86.9% of the 137 SLS tumors could be resolved into established subtypes. For 22.6% of these resolved SLS cases, primary MLH1 epimutations (2.2%) as well as previously undetected germline MMR pathogenic variants (1.5%), tumor MLH1 methylation (13.1%) or false positive dMMR IHC (5.8%) results were identified. Double somatic MMR gene mutations were the major cause of dMMR identified across each tumor type (73.9% of resolved cases, 64.2% overall, 70% of CRC, 45.5% of ECs and 70.8% of SSTs). The unresolved SLS tumors (13.1%) comprised tumors with only a single somatic (7.3%) or no somatic (5.8%) MMR gene mutations. A tumor-focused testing approach reclassified 86.9% of SLS into Lynch syndrome, sporadic dMMR or MMR-proficient cases. These findings support the incorporation of tumor sequencing and alternate MLH1 methylation assays into clinical diagnostics to reduce the number of SLS patients and provide more appropriate surveillance and screening recommendations.