World Health Organization Blue Book Research Articles

Recent Advances in Genitourinary Tumors Updates From the 5th Edition of the World Health Organization Blue Book Series.

Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice. To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology. The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours. The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice.

A repository of grade 1 and 2 meningioma MRIs in a public dataset for radiomics reproducibility tests.

Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1×1×1 mm3 . The entire dataset was reviewed by a certified medical physicist. The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.

New WHO classification 2022: urinary bladder cancer

The new World Health Organization (WHO) classification of urogenital tumors is still primarily based on anatomic location, but is also a hierarchical taxonomic classification without separate chapters for tumors of the upper urinary tract and the urethra. It clarifies aspects regarding grading and noninvasive entities. It consolidates the use of the Paris system for urinary cytology as well as various subtypes/special types of neoplasms, and incorporates general concepts of the 5th edition of the WHO blue book. In addition to mesenchymal tumors, well-differentiated neuroendocrine tumors and neuroendocrine carcinomas are addressed in separate chapters. Papillary non-invasive low- and high-grade carcinomas and carcinoma in situ remain, while dysplasia and urothelial proliferation of unknown malignant potential (UPUMP) are no longer treated as separate entities. Former variants of urothelial carcinoma are now called subtypes and aberrant differentiation and special types are more precisely defined.

Updates in Histologic Grading of Urologic Neoplasms.

Tumor histology offers a composite view of the genetic, epigenetic, proteomic, and microenvironmental determinants of tumor biology. As a marker of tumor histology, histologic grading has persisted as a highly relevant factor in risk stratification and management of urologic neoplasms (ie, renal cell carcinoma, prostatic adenocarcinoma, and urothelial carcinoma). Ongoing research and consensus meetings have attempted to improve the accuracy, consistency, and biologic relevance of histologic grading, as well as provide guidance for many challenging scenarios. To review the most recent updates to the grading system of urologic neoplasms, including those in the 2016 4th edition of the World Health Organization (WHO) Bluebook, with emphasis on issues encountered in routine practice. Peer-reviewed publications and the 4th edition of the WHO Bluebook on the pathology and genetics of the urinary system and male genital organs. This article summarizes the recently updated grading schemes for renal cell carcinoma, prostate adenocarcinomas, and bladder neoplasms of the genitourinary tract.

Prostate cancer pathology: What has changed in the last 5 years.

Prostate cancer is the most frequent non-cutaneous malignancy in men in the United States. In the last few years, many recommendations have been made available from the 2014 International Society of Urologic Pathology consensus conference, 2016 World Health Organization blue book and 2018 8th edition of American Joint Committee on Cancer Staging System. Here, we focus on four topics which are considered relevant on the basis of their common appearance in routine practice, clinical importance and 'need to improve communication between pathology reports and clinicians': prostate cancer classification, prostate cancer grading, prostate cancer staging, and current definition of clinically significant prostate cancer. Tissue biomarkers that can predict significant disease and/or upgrading and tissue-based genomics for the purpose of diagnosis and prognosis are mentioned briefly.

