Evolution of Classification: From Microscope to Genome
Historically, the traditional classification approach was based on the visual assessment of tissue by a pathomorphologist. The grading was determined by features such as mitotic index, presence of neovascularization, and cellular atypia.
In 2016, the World Health Organization radically updated the criteria. Widespread use of whole-genome sequencing has proven that genetic mutations determine tumor behavior more accurately than its appearance. The concept of an integrated diagnosis was introduced, where histology complements genetics rather than the other way around.
Key changes:
- Tumors are grouped by shared molecular markers.
- The obsolete term "primitive neuroectodermal tumor" (PNET) has been excluded.
- Gliomatosis cerebri (gliomatosis cerebri) has lost its status as an independent glioma subtype and is now classified as a specific growth pattern (variant).
Changes in Diagnostic Imaging
The classification change triggered a paradigm shift in radiology. The emphasis has shifted to radiogenomics—attempts to predict the molecular status of a neoplasm from imaging data even before surgical intervention.
Basic Methods:
- Non-contrast CT. It is not the primary method, but it is critically important in the acute deterioration of neurological status. It allows for the emergency exclusion of hydrocephalus, hemorrhage, or critical mass effect.
- Standard MRI Protocol. Must include diffusion-weighted imaging (DWI), T2, FLAIR sequences, as well as T1 before and after contrast administration. For adequate follow-up assessment, scanning parameters must be strictly standardized and kept consistent.
- Advanced MRI Techniques. Functional MRI (fMRI) and tractography are used for complex preoperative planning, differentiating the tumor from functionally eloquent brain areas.
Intra-axial Tumors
Intra-axial masses grow directly within the brain parenchyma. According to their tissue origin, they are divided into two major branches:
- Of glial origin: astrocytomas, oligodendrogliomas, glioblastomas. This is the most frequent group of intra-axial tumors. More than half of them (50–70%) are initially high-grade (glioblastoma, Grade IV).
- With neuronal phenotype: gangliogliomas, gangliocytomas, dysembryoplastic neuroepithelial tumor (DNT).
On MRI, a low-grade glioma typically appears as an area of hypointense signal on T1-weighted images and hyperintense on T2 and FLAIR. Tractography can visualize intact nerve pathways that the tumor merely displaces, and fMRI helps determine whether the mass involves the motor cortex.
Main WHO Tumor Categories (2016)
The new nomenclature requires detailing the diagnosis down to the specific mutation. The main groups include:
- Diffuse astrocytic and oligodendroglial tumors: Diffuse astrocytomas and glioblastomas (separated into IDH-mutant and IDH-wildtype), diffuse midline glioma (H3 K27M-mutant), oligodendroglioma (IDH mutation and 1p/19q codeletion are mandatory).
- Other astrocytic and ependymal tumors: Pilocytic astrocytoma, subependymoma, ependymoma (including RELA fusion-positive).
- Neuronal and mixed-neuronal-glial tumors: Ganglioglioma, central neurocytoma, paraganglioma.
- Embryonal tumors: Include CNS neuroblastoma and medulloblastomas. The latter are now strictly divided into genetic profiles (WNT-activated, SHH-activated, groups 3 and 4) and histological variants (classic, desmoplastic).
- Cranial nerve tumors: Various variants of schwannomas (cellular, plexiform).
Briefly: answers to topical questions
Which neoplasms are among the most frequent extra-axial CNS tumors?
Extra-axial CNS tumors include the following types of neoplasms:
- Meningiomas
- Cranial nerve sheath tumors
- Epidermoid and dermoid tumors
- Meningeal metastases
- Skull base tumors
- Pineal region tumors
The combination of the patient's age, the location of the lesion, and its morphology often helps narrow down the differential diagnosis of these extra-axial tumors.
Which tumors belong to the group of embryonal CNS tumors according to the WHO classification?
The group of embryonal CNS tumors includes the following neoplasms:
- Medulloblastomas (genetically and histologically defined, as well as NOS)
- Embryonal tumor with multilayered rosettes (with C19MC alteration and NOS)
- Medulloepithelioma
- CNS neuroblastoma
- CNS ganglioneuroblastoma
- Atypical teratoid/rhabdoid tumor
- CNS embryonal tumor with rhabdoid features
- CNS embryonal tumor, NOS.
What histological variants is medulloblastoma divided into?
Histologically defined medulloblastomas are subdivided into the following variants:
- Medulloblastoma, classic
- Medulloblastoma, desmoplastic/nodular
- Medulloblastoma with extensive nodularity
- Medulloblastoma, large cell/anaplastic
Medulloblastoma not otherwise specified (NOS) is singled out separately. An atypical lateral location of the tumor is more common in older patients precisely with the desmoplastic variant.
What else to study on this topic
- Molecular genetic markers (IDH mutations, 1p/19q codeletion, H3 K27M status)
- MRI semiotics of gliomas on various sequences (T1, T2, FLAIR, DWI)
- Capabilities of functional MRI and tractography in preoperative planning
- Genetic and histological subtypes of medulloblastomas (WNT, SHH)
- Tumors of the pineal region and choroid plexus
Master the entire topic in the "Diagnostic Radiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "CNS Tumor Classification" and 2,199 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 10 video lessons on the subject
Other topics in the Neuroimaging section
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.