Neuropathology Practice Research Articles

Glioblastoma: Morphologic and molecular genetic diversity

•Context.-Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification. Objective.-To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas. Data Sources.-Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed. Conclusions.-Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.

Glioblastoma

Abstract Context.—Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification. Objective.—To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas. Data Sources.—Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed. Conclusions.—Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.

Immunohistochemical Analysis of Metastatic Neoplasms of the Central Nervous System

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of "metastatic neoplasm." In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed.

Molecular Diagnostics in Central Nervous System Tumors

Central nervous system (CNS) neoplasms can be diagnostically challenging, due to remarkably wide ranges in histologic appearance, biologic behavior, and therapeutic approach. Nevertheless, accurate diagnosis is the critical first step in providing optimal patient care. As with other oncology-based specialties, there is a rapidly expanding interest and enthusiasm for identifying and utilizing new biomarkers to enhance the day-to-day practice of surgical neuropathology. In this regard, the field is primed by recent advances in basic research, elucidating the molecular mechanisms of tumorigenesis and progression in the most common adult and pediatric brain tumors. Thus far, few have made the transition into routine clinical practice, the most notable example being 1p and 19q testing in oligodendroglial tumors. However, the field is rapidly evolving and many other biomarkers are likely to emerge as useful ancillary diagnostic, prognostic, or therapeutic aids. The goal of this article is to highlight the most common genetic alterations currently implicated in CNS tumors, focusing most on those that are either already in common use in ancillary molecular diagnostics testing or are likely to become so in the near future.

PRINCIPLES AND PRACTICE OF NEUROPATHOLOGY. 2nd edition

PRINCIPLES AND PRACTICE OF NEUROPATHOLOGY. 2nd edition Edited by J. S. Nelson, H. Mena, J. E. Parisi and S. S. Schochet 2003. New York: Oxford University Press Price £135. Pp. 593. ISBN 0‐19‐512589‐4 With the rapid growth in our understanding of the molecular and pathological basis of neurological disorders, it has become increasingly difficult to include all aspects of neuropathology in one book. With the exception of a few books, such as Greenfield’s Neuropathology , most new neuropathology texts are restricted to specific areas of the speciality. This relatively slim volume aims to present readers with a concise and up‐to‐date overview of neuropathology, filling a particular niche in the market. It has been extensively rewritten by a number of eminent North American neuropathologists to include recent genetic and imaging data and with the addition of several chapters that were not included in the first edition, which was published 10 years ago. There is an introductory chapter outlining the basic procedures used in neuropathology and common pathological reactions, such as cerebral oedema, brain herniation and hydrocephalus, together with the cellular responses of neurons and glia to injury. Although the text is clear, some of the microscopic images are of poor quality, and attempting to show eosinophilic change in black and white seems rather pointless. This is followed by an extremely short (2½ pages) and not particularly useful chapter covering some …

Gamna-Gandy Bodies in Surgical Neuropathology Specimens: Observations and a Historical Note

Gamna-Gandy (G-G) bodies are classically defined as spheroidal yellow-brown foci consisting of dense fibrous tissue and collagenous fibers encrusted with iron pigments and calcium salts. These siderotic nodules were first described in the spleen early in the twentieth century and for a short time were considered to be caused by fungal infection due to the presence of unusual "bamboo-like and articulated" fibers in the lesions that vaguely mimicked mycelia forms. This notion was proven to be incorrect in the 1930s and G-G bodies are now considered to result from organization of small hemorrhages. Although originally reported in splenomegaly, G-G bodies are well-recognized findings in atrial myxomas where they form linear arrays of mineral-encrusted fibers, often at the edge of resolving hemorrhages. They rarely have been reported in lymph nodes, thymoma, thyroid adenoma, and renal cell carcinoma. Curiously, published examples of G-G bodies in central nervous system (CNS) neoplasms or vascular malformations have not appeared, despite the known tendency for bleeding, even recurrent episodes of bleeding, in several types of these lesions. Since 1999 I have accrued all the examples of G-G bodies that I have observed in my practice of surgical neuropathology. These cases are presented here and the historical aspects of the entity are reviewed.

Principles and Practice of Neuropathology (2nd edition)

Principles and Practice of Neuropathology (2nd edition)

Principles and Practice of Neuropathology, Second Edition

Principles and Practice of Neuropathology, Second Edition. Edited by James S. Nelson, Hernando Mena, Joseph E. Parisi, Sydney S. Schochet Jr. ©2003. Oxford University Press, Inc, 593 pp., $195.00. The second edition of Principles and Practice of Neuropathology by J. S. Nelson et al is welcome news for those of us involved in resident training and for the general pathologists who on occasion have to examine the nervous …

Cell proliferation and tumors of the central nervous system, part II: radiolabeling, cytometric, and immunohistochemical techniques.

