Educational Case: Histologic and Molecular Features of Diffuse Gliomas

Zhang, Sarah; William, Christopher

doi:10.1177/2374289520914021

Cited by 5 publications

(6 citation statements)

References 55 publications

(72 reference statements)

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“…To create an ideal preclinical model for BRAF V600E -mutated LGG that represents the complex and dynamic tumor microenvironment of malignant transformation, the grading and classification of gliomas need to be recapitulated as closely as possible in animal models. As indicated in Figure 3 , the WHO grading system consisting of cellular density, nuclear atypia, mitosis, necrosis, and endothelial proliferation is commonly used to evaluate malignancy based on the tumor’s histopathological appearance with high grade tumors having more aggressive microscopic features than low grade tumors ( 130 ). High grade tumors often have increased nuclear pleomorphism with variability in shape and size, as well as elongated, large, and hyperchromatic nuclei.…”

Section: Challenges For Establishing High-fidelity Braf V60...mentioning

confidence: 99%

Successes and challenges in modeling heterogeneous BRAFV600E mutated central nervous system neoplasms

Xing,

Panovska,

Petritsch

2023

Front. Oncol.

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Central nervous system (CNS) neoplasms are difficult to treat due to their sensitive location. Over the past two decades, the availability of patient tumor materials facilitated large scale genomic and epigenomic profiling studies, which have resulted in detailed insights into the molecular underpinnings of CNS tumorigenesis. Based on results from these studies, CNS tumors have high molecular and cellular intra-tumoral and inter-tumoral heterogeneity. CNS cancer models have yet to reflect the broad diversity of CNS tumors and patients and the lack of such faithful cancer models represents a major bottleneck to urgently needed innovations in CNS cancer treatment. Pediatric cancer model development is lagging behind adult tumor model development, which is why we focus this review on CNS tumors mutated for BRAFV600E which are more prevalent in the pediatric patient population. BRAFV600E-mutated CNS tumors exhibit high inter-tumoral heterogeneity, encompassing clinically and histopathological diverse tumor types. Moreover, BRAFV600E is the second most common alteration in pediatric low-grade CNS tumors, and low-grade tumors are notoriously difficult to recapitulate in vitro and in vivo. Although the mutation predominates in low-grade CNS tumors, when combined with other mutations, most commonly CDKN2A deletion, BRAFV600E-mutated CNS tumors are prone to develop high-grade features, and therefore BRAFV600E-mutated CNS are a paradigm for tumor progression. Here, we describe existing in vitro and in vivo models of BRAFV600E-mutated CNS tumors, including patient-derived cell lines, patient-derived xenografts, syngeneic models, and genetically engineered mouse models, along with their advantages and shortcomings. We discuss which research gaps each model might be best suited to answer, and identify those areas in model development that need to be strengthened further. We highlight areas of potential research focus that will lead to the heightened predictive capacity of preclinical studies, allow for appropriate validation, and ultimately improve the success of “bench to bedside” translational research.

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Section: Challenges For Establishing High-fidelity Braf V60...mentioning

confidence: 99%

Successes and challenges in modeling heterogeneous BRAFV600E mutated central nervous system neoplasms

Xing,

Panovska,

Petritsch

2023

Front. Oncol.

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“…Initially a low-grade tumour (Mixed glioma) was reported which came out to be of higher grade (Anaplastic Oligodendroglioma) due to high Ki67 index. Important histologic findings for glioma grading include nuclear atypia, mitotic activity, microvascular proliferation (MVP), and necrosis, as shown in investigations by Sarah Zhang et al 3 Nuclear atypia refers to nuclei that exhibit both size and shape variation (nuclear pleomorphism) as well as unusually thick chromatin (hyperchromasia). Grade II gliomas, the lowest subtype of gliomas, are characterised by little nuclear atypia and infrequent, if any, mitotic activity.…”

Section: Mixed Glioma (Who Grade Ii)mentioning

confidence: 99%

“…Sarah Zhang's research shows that Histopathological differences exist between diffuse astrocytomas and oligodendrogliomas, as stated in. 3 Increased nuclear pleomorphism (variability in size and form) and elongated, hyperchromatic (excessively dark nuclear staining) nuclei characterise diffuse astrocytomas. Dispersed tiny cystic spaces, known as microcystic alterations, may be seen as a distinct architectural pattern in.…”

