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1.
Mod Pathol ; 36(11): 100294, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37532182

RESUMEN

Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion-positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion-positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Niño , Adulto , Lactante , Adulto Joven , Proteínas Tirosina Quinasas/genética , Estudios Retrospectivos , Proteínas Proto-Oncogénicas/genética , Glioma/genética , Glioma/patología , Glioblastoma/genética , Mutación , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología
2.
J Natl Compr Canc Netw ; 21(7): 694-704, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37433432

RESUMEN

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Neoplasias Hepáticas , Humanos , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/terapia , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/terapia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Conductos Biliares Intrahepáticos
3.
Int J Gynecol Pathol ; 42(3): 241-246, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36867463

RESUMEN

The pathogenesis of serous ovarian tumors has been extensively investigated, with a dualistic model dividing these cancers into 2 groups. Type I tumors, including low-grade serous carcinoma, is characteristic for concurrent presence of borderline tumors, less atypical cytology, relatively indolent biologic behavior, and molecular aberrations related to the MAPK pathway with chromosomal stability. Meanwhile, type II tumors, such as high-grade serous carcinoma, are notable for no significant association with borderline tumors, higher grade cytology, more aggressive biologic behavior, and TP53 mutations along with chromosomal instability. We describe a case of morphologic low-grade serous carcinoma with focally increased cytologic atypia arising in serous borderline tumors involving both ovaries, which demonstrated highly aggressive behavior despite several years of surgical and chemotherapeutic management. Each recurrent specimen contained more uniform higher grade morphology than what was seen in the original specimen. Immunohistochemical and molecular studies in both the original tumor and the most recent recurrence demonstrate identical mutations in the MAPK genes, but with additional mutations in the latter, notably an acquisition of a variant of possible clinical significance in the SMARCA4 gene, which is associated with dedifferentiation and aggressive biologic behavior. This case challenges our current and still evolving understanding of the pathogenesis, biologic behavior, and expected clinical outcome of low-grade serous ovarian carcinomas. It also underscores the need for further investigation into this complicated tumor.


Asunto(s)
Productos Biológicos , Carcinoma , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Lesiones Precancerosas , Femenino , Humanos , Neoplasias Ováricas/patología , Lesiones Precancerosas/patología , Carcinoma/patología , Cistadenocarcinoma Seroso/patología , ADN Helicasas , Proteínas Nucleares , Factores de Transcripción
4.
J Cutan Pathol ; 50(10): 913-921, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37407520

RESUMEN

BACKGROUND: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms. METHODS: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed. RESULTS: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. CONCLUSIONS: We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.


Asunto(s)
Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Proteínas Tirosina Quinasas/genética , Hibridación Fluorescente in Situ , Proteínas Proto-Oncogénicas/genética , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Nevo de Células Epitelioides y Fusiformes/genética , Fosfoproteínas/genética , Péptidos y Proteínas de Señalización Intracelular/genética
5.
Am J Dermatopathol ; 45(5): 289-299, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36898007

RESUMEN

ABSTRACT: Telomerase reverse transcriptase promoter mutations (TPMs) have been shown to be common in melanoma and uncommon in benign nevi. To assess the use of TPMs as an ancillary diagnostic tool, we report the concordance of the TPM status with the final diagnosis in clinical cases with distinct differential diagnostic scenarios: dysplastic nevus versus melanoma, atypical Spitz nevus versus melanoma, atypical deep penetrating nevus (DPN) versus melanoma, and atypical blue nevus versus malignant blue nevus. In a control cohort, we found a positive TPM in 51/70 (73%) of the total melanomas with the highest frequency in vertical growth phase melanoma cases. Conversely, only 2/35 (6%) dysplastic nevi in our control cases were TPM-positive and b were severely atypical dysplastic nevi. Our clinical cohort of 257 cases had a positive TPM in 24% of cases diagnosed as melanoma and in 1% of cases with a benign diagnosis. The overall concordance of the TPM status with the final diagnosis was 86%. The TPM status had the greatest concordance (95%) with the final diagnosis in the atypical DPN versus melanoma group, with the rest of the groups ranging between 50% and 88%. Overall, our results suggest that TPMs are most useful in the differential diagnosis of atypical DPN versus melanoma. It also has some value in the differential diagnosis of atypical Spitz tumor versus melanoma and dysplastic nevus versus melanoma, whereas in our cohort, it did not contribute meaningfully to differentiating malignant blue nevus and atypical blue nevus.


