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Dermoscopía , Microscopía Confocal , Síndrome de Muir-Torre , Humanos , Dermoscopía/métodos , Microscopía Confocal/métodos , Femenino , Síndrome de Muir-Torre/patología , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/diagnóstico por imagen , Masculino , Pigmentación de la Piel , Adulto , Piel/patología , Piel/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.
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Neoplasias de las Glándulas Sebáceas , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias de las Glándulas Sebáceas/terapia , Neoplasias de las Glándulas Sebáceas/diagnóstico , Humanos , Síndrome de Muir-Torre/patología , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/terapia , Pronóstico , Adenocarcinoma Sebáceo/patología , Adenocarcinoma Sebáceo/terapia , Adenocarcinoma Sebáceo/diagnóstico , Dermatología/normas , Alemania , Cirugía de Mohs , Guías de Práctica Clínica como AsuntoAsunto(s)
Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Neoplasias Cutáneas , Humanos , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Neoplasias de las Glándulas Sebáceas/genética , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
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.
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Queratoacantoma , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Humanos , Queratoacantoma/diagnóstico , Queratoacantoma/genética , Queratoacantoma/patología , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Fenotipo , Neoplasias de las Glándulas Sebáceas/patologíaRESUMEN
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 â ¢C (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.
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Neoplasias del Colon , Síndrome de Muir-Torre , Neoplasias Primarias Secundarias , Humanos , Adulto , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Terapia Neoadyuvante , Inestabilidad de Microsatélites , Estudios de Seguimiento , Inhibidores de Puntos de Control Inmunológico , Proteína 2 Homóloga a MutS/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Reparación de la Incompatibilidad de ADN/genética , InmunoterapiaRESUMEN
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.
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Adenoma , Neoplasias Colorrectales , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Masculino , Humanos , Persona de Mediana Edad , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Proteína 2 Homóloga a MutS , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias de las Glándulas Sebáceas/genética , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Adenoma/diagnóstico , Adenoma/genética , Adenoma/patologíaRESUMEN
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.
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Carcinoma Basocelular , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Humanos , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Inmunohistoquímica , Estudios Retrospectivos , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias de las Glándulas Sebáceas/genética , Neoplasias de las Glándulas Sebáceas/patología , Biología MolecularRESUMEN
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.
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Adenocarcinoma Sebáceo , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Humanos , Síndrome de Muir-Torre/epidemiología , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/patología , Estudios Retrospectivos , Adenocarcinoma Sebáceo/epidemiología , Neoplasias de las Glándulas Sebáceas/epidemiología , DemografíaRESUMEN
The World Health Organization in its 2019 Classification of Breast Tumors termed breast sebaceous carcinoma as invasive breast carcinoma of no special type (IBC-NST), with a sebaceous pattern. Approximately 30 cases of IBC-NST with a sebaceous pattern have been reported in the literature, and in all cases the expression of mismatch repair proteins in tumors was normal. Here, we report a case of IBC-NST with a sebaceous pattern and high-frequency microsatellite instability (MSI-H). This case was a sporadic sebaceous pattern of IBC-NST with MSI-H and was unrelated to Muir-Torre syndrome. Its histopathological characteristics were similar to those of MSI-H-associated triple-negative breast carcinoma (TNBC) with a high histological grade but were without tumor-infiltrating lymphocytes (TILs). The tumor did not recur after 20 months of follow-up.
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Neoplasias de la Mama , Síndrome de Muir-Torre , Humanos , Femenino , Inestabilidad de Microsatélites , Recurrencia Local de Neoplasia , Síndrome de Muir-Torre/metabolismo , Síndrome de Muir-Torre/patología , Neoplasias de la Mama/genética , Linfocitos Infiltrantes de Tumor/metabolismoRESUMEN
Sebaceous adenoma of the conjunctiva is a very rare lesion of uncertain origin. It is usually associated with Muir-Torre syndrome in which neoplasms are also found in other parts of the body. We present the case of a 71-year-old man without a previous or family history of neoplasia, who presented with severe inflammation and an infection in his right eye associated with a tumor of the conjunctiva near the caruncle. The lesion was excised and histopathology revealed a sebaceous adenoma. Microsatellite instability was not observed immunohistochemically. He remains alive and well.
