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1.
Arch Pathol Lab Med ; 145(1): 46-54, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33367660

RESUMO

CONTEXT.­: The approval of pembrolizumab for treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced cancers has led to increased requests for MSI and/or MMR immunoperoxidase (IPOX) testing. Diagnoses for patients with advanced-stage cancer are frequently made from cytology specimens. OBJECTIVE.­: To investigate the feasibility of using cell block (CB) preparations of effusions for MMR IPOX evaluation. DESIGN.­: Surgical pathology cases of colorectal and endometrial carcinomas with known MMR/MSI status and matched effusions with available CBs were identified. Cell block sections were evaluated for adequacy and stained with MMR IPOX (MSH2, MSH6, MLH1, and PMS2). The CBs were reviewed, the number of tumor cells quantified, and MMR IPOX was interpreted as retained, lost, suboptimal, or noncontributory. RESULTS.­: We identified 748 cases with MMR/MSI testing on surgical specimens having matched effusions. Of these, 131 cases (17.5%) had an available CB and 53 were deemed adequate for MMR IPOX staining. MMR IPOX results between effusion CBs and surgical pathology specimens were concordant in 45 of 53 (85%), inconclusive in 6 of 53 (11%), and discordant in 2 of 53 (4%) cases. CONCLUSIONS.­: There was high concordance of MMR IPOX testing between cytologic and surgical specimens, with no false-positive and 2 false-negative CB results. Limited tumor cells, staining in cells indefinite as tumor, tumor staining heterogeneity, and lack of internal control staining were problematic in some cases. Our findings indicate that cytologic effusion specimens may be suitable substrates for MMR IPOX biomarker testing; however, inconclusive cases need to be interpreted with caution.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorretais/diagnóstico , Citodiagnóstico/métodos , Neoplasias do Endométrio , Instabilidade de Microssatélites , Síndromes Neoplásicas Hereditárias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Ascítico/patologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Derrame Pericárdico/patologia
2.
Medicine (Baltimore) ; 99(50): e23494, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327285

RESUMO

RATIONALE: Juvenile polyposis syndrome (JPS) is a rare genetic gastrointestinal disorder with hidden and variable clinical features. Early detection is crucial for good prognosis. PATIENT CONCERNS: A 20-year-old female went to hospital for fever, and was unexpectedly diagnosed as JPS during treatment. She reported no clinical signs or family history of JPS. DIAGNOSIS: Blood routine examination on hospital admission suggested a moderate anemia. Bone marrow cytology and leukemia fusion gene test were performed to rule out leukemia. Other examinations including ultrasound and computed tomography were also conducted for differential diagnosis. Further electronic colonoscopy identified more than 20 pedicle polyps located at her ileocecum and rectum. Mutation analysis detected a novel de novo pathogenic variant, c.910C>T (p.Gln304Ter) within bone morphogenetic protein receptor type 1A gene, establishing the diagnosis of JPS. INTERVENTIONS: The patient was treated with endoscopic interventions. We also provided a genetic counseling for this family. OUTCOMES: The patient's polyps were removed, some of which already had adenomatous changes. The patient received surveillance of hereditary colorectal cancer according to guidelines. LESSONS: Variable features and lack of family history probably lead to a great underestimation of potential JPS population. It is recommended to perform genetic testing by a multigene panel in individuals who have suspected symptoms of polyposis.


Assuntos
Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/diagnóstico , Diagnóstico Diferencial , Detecção Precoce de Câncer , Feminino , Febre/etiologia , Testes Genéticos , Humanos , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Síndromes Neoplásicas Hereditárias/complicações , Adulto Jovem
3.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370972

RESUMO

Juvenile polyposis syndrome (JPS) and hereditary haemorrhagic telangiectasia (HHT) are rare autosomal dominant diseases, where symptoms manifest at childhood. A 32-year-old man with no family history of JPS or HHT with SMAD4 gene mutation who developed signs and symptoms only at the age of 32, when he was an adult. In this article, we highlight the steps taken to diagnose this rare pathology, explain its pathophysiology and management.