Asunto(s)
Síndrome del Nevo Displásico , Melanoma , Nevo Azul , Nevo de Células Epitelioides y Fusiformes , Nevo Pigmentado , Neoplasias Cutáneas , Telomerasa , Humanos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Síndrome del Nevo Displásico/patología , Nevo Azul/diagnóstico , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patología , Nevo Pigmentado/patología , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/genética , Diagnóstico Diferencial , Telomerasa/genética
6.
Genes Chromosomes Cancer ; 61(2): 71-80, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34668265

RESUMEN

MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.2), the classic MECOM rearrangements resulting in RPN1-MECOM rearrangement with Mecom overexpression and GATA2 haploinsufficiency, define the distinct subtype of acute myeloid leukemia (AML), and serve as presumptive evidence for myelodysplastic syndrome based on the current World Health Organization classification. Myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements have been found to be clinically aggressive, but comparative analysis of clinicopathologic and genomic features is limited. We retrospectively studied cohorts of myeloid neoplasms with classic and nonclassic MECOM rearrangements. Cases with classic rearrangements consisted predominantly of AML, often with inv(3) or t(3;3) as the sole chromosome abnormality, whereas the group of nonclassic rearrangements included a variety of myeloid neoplasms, often with complex karyotype without TP53 mutations and similarly dismal overall survival. Immunohistochemistry revealed Mecom protein overexpression in both groups, but overexpression in cases with nonclassic rearrangements was mediated through a mechanism other than GATA2 distal enhancer involvement typical for classic rearrangement. Our results demonstrated that myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements encompass a diverse group of diseases with poor clinical outcome, overexpression of Mecom protein as a result of the nonclassic mechanism of MECOM activation.


Asunto(s)
Reordenamiento Génico/genética , Leucemia Mieloide , Proteína del Locus del Complejo MDS1 y EV11 , Adulto , Anciano , Análisis Citogenético , Femenino , Genómica , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/genética , Leucemia Mieloide/patología , Proteína del Locus del Complejo MDS1 y EV11/genética , Proteína del Locus del Complejo MDS1 y EV11/metabolismo , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Adulto Joven
7.
Genet Med ; 23(9): 1656-1663, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33958749

RESUMEN

PURPOSE: CCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management. METHODS: An international collaboration (clinical, commercial, and research laboratories) was established to collect/share information on novel and previously published PHOX2B NPARM cases. Variants were categorized by type and gene location. Categorical data were analyzed with chi-square and Fisher's exact test; further pairwise comparisons were made on significant results. RESULTS: Three hundred two individuals with PHOX2B NPARMs were identified, including 139 previously unreported cases. Findings demonstrate significant associations between key phenotypic manifestations of CCHS and variant type, location, and predicted effect on protein function. CONCLUSION: This study presents the largest cohort of PHOX2B NPARMs and associated phenotype data to date, enabling genotype-phenotype studies that will advance personalized, anticipatory management and help elucidate pathological mechanisms. Further characterization of PHOX2B NPARMs demands longitudinal clinical follow-up through international registries.


Asunto(s)
Genes Homeobox , Proteínas de Homeodominio , Estudios de Asociación Genética , Proteínas de Homeodominio/genética , Humanos , Hipoventilación/congénito , Mutación , Apnea Central del Sueño
8.
BMC Infect Dis ; 21(1): 740, 2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344305

RESUMEN

BACKGROUND: We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease. CASE PRESENTATION: A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department. Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient's symptoms resolved with steroid therapy and expectant management. CONCLUSIONS: This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy.


