Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 115
Filter
1.
Dermatol Online J ; 30(1)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38762859

ABSTRACT

Patients with Muir-Torre syndrome may have a systemic malignancy and a sebaceous neoplasm such as an adenoma, epithelioma, and/or carcinoma. The syndrome usually results from a germline mutation in one or more mismatch repair genes. Iatrogenic or acquired immunosuppression can promote the appearance of sebaceous tumors, either as an isolated event or as a feature of Muir-Torre syndrome and may unmask individuals genetically predisposed to the syndrome. Two iatrogenically immunosuppressed men with Muir-Torre syndrome features are described. Similar to these immunocompromised men, Muir-Torre syndrome-associated sebaceous neoplasms have occurred in solid organ transplant recipients, human immunodeficiency virus-infected individuals, and patients with chronic diseases who are treated with immunosuppressive agents. Muir-Torre syndrome-associated sebaceous neoplasms occur more frequently and earlier in kidney recipients, who are receiving more post-transplant immunosuppressive agents, than in liver recipients. The development of sebaceous neoplasms is decreased by replacing cyclosporine or tacrolimus with sirolimus or everolimus. Specific anti-cancer vaccines or checkpoint blockade immunotherapy may merit exploration for immune-interception of Muir-Torre syndrome-associated sebaceous neoplasms and syndrome-related visceral cancers. We suggest germline testing for genomic aberrations of mismatch repair genes should routinely be performed in all patients-both immunocompetent and immunosuppressed-who develop a Muir-Torre syndrome-associated sebaceous neoplasm.


Subject(s)
DNA Mismatch Repair , Germ-Line Mutation , Immunosuppressive Agents , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Humans , Muir-Torre Syndrome/genetics , Male , DNA Mismatch Repair/genetics , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Sebaceous Gland Neoplasms/genetics , Middle Aged , MutS Homolog 2 Protein/genetics , Immunocompromised Host , MutL Protein Homolog 1/genetics , Skin Neoplasms/genetics , DNA Mutational Analysis
3.
Am J Dermatopathol ; 46(3): 162-166, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38170727

ABSTRACT

ABSTRACT: Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.


Subject(s)
Keratoacanthoma , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Humans , Keratoacanthoma/diagnosis , Keratoacanthoma/genetics , Keratoacanthoma/pathology , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/pathology , Phenotype , Sebaceous Gland Neoplasms/pathology
4.
Dermatol Surg ; 49(12): 1122-1127, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37962979

ABSTRACT

BACKGROUND: Sebaceous carcinoma (SC) is a rare, potentially recurrent, and life-threatening cutaneous malignancy that can be associated with Muir-Torre syndrome (MTS), a DNA mismatch repair-driven genodermatosis. Earlier studies examining factors associated with recurrence have focused on periocular tumors only. OBJECTIVE: Examine outcomes of SC and identify factors associated with recurrence. MATERIALS AND METHODS: Retrospective study from 2 tertiary care centers. RESULTS: Sixty-seven cases from 63 patients were identified, including 7 cases of MTS and 13 arising in the context of immunosuppression. Fifty-five cases (82.1%) were treated with complete circumferential peripheral and deep margin assessment (CCPDMA) methods. Five recurrences developed during the postoperative period. On univariate analysis, periocular location (odds ratio [OR] 7.6, p = .0410), and lesion size ≥2 cm (OR 9.6, p = .005) were associated with recurrence, whereas CCPDMA (OR 0.052, p = .0006) was inversely associated with recurrence. On multivariate analysis, only lesion size ≥2 cm (OR 9.6, p = .0233) and CCPDMA approaches (OR 0.052, p = .007) were significant. CONCLUSION: Non-complete circumferential peripheral and deep margin assessment methods and large lesion size were independent risk factors predicting recurrence, whereas anatomic subtype and MTS status were not. These findings can assist in identifying SC cases that may benefit from more aggressive treatment and closer surveillance.


Subject(s)
Adenocarcinoma, Sebaceous , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Humans , Retrospective Studies , Cohort Studies , Adenocarcinoma, Sebaceous/surgery , Adenocarcinoma, Sebaceous/pathology , Muir-Torre Syndrome/genetics , Sebaceous Gland Neoplasms/surgery , Sebaceous Gland Neoplasms/pathology
5.
Tumori ; 109(6): NP27-NP31, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37880978

ABSTRACT

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.