Assuntos
Anemia Ferropriva/diagnóstico , Gastrite/diagnóstico , Polipose Intestinal/congênito , Pólipos Intestinais/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Telangiectasia Hemorrágica Hereditária/diagnóstico , Adulto , Idade de Início , Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/genética , Colo/diagnóstico por imagem , Colo/patologia , Endoscopia Gastrointestinal , Gastrectomia , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Gastrite/cirurgia , Helicobacter heilmannii/isolamento & purificação , Hematínicos/administração & dosagem , Humanos , Hiperplasia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Polipose Intestinal/complicações , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Pólipos Intestinais/genética , Masculino , Mutação , Síndromes Neoplásicas Hereditárias/complicações , Síndromes Neoplásicas Hereditárias/genética , Índice de Gravidade de Doença , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/genética , Tomografia Computadorizada por Raios X
4.
Rev Fac Cien Med Univ Nac Cordoba ; 77(4): 385-386, 2020 12 21.
Artigo em Espanhol | MEDLINE | ID: mdl-33351390

RESUMO

Mr. Editor, The National Comprehensive Cancer Network (NCCN) has determined that when a syndrome of predisposition to cancer is suspected, it is necessary to refer the patient for genetic evaluation because of the implications for diagnosis and management, as well as follow-up in the family (1). The genetic evaluation includes the description of the personal/family history and the request for the corresponding genetic study.


Assuntos
Neoplasias Gastrointestinais , Síndromes Neoplásicas Hereditárias , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética
5.
BMC Med Genet ; 21(1): 196, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032550

RESUMO

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. CASE PRESENTATION: Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband's children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSIONS: Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.


Assuntos
Polipose Adenomatosa do Colo/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Mutação em Linhagem Germinativa , Polipose Intestinal/congênito , Mutação de Sentido Incorreto , Síndromes Neoplásicas Hereditárias/genética , Polipose Adenomatosa do Colo/diagnóstico , Adulto , Saúde da Família , Feminino , Testes Genéticos , Heterozigoto , Humanos , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Masculino , Síndromes Neoplásicas Hereditárias/diagnóstico , Linhagem , Proteína Smad4/genética
6.
Clin Dermatol ; 38(4): 432-454, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972602

RESUMO

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected.


Assuntos
Síndromes Neoplásicas Hereditárias , Dermatopatias Genéticas , Síndrome do Nevo Basocelular , Síndrome de Birt-Hogg-Dubé , Complexo de Carney , Neoplasias Colorretais Hereditárias sem Polipose , Diagnóstico Precoce , Feminino , Síndrome de Gardner , Testes Genéticos , Síndrome do Hamartoma Múltiplo , Humanos , Masculino , Neoplasia Endócrina Múltipla , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndromes Neoplásicas Hereditárias/terapia , Neurofibromatoses , Pele/patologia , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/terapia
7.
Clin Dermatol ; 38(4): 467-476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972605

RESUMO

Basal cell nevus syndrome, also known as Gorlin syndrome, is a hereditary cancer syndrome associated with multiple basal cell carcinomas, congenital defects, and nondermatologic tumors. This disease is autosomal dominant with variable expressivity and is caused by abnormalities in the sonic hedgehog signaling pathway. Management requires a multidisciplinary approach and should include the biopsychosocial needs of patients and their families. Genetic testing is necessary to confirm an unclear diagnosis, evaluate at-risk relatives, and assist with family planning.


