Neuro-Oncology for the Clinical Neurologist E-Book

Roy E. Strowd

• Publisher: Elsevier
• Year: 2020
• ISBN:
  9780323694957
• Topic: Medicina
• Subtopic: Neurología

In the growing field of neuro-oncology, the past few years have witnessed rapid advances in tumor classification, treatment modalities, and the role of neurologists and neuro-oncologists. Neuro-Oncology for the Clinical Neurologist is a first-of-its-kind resource that focuses on patient-clinical scenarios relevant to the practicing neurologist—bringing you up to date with everything from basic principles and neuro-oncology imaging consults to neurologic complications of radiation, systemic, and immune-based therapies, and much more.

• Focuses on the clinical management of patients typically encountered by neurologists and neurology trainees.
• Provides clinically relevant updates in five key areas of neuro-oncology: primary CNS tumors, brain and leptomeningeal metastases, inherited tumor syndromes of the nervous system (e.g. neurofibromatosis), paraneoplastic and immune-mediated neurological complications of cancer, and neurological complications of cancer treatments.
• Includes a summary of clinical pearls and a reference list of clinical cases.
• Anchors each chapter with patient cases and clinical scenarios, provides evidence-based discussion, and explains patient management.
• Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.

Section 1

Basic principles of neuro-oncology

Outline

Chapter 1. Fundamentals of neuropathology: introduction to neuropathology and molecular diagnostics

Chapter 2. Surgical considerations for brain and spine tumors

Chapter 3. Introduction to radiation therapy

Chapter 4. Evidence-based approaches to chemotherapy for gliomas

Chapter 1: Fundamentals of neuropathology

Introduction to neuropathology and molecular diagnostics

Sonika Dahiya, and Shakti Ramkissoon

1. Introduction
2. Histologic classification of central nervous system tumors
3. Molecular characterization of central nervous system tumors
4. Clinical cases
   1. Case 1.1 Characteristic Histopathological and Molecular Features of Glioblastoma
   2. Case 1.2 Use of Molecular Testing to Define the Diagnosis of WHO Grade 2, Olidoendroglioma
   3. Case 1.3 Use of Genomic Profiling to Establish a Diagnosis of WHO Grade 2, Astrocytoma
   4. Case 1.4 Histopathological and Molecular Findings for WHO Grade 3, Anaplastic Astrocytoma
   5. Case 1.5 Pathologic Assessment of Dural-Based Meningioma
   6. Case 6 Histopathology of a Benign Peripheral Nerve Sheath Tumor: Schwannoma VS Neurofibroma
5. Conclusion

Introduction

In typical cases, the clinical workflow for brain tumors begins with imaging studies; however, despite the increased sensitivity and capabilities of these methodologies, diagnosing brain tumors requires histopathologic evaluation of tissue. It is imperative for clinicians to understand how brain tumors are classified so that they can better counsel patients at the time of initial presentation, accurately describe prognosis, and prioritize management of medical or neurological comorbidities based on the anticipated behavior of the tumor.

Tumor classification has historically relied primarily upon morphologic features identified by light microscopy. In the past decade, integration of high-throughput genomic testing into routine clinical workflows has refined the approach to diagnosing brain tumors. ¹ In this chapter, we explore tumor classification from traditional microscope-based approaches to currently available methodologies. We review genomic profiling and introduce the concept of an integrated diagnosis.

The chapter begins with a discussion of the histologic assessment of brain tumors, which is often the first data to be reported after a tumor surgery. This is followed by a discussion of molecular profiling, which is used to further classify these tumors, guide prognosis, and predict response to therapy. Molecular data typically returns in the weeks following surgery. Finally, we review a series of common case scenarios and integrate the histologic and molecular data into a final integrated diagnosis that clinicians can use to help manage and counsel these patients.

Histologic classification of central nervous system tumors

The primary method of diagnostic neuropathology and brain tumor classification remains microscopic evaluation of hematoxylin and eosin (H&E)–stained tissue sections by light microscopy. This approach has experienced relatively few changes over the past several decades with generations of pathologists still undergoing specialized training focused on learning to read or interpret stained sections on glass slides.

The process of converting a portion of resected brain tissue to an H&E stained section is the first step to achieve a tissue-based diagnosis. Brain tissues removed at the time of surgery can range from small biopsies, such as needle core biopsies, to large resections that often occur during a tumor debulking surgery. Once the fresh tissue reaches the laboratory, the sample is subjected to fixation in formalin-based solutions that serve to preserve tissues and cells.

Formalin-fixed tissues then undergo a series of steps, commonly referred to as tissue processing, which prepares the formalin-fixed tissues for embedding into a block of paraffin wax. Once the tissue fragment is embedded in paraffin and mounted into a cassette, this “block” serves as the final medium where the tissue can be safely stored for years (even decades). Importantly, this processing method preserves the integrity of the tissues for later use. Formalin-fixed paraffin-embedded (FFPE) samples are the mainstay of both traditional microscopic analysis and serve as the starting medium for most tissue-based molecular and genomic assays currently available.

Once a tissue sample is converted to an FFPE block, sections (5 microns thickness) can be cut from the block, placed onto glass slides, and subjected to staining with the dyes hematoxylin and eosin. Hematoxylin stains nucleic acids a deep blue-to-purple color, which readily highlights the nuclei of cells. Eosin stains other cellular components, like proteins, with a bright pink color that contrasts with the blue hematoxylin-stained nuclei—together these two dyes serve as the basis for all H&E-based tumor classification.

Brain tumor classification based on H&E features relies on the fact that the histologic appearance of these tumors is consistent from one patient to another. In fact, the features are so reproducible that they have been codified into the World Health Organization (WHO) Classification of Tumors of the Central Nervous System, which outlines the microscopic features present in all brain tumors and serves as the central resource to ensure all patients around the world are diagnosed and graded using the same criteria.

Tumor Grading. Unlike other tumors, which are staged based on size, lymph node involvement, and presence or extent of metastases (e.g., TNM classification), staging is not used for gliomas, which rarely spread beyond the central nervous system (CNS). Instead, gliomas are graded from grade I to IV and are broadly divided into low- and high-grade tumors. Grade I and II are considered “low grade” and grade III and IV as “high grade”; of these, grade I tumors are generally well circumscribed, whereas grades II–IV are diffusely infiltrating, albeit with some exceptions such as ependymoma and pleomorphic xanthoastrocytoma which tend to be well circumscribed despite conforming to grade II. The histologic features assessed to establish glioma grading include atypia, mitoses, endothelial or microvascular proliferation, and necrosis. Grade I tumors such as pilocytic astrocytomas are most commonly encountered in the pediatric setting. Although such tumors do occur in the adult population, the use of the term “lower-grade gliomas” in adults largely refers to infiltrating grade II tumors such as diffuse astrocytoma and oligodendroglioma. Grade III tumors include anaplastic astrocytoma (AA3) and anaplastic oligodendroglioma (AO3), whereas glioblastoma (GBM) is considered a grade IV astrocytoma. Progression of brain tumors from low to high grade does occur, most commonly in adul...