Subject(s)
Colonic Neoplasms , Muir-Torre Syndrome , Neoplasms, Second Primary , Humans , Adult , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/pathology , Neoadjuvant Therapy , Microsatellite Instability , Follow-Up Studies , Immune Checkpoint Inhibitors , MutS Homolog 2 Protein/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , DNA Mismatch Repair/genetics , Immunotherapy
6.
Dermatology ; 239(6): 889-897, 2023.
Article in English | MEDLINE | ID: mdl-37717564

ABSTRACT

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.


Subject(s)
Carcinoma, Basal Cell , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Humans , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/pathology , Immunohistochemistry , Retrospective Studies , Sebaceous Gland Neoplasms/diagnosis , Sebaceous Gland Neoplasms/genetics , Sebaceous Gland Neoplasms/pathology , Molecular Biology
7.
J Surg Oncol ; 128(8): 1380-1384, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37706607

ABSTRACT

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.


Subject(s)
Adenoma , Colorectal Neoplasms , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Male , Humans , Middle Aged , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/pathology , MutS Homolog 2 Protein , Sebaceous Gland Neoplasms/diagnosis , Sebaceous Gland Neoplasms/genetics , Sebaceous Gland Neoplasms/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Adenoma/diagnosis , Adenoma/genetics , Adenoma/pathology
9.
J Cancer Res Clin Oncol ; 149(9): 6445-6454, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36763173

ABSTRACT

PURPOSE: The immune microenvironment of sebaceous neoplasms (SNs) has been poorly explored, especially in benign lesions, and never correlated to the mismatch repair (MMR) status. METHODS: We conducted an immuno-histological study to analyze the immune microenvironment of SNs. A tissue microarray was constructed including sebaceous adenomas (SAs), sebaceomas (Ss) and sebaceous carcinomas (SCs) to performed immuno-histological analysis of T cells, B cells, macrophages, dendritic cells, and expression of Programmed Death-1 (PD-1) and Programmed Death Ligand 1 (PD-L1). An automatized count was performed using the QuPath® software. Composition of the cellular microenvironment was compared to the aggressiveness, the MMR status, and to Muir-Torre syndrome (MTS). RESULTS: We included 123 SNs (43 SAs, 19 Ss and 61 SCs) for which 71.5% had a dMMR phenotype. A higher infiltration of macrophages (CD68 +) of M2 phenotype (CD163 +) and dendritic cells (CD11c +) was noticed in SCs compared to benign SNs (SAs and Ss). Programmed cell death ligand-1 but not PD-1 was expressed by more immune cells in SCs compared to benign SNs. No difference in the immune cell composition regarding the MMR status, or to MTS was observed. CONCLUSION: In SNs, M2 macrophages and dendritic cells infiltrates are associated with the progression and the malignant transformation of tumors. High PD-L1 expression in immune cells in SCs is an argument for the use of immunotherapy by anti-PD1 or PD-L1 in metastatic patients. The lack of correlation between the composition of immune cells in SNs and the MMR status emphasizes the singularity of SNs among MMR-associated malignancies.


Subject(s)
Muir-Torre Syndrome , Neoplastic Syndromes, Hereditary , Sebaceous Gland Neoplasms , Humans , B7-H1 Antigen/genetics , DNA Mismatch Repair , Sebaceous Gland Neoplasms/genetics , Sebaceous Gland Neoplasms/metabolism , Sebaceous Gland Neoplasms/pathology , Muir-Torre Syndrome/genetics , Tumor Microenvironment
10.
Am J Clin Dermatol ; 24(3): 375-380, 2023 May.
Article in English | MEDLINE | ID: mdl-36695997

ABSTRACT

Muir-Torre syndrome (MTS) is a rare autosomal dominant genetic condition resulting from microsatellite instability which is caused by mutations in DNA mismatch repair genes. This disorder predisposes individuals to skin tumors and visceral malignancies and may be precipitated in immunocompromised or transplant patients. MTS requires close cancer surveillance for the patient and family because of the tendency to develop aggressive internal malignancies and sebaceous carcinoma. Immunohistochemistry and or genetic testing can confirm the diagnosis of MTS. This review offers an update to the guidelines, diagnosis, and management of MTS while offering a unique perspective on an important but lesser-known syndrome.


