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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Poliposis Intestinal/congénito , Poliposis Intestinal/diagnóstico , Poliposis Intestinal/complicaciones , Poliposis Intestinal/genética , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/complicaciones , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/diagnóstico , Adulto , Masculino , Femenino , Angiografía CerebralRESUMEN
The nervous system is commonly involved in a wide range of genetic tumor-predisposition syndromes. The classification of genetic tumor syndromes has evolved during the past years; however, it has now become clear that these syndromes can be categorized into a relatively small number of major mechanisms, which form the basis of the new 5th edition of the World Health Organization book (beta online version) on genetic tumor syndromes. For the first time, the World Health Organization has also included a separate chapter on genetic tumor syndromes in the latest edition of all the multisystem tumor series, including the 5th edition of CNS tumors. Our understanding of these syndromes has evolved rapidly since the previous edition (4th edition, 2016) with recognition of 8 new syndromes, including the following: Elongator protein complex-medulloblastoma syndrome, BRCA1-associated protein 1 tumor-predisposition syndrome, DICER1 syndrome, familial paraganglioma syndrome, melanoma-astrocytoma syndrome, Carney complex, Fanconi anemia, and familial retinoblastoma. This review provides a description of these new CNS tumor syndromes with a focus on imaging and genetic characteristics.
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Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Síndromes Neoplásicos Hereditarios , Neoplasias del Sistema Nervioso , Neoplasias de la Retina , Humanos , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso/genética , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Predisposición Genética a la Enfermedad , Organización Mundial de la Salud , Ribonucleasa III/genética , ARN Helicasas DEAD-box/genéticaRESUMEN
Background Noninvasive in vivo detection of fumarate accumulation may help identify fumarate hydratase deficiency in renal cancer related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. Purpose To investigate the feasibility of MR spectroscopy (MRS) in detecting elevated fumarate levels in HLRCC-associated renal cancers. Materials and Methods This study included an experimental xenograft mouse model and prospective clinical cohort. First, MRS was performed on patient-derived tumor xenograft models and control models to detect fumarate. Then, consecutive participants with clinical suspicion of HLRCC-associated renal tumors were enrolled. For the detection of fumarate, MRS results were classified as detected, borderline, undetected, or technical failure. The sensitivity, specificity, and accuracy of MRS for diagnosing HLRCC-associated renal cancer were assessed. The signal-to-noise ratio (SNR) of the fumarate peak was calculated and evaluated with receiver operating characteristic curve analysis. Results Fumarate peaks were detected at 6.54 parts per million in all three patient-derived xenograft models. A total of 38 participants (21 men; mean age, 47 years [range, 18-71 years]) with 46 lesions were analyzed. All primary HLRCC-associated renal cancers showed a fumarate peak; among the seven metastatic HLRCC-associated lesions, a fumarate peak was detected in three lesions and borderline in two. When only detected peaks were regarded as positive findings, the sensitivity, specificity, and accuracy of MRS at the lesion level were 69% (nine of 13 lesions), 100% (33 of 33 lesions), and 91% (42 of 46 lesions), respectively. When borderline peaks were also included as a positive finding, the sensitivity, specificity, and accuracy reached 85% (11 of 13 lesions), 88% (29 of 33 lesions), and 87% (40 of 46 lesions), respectively. The SNR of fumarate showed an area under the receiver operating characteristic curve of 0.87 for classifying HLRCC-associated tumors. Conclusion MR spectroscopy of fumarate was sensitive and specific for hereditary leiomyomatosis and renal cell carcinoma-associated tumors. © RSNA, 2022 Online supplemental material is available for this article.