Section: Pilocytic Astrocytoma and Diffuse Astrocytoma (Grade Iii)mentioning

confidence: 99%

Role of immunohistochemistry as a real mentor in diagnostic histopathology

Agarwal,

Ete,

Saxena

2023

IJPO

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: The goals and objectives of this study are to find out the number of cases where IHC was used to solve discrepant cases of histopathology. This gives an idea as to what percentage of cases required IHC for diagnostic evaluation. : This research is a combined retrospective and prospective analysis of a three-year time frame, beginning in January 2017 and ending in December 2019. Only those cases of benign and malignant neoplasms which have undergone IHC in our department are part of this study. Total of 67 cases were studied using routine H&E and IHC stain. Slides were evaluated by light microscopy. Using specific monoclonal or polyclonal antibodies, paraffin sections were stained immunohistochemically (IHC) using a Peroxidase antiperoxidase (PAP) technique.: There were a total of 23,558 biopsy reports made in the field of surgical pathology. Out of a total of 67 cases requested for IHC, 36 cases (53.7%) had histopathological diagnosis concordant with IHC diagnosis. While in 25 cases (37.31%) histopathological diagnosis was discordant with IHC diagnosis. In 6 cases (8.95%) conclusive diagnosis could not be derived.: From this study, we concluded that IHC plays a significant role in the definitive typing and grading of tumours. When trying to characterise a tumour, it's best to use an antigenic profile of both positive and negative markers, which may be achieved by a panel method consisting of well-chosen antibodies. It also brings about the conclusion that internal and external quality control plays an important part in routine Histopathology, which should not be undermined. Both QC and IHC must be made a routine part of Histopathology. Since we began comparing histology and IHC diagnosis three years ago, we've seen a significant uptick in the quality of our performance evaluations, patient care, and general laboratory practises.

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“…Diffuse astrocytomas (DAs) are slow growing, grade II tumours that are believed to arise from astrocytes in the cerebral hemisphere of the brain [47,48]. As its name suggests these tumour cells have the tendency to grow and infiltrate normal, healthy tissue making them difficult to remove completely during surgery [49].…”

Section: Diffuse Astrocytomasmentioning

confidence: 99%

“…Appearance of the tissue is only moderately different from a normal brain, however, cells appear abnormal under the microscope and slightly increased in number [50]. Some common symptoms associated with diffuse astrocytoma's include headaches and seizures [47]. Additional symptoms may occur and are dependent on the location and size of the tumour as well as its impact on a patient's neurological function.…”

Section: Diffuse Astrocytomasmentioning

confidence: 99%

An Overview of Central Nervous System Tumours

Flepisi

Balmith

2021

SciMed. J.

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Central nervous system (CNS) tumours refer to tumours that occur in the tissues of the brain and/or spinal cord. These tumours arise as a result of abnormal growth of cells and may begin in different parts of the brain or spinal cord. There are many types of CNS tumours, which are further divided into subtypes. Despite decades of research conducted, CNS tumours remain among the deadliest of all cancers. It is most often challenging to treat these tumours, due to the risks involved, and biological characteristics associated with them. The classification, grading, and characterisation of CNS tumour plays a pivotal role in the management thereof. The current review provides an overview of CNS tumours, classification, grading and treatment, as well as their characterisation with specific focus on gliomas, ependymomas, oligodendrogliomas, meningiomas, medulloblastomas, schwannomas, gangliogliomas, and craniopharyngiomas. Doi: 10.28991/SciMedJ-2021-0304-8 Full Text: PDF

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Educational Case: Histologic and Molecular Features of Diffuse Gliomas

Cited by 5 publications

References 55 publications

Successes and challenges in modeling heterogeneous BRAFV600E mutated central nervous system neoplasms

Successes and challenges in modeling heterogeneous BRAFV600E mutated central nervous system neoplasms

Role of immunohistochemistry as a real mentor in diagnostic histopathology

An Overview of Central Nervous System Tumours

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