Subject(s)
Muir-Torre Syndrome , Humans , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/therapy , Mutation , Immunocompromised Host , Genetic Testing
11.
Fam Cancer ; 22(2): 167-175, 2023 04.
Article in English | MEDLINE | ID: mdl-36418753

ABSTRACT

A subset of patients with Lynch Syndrome demonstrates cutaneous manifestations of the disorder. Characterization of these Lynch-related skin lesions could help in early recognition of patients with Lynch Syndrome. A broad search of the literature on OVID Medline and Embase was carried out to capture papers reporting cutaneous manifestations in Lynch Syndrome patients. The results were uploaded into Mendeley reference management software. The PRISMA workflow was used in the literature selection process. In this systematic review, data were collected from 961 cases from 413 studies, including 380 molecularly confirmed Lynch Syndrome cases. The main skin lesions were: Sebaceous adenomas (43%), sebaceous carcinomas (27%), keratoacanthomas (16%), sebaceomas (13%), squamous cell carcinomas (23%), and basal cell carcinomas (10%). MSH2 variants were the most common underlying genotype (72%). Assessment of mismatch repair by immunohistochemistry, microsatellite instability analysis, or both were performed on 328 skin lesions from 220 (58%) molecularly confirmed cases. In those skin lesions, 95% of Immunohistochemistry and 90% of the microsatellite instability test results were concordant with the underlying genotype. Sebaceous skin lesions are well-recognised phenotypic features of Lynch Syndrome. Our results show that squamous and basal cell carcinomas are relatively common in patients with Lynch syndrome; however, available evidence cannot confirm that Lynch syndrome is causal. Immunohistochemistry and/or microsatellite instability testing of skin tumours in patients with a family history of Lynch Syndrome-associated cancers may be a useful approach in identifying patients requiring referral to Clinical Genetics and/or consideration of germline genetic testing for Lynch Syndrome.


Subject(s)
Carcinoma, Basal Cell , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Humans , Muir-Torre Syndrome/genetics , Microsatellite Instability , Sebaceous Gland Neoplasms/genetics , Genotype , MutS Homolog 2 Protein/genetics
13.
Acta Dermatovenerol Croat ; 31(3): 144-147, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38439724

ABSTRACT

Muir-Torre syndrome (MST) is a rare autosomal dominant subtype of hereditary non-polyposis colorectal carcinoma. The diagnosis is established based on the coexistence of sebaceous gland tumors and visceral organ malignancies. Mutations in the mismatch repair genes are responsible for Muir-Torre syndrome. Internal malignancies seen in MTS are most commonly colorectal, gastrointestinal system, endometrial, genitourinary system, breast, lung, brain, and hepatobiliary system malignancies. Detection of sebaceous neoplasia is essential in investigating Muir-Torre syndrome, allowing early detection of internal malignancies. Herein, we present the case of a patient with sebaceous adenomas, internal malignancies, and a new mutation detected during the genetic examination.


Subject(s)
Muir-Torre Syndrome , Humans , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , MutS Homolog 2 Protein/genetics , Mutation
14.
Int J Gynecol Pathol ; 41(6): 608-614, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-35077082

ABSTRACT

Sebaceous carcinoma is an uncommon primary cutaneous neoplasm which may be associated with mismatch repair (MMR) abnormalities and sometimes with Muir-Torré syndrome. These neoplasms rarely arise in the ovary within a teratoma/ dermoid cyst. We report a sebaceous carcinoma arising in an ovarian teratoma in a 49-yr old (the 14th case reported in the literature) which exhibited loss of expression of MMR proteins MSH2 and MSH6. A germline mutation c.1102C>T was present in exon 7 of the MSH2 gene, the first report of a germline mutation associated with this tumor type. In reporting this case, we review prior reports of primary ovarian sebaceous carcinoma. We recommend that all sebaceous carcinomas of the ovary undergo immunohistochemistry for MMR proteins for investigation of possible Lynch syndrome.


Subject(s)
Carcinoma , Muir-Torre Syndrome , Teratoma , Female , Humans , MutS Homolog 2 Protein/genetics , MutS Homolog 2 Protein/metabolism , DNA Mismatch Repair/genetics , DNA-Binding Proteins/genetics , Muir-Torre Syndrome/complications , Muir-Torre Syndrome/genetics , Teratoma/genetics , Germ-Line Mutation
15.
J Eur Acad Dermatol Venereol ; 36 Suppl 1: 74-76, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34855250

ABSTRACT

Keratoacanthoma (KA) and well-differentiated cutaneous squamous cell carcinoma (cSCC) are hardly distinguishable clinically and histologically. They both can be seen in patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome, corresponding to DNA microsatellite instability. In our case, a young man had the excision of two rapidly growing skin tumours for which distinction between KA and cSCC was initially clinically and pathologically challenging. The diagnosis of well-differentiated cSCCs was made and the patient was treated with surgery. Ten years after the first cSCC, he was diagnosed with Muir-Torre syndrome, a variant of Lynch syndrome, with an heterozygote mutation of the MSH2 gene. This later diagnosis allowed to screen his family members for the same mutation and to adopt an appropriate follow-up regarding the risk of digestive tumours for him and his family. Furthermore, it is important to know that, in case of non-resectable cSCC occurring in this patient, immunotherapy using anti-PD1 antibody would probably be effective due to the known increased immunogenicity of MMR deficient tumours.


