Imaging Cancer in Neuroradiology

Neuroimaging plays a pivotal role in the diagnosis, management, and prognostication of brain tumors. Recently, the World Health Organization published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS5), which places greater emphasis on tumor genetics and molecular markers to complement the existing histological and immunohistochemical approaches. Recent advances in computational power allowed modern neuro-oncological imaging to move from a strictly morphology-based discipline to advanced neuroimaging techniques with quantifiable tissue characteristics such as tumor cellularity, microstructural organization, hemodynamic, functional, and metabolic features, providing more precise tumor diagnosis and management. The aim of this review is to highlight the key imaging features of the recently published CNS5, outlining the current imaging standards and summarizing the latest advances in neuro-oncological imaging techniques and their role in complementing traditional brain tumor imaging and management.     

Depressive symptoms and executive function in relation to survival in patients with glioblastoma

Journal of Neuro-Oncology - With the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), diagnosis of glioma is based on molecular parameters in...     

Molecular pathology of tumors of the central nervous system

Since the update of the 4th edition of the WHO Classification of Central Nervous System (CNS) Tumors published in 2016, particular molecular characteristics are part of the definition of a subset of these neoplasms. This combined ‘histo-molecular’ approach allows for a much more precise diagnosis of especially diffuse gliomas and embryonal CNS tumors. This review provides an update of the most important diagnostic and prognostic markers for state-of-the-art diagnosis of primary CNS tumors. Defining molecular markers for diffuse gliomas are IDH1/IDH2 mutations, 1p/19q codeletion and mutations in histone H3 genes. Medulloblastomas, the most frequent embryonal CNS tumors, are divided into four molecularly defined groups according to the WHO 2016 Classification: wingless/integrated (WNT) signaling pathway activated, sonic hedgehog (SHH) signaling pathway activated and tumor protein p53 gene (TP53)-mutant, SHH-activated and TP53-wildtype, and non-WNT/non-SHH-activated. Molecular characteristics are also important for the diagnosis of several other CNS tumors, such as RELA fusion-positive subtype of ependymoma, atypical teratoid rhabdoid tumor (AT/RT), embryonal tumor with multilayered rosettes, and solitary fibrous tumor/hemangiopericytoma. Immunohistochemistry is a helpful alternative for further molecular characterization of several of these tumors. Additionally, genome-wide methylation profiling is a very promising new tool in CNS tumor diagnostics. Much progress has thus been made by translating the most relevant molecular knowledge into a more precise clinical diagnosis of CNS tumors. Hopefully, this will enable more specific and more effective therapeutic approaches for the patients suffering from these tumors.     

The Integrated Histopathologic and Molecular Approach to Adult-type Diffuse Astrocytomas: Status of the Art,Based on the 2021 WHO Classification of Central Nervous System Tumors

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) improved our understanding of the brain neoplasm biology. In more details, differences between diffuse gliomas that primarily occur in adults and those that primarily occur in children have been identified by the terms “adult-type” and “pediatric-type” diffuse gliomas. More importantly, both diagnostic and grading criteria for adult-type diffuse astrocytomas have been modified, by adopting novel molecular markers: diffuse astrocytomas, IDH-mutant have been grouped into a single entity and graded as CNS WHO grades 2, 3, or 4, with the assignment of Grade 4 in the presence of CDKN2A/B homozygous deletion, regardless of the histology [1]. Additionally, at least one of the following genetic alterations has been considered as sufficient to confer to astrocytomas, IDH wild type, a CNS WHO grade 4: i) TERT promoter mutation, ii) EGFR gene amplification, iii) combined gain of whole chromosome 7 and loss of whole chromosome 10 [+7/−10]. However, histology remains the solid basis to support these new complementary molecular data, and an integrated diagnosis is highly recommended.     

Consensus conference on cancer registration of brain and central nervous system tumors

The passage of Public Law 107-260, the Benign Brain Tumor Cancer Registries Amendment Act, in October 2002 has made the collection of all primary brain tumors a reality. However, at the first Consensus Conference on Brain Tumor Definition for Registration in 2002, and during the development of training materials for benign brain tumor collection, several issues were identified that were tabled for future discussion. These and other issues were addressed at the subsequent 2003 Consensus Conference on Cancer Registration of Brain and Central Nervous System Tumors, at which the Central Brain Tumor Registry of the United States facilitated a discussion among epidemiologists, neurosurgeons, and neuropathologists. Multidisciplinary consensus was reached on four points, for which the following recommendations were made: (1) amend the histology coding scheme for cysts and tumor-like lesions that currently have a code in the third edition of the International Classification of Disease for Oncology (ICDO), (2) collect data on all instances of specific cysts and tumor-like lesions that are located in brain and other CNS sites but currently lack ICDO codes, (3) establish a new ICDO topography site for skull base tumors for the brain and CNS, and (4) collect data on genetic syndromes in patients diagnosed with brain or CNS tumors. We view this conference as part of a continuing process. Because classification of primary intracranial and other CNS tumors is dynamic, and the registration and coding of these tumors will need to be periodically reviewed.     

