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1.
Curr Neurol Neurosci Rep ; 20(7): 23, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32445025

RESUMO

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.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Glioma/diagnóstico , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas de Diagnóstico Molecular , Organização Mundial da Saúde
2.
Pediatr Blood Cancer ; 66(1): e27484, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270496

RESUMO

CD5 antigen expression in B-cell acute lymphoblastic leukemia (B-ALL) is exceptionally rare. There are six detailed case reports in the literature, with only 16 cases described. Case series analyzing the frequency of aberrant B-ALL immunophenotypes suggest that this variant may occur in as little as 2-4.5% of all B-ALL cases, with one series having no CD5+ positive cases. Herein we report a case of CD5+ B-ALL in a 15-year-old female, and review the previously reported cases. As limited information is available, more data from prospective clinical trials are required to determine whether CD5 positivity portends a poorer prognosis.


Assuntos
Antígenos CD5/metabolismo , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Evolução Fatal , Feminino , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
3.
Transfusion ; 58(2): 456-460, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29230832

RESUMO

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.


Assuntos
Leucaférese , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Complicações Neoplásicas na Gravidez/terapia , Adulto , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Complicações Neoplásicas na Gravidez/diagnóstico
4.
J Alzheimers Dis ; 92(1): 241-260, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744338

RESUMO

BACKGROUND: Phosphorylated cytoplasmic tau inclusions correlate with and precede cognitive deficits in Alzheimer's disease (AD). However, pathological tau accumulation and relationships to synaptic changes remain unclear. OBJECTIVE: To address this, we examined postmortem brain from 50 individuals with the full spectrum of AD (clinically and neuropathologically). Total tau, pTau231, and AMPA GluR1 were compared across two brain regions (entorhinal and middle frontal cortices), as well as clinically stratified groups (control, amnestic mild cognitive impairment, AD dementia), NIA-AA Alzheimer's Disease Neuropathologic Change designations (Not, Low, Intermediate, High), and Braak tangle stages (1-6). Significant co-existing pathology was excluded to isolate changes attributed to pathologic AD. METHODS: Synaptosomal fractionation and staining were performed to measure changes in total Tau, pTau231, and AMPA GluR1. Total Tau and pTau231 were quantified in synaptosomal fractions using Quanterix Simoa HD-X. RESULTS: Increasing pTau231 in frontal postsynaptic fractions correlated positively with increasing clinical and neuropathological AD severity. Frontal cortex is representative of early AD, as it does not become involved by tau tangles until late in AD. Entorhinal total tau was significantly higher in the amnestic mild cognitive impairment group when compared to AD, but only after accounting for AD associated synaptic changes. Alterations in AMPA GluR1 observed in the entorhinal cortex, but not middle frontal cortex, suggest that pTau231 mislocalization and aggregation in postsynaptic structures may impair glutamatergic signaling by promoting AMPA receptor dephosphorylation and internalization. CONCLUSION: Results highlight the potential effectiveness of early pharmacological interventions targeting pTau231 accumulation at the postsynaptic density.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/patologia , Proteínas tau/metabolismo , Densidade Pós-Sináptica/metabolismo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Encéfalo/patologia , Disfunção Cognitiva/patologia
6.
Chin Clin Oncol ; 10(4): 38, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118826

RESUMO

In 2016, the World Health Organization (WHO) released the most recent update to the classification of central nervous system tumors. This update has led to the reshaping of tumor identification and subsequently changed current understanding of treatment options for patients. Moreover, the restructuring of the classification of central nervous system tumors to include molecular markers has led to the need to re-evaluate how to interpret pivotal trials. These trials originally enrolled patients purely based upon histologic diagnoses without the use of adjunctive, and frequently diagnostic molecular testing. With this new paradigm also comes the need to assess how one should incorporate molecular markers into current trials as well as shape future trials. First, we will discuss updates on the molecular classification of glioblastoma (GBM) (and its histologic mimics). This will be followed by a review of key pivotal trials which have defined our standard of care for glioblastoma within the context of molecular classification of their study populations. This will be followed by preliminary results of ongoing phase 3 cooperative group trials for high-grade gliomas that were initiated prior to routine molecular classification of tumors and how one could interpret these results in light of advances in molecular classification. Finally, we will end with suggestions for future clinical trial design with a focus on enrollment based upon molecular diagnostics.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/terapia , Ensaios Clínicos como Assunto , Glioblastoma/classificação , Glioblastoma/terapia , Glioma/classificação , Glioma/terapia , Humanos , Técnicas de Diagnóstico Molecular , Organização Mundial da Saúde
7.
Acta Neuropathol Commun ; 9(1): 61, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827698