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Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Neoplasias Uterinas , Femenino , Humanos , Ratones , Animales , Leiomiomatosis/diagnóstico por imagen , Leiomiomatosis/patología , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Estudios Prospectivos , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/patología , Síndrome , Fumaratos , Espectroscopía de Resonancia MagnéticaRESUMEN
A wide spectrum of hereditary syndromes predispose patients to distinct pancreatic abnormalities, including cystic lesions, recurrent pancreatitis, ductal adenocarcinoma, nonductal neoplasms, and parenchymal iron deposition. While pancreatic exocrine insufficiency and recurrent pancreatitis are common manifestations in cystic fibrosis and hereditary pancreatitis, pancreatic cysts are seen in von Hippel-Lindau disease, cystic fibrosis, autosomal dominant polycystic kidney disease, and McCune-Albright syndrome. Ductal adenocarcinoma can be seen in many syndromes, including Peutz-Jeghers syndrome, familial atypical multiple mole melanoma syndrome, Lynch syndrome, hereditary breast and ovarian cancer syndrome, Li-Fraumeni syndrome, and familial pancreatic cancer syndrome. Neuroendocrine tumors are commonly seen in multiple endocrine neoplasia type 1 syndrome and von Hippel-Lindau disease. Pancreatoblastoma is an essential component of Beckwith-Wiedemann syndrome. Primary hemochromatosis is characterized by pancreatic iron deposition. Pancreatic pathologic conditions associated with genetic syndromes exhibit characteristic imaging findings. Imaging plays a pivotal role in early detection of these conditions and can positively affect the clinical outcomes of those at risk for pancreatic malignancies. Awareness of the characteristic imaging features, imaging-based screening protocols, and surveillance guidelines is crucial for radiologists to guide appropriate patient management. ©RSNA, 2021.
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Neoplasia Endocrina Múltiple Tipo 1 , Síndromes Neoplásicos Hereditarios , Neoplasias Pancreáticas , Predisposición Genética a la Enfermedad , Humanos , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Páncreas , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/genéticaRESUMEN
Tumor predisposition syndromes represent a heterogeneous group of multiorgan disorders, with many having substantial central nervous system involvement. This article highlights the common and uncommon manifestations of these syndromic disorders, the underlying genetic pathways, and the imaging findings. Radiologists must be aware of the diagnostic criteria, optimal imaging techniques (both for diagnosis and surveillance), as well as the innumerable imaging manifestations of these syndromes. Multidisciplinary approach and teamwork are essential in managing these patients, with imaging having a central role as more of these patients get diagnosed earlier and survive longer.
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Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , HumanosRESUMEN
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.
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Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ipilimumab/uso terapéutico , Leiomiomatosis/terapia , Síndromes Neoplásicos Hereditarios/terapia , Nivolumab/uso terapéutico , Neoplasias Cutáneas/terapia , Neoplasias Uterinas/terapia , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/genética , Mutación de Línea Germinal , Humanos , Leiomiomatosis/diagnóstico por imagen , Leiomiomatosis/genética , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Linaje , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/genética , Tomografía Computarizada por Rayos X , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/genéticaRESUMEN
Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare cancer-predisposition syndrome associated with a high risk of developing a spectrum of malignancies in childhood and adolescence, including brain tumours. In this report, we present the case of an 8-year-old boy with acute headache, vomiting and an episode of unconsciousness in whom brain imaging revealed a high-grade glioma (HGG). The possibility of an underlying diagnosis of CMMRD was suspected radiologically on the basis of additional neuroimaging findings, specifically the presence of multiple supratentorial and infratentorial developmental venous anomalies (DVAs) and malformations of cortical development (MCD), namely, heterotopic grey matter. The tumour was debulked and confirmed to be a HGG on histopathology. The suspected diagnosis of CMMRD was confirmed on immunohistochemistry and genetic testing which revealed mutations in PMS2 and MSH6. The combination of a HGG, multiple DVAs and MCD in a paediatric or young adult patient should prompt the neuroradiologist to suggest an underlying diagnosis of CMMRD. A diagnosis of CMMRD has an important treatment and surveillance implications not only for the child but also the family in terms of genetic counselling.