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Adenoma , Síndrome de Muir-Torre , Neoplasias de las Glándulas Sebáceas , Adenoma/complicaciones , Adenoma/patología , Anciano , Conjuntiva/patología , Humanos , Masculino , Síndrome de Muir-Torre/complicaciones , Síndrome de Muir-Torre/patología , Neoplasias de las Glándulas Sebáceas/complicaciones , Neoplasias de las Glándulas Sebáceas/patologíaRESUMEN
ABSTRACT: Cutaneous adnexal tumors are benign and malignant neoplasms that undergo morphological differentiation into cutaneous adnexa, comprising pilosebaceous, eccrine, or apocrine units. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues at a similar resolution as conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, potentiating its wide application, especially for benign and malignant skin tumors. We describe the use of reflectance confocal microscopy in cases of trichoepithelioma, sebaceoma, and fibrofolliculoma and correlate the resulting clinical, histopathological, and confocal microscopy images.
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Síndrome de Muir-Torre/patología , Neoplasias de Anexos y Apéndices de Piel/patología , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Cutáneas/patología , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Muir-Torre/diagnóstico , Neoplasias de Anexos y Apéndices de Piel/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Neoplasias Cutáneas/diagnósticoRESUMEN
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.
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Carcinoma de Células Escamosas/genética , Pruebas Genéticas/métodos , Melanoma/genética , Síndrome de Muir-Torre/genética , Neoplasias Cutáneas/genética , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Pruebas Genéticas/normas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Síndrome de Muir-Torre/patología , Proteína 2 Homóloga a MutS/genética , Mutación , Receptor Notch1/genética , Receptor Notch2/genética , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ADN/normas , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/genéticaRESUMEN
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.
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Regiones no Traducidas 3'/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Proteínas de Unión al ADN/genética , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Secuencia de Bases , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Mutación de Línea Germinal/genética , Heterocigoto , Humanos , Masculino , Proteína 2 Homóloga a MutS/genética , Linaje , Fenotipo , Probabilidad , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Muir-Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the presence of at least one cutaneous sebaceous tumor and one visceral malignancy, arising mostly from the gastrointestinal tract. We present the case of a 63-year-old man with several cutaneous and visceral neoplasias in the context of MTS, and a pelvic lymph node lesion diagnosed initially as metastatic sebaceous carcinoma, but later identified as metastasis from a newly diagnosed prostatic adenocarcinoma. Histological similarities between these 2 lesions are discussed. A systematic literature review was conducted evaluating all published cases of patients with MTS in which metastases were reported. Eighteen articles were included in the final synthesis, representing 20 patients with a total of 26 metastases. Seventeen patients (85%) exhibited metastases originating from MTS-related neoplasms, whereas only 2 patients (11%) exhibited metastases from concomitant malignancies. Of the 85% of patients with metastases from MTS-related malignancies, most originated from noncutaneous sources (78% from visceral neoplasms and 22% from sebaceous carcinomas). When stratifying according to metastases, 23 cases (88%) originated from MTS-related lesions, whereas only 3 (12%) originated from unrelated malignancies. Our findings thus demonstrate that most metastases found in MTS patients (88%) do indeed originate from MTS-related neoplasms. Nevertheless, it remains imperative that a broad differential diagnosis is maintained when assessing a novel lesion, to avoid misdiagnoses, as in the present case, with significant therapeutic and prognostic implications.
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Adenocarcinoma/secundario , Síndrome de Muir-Torre/patología , Neoplasias de la Próstata/patología , Neoplasias de las Glándulas Sebáceas/patología , Adenocarcinoma/química , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia , Toma de Decisiones Clínicas , Errores Diagnósticos , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Síndrome de Muir-Torre/metabolismo , Síndrome de Muir-Torre/terapia , Valor Predictivo de las Pruebas , Neoplasias de la Próstata/química , Neoplasias de la Próstata/terapia , Neoplasias de las Glándulas Sebáceas/química , Neoplasias de las Glándulas Sebáceas/terapiaRESUMEN
Importance: Appropriate use criteria for Muir-Torre syndrome (MTS) screening suggest that mismatch repair protein (MMRP) immunohistochemical (IHC) testing is usually appropriate in patients with 2 or more sebaceous neoplasms (SNs). While MTS is known to be caused by a germline mutation in mismatch repair genes, data are limited as to whether individual sebaceous tumors in these patients with multiple lesions show identical MMRP IHC staining patterns. Objective: To determine concordance of MMRP IHC staining patterns in lesions of patients with MTS who have multiple SNs. Design, Setting, and Participants: This retrospective single-center case series evaluated 38 SNs in 11 patients with MTS confirmed by genetic testing for MMRP IHC staining patterns. Tumor sites were classified as either facial or extrafacial. Data were collected between January 1, 2007, and January 1, 2018. Main Outcomes and Measures: In each patient, MMRP IHC staining patterns for SNs were compared with one another to evaluate intrapatient concordance between lesions, and to the patient's known germline mutation. Results: A total of 11 patients (7 women and 4 men) with MTS, with a mean (SD) age of 59.3 (10.6) years at time of SN biopsy, were identified. There was high concordance between MMRP IHC staining results (2-4 lesions per patient) and the patient's mutation status, with 36 of 38 total lesions (95%) matching (sensitivity, 94.7%; 95% CI, 82.3%-99.4%). Extrafacial site tumors represented 16 of 38 total lesions (42%) and demonstrated 100% concordance of IHC results to germline mutation. Only 1 of 11 patients (9%) demonstrated discordant results, with both lesions in this patient occurring on a facial site. Conclusions and Relevance: In patients with known MTS, SNs present with highly concordant MMRP IHC staining profiles across multiple lesions. There is also a strong association with underlying germline mutations. A diagnosis of MTS might be supported by MMRP IHC when the pretest probability is high.