Assuntos
Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/terapia , Terapia de Alvo Molecular , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Adulto , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/patologia , Feminino , Testes Genéticos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Comunicação Interdisciplinar , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/patologia , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Receptor Patched-2/genética , Receptor Patched-2/metabolismo , Equipe de Assistência ao Paciente , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Pele/patologia , Adulto Jovem
8.
Pathologe ; 41(5): 535-549, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32780213

RESUMO

BACKGROUND: Monogenic hereditary tumor syndromes or tumor disposition syndromes (TDS) are based on germline/constitutional mutations in key genes of carcinogenesis. Early onset and a clustering of tumors belonging to a typical spectrum in the personal or family history are indicators for a hereditary form. In particular, rare specific tumors occur relatively frequently in the context of TDS. METHODS: Based on a literature search the current article presents information on which TDS should be considered for differential diagnosis (DD) in the presence of a rare tumor. RESULTS: The identification of a causal germline mutation in the index patient is important for the DD, the evaluation of recurrence risks, and predictive testing of asymptomatic at-risk family members. In TDS with autosomal dominant inheritance, it is often possible to identify several high-risk individuals in the affected families. CONCLUSION: Early detection and correct classification are of high clinical relevance as the patients and persons at risk can often be offered effective preventive procedures (surveillance, prophylactic operations), and in some cases, special therapeutic options exist. TDS are paradigmatic for an extremely successful concept of preventive oncology and personalized medicine. The introduction of new methods of high-throughput sequencing (next generation sequencing) enables a more effective genetic diagnosis, but also poses a challenge for the interpretation of findings and counseling. Referral to multidisciplinary expert centers is useful for care of the families.


Assuntos
Predisposição Genética para Doença , Síndromes Neoplásicas Hereditárias , Predisposição Genética para Doença/genética , Testes Genéticos , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética
9.
Rev. senol. patol. mamar. (Ed. impr.) ; 33(2): 57-60, abr.-jun. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-197285

RESUMO

OBJECTIVE: Cowden Syndrome belongs to a group of disorders that are associated with germline mutations in the tumor suppressor gene, phosphatase and tensin homolog (PTEN). The prevalence has been estimated to be 1 in 200,000-250,000. However, this prevalence may be underestimated due to many factors. Better understand Cowden Syndrome among our local population to provide genetic counseling and appropriate screening for different types of neoplasms associated to Cowden Syndrome. MATERIAL AND METHODS: Case series analysis based on data maintained by the Breast Cancer and Hereditary Cancer Departments of the AC Camargo Cancer Center, a large specialized hospital in Brazil. RESULTS: Five cases are presented according to their diagnostic criteria, cancer rates, and outcomes for Cowden Syndrome. CONCLUSION: These cases highlight the need for a multi-institutional evaluation of Cowden Syndrome cases in order to better comprehend its prevalence in Brazil. To improve the outcome of patients with CS, a greater understanding of this syndrome is needed, as well as recognition of the value of periodic screening


OBJETIVO: El síndrome de Cowden (SC) pertenece a un grupo de trastornos asociados a las mutaciones germinales en el gen supresor del tumor, homólogo de fosfatasa y tensina (PTEN). La prevalencia ha sido estimada en uno por cada 200.000-250.000 sujetos. Sin embargo, esta prevalencia puede subestimarse debido a muchos factores. Nuestro objetivo es hacer que nuestra población local comprenda mejor el SC para proporcionar asesoramiento genético, así como un cribado adecuado para los diferentes tipos de neoplasias asociadas a dicho síndrome. MATERIAL Y MÉTODOS: Análisis de una serie de casos basado en los datos mantenidos por los Departamentos de Cáncer de Mama y Cáncer Hereditario del Centro para el Cáncer AC Camargo, un gran hospital especializado de Brasil. RESULTADOS: Se presentan 5 casos con arreglo a sus criterios diagnósticos, tasas de cáncer y resultados para el SC. CONCLUSIÓN: Estos casos subrayan la necesidad de realizar una evaluación multi-institucional de los casos del SC, a fin de comprender mejor su prevalencia en Brasil. Para mejorar el resultado de los pacientes con SC se necesita una mayor comprensión del mismo, así como el reconocimiento del valor del cribado periódico


Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Síndrome do Hamartoma Múltiplo/patologia , Neoplasias da Mama/patologia , Detecção Precoce de Câncer/métodos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndrome do Hamartoma Múltiplo/genética , Doenças Genéticas Inatas/diagnóstico , Neoplasias da Mama/genética , Programas de Rastreamento/organização & administração , Estudos Retrospectivos
10.
Surg Clin North Am ; 100(3): 483-498, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402295

RESUMO

For most individuals, cancer development is multifactorial; however, up to 10% of all cancers are related to an inherited genetic mutation. As health care shifts to having a greater emphasis on prevention, care providers, including general surgeons, will need to play a role in identifying patients at high risk for cancer development. Genetic testing provides a tool to determine those patients with a genetic mutation and to whom appropriate preventive care and treatment may be offered. It is imperative for general surgeons to understand the role genetics plays in the care of individual patients and their relatives.