Coexpression of glial and neuronal markers in the neurocytic rosettes of rosette-forming glioneuronal tumors

Rosette-forming glioneuronal tumor of the fourth ventricle (RGNT) is a new entity in the WHO 2007 Classification of Tumors of the Central Nervous System. RGNT has two components: neurocytic rosettes and low-grade gliomas. Neurocytic rosettes are conventionally described as consisting of uniform neurocytes. However, some studies have reported rosette-forming tumor cells that expressed glial markers such as Olig2. We indicated the expression of glial markers including Olig2, cyclinD1, glial fibrillary acidic protein (GFAP), and platelet-derived growth factor receptor alpha (PDGFRα) in the neurocytic rosettes in our previous study, and we suggested that these tumor cells had a heterogeneous nature. In this study, we used double and triple immunostaining to demonstrate that these tumor cells have both glial and neuronal characteristics. We found that rosette-forming tumor cells coexpressed Olig2/cyclinD1 and synaptophysin. Furthermore, the cores of the rosettes coexpressed GFAP/PDGFRα in the peripheral zone and synaptophysin in the central zone. These findings imply that rosette-forming tumor cells have a similar nature to neuronal-glial progenitor cells, and we believe that the nomination “neurocytic rosette” may be unsuitable given their heterogeneous nature. Our study appears to clarify some of the properties of RGNT tumor cells and may help elucidate the histogenesis of RGNT.     

WHO胸部肿瘤分类（第5版）中胸膜、心包及胸腺肿瘤部分解读

国际癌症研究机构（International Agency for Research on Cancer,IARC）于2021年5月出版了《WHO胸部肿瘤分类（第5版）》。与2015年出版的《WHO胸部肿瘤分类（第4版）》相比,《WHO胸部肿瘤分类（第5版）》变更了主要章节的框架,新增和调整部分疾病的命名和分类,并充实了流行病学、病因学、组织病理学和分子遗传学等相关内容。现就《WHO胸部肿瘤分类（第5版）》中胸膜、心包及胸腺肿瘤分类变化较大的内容予以简要介绍。     

2007年WHO神经系统肿瘤分类（第四版）几个新增肿瘤类型

2007年新修改的WHO关于神经系统肿瘤分类(第4版)共增加了七种新的肿瘤类型,包括血管中心性胶质瘤、毛细胞粘液样星形细胞瘤、垂体细胞瘤、乳头状胶质神经元肿瘤、第四脑室菊形团形成的胶质神经元肿瘤,松果体区乳头状肿瘤和腺垂体梭形细胞嗜酸细胞瘤,学习和掌握这些肿瘤的临床、形态、免疫和遗传学特点,对作好神经系统肿瘤的临床与病理诊断大有裨益。     

Understanding the Revised Fourth Edition of the World Health Organization Classification of Tumours of the Central Nervous System (2016) for Clinical Decision-making: A Guide for Oncologists Managing Patients with Glioma

The recognition of specific molecular prognostic factors has altered the management of primary brain tumours over the past decade. These factors have allowed stratification of morphologically similar tumours into different prognostic groups and are now also being used to determine clinical trial eligibility. Many of these factors have been included in the revised fourth edition of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System, released in May 2016. This revised edition places greater emphasis on molecular testing and, for certain tumour types, molecular testing is required for diagnosis. Many pathology departments have also adopted the four-tiered report format suggested in the Haarlem guidelines, and provide a final ‘integrated diagnosis’ incorporating a morphological diagnosis, the WHO grade and molecular findings. Pathologists need to perform and report these molecular tests in a timeframe that is relevant for clinical decision-making. Clinicians need to understand and incorporate these changes into their daily practice, as they have direct effects on both the type and intent of therapeutic interventions.     