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Biomarcadores de Tumor/análisis , Reparación de la Incompatibilidad de ADN , Síndrome de Muir-Torre/diagnóstico , Neoplasias de las Glándulas Sebáceas/diagnóstico , Glándulas Sebáceas/patología , Anciano , Biomarcadores de Tumor/genética , Biopsia , Proteínas de Unión al ADN/análisis , Proteínas de Unión al ADN/genética , Estudios de Factibilidad , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/análisis , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Síndrome de Muir-Torre/genética , Síndrome de Muir-Torre/patología , Homólogo 1 de la Proteína MutL/análisis , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/análisis , Proteína 2 Homóloga a MutS/genética , Estudios Retrospectivos , Neoplasias de las Glándulas Sebáceas/genética , Neoplasias de las Glándulas Sebáceas/patologíaRESUMEN
Immune checkpoint blockade therapy provides substantial benefits for subsets of patients with advanced cancer, but its utility for cancer prevention is unknown. Lynch syndrome (MIM 120435) is characterized by defective DNA mismatch repair and predisposition to multiple cancers. A variant of Lynch syndrome, Muir-Torre syndrome (MIM 158320), is characterized by frequent gastrointestinal tumors and hyperplastic or neoplastic skin tumors. We report the case of a man with Muir-Torre syndrome who had 136 cutaneous or visceral hyperplastic or neoplastic lesions over a period of 19 years (mean 7.5 neoplasms/year, range 2-26) prior to receiving pembrolizumab immunotherapy as part of multi-modality treatment for invasive bladder cancer. He not only had a complete response of the bladder cancer, but also was noted to have an absence of new cancers during a 22-month follow-up period. This case adds to the rationale for exploring the utility of immune checkpoint blockade for cancer prevention, particularly for patients with DNA repair deficits.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Síndrome de Muir-Torre/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Muir-Torre/inmunología , Síndrome de Muir-Torre/patología , PronósticoRESUMEN
Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.
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Síndrome de Muir-Torre/genética , Proteína 2 Homóloga a MutS/genética , Femenino , Mutación del Sistema de Lectura , Humanos , Persona de Mediana Edad , Síndrome de Muir-Torre/patología , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patologíaRESUMEN
A 64-year-old man was referred to our dermatology clinic with a diagnosis of Muir-Torre syndrome (MTS), he had a history of multiple sebaceous carcinomas and sebaceous adenomas removed over the years. The patient has also had visceral cancer and had undergone a colon resection 17 years before to treat colon cancer and was recently diagnosed with invasive high-grade urothelial carcinoma of the right ureter. In addition, the patient has an extensive family history of cancer; a pedigree was constructed to document this history (Figure 1). Of note is that the patient's mother and father were second cousins. The patient's father was diagnosed with lung cancer at age 57 and died of colon cancer at the age of 72. The patient's mother died of colon cancer at age 74. The patient has three siblings: a sister and two brothers. The sister died of bone cancer at age 42. One brother had a number of cancers including colon, kidney, and skin cancers and died at age 53. His other brother is alive and has a history of colon cancer, kidney cancer, and ureteral cancer. The patient has five children. He has a 40-year-old son who, at the age of 30, was diagnosed with testicular cancer. His daughters are 47, 44, 39, and 34, with no history of malignancy to date. The patient had three maternal aunts, all of whom succumbed to colon cancer, as well as two paternal uncles who died of lung cancer. The patient's maternal grandfather was a smoker and he also died of lung cancer.