Assuntos
Neoplasias/genética , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Análise Mutacional de DNA , Feminino , Aconselhamento Genético , Testes Genéticos , Humanos , Masculino , Neoplasias/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Linhagem , Cuidado Pré-Concepcional , Medição de Risco , Neoplasias Gástricas/genética
11.
Cutis ; 105(3): 132-136, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32352437

RESUMO

Many pediatric skin conditions can be safely monitored with minimal intervention, but certain skin conditions are emergent and require immediate attention and proper assessment of the neonate, infant, or child. We review the following pediatric dermatology emergencies so that clinicians can detect and accurately diagnose these conditions to avoid delayed treatment and considerable morbidity and mortality if missed: staphylococcal scalded skin syndrome (SSSS), impetigo, eczema herpeticum (EH), Langerhans cell histiocytosis (LCH), infantile hemangioma (IH), and IgA vasculitis.


Assuntos
Dermatopatias/diagnóstico , Criança , Diagnóstico Diferencial , Emergências , Hemangioma Capilar/diagnóstico , Hemangioma Capilar/terapia , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/terapia , Humanos , Impetigo/diagnóstico , Impetigo/terapia , Erupção Variceliforme de Kaposi/diagnóstico , Erupção Variceliforme de Kaposi/terapia , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/terapia , Púrpura de Schoenlein-Henoch/diagnóstico , Púrpura de Schoenlein-Henoch/terapia , Dermatopatias/terapia , Síndrome da Pele Escaldada Estafilocócica/diagnóstico , Síndrome da Pele Escaldada Estafilocócica/terapia , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapia
12.
Medicina (B Aires) ; 80(2): 181-184, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32282328

RESUMO

Most pituitary adenomas are sporadic, but 3-5% can occur in a family and hereditary context. This is the case of multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC) and familial isolated pituitary adenomas (FIPA). FIPA is an infrequent condition that occurs in a family context, not associated with MEN type1 or CNC. FIPA kindred can be homogeneous (all adenomas affected in the family having the same tumor phenotype) or heterogeneous (different tumor phenotypes in the affected members). We describe a Congolese family in which two sisters and a cousin were diagnosed with a prolactinoma (homogenous FIPA) at the ages of 29, 32 and 40 years, respectively. The patients presented with macroadenomas at the time of diagnosis, non-invasive tumors and good biological response to cabergoline treatment (maximum dose of 1.5 mg/weekly). Of these two sisters, one went through a pregnancy without complications. Because no MEN1 and CNC clinical and biochemical features were detected during the 12-year follow-up, these genes were not investigated. The genetic analysis of the aryl hydrocarbon receptor interacting protein (AIP) was normal. As nearly 80% of patients with FIPA do not have a mutation in the AIP gene, future studies in these families are required to identify other affected genes involved in their physiopathology.


Assuntos
Adenoma/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Neoplasias Hipofisárias/genética , Adenoma/diagnóstico , Adulto , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Hipofisárias/diagnóstico
13.
Am J Surg Pathol ; 44(7): e47-e65, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32251007