WHO胸部肿瘤分类（第5版）中肺肿瘤部分解读

国际癌症研究机构（International Agency for Research on Cancer，IARC）于2021年5月出版了《WHO胸部肿瘤分类（第5版）》。与2015年出版的《WHO胸部肿瘤分类（第4版）》相比，《WHO胸部肿瘤分类（第5版）》变更了主要章节的框架，新增和调整了部分疾病的命名和分类，并充实了流行病学、病因学、组织病理学和分子遗传学等相关内容。现就《WHO胸部肿瘤分类（第5版）》中肺肿瘤分类变化较大的内容予以简要介绍。     

The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015

The 2021 WHO Classification of Thoracic Tumours was published earlier this year, with classification of lung tumors being one of the chapters. The principles remain those of using morphology first, supported by immunohistochemistry, and then molecular techniques. In 2015, there was particular emphasis on using immunohistochemistry to make classification more accurate. In 2021, there is greater emphasis throughout the book on advances in molecular pathology across all tumor types. Major features within this edition are (1) broader emphasis on genetic testing than in the 2015 WHO Classification; (2) a section entirely dedicated to the classification of small diagnostic samples; (3) continued recommendation to document percentages of histologic patterns in invasive nonmucinous adenocarcinomas, with utilization of these features to apply a formal grading system, and using only invasive size for T-factor size determination in part lepidic nonmucinous lung adenocarcinomas as recommended by the eighth edition TNM classification; (4) recognition of spread through airspaces as a histologic feature with prognostic significance; (5) moving lymphoepithelial carcinoma to squamous cell carcinomas; (6) update on evolving concepts in lung neuroendocrine neoplasm classification; (7) recognition of bronchiolar adenoma/ciliated muconodular papillary tumor as a new entity within the adenoma subgroup; (8) recognition of thoracic SMARCA4-deficient undifferentiated tumor; and (9) inclusion of essential and desirable diagnostic criteria for each tumor.     

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.     

2016年版WHO淋巴肿瘤分类概述

2016年WHO淋巴肿瘤的修订版问世,内容较2008年版有些变化.文章结合过去8年内的一些临床、病理、遗传学和分子生物学的进展,阐明了一些非常早期的淋巴增生性病变的诊断和临床处理,修饰了一些淋巴瘤的诊断标准,深化了遗传学/分子生物学在多种淋巴瘤诊治中的意义.新的分类中也加入了少数临时的淋巴瘤类型.     

Gliomatosis Cerebri

Gliomatosis Cerebri （GC） is a rare tumor of the central nervous system. It is defined as a diffuse glial tumor that extensively infiltrates the brain, involving more than two lobes. And it is listed as a subtype of astrocytic tumors according to the newest 2007 （4th edition） WHO classification of tumors of the Central Nervous System. GC can be subdivided into Type I and Type II. Clinical findings for patients with GC are usually subtle and nonspecific. The lesions of GC generally show hypo, or isodensity on CT; a poorly defined diffuse hypoor isointense signal on Tl-weighted images, and a scattered diffuse hyperintense signal on T2-weighted images. Histological examination of GC reveals widespread infiltration of neoplastic glial cells with minimal destruction of pre-existing structures. Diagnosis of GC can be ascertained on the basis of a combination of clinical, radiological and pathological data. The treatment of GC includes radiotherapy and chemotherapy; however, the optimal therapeutic strategy is still not well established and prognosis of GC remains poor. This report reviews in detail the aspects of GC mentioned above, and three controversial issues are also discussed in the report.     

Gliomatosis Cerebri

Gliomatosis Cerebri (GC) is a rare tumor of the central nervous system. It is defined as a diffuse glial tumor that extensively infiltrates the brain, involving more than two lobes. And it is listed as a subtype of astrocytic tumors according to the newest 2007 (4th edition) WHO classification of tumors of the Central Nervous System. GC can be subdivided into Type Ⅰ and Type Ⅱ. Clinical findings for patients with GC are usually subtle and nonspecific. The lesions of GC generally show hypo, or isodensity on CT; a poorly defined diffuse hypo-or isointense signal on T1-weighted images, and a scattere ddiffuse hyperintense signal on T2-weighted images. Histological examination of GC reveals widespread infiltration of neoplastic glial cells with minimal destruction of pre-existing structures.Diagnosis of GC can be ascertained on the basis of a combination of clinical, radiological and pathological data. The treatment of GC includes radiotherapy and chemotherapy; however, the optimal therapeutic strategy is still not well established and prognosis of GC remains poor. This report reviews in detail the aspects of GC mentioned above, and three controversial issues are also discussed in the report.     

The WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts. A commentary on the second edition.

