Introduction to CNS Neoplasms and Nonneoplastic Cysts

Main Text

Preamble

CNS neoplasms are both (1) classified and (2) graded. The universally accepted classification of these tumors is sponsored by the WHO. The 2nd edition of Osborn’s Brain was based on the 4th edition of the WHO Classification of Tumours of the Central Nervous System published in 2016. With rapid advancements in the molecular diagnostics of these tumors, a new (5th) edition of the famed “Blue Book” was published in late 2021.

This introduction presents an overview of major changes incorporated into the 5th edition WHO. We begin with a brief introduction to CNS tumor taxonomy, nomenclature, classification, and grading. We introduce the concept of a pathologic “integrated diagnosis” and emphasize its importance in stratifying patients for treatment.

We close the introduction with a brief summary of the major diagnostic categories/groupings of CNS neoplasms.

CNS Tumor Taxonomy

Preamble

CNS neoplasms are both classified and graded. Traditionally, classification assigned CNS neoplasms to discrete categories based on the histologic similarity of tumor cells to normal or embryonic constituents of the nervous system. Hence, terms like “astrocytoma” and “meningioma” were used.

In 2016, the concept of incorporating molecular markers as key aspects of the classification of CNS tumors was introduced. As the molecular foundations of these tumors have been rapidly elucidated, these features have been utilized to group some tumors into families (types) and subtypes. The combination of molecular profiling with histologic features ideally results in an “integrated diagnosis” that can then be used to stratify patients for treatment.

CNS Tumor Nomenclature and Classification

The 5th edition WHO has made tumor nomenclature generally more consistent and simple. In previous editions, some entities incorporated anatomic site into the entity name, e.g., “chordoid glioma ‘of the third ventricle'” is now simply “chordoid glioma.”

Some exceptions where location, age, or genetic modifiers have specific diagnostic or clinical utility have been retained in the 5th edition (e.g., “central neurocytoma” and “extraventricular neurocytoma”). In other cases, names retained histopathologic or anatomic features that are characteristically but not invariably present (e.g., myxopapillary ependymomas are not always myxoid or papillary, and diffuse midline gliomas (16-1)are usually but not always exactly midline).

Some tumor names with historical associations that are deeply embedded in common usage have also been retained. Thus, the term “medulloblastoma” continues to be used in the 5th edition (even though a medulloblast has never been identified). Genetically defined tumor subtypes with vastly differing prognoses and treatment are grouped together as “medulloblastomas” but are now defined and subtyped by their molecular features (e.g., medulloblastoma, WNT-activated).

Gene and protein nomenclature in the 5th edition mostly utilizes the Human Genome Organization (HUGO) and Human Genome Variation Society (HGVS) systems for gene symbols and gene names. Gene symbols (e.g., IDH1) are presented in italics, but proteins and gene groups (e.g., the family of IDH genes) are not italicized.

CNS Tumor Grading

Tumors are both classified and graded. In the 2016 classification, tumor grading reflected overall expected clinical-biological behavior and represented a combination of histopathology findings and expected natural history. For example, diffuse astrocytic tumors were assigned to three different tumor types: Diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV).

In the 5th edition, CNS neoplasms are graded within tumor types rather than across different types. In the current classification, a diffuse adult-type glioma might be identified microscopically and immunohistochemically as an IDH-mutant astrocytoma, then assigned a grade (CNS WHO grades 2-4) according to its molecular profile. Here, all IDH-mutant astrocytomas are considered a single type and graded within that specific tumor type.

Grading is also no longer entirely histologic. As many molecular markers now provide powerful prognostic information, they have been fully incorporated into determining tumor grade in the 5th edition. For example, an IDH-mutant astrocytoma (tumor type) can be designated grade 2, 3, or 4. Modifier terms, such as “anaplastic,” have been eliminated. Thus, an “anaplastic astrocytoma” with appropriate histologic and molecular features would now be diagnosed as “astrocytoma, IDH-mutant, CNS WHO grade 3.”

Molecular parameters may—and often do—override histologic findings in assigning tumor grade. An adult-type diffusely infiltrating glioma with astrocytic features, IDH1 or IDH2 mutation, and absence of 1p/19q codeletion can be a grade 2, 3, or 4 tumor. Presence of homozygous deletion of CDKN2A results in the diagnosis of astrocytoma, IDH-mutant, CNS WHO grade 4, even if histologic features like frank anaplasia, microvascular proliferation, and necrosis are absent.

A notable change in the 5th edition is that Arabic numerals (1-4) have now replaced Roman numerals (I-IV). Because CNS tumor grading differs from other (non-CNS) tumor grading, the term “CNS WHO grade _” is now used when assigning tumor grade to a particular entity.

Integrated (“Layered”) Diagnosis

With the increasing importance of molecular information in CNS tumor classification and prognosis, modern neuropathologic reports now combine different data types into a single integrated (“layered”) diagnosis. These reports are headed by an integrated diagnosis at the top followed by layers that delineate histologic, molecular, and other key types of information.

Information included in a layered neuropathologic report include tumor site at the top followed by integrated diagnosis (a combination of tissue-based histologic and molecular diagnosis), histopathologic classification, CNS WHO grade, and specific molecular information (listed). An example of such a layered report is shown in the next box.

If complete molecular classification is incomplete or not available, the modifier “NOS” (not otherwise specified) is included in the diagnosis. The modifier “NEC” (not elsewhere classified) is added to denote tumors that have been fully characterized but do not fit within the established classification system.

CEREBRUM

Integrated Diagnosis

• Diffuse astrocytoma, IDH-mutant, CNS WHO grade 2

Only gold members can continue reading. Log In or Register to continue