Subject(s)
Carcinoma, Squamous Cell , Keratoacanthoma , Muir-Torre Syndrome , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/surgery , DNA Mismatch Repair/genetics , Humans , Keratoacanthoma/diagnosis , Keratoacanthoma/genetics , Keratoacanthoma/surgery , Male , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , MutS Homolog 2 Protein/genetics
16.
Clin Exp Dermatol ; 47(3): 602-604, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34762321

ABSTRACT

Patients with Muir-Torre syndrome (MTS) commonly have germline mismatch repair mutations in MLH1, MSH2 or MSH6, with a strong predominance in MSH2. A subset of approximately one-third of patients will instead have an autosomal recessive base excision repair mutation in MUTYH called MUTYH polyposis. To the best of our knowledge, this is the first report of coexisting germline MSH2 and MUTYH mutations in a patient with MTS.


Subject(s)
DNA Glycosylases/genetics , Germ-Line Mutation , Muir-Torre Syndrome/genetics , MutS Homolog 2 Protein/genetics , Adult , Diagnosis, Differential , Humans , Male , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/surgery
17.
Genes (Basel) ; 12(5)2021 05 20.
Article in English | MEDLINE | ID: mdl-34065301

ABSTRACT

BACKGROUND: We investigated the mutational landscape of skin tumors in patients with Muir-Torre Syndrome (MTS) a hereditary autosomal dominant mismatch repair disorder of increased cancer susceptibility, and examined mutations other than in the DNA mismatch repair (MMR) genes. METHODS: This retrospective single-center case series included seven patients with the diagnosis of Muir-Torre Syndrome with precise medical history and family history. Mutational analysis of tumor samples Formalin-fixed paraffin-embedded tissue blocks of skin lesions associated with Muir-Torre Syndrome were used for further analysis. All skin tumors were analyzed with the Oncomine Comprehensive Assay v3 (Life Technologies), which includes 161 of the most relevant cancer driver genes. RESULTS: Eleven skin neoplasms (nine sebaceous tumors, one melanoma, one cutaneous squamous cell carcinoma) were diagnosed in seven patients. In two patients, visceral malignancies preceded the diagnosis of the skin tumors and one patient was diagnosed with a visceral malignancy after a sebaceous tumor. History of familial cancer of Lynch Syndrome (LS) was reported in three patients. The most frequently detected mutation was in the MSH2 gene, followed by mutations in the NOTCH1/2 and TP53 gene. Conclusion, this study provides a molecular analysis of Muir-Torre Syndrome associated and non-associated skin tumors in patients with Muir-Torre Syndrome. Patients with sebaceous lesions should undergo microsatellite instability analysis and accurate evaluation of personal and family history to detect a possible Muir-Torre syndrome. As secondary malignancies may appear years after the first occurrence of sebaceous tumors, lifelong screening is mandatory.


Subject(s)
Carcinoma, Squamous Cell/genetics , Genetic Testing/methods , Melanoma/genetics , Muir-Torre Syndrome/genetics , Skin Neoplasms/genetics , Aged , Carcinoma, Squamous Cell/pathology , Female , Genetic Testing/standards , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/standards , Humans , Male , Melanoma/pathology , Middle Aged , Muir-Torre Syndrome/pathology , MutS Homolog 2 Protein/genetics , Mutation , Receptor, Notch1/genetics , Receptor, Notch2/genetics , Sequence Analysis, DNA/methods , Sequence Analysis, DNA/standards , Skin Neoplasms/pathology , Tumor Suppressor Protein p53/genetics
18.
Surg Pathol Clin ; 14(2): 273-284, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34023105

ABSTRACT

Sebaceous neoplasia primarily includes sebaceous adenoma, sebaceoma, and sebaceous carcinoma (SC). Sebaceous adenoma, sebaceoma, and a subset of cutaneous SC are frequently associated with defective DNA mismatch repair resulting from mutations in MLH1, MSH2, or MSH6. These tumors can be sporadic or associated with Muir-Torre syndrome. SCs without defective DNA mismatch repair have ultraviolet signature mutation or paucimutational patterns. Ocular SCs have low mutation burdens and frequent mutations in ZNF750. Some ocular sebaceous carcinomas have TP53 and RB1 mutations similar to cutaneous SC, whereas others lack such mutations and are associated with human papilloma virus infection.