Endocrine Tumors—Part 1

FigureFigureSince the third volume of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs was published in 2004, more than a decade ago, the following remarkable accomplishments have been achieved and included in the new fourth volume released in June of 2017. biologic behavior and prognosis new therapies and corresponding surrogate biomarkers immunophenotypes and molecular pathology genetic background of the tumors The new WHO volumes contain the following chapters: Tumors of the Pituitary Tumors of the Thyroid Gland Tumors of the Parathyroid Gland Tumors of the Adrenal Cortex Tumors of the Adrenal Medulla and Extra-adrenal Paraganglia Neoplasms of the Neuroendocrine Pancreas Inherited Tumor Syndromes In order to make new fourth WHO classification practically familiar among surgical pathologists and other professionals dealing with endocrine tumors, AJSP-RR is publishing 2 issues devoted to the fourth WHO classification of the endocrine tumors. Each chapter in WHO blue book has the structure with the items in order: Definition, Synonyms, Epidemiology, Etiology, Localization, Clinical Features (including diagnostic tests, Imaging), Macroscopy, Microscopy, Genetic Profile, Genetic Susceptibility, Prognosis, and Predictive Factors. This first AJSP-RR issue includes reviews on the following topics: (1) pituitary (Osamura), (2) medullary thyroid carcinoma (DeLellis), (3) nonmedullary thyroid cancers (Lam), and (4) adrenal cortex (Sasano). We have also included a case report devoted to cytopathology of paragangliomas. PITUITARY GLAND The fourth edition devotes attention to the transcription factors, which are involved in the differentiation pathways linked to particular hormone production; it has been shown that pituitary adenomas are derived from the differentiated anterior pituitary cells: somatotroph, lactotroph, thyrotroph, and so on. Therefore, the nomenclature of adenomas has been changed to somatotroph adenoma, lactotroph adenoma, thyrotroph adenoma, and others. The atypical adenoma category proposed in 2004 (Ki-67 >3% and p53 positive) is no longer included in the new WHO classification because its incidence is low and its significance for prognosis is not evident. Instead, the fourth edition proposes to use morphologic features that portend aggressive behavior, for example, sparsely granulated somatotroph adenoma with fibrous bodies, Crooke’s adenoma, and others. SSTR2, SSTR5, MGMT, and MSH6 are the predictive biomarkers that can be detected by immunohistochemistry. Familial tumor syndromes include 10 genetic alterations, and growth hormone (GH), prolactin (PRL) production in these conditions has been emphasized. THYROID Epithelial tumors: The most important achievement in the area of thyroid pathology is molecular genetics characterization of well-differentiated, follicular-patterned thyroid tumors composed of follicular cells with a differential diagnosis of papillary versus follicular and benign versus malignant. Several new categories have been introduced for papillary thyroid carcinoma. Several categories remained in the intermediate group between follicular adenoma versus follicular carcinoma/follicular variant of papillary carcinoma. These tumors sometimes are designated as “tumors of uncertain malignancy” and are still under discussion. “Noninvasive follicular thyroid neoplasm with papillary-like nuclear features” was adopted as a new terminology for the indolent tumors with particular nuclear appearance. Poorly differentiated carcinoma and oncocytoma were recognized as distinct entities. Medullary thyroid carcinoma is a unique tumor that produces calcitonin and carcinoembryonic antigen and is a part of multiple endocrine neoplasia type 2 syndrome. In the fourth edition, morphologic appearance is emphasized along with notable variants. Genetic molecular aberrations including RET and RAS are included in the discussion. ADRENAL CORTEX This review includes the Weiss criteria for malignancy in adrenal cortical tumors and Weiss and Lin-Weiss-Bisceglia criteria of malignancy in oncocytic adrenal cortical neoplasms. It is noteworthy to mention that various molecular parameters can distinguish adenomas from carcinomas. Carcinomas can be further divided into good and poor prognostic groups. Various hereditary syndromes are also included in this review. IN THE SECOND INSTALLMENT OF THIS ISSUE The second installment of the endocrine topics will contain review articles reflecting the WHO 2017 positions on the following: tumors of the adrenal medulla and extra-adrenal paraganglia, neuroendocrine tumors of the pancreas and inherited endocrine tumor syndromes.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space.

Chapter3 "Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space" of the World Health Organization (WHO) Blue Book 2017 "Classification of Head and Neck Tumours" shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial-mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate- and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What Is New in the 2017 WHO Blue Book for Tumors and Tumor-Like Lesions of the Neck and Lymph Nodes.

The World Health Organization (WHO) 2017 Classification of Head and Neck Tumors ("Blue Book") will now include a new chapter on tumors and tumor-like lesions of the neck and lymph nodes, which was not included in the previous edition. Tumors and tumor-like lesions, including a variety of cysts and metastases, can arise in any component in the neck, including soft tissue, lymph nodes, and developmental remnants. The pathology and clinical features of metastatic carcinoma of unknown primary in the head and neck has changed dramatically in the last several years. Many of these tumors which were previously diagnosed as unknown primary are now identified as oropharyngeal and nasopharyngeal carcinomas related to human papillomavirus (HPV), less commonly to Epstein-Barr virus (EBV) and occasionally even to Merkel cell polyomavirus. Many unusual features can arise in these metastases, such as undifferentiated morphology, extensive cystic change with central degeneration, gland formation, and even ciliated cells. Rarely, carcinoma in the neck can arise in association with a heterotopic tissue, primarily thyroid or salivary gland tissue. Tumor-like lesions include branchial cleft cysts, thyroglossal duct cyst, dermoid and teratoid cyst, and ranula. Pathologists should be familiar with the diagnostic features and clinicopathologic corrections of these neck lesions in order to correctly diagnosis them and to provide for proper clinical management. This article will briefly describe the pathologic and clinical features of these entities as they are covered in the new 2017 Blue Book.