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Neoplasias Encefálicas , Neoplasias Colorrectales , Glioma , Malformaciones del Desarrollo Cortical , Síndromes Neoplásicos Hereditarios , Adolescente , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Niño , Reparación de la Incompatibilidad de ADN , Glioma/diagnóstico por imagen , Glioma/genética , Humanos , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Mutación , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , NeuroimagenRESUMEN
Hereditary ovarian tumour syndromes are a diverse group of hereditary syndromes characterised by the development of specific histotypes of ovarian neoplasms. While BRCA syndromes are exclusively associated with high-grade serous carcinomas, patients with Lynch syndrome show a preponderance of endometrioid subtype of ovarian and endometrial carcinomas. Distinct non-epithelial phenotypes, such as sex cord stromal tumours with annular tubules, Sertoli-Leydig cell tumours, and small cell carcinoma of the hypercalcaemic type occur in patients with Peutz-Jeghers, DICER1, and rhabdoid tumour predisposition syndromes, respectively. Gorlin-Goltz syndrome is characterised by the development of bilateral, multiple ovarian fibromas in 14-24% of patients. Ovarian steroid cell tumours and broad ligament papillary cystadenomas are characteristically found in women with von Hippel-Lindau syndrome. Recent studies have allowed the characterisation of tumour genetics and associated oncological pathways that contribute to tumourigenesis. Implications of the diagnosis of these syndromes on screening, management, and prognosis are discussed.
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Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/genética , Síndrome del Nevo Basocelular/diagnóstico por imagen , Síndrome del Nevo Basocelular/genética , Síndrome del Nevo Basocelular/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico por imagen , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , ARN Helicasas DEAD-box/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Mutación de Línea Germinal , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/genética , Neoplasias Renales/patología , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Ováricas/patología , Síndrome de Peutz-Jeghers/diagnóstico por imagen , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patología , Blastoma Pulmonar/diagnóstico por imagen , Blastoma Pulmonar/genética , Blastoma Pulmonar/patología , Tumor Rabdoide/diagnóstico por imagen , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Ribonucleasa III/genética , Enfermedad de von Hippel-Lindau/diagnóstico por imagen , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/patologíaRESUMEN
Up to 8% of renal cancers are thought to have a hereditary component. Several hereditary renal cancer syndromes have been identified over the last few decades. It is important for the radiologist to be aware of findings associated with hereditary renal cancer syndromes to detect tumors early, enroll patients in appropriate surveillance programs, and improve outcomes for the patient and affected family members. This review discusses from a radiologist's perspective well-known hereditary renal cancer syndromes and emerging genetic mutations associated with renal cancer that are less well characterized, focusing on imaging features and known associations.
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Carcinoma de Células Renales/diagnóstico por imagen , Diagnóstico por Imagen/métodos , Neoplasias Renales/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Esclerosis Tuberosa/diagnóstico por imagen , Enfermedad de von Hippel-Lindau/diagnóstico por imagen , Humanos , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is a disease marked by high rates of mortality; it is mostly incurable at the time of diagnosis. Only about 7% of patients survive 5 years after diagnosis. Diagnosis at a late stage and rapid progression with minimal response to available treatments are the main reasons for this poor outcome. It is crucial to identify individuals at high risk of developing PDAC so preventive and early detection measures can be employed. Approximately 10% to 15% of PDAC cases have a hereditary or familial basis. In the majority of PDAC cases, no main causative gene has been identified, but several known germline pathogenic mutations have been shown to be related to an increased risk of this cancer. The presence of 2 or more patients with pancreatic cancer within the circle of first-degree relatives, without the presence of a causative germline mutation, is defined as familial pancreatic cancer; this accounts for 4% to 10% of PDAC. Based on the growing evidence supporting the benefit of germline genetic testing in patients with PDAC, both the American Society of Clinical Oncology and the National Comprehensive Cancer Network recently updated their guidelines to include recommendations around genetic testing for patients with pancreatic cancer. However, there is no general consensus on the group of patients and individuals who should be studied and screened. We present a demonstrative case and review the available data on hereditary and familial PDAC.
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Carcinoma Ductal Pancreático/genética , Carcinoma/genética , Mutación de Línea Germinal , Neoplasias Pancreáticas/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/diagnóstico por imagen , Carcinoma/terapia , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/terapia , Pruebas Genéticas/métodos , Humanos , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Pancreatectomía/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/terapia , Factores de RiesgoRESUMEN
Cutaneous leiomyomas are rare, sporadic, or inherited benign tumors arising from smooth muscle cells of the skin associated with various disorders. We present a case of multiple cutaneous leiomyomas showing increased FDG uptake with SUVmax of 19.9. This case indicates cutaneous leiomyoma should be considered as a rare differential diagnosis in patients with hypermetabolic cutaneous lesions. Careful correlation with clinical history is needed to avoid misdiagnosis.