Asunto(s)
COVID-19 , Linfadenitis Necrotizante Histiocítica , Linfadenopatía , Adulto , Diagnóstico Diferencial , Linfadenitis Necrotizante Histiocítica/complicaciones , Linfadenitis Necrotizante Histiocítica/diagnóstico , Humanos , Ganglios Linfáticos , Linfadenopatía/diagnóstico , Linfadenopatía/etiología , Masculino , SARS-CoV-2
9.
J Pediatr Hematol Oncol ; 43(6): e819-e825, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33769390

RESUMEN

The diagnostic criteria for juvenile myelomonocytic leukemia have recently been revised to include clinical findings and RAS-pathway gene mutations per the 2016 World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Differing clinical behaviors have been observed in cases with CBL versus other RAS-pathway gene (RAS-p) mutations, notably the patients with CBL mutations can be self-limiting with spontaneous resolution. Additional clinical characteristics and histopathologic findings between these subsets are less well-described. We performed a retrospective search and identified cases with either CBL or RAS-p mutations, as per targeted and/or massively parallel sequencing. Eight patients had sufficient material for review, including cytogenetic studies and peripheral blood, bone marrow aspirate, and/or biopsy with flow cytometry analyses. Three patients showed CBL mutations and lower percentages of hemoglobin F and peripheral blood absolute monocyte counts, lesser degrees of leukocytosis compared with the RAS-p cohort, and normal megakaryocyte morphology and myeloblast immunophenotypes. Two of these patients were managed with observation only and experienced resolution of their disease. The patients with RAS-p mutations had severe thrombocytopenia, moderate to severe anemia, and experienced variable clinical outcomes. Abnormal megakaryocyte morphology and decreased numbers of megakaryocytes were seen in cases with RAS-p mutations. In addition, 3 of 4 cases with flow cytometry data demonstrated aberrant CD7 expression in myeloblasts. Our study is the first to identify morphologic and immunophenotypic differences between juvenile myelomonocytic leukemia cases with CBL or RAS-p mutations, and further supports previous reports of significantly different clinical behaviors between these subsets of patients.


Asunto(s)
Leucemia Mielomonocítica Juvenil/genética , Mutación , Proteínas Proto-Oncogénicas c-cbl/genética , Proteínas ras/genética , Niño , Preescolar , Femenino , Humanos , Inmunofenotipificación , Lactante , Leucemia Mielomonocítica Juvenil/diagnóstico , Masculino
10.
Curr Neurol Neurosci Rep ; 20(7): 23, 2020 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-32445025

RESUMEN

PURPOSE OF REVIEW: Molecular testing has become essential for the optimal workup of central nervous system (CNS) tumors. There is a vast array of testing from which to choose, and it can sometimes be challenging to appropriately incorporate findings into an integrated report. This article reviews various molecular tests and provides a concise overview of the most important molecular findings in the most commonly encountered CNS tumors. RECENT FINDINGS: Many molecular alterations in CNS tumors have been identified over recent years, some of which are incorporated into the 2016 World Health Organization (WHO) classification and the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) updates. Array-based methylation profiling has emerged over the past couple of years and will likely replace much of currently used ancillary testing for diagnostic purposes. A combination of next-generation sequencing (NGS) panel and copy number array is ideal for diffuse gliomas and embryonal tumors, with a low threshold to employ in other tumor types. With the recent advances in molecular diagnostics, it will be ever more important for the pathologist to recognize the molecular testing available, which tests to perform, and to appropriately integrate results in light of clinical, radiologic, and histologic findings.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Glioma/diagnóstico , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Técnicas de Diagnóstico Molecular , Organización Mundial de la Salud
11.
J Pediatr Hematol Oncol ; 42(4): e258-e261, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31343482

RESUMEN

T-cell therapy-related acute lymphoblastic leukemia (T-t-ALL) is a rare condition associated with previous cytotoxic therapy for another disease. Here we report T-t-ALL with inv(11)(q21q23), which involves KMT2A and MAML2, a transcriptional coactivator of NOTCH proteins, that occurred after chemotherapy for Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. This case describes the youngest patient with T-t-ALL harboring inv(11)(q21q23) and is the first independent report following an initial series also occurring in children. Our results lend further support to the observation that the KMT2A-MAML2 fusion gene resulting from inv(11)(q21q23) is likely a recurrent cytogenetic abnormality in T-t-ALL and appears to be associated with pediatric cases.