A variety of techniques have been developed to evaluate cell proliferation. Many of these methods provide a more accurate means of assessing the true proliferation rate of a given neoplasm, as compared with the simple assessment of mitotic activity. Similar to the evaluation of mitotic activity, these methods are also subject to limitations associated with tumor heterogeneity and interobserver variability. This paper reviews a variety of methodologies including radiolabeling, flow cytometric, and immunohistochemical that have been used in recent years to evaluate cell proliferation in brain neoplasms. Factors that affect these methodologies and their practical application to routine practice of diagnostic neuropathology will be explored.

Julius Hallervorden’s wartime activities: Implications for science under dictatorship

The eponym Hallervorden-Spatz syndrome recalls Julius Hallervorden’s and Hugo Spatz’s original description of this pediatric neurodegenerative disorder. Julius Hallervorden’s important contribution to the practice of neuropathology over a long career cannot be underestimated. However, his work as a pathologist during the Third Reich put him in close proximity with the implementation of biologic solutions (i.e., euthanasia) targeting those individuals with significant intellectual or physical disabilities in chronic-care facilities. The Nazi program of active euthanasia provided a scientific opportunity to gain quick access to pathologic materials. This opportunity was recognized and used by Hallervorden to achieve personal scientific objectives and research efforts. These efforts resulted in a number of postwar scientific publications using materials obtained through the euthanasia program. The participation of distinguished academic physicians in such a program provides a cautionary tale of the potential results of ethical compromise and the effects of the abrogation of personal autonomy in the setting of a totalitarian dictatorship.

Why do we remember Dorothy Russell?

Dorothy Russell (1985-1983), one of the leading figures in the brief history of British neuropathology, is remembered by the Society in a biennial Memorial Lecture. So rapid is progress in the Neurosciences and so short our memories, that for a younger generation of neuropathologists she is probably no more than a name associated with a large recently revised textbook on brain tumours. However, together with Godwin Greenfield, Dorothy Russell had a profound and lasting influence on the development and practice of Neuropathology throughout the world.

Diagnostic discrepancies and their clinical impact in a neuropathology referral practice.

During the course of their neuropathology practice, the authors received cases to review in consultation. In some cases, the patients came to the authors' hospital for therapy; in others, the primary pathologists requested a consultation. Because changes in diagnosis might significantly alter patient management, protocol entry, care costs, or the potential for physician liability, the authors determined the frequency and degrees of their disagreements with the original diagnoses submitted to them. The authors reviewed the first 500 brain or spinal cord biopsy cases that were submitted to their neuropathology consultation service for a second opinion in 1995. Disagreements were coded into 10 categories, but were grouped for this analysis as follows: serious (having immediate significance for therapy or intervention), less serious but potentially substantial (calling for a change in type or grade of glioma), minor (adding or deleting information), and those in which the authors made the first diagnosis themselves. There was some degree of disagreement between the original and review diagnoses in 214 (42.8%) of the 500 cases. Disagreements were counted as serious in 44 cases (8.8%), less serious but substantial in 96 cases (19.2%), and minor in 50 cases (10.0%); the authors made the first diagnosis in 24 cases (4.8%). Clinically important diagnostic errors that can affect immediate patient care decisions occur in a substantial number of brain and spinal cord biopsy cases. Thus, seeking expert neuropathology consultation is prudent and cost-effective for pathologists who are less experienced with these types of cases. Cost savings in case management might result from confirmation of diagnosis before definitive therapy is administered to the patients. The rates of discrepancy between original diagnoses and second opinions in other subspecialties of pathology should be examined.

Principles and Practice of Neuropathology

Principles and Practice of Neuropathology

Neuropsychiatry aspects of human neurocysticercosis

Used to neuropathology practice, in the XIX century psychiatrists were much interested in neurocysticercosis. After the beginning of the twentieth century, they seldom sudied it. In order to verify the present epidemiological and clinical relevance of neurocysticercosis, particularly in psychiatry, autopsies and living psychiatric inpatients were examined, in an endemic area […] Neuropsychiatry aspects of human neurocysticercosis

Principles and Practice of Neuropathology

Principles and Practice of Neuropathology

Principles and practice of neuropathology. Edited by J. S. Nelson, J. E. Parisi, and S. S. Schochet, Jr, St. Louis, Mosby–Year Book. 1993, 625 pp, illustrated, $119.00

Annals of NeurologyVolume 35, Issue 2 p. 253-253 Book Review Principles and practice of neuropathology. Edited by J. S. Nelson, J. E. Parisi, and S. S. Schochet, Jr, St. Louis, Mosby–Year Book. 1993, 625 pp, illustrated, $119.00 Edward H. Koo, Edward H. Koo Boston, MASearch for more papers by this author Edward H. Koo, Edward H. Koo Boston, MASearch for more papers by this author First published: February 1994 https://doi.org/10.1002/ana.410350238Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume35, Issue2February 1994Pages 253-253 RelatedInformation