RESUMO

Renal cell carcinoma (RCC) subtypes are increasingly being discerned via their molecular underpinnings. Frequently this can be correlated to histologic and immunohistochemical surrogates, such that only simple targeted molecular assays, or none at all, are needed for diagnostic confirmation. In clear cell RCC, VHL mutation and 3p loss are well known; however, other genes with emerging important roles include SETD2, BAP1, and PBRM1, among others. Papillary RCC type 2 is now known to include likely several different molecular entities, such as fumarate hydratase (FH) deficient RCC. In MIT family translocation RCC, an increasing number of gene fusions are now described. Some TFE3 fusion partners, such as NONO, GRIPAP1, RBMX, and RBM10 may show a deceptive fluorescence in situ hybridization result due to the proximity of the genes on the same chromosome. FH and succinate dehydrogenase deficient RCC have implications for patient counseling due to heritable syndromes and the aggressiveness of FH-deficient RCC. Immunohistochemistry is increasingly available and helpful for recognizing both. Emerging tumor types with strong evidence for distinct diagnostic entities include eosinophilic solid and cystic RCC and TFEB/VEGFA/6p21 amplified RCC. Other emerging entities that are less clearly understood include TCEB1 mutated RCC, RCC with ALK rearrangement, renal neoplasms with mutations of TSC2 or MTOR, and RCC with fibromuscular stroma. In metastatic RCC, the role of molecular studies is not entirely defined at present, although there may be an increasing role for genomic analysis related to specific therapy pathways, such as for tyrosine kinase or MTOR inhibitors.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Mutação , Metástase Neoplásica , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/metabolismo , Síndromes Neoplásicas Hereditárias/patologia , Patologia Clínica , Patologia Molecular , Prognóstico , Sociedades Médicas , Urologia
14.
Magy Onkol ; 64(1): 25-31, 2020 Mar 17.
Artigo em Húngaro | MEDLINE | ID: mdl-32181759

RESUMO

The technical developments lead to revolution and speed-up of molecular genetic diagnostics of hereditary cancer syndromes. In those apparently sporadic, solid tumors where the chance of inheritance is higher than 10%, the molecular genetic analysis is indicated. Nowadays these tests are performed using next generation sequencing technologies which allow parallel testing of multiple genes. However, in well-defined cancer syndromes where the clinical presentation clearly suggests the diagnosis and the disease is monogenic, targeted testing is still recommended. Clinical indication of molecular genetic testing and its interpretation is a complex procedure; all steps are regulated. Beside ethical and legal aspects both the laboratory, bioinformatic steps and the interpretation of the results require strong supervision and control. The current review summarizes the genetic alterations responsible for hereditary cancer syndromes and molecular genetic methods which are used during diagnostics in everyday practice.


Assuntos
Análise Mutacional de DNA/métodos , Testes Genéticos/métodos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Patologia Molecular/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos
15.
Magy Onkol ; 64(1): 56-61, 2020 Mar 17.
Artigo em Húngaro | MEDLINE | ID: mdl-32181763

RESUMO

Based on our current knowledge, 5-10% of all malignancies are part of hereditary cancer syndromes. Although the increasing diagnostic role of molecular genetic testing makes us able to recognize more hereditary cancer patients, the careful exploration of family and clinical history by physicians is still the most important step for the diagnosis. In our review we deal with mesenchymal tumours associated with hereditary syndromes. Sarcomas comprise only 1% of all malignancies, but they often associate with familiar diseases so they can serve as an indicator of these syndromes. The diagnosis of hereditary cancer predisposition syndromes is essential to ensure appropriate therapy and follow-up for our patients.


Assuntos
Predisposição Genética para Doença , Síndromes Neoplásicas Hereditárias/genética , Sarcoma/genética , Testes Genéticos , Humanos , Mesenquimoma/diagnóstico , Mesenquimoma/genética , Síndromes Neoplásicas Hereditárias/diagnóstico , Sarcoma/diagnóstico
17.
Indian J Pathol Microbiol ; 63(Supplement): S7-S17, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32108620