Asunto(s)
Inversión Cromosómica , Cromosomas Humanos Par 11 , N-Metiltransferasa de Histona-Lisina/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Neoplasias Primarias Secundarias/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Transactivadores/genética , Preescolar , Humanos , Masculino , Neoplasias Primarias Secundarias/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
12.
Am J Med Genet A ; 179(3): 503-506, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30672101

RESUMEN

Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.


Asunto(s)
Enfermedades Asintomáticas , Variación Genética , Proteínas de Homeodominio/genética , Hipoventilación/congénito , Apnea Central del Sueño/diagnóstico , Apnea Central del Sueño/genética , Factores de Transcripción/genética , Femenino , Humanos , Hipoventilación/diagnóstico , Hipoventilación/genética , Hipoventilación/terapia , Masculino , Mutación , Linaje , Fenotipo , Apnea Central del Sueño/terapia
13.
Cancer ; 124(16): 3381-3389, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29905933

RESUMEN

BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase-deficient RCC (1.4%), and succinate dehydrogenase-deficient RCC (0.5%). Other subtypes included tuberous sclerosis-associated RCC (4.2%), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8%), thyroid-like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2%) or EB (TFEB) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018. © 2018 American Cancer Society.


Asunto(s)
Carcinoma de Células Renales/genética , Pruebas Genéticas , Oncología Médica/tendencias , Pediatría/tendencias , Adolescente , Adulto , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Niño , Preescolar , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Translocación Genética , Adulto Joven
17.
J Pediatr ; 184: 172-177.e1, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28410084

RESUMEN

OBJECTIVES: To determine whether certain characteristic electroencephalography (EEG) features are indicative of a genetic cause in early-life epilepsy. STUDY DESIGN: We enrolled a total of 100 patients with infantile-onset (<3 years) epilepsy due to known genetic cause (n = 50) and nongenetic cause (acquired, structural, or unknown, n = 50). The genetic group was classified into synaptopathies, channelopathies, mTOR (mammalian target of rapamycin)-opathies, and chromosomal abnormalities. The nongenetic group included epilepsy of unknown cause and structural abnormalities such as brain tumor, focal cortical dysplasia and encephalomalacia. The clinical features, magnetic resonance imaging, and video EEG obtained before 3 years of age and again at follow-up were reviewed. Specifically, the background rhythms and patterns of interictal epileptiform discharges were analyzed to define the EEG characteristics. RESULTS: The genetic group was more likely to have seizure recurrence beyond infancy and significant developmental delay (P <.01). The genetic and nongenetic groups showed different EEG patterns in the initial EEGs that persisted in follow-up EEGs. Diffuse slowing with pleomorphic focal/multifocal epileptiform discharges were present more often in the genetic (86%) compared with the nongenetic group (20%) in the initial EEGs (P <.01). The last available follow-up EEG features were similar (81% in genetic versus 17% in nongenetic) to the EEG performed prior to 3 years of age. CONCLUSIONS: Our findings suggest a simple guide for genetic screening in children with early-onset epilepsy. Genetic testing may be indicated and useful in infants with delayed development, no obvious cause, and significant EEG background slowing with pleomorphic focal or multifocal epileptiform discharges.