RESUMO

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Retinoblastoma/patologia , Ubiquitina-Proteína Ligases/genética , Rearranjo Gênico , Genes do Retinoblastoma/genética , Humanos , Lactente , Masculino , Proteínas de Fusão Oncogênica
8.
Ther Apher Dial ; 24(2): 215-220, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31211482

RESUMO

High-quality evidence supporting clinical practice is lacking in apheresis. A potential source of evidence is provided by abstracts submitted to the Annual Meetings of the American Association of Blood Banks (AABB) and the American Society for Apheresis (ASFA). However, there is potential for study conclusions to be altered significantly following abstract presentations prior to publications in peer-reviewed journals. Therefore, we evaluated the discordance rate between apheresis-related meeting abstracts and their corresponding published articles. Abstracts accepted to either AABB or ASFA Annual Meetings from 2005 to 2012 and corresponding PubMed-indexed peer-reviewed articles' abstracts published prior to 9/2014 were reviewed for altered methods, results, and conclusions. When present, changes were evaluated for clinical significance. During the 8-year period, 198 out of 1152 abstracts were published as peer-reviewed articles. Of these, 36 (18.2%) presented discordant results, six of which (16.7%) were potentially clinically significant. An alteration in results (58.3%) was the leading reason for discordance. The discordance rate for ASFA abstracts was significantly higher (HR = 4.69, P = 0.0028) than the AABB ones. However, clinically significant alterations occurred more frequently among AABB abstracts (P = 0.025). Approximately 18% of meeting abstracts demonstrated alterations prior to publication in peer-reviewed journals. Given that approximately one in six changes represented clinically significant alterations, potentially affecting clinical practice, we recommend caution when modifying one's clinical practice based on abstract presentations at Annual Meetings. Future studies involving abstracts from both the International Society for Apheresis and the World Apheresis Association should also be performed.


Assuntos
Indexação e Redação de Resumos/normas , Remoção de Componentes Sanguíneos , Revisão da Pesquisa por Pares/normas , Publicações Periódicas como Assunto/estatística & dados numéricos , Congressos como Assunto , Humanos , Editoração/estatística & dados numéricos , Sociedades Médicas
9.
Int J Pediatr Otorhinolaryngol ; 129: 109785, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31770666

RESUMO

A 15-year-old female presented for evaluation of progressive hearing loss over a year. Computed tomographic imaging revealed a 11 x 6 × 6 mm osseous lesion with 'groundglass' appearance within the left posterior petrous bone lateral to vestibular aqueduct suspicious for an endolymphatic sac tumor. Surgical excision revealed fibrous dysplasia on histological analysis. Fibrous dysplasia of the temporal bone is not uncommon, but few cases of extension causing sensorineural hearing loss exist in the literature. We describe the first reported case of fibrous dysplasia mimicking an endolymphatic sac tumor; interestingly, the patient also showed hearing improvement immediately following removal.


Assuntos
Neoplasias da Orelha/diagnóstico por imagem , Displasia Fibrosa Óssea/complicações , Displasia Fibrosa Óssea/diagnóstico por imagem , Perda Auditiva Neurossensorial/etiologia , Adolescente , Diagnóstico Diferencial , Saco Endolinfático , Feminino , Displasia Fibrosa Óssea/patologia , Displasia Fibrosa Óssea/cirurgia , Humanos , Osso Petroso/patologia , Tomografia Computadorizada por Raios X
10.
Lab Med ; 50(2): 208-211, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30169652

RESUMO

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.


Assuntos
Anticoagulantes/uso terapêutico , Fondaparinux/uso terapêutico , Trombocitopenia/tratamento farmacológico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Monitoramento de Medicamentos , Feminino , Fondaparinux/administração & dosagem , Heparina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Curva ROC , Trombocitopenia/induzido quimicamente
11.
Lab Med ; 48(2): 108-112, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28444398

RESUMO

Many studies have suggested that inappropriate plasma usage is common. An important factor contributing to futile plasma administration in most patients is the nonlinear relationship between coagulation-factor levels and the volume of plasma transfused. In this review, a validated mathematical model and data from the literature will be used to illuminate 3 key properties of plasma transfusion. Those properties are as follows: the effect of plasma transfusion on international normalized ratio (INR) is transient; for the same volume of transfused plasma, a greater reduction in INR is observed at higher initial INRs; and the effect of plasma transfusion on INR correction (ie, the difference between initial and final INRs) diminishes as more plasma is transfused. Frequent misunderstanding of these properties may contribute to inappropriate plasma usage. Therefore, this review will assist physicians in navigating these common pitfalls. Stronger understanding of these principles may result in a reduction of inappropriate plasma transfusions, thus potentially enhancing patient safety and reducing healthcare costs.


Assuntos
Transfusão de Componentes Sanguíneos , Humanos , Coeficiente Internacional Normatizado , Guias de Prática Clínica como Assunto , Tempo de Protrombina
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