RESUMO

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant syndrome wherein affected individuals are at risk for the development of cutaneous leiomyomas, early-onset multiple uterine leiomyomas, and an aggressive subtype of renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene, which inactivates the enzyme and alters the function of the tricarboxylic acid/Krebs cycle. This article reviews the hitherto described morphologic features of HLRCC-associated renal cell carcinoma (RCC) and outlines the differential diagnosis and ancillary use of immunohistochemistry and molecular diagnostics for these tumors. The morphologic spectrum of HLRCC-associated RCC is wide and histologic features, including tumor cells with prominent nucleoli, perinucleolar halos, and multiple architectural patterns within the same tumor, which are suggestive of this diagnosis. FH immunohistochemistry in conjunction with genetic counseling and germline FH testing are the important parameters for detection of this entity. These kidney tumors warrant prompt treatment as even smaller sized lesions can demonstrate aggressive behavior and systemic oncologic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Leiomiomatose/diagnóstico , Síndromes Neoplásicas Hereditárias/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Uterinas/diagnóstico , Diagnóstico Diferencial , Fumarato Hidratase/genética , Testes Genéticos , Humanos , Imuno-Histoquímica , Leiomiomatose/fisiopatologia , Síndromes Neoplásicas Hereditárias/fisiopatologia , Neoplasias Cutâneas/fisiopatologia , Neoplasias Uterinas/fisiopatologia
19.
Ann Thorac Surg ; 109(2): e87-e90, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31279790

RESUMO

Management of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to date. The risks of potential malignant behavior and long-term cardiovascular morbidity have to be weighed against the risks of treatment complications. We report the multidisciplinary and shared decision-making approach that resulted in successful surgical removal of 3 paragangliomas in a SDHD mutation carrier.


Assuntos
DNA de Neoplasias/genética , Neoplasias de Cabeça e Pescoço/genética , Mutação , Neoplasias Primárias Múltiplas/genética , Succinato Desidrogenase/genética , Neoplasias Torácicas/genética , Adulto , Análise Mutacional de DNA , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/metabolismo , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/metabolismo , Paraganglioma/diagnóstico , Paraganglioma/genética , Paraganglioma/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Succinato Desidrogenase/metabolismo , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/metabolismo
20.
Histopathology ; 76(3): 366-374, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31479159

RESUMO

AIMS: Colorectal carcinomas (CRC) with mismatch repair (MMR) deficiency have increased tumour mutation burden and respond to immune check-point inhibitor therapy. The Cancer Genome Atlas identified hypermutated CRCs with somatic mutations in DNA polymerase ε (POLE) with mutation burdens exceeding that of MMR-deficient CRCs. METHODS AND RESULTS: To identify the morphological, immunophenotypical and molecular features of POLE-mutated CRCs, 63 consecutive MMR-intact CRCs were evaluated by Sanger sequencing for POLE exonuclease domain mutations in exons 9, 11, 13 and 14 and confirmed by next-generation sequencing. Tumour immune microenvironment and IMMUNOSCORE®1 were assessed in POLE-mutated CRCs using immunohistochemistry to detect CD3+ /CD8+ tumour-infiltrating lymphocytes and compared to 59 non-POLE mutated MMR-intact CRC, 10 non-POLE mutated MMR-deficient CRCs and 223 normal colonic mucosa. CONCLUSIONS: A total of 4.8% CRC (four MMR-intact primary and one MMR-intact metastasis) harboured POLE mutations in amino acid 286 in exon 9 (p.P286R) or exon 13 (p.V411L). POLE-mutated CRCs arose in the transverse colon and rectum, were male-predominant, younger and showed increased tumour-infiltrating lymphocytes and immune cells at the tumour-stromal interface. The patient with metastatic POLE-mutated CRC was placed on PD-1 inhibitor treatment with marked and sustained response. These data indicate that POLE-mutated CRCs have hypermutated phenotypes despite MMR-intact status, with mutation burdens higher than that in microsatellite-unstable CRCs. Given the recent approval for treatment of microsatellite-unstable cancer with immune check-point inhibitors, assessment of POLE status may help to guide therapeutic decisions for hypermutated tumours with intact MMR that would otherwise be missed by routine testing.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Colorretais/genética , DNA Polimerase II/genética , Síndromes Neoplásicas Hereditárias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/metabolismo , Éxons/genética , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Linfócitos do Interstício Tumoral/patologia , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Mutação , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/patologia , Fenótipo
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