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Fluorodesoxiglucosa F18/metabolismo , Leiomiomatosis/metabolismo , Síndromes Neoplásicos Hereditarios/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Uterinas/metabolismo , Transporte Biológico , Diagnóstico Diferencial , Femenino , Humanos , Leiomiomatosis/diagnóstico por imagen , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagenRESUMEN
PURPOSE: To retrospectively investigate the radiological presentations of HLRCC-associated renal tumors to facilitate accurate lesion characterization and compare these presentations with simple cysts and characteristics of other subtypes of renal cell carcinoma (RCC) as reported in the literature. METHODS: The MRI and CT imaging characteristics of 39 pathologically confirmed lesions from 30 patients (20 male, 10 female) with HLRCC syndrome were evaluated by two radiologists. Patients had an average age at diagnosis of 43.8 ± 13.1 years. Lesion characteristics including laterality, homogeneity, diameter (cm), nodularity, septations, T1 and T2 signal intensity, enhancement, and restricted diffusion were recorded. Imaging characteristics of the lesions were further compared to characteristics of benign simple cysts surgically removed at the same time point. RESULTS: The examined lesions had a mean diameter of 5.06 ± 3.80 cm, an average growth rate of 2.91 × 10-3 cm/day and an estimated annual growth rate of 1.06 cm/year. 50% of lesions demonstrated nodularity, 65% were mostly T2-hyperintense, 83% demonstrated restricted diffusion in solid portions of the lesions, and 65% had well-defined margins. 76% of patients demonstrated extra-renal manifestations, 53% lymphadenopathy, and 43% distant metastasis. CONCLUSIONS: Our analysis confirmed that while HLRCC-associated renal lesions demonstrate diversity in imaging presentations, the majority are unilateral and solitary, T2-hyperintense, heterogeneous with well-defined margins, and frequently demonstrate restricted diffusion and nodularity.
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Carcinoma de Células Renales , Neoplasias Renales , Leiomiomatosis , Síndromes Neoplásicos Hereditarios , Adulto , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Leiomiomatosis/diagnóstico por imagen , Leiomiomatosis/cirugía , Masculino , Persona de Mediana Edad , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Genetic syndromes are an infrequently encountered but challenging group of conditions for both pediatric and adult radiologists given the multitude of possible findings and important complications associated with these syndromes. This article reviews characteristic syndromic imaging features, as well as discussing important complications and screening recommendations for a selected group of clinically relevant genetic syndromes affecting both pediatric and adult populations.
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Diagnóstico por Imagen/métodos , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Enfermedad de von Hippel-Lindau/diagnóstico por imagen , Adulto , Niño , HumanosRESUMEN
In addition to the well-characterized BRCA1 and BRCA2 hereditary breast and ovarian cancer syndromes, many other syndromes that are associated with genetic mutations predispose individuals to an increased risk of breast and gynecologic malignancies. Many mutated genes encode for tumor-suppressor products and are inherited in an autosomal dominant manner. Mutations markedly increase an individual's lifetime risk of cancers in different organ systems, depending on the associated syndrome. These syndromes include Lynch syndrome, the most common hereditary cause of endometrial cancer, and Peutz-Jeghers syndrome, which increases the risks of breast cancer, ovarian cancer, and cervical adenoma malignum. Li-Fraumeni syndrome and Cowden syndrome increase the risk of breast cancer, and Gorlin syndrome increases the risk of ovarian fibromas. With advances in genetic testing, clinicians' knowledge and awareness of the numerous additional genes associated with breast and ovarian cancers, such as ATM, CHEK2, and PALB2, are rapidly expanding. Radiologists have essential roles in patient management, which include developing optimal screening protocols for these patients and closely monitoring them for the development or recurrence of disease-specific malignancies. Radiologists' roles continue to increase and evolve as more mutations are identified and high-risk imaging screening recommendations expand to identify these patients. Understanding the epidemiologic, genetic, and pathophysiologic features and the cancers associated with these syndromes enables radiologists to appropriately contribute to patient management, ensure accurate and timely diagnosis, and make syndrome-specific imaging recommendations. ©RSNA, 2020.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Neoplasias de los Genitales Femeninos/diagnóstico por imagen , Neoplasias de los Genitales Femeninos/genética , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , HumanosRESUMEN
Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants in the fumarate hydratase (FH) gene. It is characterized by cutaneous and uterine leiomyomas and an increased risk of developing renal cell carcinoma (RCC), which is usually adult-onset. HLRCC-related RCC tends to be aggressive and can metastasize even when the primary tumor is small. Data on children and adolescents are scarce. Herein, we report two patients from unrelated Dutch families, with HLRCC-related RCC at the ages of 15 and 18 years, and a third patient with an FH mutation and complex renal cysts at the age of 13. Both RCC's were localized and successfully resected, and careful MRI surveillance was initiated to monitor the renal cysts. One of the patients with RCC subsequently developed an ovarian Leydig cell tumor. A review of the literature identified 10 previously reported cases of HLRCC-related RCC in patients aged younger than 20 years, five of them presenting with metastatic disease. These data emphasize the importance of recognizing HLRCC in young patients to enable early detection of RCC, albeit rare. They support the recommendations from the 2014 consensus guideline, in which genetic testing for FH mutations, and renal MRI surveillance, is advised for HLRCC family members from the age of 8-10 years onwards.
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Carcinoma de Células Renales/genética , Fumarato Hidratasa/genética , Neoplasias Renales/genética , Leiomiomatosis/genética , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Cutáneas/genética , Neoplasias Uterinas/genética , Adolescente , Carcinoma de Células Renales/diagnóstico por imagen , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Leiomiomatosis/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Países Bajos , Linaje , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Uterinas/diagnóstico por imagenAsunto(s)
Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Ultrasonografía/métodos , Administración Tópica , Biopsia/métodos , Niño , Diagnóstico Diferencial , Femenino , Pruebas Genéticas/métodos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Masculino , Madres , Síndromes Neoplásicos Hereditarios/tratamiento farmacológico , Sirolimus/administración & dosificación , Sirolimus/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Resultado del Tratamiento , Ultrasonografía Doppler en ColorRESUMEN
Constitutional mismatch repair deficiency is a rare cancer predisposition syndrome caused by biallelic mutations in one of the four mismatch repair genes. Patients are predisposed to various tumors including hematological malignancies, brain tumors and colorectal carcinomas. Phenotypic overlap with Neurofibromatosis-1 is well known, with most patients presenting with café-au-lait macules. Other common features include axillary and/or inguinal freckling and intracranial MRI foci of high T2W/FLAIR signal intensity similar to the typical FASI seen in Neurofibromatosis-1. In this cohort of eight patients with constitutional mismatch repair deficiency we describe overlapping phenotypical features with Tuberous Sclerosis complex. In addition to "ash-leaf like" hypomelanotic macules (five patients), we detected intracranial tuber-like lesions (three patients), renal cysts (three patients) and renal angiomyolipomas (two patients). All our patients also had Neurofibromatosis-1 like features, mainly café-au-lait macules. This study suggests that features of Tuberous sclerosis especially when overlapping with those of Neurofibromatosis 1 or malignancies atypical for these syndromes should raise the possibility of constitutional mismatch repair deficiency. Correct diagnosis is essential for appropriate genetic counseling and pre-emptive cancer surveillance.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Reparación de la Incompatibilidad de ADN/genética , Neoplasias/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Esclerosis Tuberosa/diagnóstico , Adolescente , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Manchas Café con Leche/diagnóstico , Manchas Café con Leche/genética , Manchas Café con Leche/patología , Niño , Preescolar , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Masculino , Mutación/genética , Neoplasias/diagnóstico por imagen , Neoplasias/genética , Neoplasias/patología , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/patología , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/genética , Neurofibromatosis 1/patología , Linaje , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/patologíaRESUMEN