Asunto(s)
Electroencefalografía , Epilepsia/diagnóstico por imagen , Epilepsia/genética , Mutación , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos
18.
Pediatr Blood Cancer ; 64(9)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28266766

RESUMEN

Patients with acute myeloid leukemia (AML) who relapse after hematopoietic stem cell transplantation (HCT) have dismal outcomes. Our ability to predict those at risk for relapse is limited. We examined chimerism trends post-HCT in 63 children who underwent HCT for AML or myelodysplastic syndrome (MDS). Mixed T-cell chimerism at engraftment and absence of chronic graft versus host disease (cGVHD) were associated with relapse (P = 0.04 and P = 0.02, respectively). Mixed T-cell chimerism at engraftment was predictive in patients without cGVHD (P = 0.03). Patients with engraftment mixed T-cell chimerism may warrant closer disease monitoring and consideration for early intervention.


Asunto(s)
Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/terapia , Linfocitos T/inmunología , Adolescente , Niño , Preescolar , Quimerismo , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Quimera por Trasplante , Adulto Joven
19.
Genes Chromosomes Cancer ; 55(5): 442-51, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26773439

RESUMEN

Knowledge of the clinicopathological and molecular spectrum of pediatric renal cell carcinomas (RCC) remains limited, and approximately 16%-24% of these neoplasms cannot be classified into specific subtypes. In this review of 168 pediatric RCC prospectively registered on Children's Oncology Group AREN03B2 protocol, six RCC (3.5%) that demonstrated a unique epithelioid morphology and a peculiar immunophenotypic profile that includes expression of ALK, TFE3, and retention of INI1 was identified. Further investigation revealed ALK rearrangements in all cases, manifested molecularly by fusion transcripts of either VCL-ALK (3 patients all with sickle cell trait which had been previously reported) or TPM3-ALK (3 patients, none with sickle cell trait). Based on the shared unique morphologic, immunophenotypic, and genetic features, it was proposed that these neoplasms belonged to a distinct subgroup of RCC frequently occurring in pediatric patients, which they have termed as ALK-rearranged RCC. Importantly, additional therapeutic options may be available for these patients.


Asunto(s)
Carcinoma de Células Renales/genética , Orden Génico , Neoplasias Renales/genética , Proteínas Tirosina Quinasas Receptoras/genética , Quinasa de Linfoma Anaplásico , Niño , Humanos , Hibridación Fluorescente in Situ
20.
Am J Dermatopathol ; 38(11): 842-845, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27763904

RESUMEN

Mammary analog secretory carcinoma (MASC) is a recently described tumor of the salivary glands named for its morphological and molecular similarity to secretory carcinoma of the breast. Many primary carcinomas arising from the adnexal glands also share similar morphology to those arising from the breast. Brandt et al first described primary cutaneous MASC in 2009 and since then only 2 other cases have been reported. Herein, we describe a long-standing mass on the arm of an otherwise healthy 40-year-old female. Histologic examination revealed a circumscribed but unencapsulated, nodular tumor composed of bland epithelial cells arranged in solid and microcystic growth patterns. The cells showed vacuolated cytoplasm and round to oval nuclei with vesicular chromatin. Intraluminal homogenous eosinophilic secretions were present. Mitotic figures were not identified. The tumor cells stained positive for CK8/18, CK7, and S100 but were negative for other markers performed, including estrogen receptor, progesterone receptor, HER2/neu, paired box 8 (PAX8), and thyroid transcription factor 1 (TTF1). As the patient clinically had no other masses or known carcinomas, a diagnosis of primary cutaneous MASC was rendered. The ETV6-NTRK3 fusion transcript was subsequently detected by reverse transcriptase polymerase chain reaction amplification, further supporting the diagnosis. We present this case to review the histologic features of MASC and highlight the importance of recognizing this lesion not only as a possible cutaneous metastasis but also as a primary cutaneous tumor.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Carcinoma/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Cutáneas/genética , Translocación Genética , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma/química , Carcinoma/patología , Carcinoma/cirugía , Humanos , Inmunohistoquímica , Valor Predictivo de las Pruebas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/química , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía
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