What is new in Genitourinary Pathology? Recent developments and highlights of the new 2016 World Health Organization classification of tumors of the urinary system and male genital organs

The recently published 2016 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs stems from the accumulated knowledge and data collected during the last 12 years, since the previous edition of the WHO “blue book” 2004. The major changes in prostate pathology include the introduction of a novel grading system for prostate cancer (Grade Groups/International Society of Urological Pathology (ISUP) grades 1–5), the recognition of intraductal carcinoma as a new entity, and the terminological changes regarding the neuroendocrine prostatic neoplasms. In bladder and urothelial tract, within the spectrum of flat and non-invasive lesions, a newly introduced term “urothelial proliferation of uncertain malignant potential” replaced the term “urothelial hyperplasia”, and the term “urothelial dysplasia” was better defined. A category of “invasive urothelial carcinoma with divergent differentiation” was introduced for tumors showing a component of “usual type” urothelial carcinoma combined with other morphologies. A new WHO/ISUP renal tumor grading system was recommended (Grade 1–4). The definition of renal papillary adenoma was modified and expanded to include papillary neoplasms measuring up to 1.5 cm. Several new epithelial renal tumors were recognized as new entities including: hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome–associated RCC, succinate dehydrogenase–deficient RCC, tubulocystic RCC, acquired cystic disease–associated RCC, and clear cell papillary RCC. In testis pathology, intratubular proliferations of testicular germ cell tumors were renamed as “germ cell neoplasia in-situ” (GCNIS), and the testicular neoplasms were divided into two main groups: derived from or unrelated to GCNIS. A major change in penile pathology was the introduction of a new classification of penile squamous cell carcinoma, based on the presence of human papillomavirus (HPV), which characterizes penile tumor subtypes as HPV-related or non-HPV-related. A similar distinction was introduced for the preneoplastic penile intraepithelial precursor lesion (PeIN) into non-HPV related (differentiated PeIN) and HPV-related types (undifferentiated PeIN). In this review, we provide a summary and highlight the changes in the genitourinary pathology introduced by the 2016 WHO blue book, and we also discuss some recent developments that may impact the practice of genitourinary pathology in the near future.

Genomic Correlates to the Newly Proposed Grading Prognostic Groups for Prostate Cancer

Recommendations by the International Society of Urologic Pathology and 2016 World Health Organization blue book propose the use of a five-tiered prostate cancer (PCa) grading system. The five prognostic grade groupings (PGGs) ranging from 1 to 5 are defined as Gleason grades ≤6, 3+4, 4+3, 8, and >8, respectively. Recent work suggests that each group is associated with a distinct risk of biochemical PCa recurrence. In this study, we sought genomic support for PGGs using whole-exome and whole-genome sequencing data for 426 clinically localized PCas treated by radical prostatectomy. After adjustment for tumor purity for the sequencing data, we observed a significant frequency increase in genomic amplifications and deletions (p=0.013) and in nonsynonymous point mutations (p=0.008) with increasing risk group. Interestingly, PGG1 (low risk) was entirely haploid, whereas PGG2–5 exhibited increasing polyploidy frequency. Principal component analysis of genomic profiles revealed that PGG1, PGG2, and PGG3 represent distinct classes, but PGG4 and PGG5 exhibit genomic similarity. Together, these observations for the largest PCa genomic data set to date provide support for increasing genomic alterations with increasing PGG. This is the first genomic correlation of the PGG system. Future work will need to explore the clinical utility of PGGs in prospective studies with long-term follow-up. Patient summaryGleason grading for prostate cancer provides important information for guiding clinical care. A new proposal by leading pathologists favors translating Gleason grades into five risk categories. In this study, a comprehensive analysis of the largest genomic data set on prostate cancer to date, we demonstrate molecular support for this new five-tiered system.