The second edition of the WHO Histological Classification of Tumors of the Gallbladder and Extrahepatic Bile Ducts is more comprehensive and detailed than the previous one. Advances in our understanding of dysplasia, carcinoma in situ, various lines of differentiation among the carcinomas, and the recognition of a variety of tumor-like lesions have resulted in more than three times as many entities in the current classification as in the previous one. The new edition should facilitate pathologic, epidemiologic, and therapeutic comparisons.     

The 2021 WHO Classification of Tumors of the Pleura: Advances Since the 2015 Classification

Substantial changes in the 2021 WHO Classification of Tumors of the Pleura and Pericardium since the 2015 WHO Classification include the following: (1) pleural and pericardial tumors have been combined in one chapter whereas in the 2015 WHO, pericardial tumors were classified with cardiac tumors; (2) well-differentiated papillary mesothelioma has been renamed well-differentiated papillary mesothelial tumor given growing evidence that these tumors exhibit relatively indolent behavior; (3) localized and diffuse mesothelioma no longer include the term “malignant” as a prefix; (4) mesothelioma in situ has been added to the 2021 classification because these lesions can now be recognized by loss of BAP1 and/or MTAP by immunohistochemistry and/or CDKN2A homozygous deletion by fluorescence in situ hybridization; (5) the three main histologic subtypes (i.e., epithelioid, biphasic, and sarcomatoid) remain the same but architectural patterns and cytologic and stromal features are more formally incorporated into the 2021 classification on the basis of their prognostic significance; (6) nuclear grading for epithelioid diffuse mesothelioma is introduced, and it is recommended to record this and other histologically prognostic features in pathology reports; (7) BAP1, EZH2, and MTAP immunohistochemistry have been found to be useful in separating benign mesothelial proliferations from mesothelioma; (8) biphasic mesothelioma can be diagnosed in small biopsies having both epithelioid and sarcomatoid components even if the amount of one component is less than 10%; and (9) the most frequently altered genes in diffuse pleural mesothelioma include BAP1, CDKN2A, NF2, TP53, SETD2, and SETDB1.     

The World Health Organization's Histological Classification of Lung Tumors: a comparison of the first and second editions

Revision of the WHO Histological Classification of Lung Tumors of 1967 has resulted in the 1981 publication of the second edition. The main features of the revisions have been summarized. Squamous cell carcinoma (epidermoid carcinoma) has the same definition as in the original version, ie, the identification of keratin and/or intercellular bridges by light microscopy. Three degrees of histological differentiation have been described. Dysplasia and carcinoma in situ have been discussed. Small cell carcinoma has been divided into oat cell carcinoma, an intermediate cell type and a category for oat cell carcinomas combined with other major types. Adenocarcinoma includes the acinar, papillary and bronchiolo-alveolar forms, and the solid carcinomas with mucus formation (previously part of the large cell carcinoma group). A number of less common tumors and tumor-like lesions have been defined. None of the changes in the revision are considered to be a major departure from the original classification. This is intended in order to preserve comparability between data collected with each edition. The need for utilizing standardized nomenclature, diagnostic criteria, and tabulation formats is stressed.     

Imaging correlates for the 2016 update on WHO classification of grade II/III gliomas: implications for IDH, 1p/19q and ATRX status

The 2016 World Health Organization Classification of Tumors of the Central Nervous System incorporates the use of molecular information into the classification of brain tumors, including grade II and III gliomas, providing new prognostic information that cannot be delineated based on histopathology alone. We hypothesized that these genomic subgroups may also have distinct imaging features. A retrospective single institution study was performed on 40 patients with pathologically proven infiltrating WHO grade II/III gliomas with a pre-treatment MRI and molecular data on IDH, chromosomes 1p/19q and ATRX status. Two blinded Neuroradiologists qualitatively assessed MR features. The relationship between each parameter and molecular subgroup (IDH-wildtype; IDH-mutant-1p/19q codeleted-ATRX intact; IDH-mutant-1p/19q intact-ATRX loss) was evaluated with Fisher’s exact test. Progression free survival (PFS) was also analyzed. A border that could not be defined on FLAIR was most characteristic of IDH-wildtype tumors, whereas IDH-mutant tumors demonstrated either well-defined or slightly ill-defined borders (p?=?0.019). Degree of contrast enhancement and presence of restricted diffusion did not distinguish molecular subgroups. Frontal lobe predominance was associated with IDH-mutant tumors (p?=?0.006). The IDH-wildtype subgroup had significantly shorter PFS than the IDH-mutant groups (p?<?0.001). No differences in PFS were present when separating by tumor grade. FLAIR border patterns and tumor location were associated with distinct molecular subgroups of grade II/III gliomas. These imaging features may provide fundamental prognostic and predictive information at time of initial diagnostic imaging.