Subject(s)
Adenocarcinoma, Sebaceous , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Adenocarcinoma, Sebaceous/genetics , DNA Mismatch Repair , Humans , Molecular Biology , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Sebaceous Gland Neoplasms/genetics , Transcription Factors , Tumor Suppressor Proteins
19.
J Dermatol ; 48(5): 690-694, 2021 May.
Article in English | MEDLINE | ID: mdl-33523490

ABSTRACT

Muir-Torre syndrome is a hereditary condition characterized by occurrence of sebaceous neoplasms or keratoacanthomas and visceral tumors. The most common mechanism for this syndrome is a constitutional defect in the mismatch repair genes. We report the case of a 67-year-old woman with a mutator L homologue 1 (MLH1) mutation. She had a history of endometrial and colorectal cancers. The patient presented with a typical keratoacanthoma on the right cheek and numerous sebaceous neoplasms on the face and trunk. Seven sebaceous adenomas and a low-grade sebaceous carcinoma were excised. Most sebaceous adenomas showed dermoscopic features such as some yellow comedo-like globules and curved vessels in creamy-white areas. Moreover, they revealed pathological features such as keratoacanthoma-like architecture and peritumoral or intratumoral lymphocytes. One of these sebaceous adenomas indicated histopathologically spontaneous regression and another was continuous with the hair follicle. Immunohistochemical staining for mismatch repair proteins revealed loss of expression for MLH1 and postmeiotic segregation increased 2 (PMS2) proteins in tumor cells nuclei in both keratoacanthoma and sebaceous adenoma. Nuclei in overhanging epithelial lips of the keratoacanthoma were also negative. These findings suggest that the type of Muir-Torre syndrome-related cutaneous tumor may have been affected by mismatch repair protein deficient sites in the pilosebaceous unit.


Subject(s)
Adenocarcinoma, Sebaceous , Keratoacanthoma , Muir-Torre Syndrome , Sebaceous Gland Neoplasms , Adenocarcinoma, Sebaceous/diagnosis , Adenocarcinoma, Sebaceous/genetics , Aged , Female , Humans , Keratoacanthoma/diagnosis , Keratoacanthoma/genetics , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/genetics , Mutation , Sebaceous Gland Neoplasms/diagnosis , Sebaceous Gland Neoplasms/genetics
20.
Cancer Genet ; 254-255: 1-10, 2021 06.
Article in English | MEDLINE | ID: mdl-33516942

ABSTRACT

A MSH6 3'UTR variant (c.*23_26dup) was found in 13 unrelated families consulted for Lynch/Muir-Torre Syndrome. This variant, which is very rare in the genomic databases, was absent in healthy controls and strongly segregated with the disease in the studied pedigrees. All tumors were defective for MSH2/MSH6/MSH3 proteins expression, but only MSH2 somatic pathogenic mutations were found in 5 of the 12 sequenced tumors. Moreover, we had no evidence of MSH6 transcript decrease in carriers, whereas MSH2 transcript was downregulated. Additional evaluations performed in representative carriers, including karyotype, arrayCGH and Linked-Reads whole genome sequencing, failed to evidence any MSH2 germline pathogenic variant. Posterior probability of pathogenicity for MSH6 c.*23_26dup was obtained from a multifactorial analysis incorporating segregation and phenotypic data and resulted >0.999, allowing to classify the variant as pathogenic (InSiGHT Class 5). Carriers shared a common haplotype involving MSH2/MSH6 loci, then a cryptic disease-associated variant, linked with MSH6 c.*23_26dup, cannot be completely excluded. Even if it is not clear whether the MSH6 variant is pathogenic per se or simply a marker of a disease-associated MSH2/MSH6 haplotype, all data collected on patients and pedigrees prompted us to manage the variant as pathogenic and to offer predictive testing within these families.


Subject(s)
3' Untranslated Regions/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , DNA-Binding Proteins/genetics , Muir-Torre Syndrome/genetics , Muir-Torre Syndrome/pathology , Base Sequence , Case-Control Studies , Female , Gene Expression Regulation , Germ-Line Mutation/genetics , Heterozygote , Humans , Male , MutS Homolog 2 Protein/genetics , Pedigree , Phenotype , Probability , RNA, Messenger/genetics , RNA, Messenger/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...