Pheochromocytoma and Extra-adrenal Paraganglioma: Updates

Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These developments are concurrent with the publication and dissemination of the 2004 World Health Organization bluebook on pathology and genetics of endocrine tumors. To summarize new information required by pathologists for effective participation in patient management and research. Literature review and primary material from Tufts Medical Center. The World Health Organization reserves the term pheochromocytoma for tumors arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often adrenergic phenotype, relatively low rate of malignancy, and predilection to occur in particular hereditary syndromes. Malignancy is defined by presence of metastases not local invasion. Occult germline mutations characteristic of familial syndromes are now found in more than 20% of patients with apparently sporadic tumors, bringing the percentage of tumors with a known genetic basis close to 30%. In addition, tumor location and risk of malignancy vary with the underlying genetic defect. The "10 percent rule" for pheochromocytoma/paraganglioma--10% familial, 10% malignant, 10% extra-adrenal--is therefore no longer tenable. Current roles of pathology are limited to diagnosing primary or metastatic tumors and identifying features suggestive of malignant potential or hereditary disease. Future roles may involve more definitive assessment of malignancy, genotype-phenotype correlation, and identification of targets for therapy.

Pheochromocytoma and Extra-adrenal Paraganglioma: Updates

Abstract Context.—Advances in genetics and gene expression profiling have led to new ways of thinking about the pathobiology of pheochromocytoma and extra-adrenal paraganglioma. These developments are concurrent with the publication and dissemination of the 2004 World Health Organization bluebook on pathology and genetics of endocrine tumors. Objective.—To summarize new information required by pathologists for effective participation in patient management and research. Data Sources.—Literature review and primary material from Tufts Medical Center. Conclusions.—The World Health Organization reserves the term pheochromocytoma for tumors arising from chromaffin cells in the adrenal medulla. Closely related tumors in extra-adrenal sympathetic and parasympathetic paraganglia are classified as extra-adrenal paragangliomas. A pheochromocytoma is an intra-adrenal sympathetic paraganglioma. Although arbitrary, this nomenclature emphasizes important distinctive properties of intra-adrenal tumors, including an often...

Surgical Neuropathology Update: A Review of Changes Introduced by the WHO Classification of Tumours of the Central Nervous System, 4th Edition

The World Health Organization (WHO) recently published its 4th edition of the classification of tumors of the central nervous system, incorporating a substantial number of important changes to the previous version (WHO 2000). The new WHO classification introduces 7 changes in the grading of central nervous system neoplasms, ranging in significance from minor to major, in categories of anaplastic oligoastrocytomas, meningiomas, choroid plexus tumors, pineal parenchymal tumors, ganglioglioma, cerebellar liponeurocytoma, and hemangiopericytomas. The 4th edition also introduces 10 newly codified entities, variants, and patterns, as well as 1 new genetic syndrome. A number of established brain tumors are reorganized, including medulloblastomas and primitive neuroectodermal tumors, in an attempt to more closely align classification with current understanding of central nervous system neoplasia. To summarize and discuss the most significant updates in the 4th edition for the practicing surgical pathologist, including (1) changes in grading among established entities; (2) newly codified tumor entities, variants, patterns, and syndromes; and (3) changes in the classification of existing brain tumors. The primary source for this review is the WHO Classification of Tumours of the Central Nervous System, 4th edition. Other important sources include the 3rd edition of this book and the primary literature that supported changes in the 4th edition. The new edition of the WHO blue book reflects advancements in the understanding of brain tumors in terms of classification, grading, and new entities. The changes introduced are substantial and will have an impact on the practice of general surgical pathologists and neuropathologists.

The WHO Classification of Tumors of the Nervous System

The new World Health Organization (WHO) classification of nervous system tumors, published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma. Several histological variants were added, including tanycytic ependymoma, large cell medulloblastoma, and rhabdoid meningioma. The WHO grading scheme was updated and, for meningiomas, extensively revised. In recognition of the emerging role of molecular diagnostic approaches to tumor classification, genetic profiles have been emphasized, as in the distinct subtypes of glioblastoma and the already clinically useful 1p and 19q markers for oligodendroglioma and 22q/INI1 for atypical teratoid/rhabdoid tumors. In accord with the new WHO Blue Book series, the actual classification is accompanied by extensive descriptions and illustrations of clinicopathological characteristics of each tumor type, including molecular genetic features, predictive factors, and separate chapters on inherited tumor syndromes. The 2000 WHO classification of nervous system tumors aims at being used and implemented by the neuro-oncology and biomedical research communities worldwide.