The neural crest is an important transient structure that develops during embryogenesis in vertebrates. Neural crest cells are multipotent progenitor cells that migrate and develop into a diverse range of cells and tissues throughout the body. Although neural crest cells originate from the ectoderm, they can differentiate into mesodermal-type or endodermal-type cells and tissues. Some of these tissues include the peripheral, autonomic, and enteric nervous systems; chromaffin cells of the adrenal medulla; smooth muscles of the intracranial blood vessels; melanocytes of the skin; cartilage and bones of the face; and parafollicular cells of the thyroid gland. Neurocristopathies are a group of diseases caused by the abnormal generation, migration, or differentiation of neural crest cells. They often involve multiple organ systems in a single person, are often familial, and can be associated with the development of neoplasms. As understanding of the neural crest has advanced, many seemingly disparate diseases, such Treacher Collins syndrome, 22q11.2 deletion syndrome, Hirschsprung disease, neuroblastoma, neurocutaneous melanocytosis, and neurofibromatosis, have come to be recognized as neurocristopathies. Neurocristopathies can be divided into three main categories: dysgenetic malformations, neoplasms, and combined dysgenetic and neoplastic syndromes. In this article, neural crest development, as well as several associated dysgenetic, neoplastic, and combined neurocristopathies, are reviewed. Neurocristopathies often have clinical manifestations in multiple organ systems, and radiologists are positioned to have significant roles in the initial diagnosis of these disorders, evaluation of subclinical associated lesions, creation of treatment plans, and patient follow-up. Online supplemental material is available for this article. ©RSNA, 2019.
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Anomalías Congénitas/embriología , Neoplasias/embriología , Cresta Neural/patología , Síndrome de Deleción 22q11/diagnóstico por imagen , Síndrome de Deleción 22q11/embriología , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/embriología , Síndrome CHARGE/diagnóstico por imagen , Síndrome CHARGE/embriología , Linaje de la Célula , Movimiento Celular , Anomalías Congénitas/diagnóstico por imagen , Enfermedades en Gemelos , Desarrollo Embrionario , Síndrome de Goldenhar/diagnóstico por imagen , Síndrome de Goldenhar/embriología , Enfermedad de Hirschsprung/diagnóstico por imagen , Enfermedad de Hirschsprung/embriología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Disostosis Mandibulofacial/diagnóstico por imagen , Disostosis Mandibulofacial/embriología , Neoplasias/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/embriología , Cresta Neural/embriología , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/embriología , Síndromes Neurocutáneos/diagnóstico por imagen , Síndromes Neurocutáneos/embriología , Nevo Pigmentado/diagnóstico por imagen , Nevo Pigmentado/embriología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/embriología , Tomografía Computarizada por Rayos XRESUMEN
DICER1 syndrome is a highly pleiotropic tumor predisposition syndrome that has been increasingly recognized in the last 10 years. Diseases in the syndrome result from mutations in both copies of the gene DICER1, a highly conserved gene that is critically implicated in micro-ribonucleic acid (miRNA) biogenesis and hence modulation of messenger RNAs. In general, susceptible individuals carry an inherited germline mutation that disables one copy of DICER1; within tumors, a very characteristic second mutation alters function of the other gene copy. About 20 hamartomatous, hyperplastic or neoplastic conditions comprise DICER1 syndrome. Most are not life-threatening, but some are aggressive malignancies. There are many unaffected carriers because penetrance is generally low; however, clinically occult thyroid nodules and lung cysts are frequent. Rare diseases of early childhood were the first recognized conditions in DICER1 syndrome, while other conditions affect adolescents and adults. The hallmarks of DICER1 syndrome are certain rare tumors including pleuropulmonary blastoma; cystic nephroma; ovarian Sertoli-Leydig cell tumor; sarcomas of the cervix, kidneys and cerebrum; pituitary blastoma; ciliary body medulloepithelioma; and nasal chondromesenchymal hamartoma. Radiologists are often the first practitioners to observe these diverse manifestations and play a primary role in recognizing DICER1 syndrome.
Asunto(s)
ARN Helicasas DEAD-box/genética , Predisposición Genética a la Enfermedad , Síndromes Neoplásicos Hereditarios/diagnóstico por imagen , Síndromes Neoplásicos Hereditarios/genética , Ribonucleasa III/genética , Niño , Diagnóstico Diferencial , Mutación de Línea Germinal , Humanos , Enfermedades RarasRESUMEN
Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.