Serdar Balcı

Central Nervous System Tumors

Serdar BALCI, MD

CNS Tumors

Characteristics of CNS tumors

CNS Tumors

Classification of CNS Tumors

Cell of Origin based classification

The most important feature for differential diagnosis

Localization, localization, localization …


Radiologic features

Histomorphologic features

Genetic features

Localisation of CNS tumors

Spread of CNS tumors

Metastatic spread of brain tumors to other regions of the body is rare

Spinal subarachnoid tumor seeding

Autopsy Pathology: A Manual and Atlas

Grading of CNS tumors

Grading is based on histological subtype

Grade I tumors

Grade II tumors

Grade III tumors

Grade IV tumors

Benign, Resection is cure

Progression can be seen



Grading of CNS gliomas

Increasing tumor malignancy is associated with more cytologic anaplasia, increased cell density, necrosis, and mitotic activity

Grade I tumors

Grade II tumors

Grade III tumors

Grade IV tumors


Pilocytic Astrocytoma, Grade I

pilocytic astrocytoma

Autopsy Pathology: A Manual and Atlas

Pilocytic Astrocytoma


Mural nodule in the wall of the cyst

If solid, usually well circumscribed

Bipolar cells with long, thin “hairlike” processes


Rosenthal fibers, eosinophilic granular bodies, and microcysts are often present

Necrosis and mitoses are very rare

Diffuse Astrocytomas

Infiltrating pontine glioma (astrocytoma)

Autopsy Pathology: A Manual and Atlas

Diffusely infiltrating astrocytoma

Autopsy Pathology: A Manual and Atlas

Well-differentiated astrocytomas are poorly defined, gray, infiltrative tumors that expand and distort the invaded brain without forming a discrete mass

Robbins Basic Pathology

Infiltration beyond the grossly evident margins is always present

Cut surface of the tumor is either firm or soft and gelatinous

Cystic degeneration may be seen

Robbins Basic Pathology

Clinical Neuropathology Text and Color Atlas

Practical Surgical Neuropathology

Brain Tumor Pathol (2011) 28:177–183

Brain Tumor Pathol (2011) 28:177–183

Defects in tricyclic carbon cycle

Isocitrate dehydrogenase mutations cause accumulation of byproducts

Most important discovery in malignant CNS tumors

Cancer Cell. 2010 Jan 19;17(1):7-9

N Engl J Med 2009;360:765-73.

Well-differentiated astrocytomas

Mild to moderate increase in the number of glial cell nuclei

Variable nuclear pleomorphism

Intervening feltwork of fine, glial fibrillary acidic protein (GFAP)-positive astrocytic cell processes that give the background a fibrillary appearance

Transition between neoplastic and normal tissue is indistinct

Tumor cells can be seen infiltrating normal tissue many centimeters from the main lesion

Anaplastic astrocytomas, Grade III

More densely cellular

Greater nuclear pleomorphism

Mitotic figures

Practical Surgical Neuropathology

Glioblastoma, Grade IV

Loss-of-function mutations in the p53 and Rb tumor suppressor pathways

Gain-of-function mutations in the oncogenic PI3K pathways

Mutations that alter the enzymatic activity of two isoforms of the metabolic enzyme isocitrate dehydrogenase (IDH1 and IDH2) are common in lower-grade astrocytomas

Immunostaining for the mutated form of IDH1 has become an important diagnostic tool in evaluating biopsy specimens for the presence of low-grade astrocytoma



Necrotic, hemorrhagic, infiltrating mass

Robbins Basic Pathology

Glioblastoma multiforme

Autopsy Pathology: A Manual and Atlas


densely cellular tumor with necrosis and pseudopalisading of tumor cell nuclei

Robbins Basic Pathology

Clinical Neuropathology Text and Color Atlas

Practical Surgical Neuropathology

Practical Surgical Neuropathology



Oligodendroglioma tumor cells have round nuclei, often with a cytoplasmic halo

Blood vessels in the background are thin and can form an interlacing pattern

Robbins Basic Pathology

Deletions of chromosomes 1p and 19q

1p and 19q loss typically occur together

Tumors with deletions of 1p and 19q are usually highly responsive to chemotherapy and radiotherapy

Well-differentiated oligodendrogliomas (WHO grade II/IV)

Anaplastic oligodendroglioma (WHO grade III/IV)

More aggressive subtype

Higher cell density

Nuclear anaplasia

Mitotic activity



Fourth ventricle

Solid or papillary masses

Extending from the ventricular floor

Anaplastic ependymoma

Increased cell density

High mitotic rates


Less evident ependymal differentiation

Robbins Basic Pathology


Neuronal Tumors

Central neurocytoma

Low-grade neoplasm

Within and adjacent to the ventricular system

Most commonly the lateral or third ventricles

Evenly spaced, round, uniform nuclei

Islands of neuropil


Dysembryoplastic neuroepithelial tumor (DNET)


Embryonal (Primitive) Neoplasms


Located in the midline of the cerebellum

Lateral tumors occur more often in adults

Often well circumscribed, gray, and friable

May extend to the surface of the cerebellar folia and involve the leptomeninges

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Extremely cellular

Sheets of anaplastic (small blue) cells

Small, with little cytoplasm

Hyperchromatic nuclei

Abundant mitosis

Robbins Basic Pathology

Focal neuronal differentiation

Homer Wright or neuroblastic rosette

Resembles the rosettes in neuroblastomas

Primitive tumor cells surrounding central neuropil

-delicate pink material formed by neuronal processes

Genetic of medulloblastoma


Primary CNS Lymphoma


Primary brain germ cell tumors




WHO grade I/IV

well-defined dura-based masses

compress the brain but do not invade it

Extension into the overlying bone may be present

Robbins Basic Pathology

Parasagittal meningioma

Autopsy Pathology: A Manual and Atlas

Intraosseous meningioma

Autopsy Pathology: A Manual and Atlas

Histologic patterns of Meningioma

Robbins Basic Pathology

Atypical meningiomas (WHO grade II/IV)

prominent nucleoli

increased cellularity

pattern-less growth

higher mitotic rate

More aggressive local growth

Higher rate of recurrence

Require therapy in addition to surgery

Anaplastic (malignant) meningiomas (WHO grade III/IV)

Highly aggressive tumors

May resemble a high-grade sarcoma or carcinoma

usually some histologic evidence of a meningothelial cell origin


Metastatic Tumors

Mostly carcinomas

1/4-1/2 of intracranial tumors

Most common primary sites

Lung, breast, skin (melanoma), kidney, and gastrointestinal tract

Form sharply demarcated masses

Often at the gray-white junction, and elicit edema

The boundary between tumor and brain parenchyma is sharp at the microscopic level as well, with surrounding reactive gliosis

Direct and localized effects


Metastatic spread of brain tumors to other regions of the body is rare

Brain is not protected against spread of distant tumors

Carcinomas are the dominant type of systemic tumors that metastasize to the nervous system

Metastatic melanoma

Metastatic lesions are distinguished grossly from most primary central nervous system tumors by their multicentricity and well-demarcated margins

The dark color of the tumor nodules in this specimen is due to the presence of melanin

Robbins Basic Pathology

Paraneoplastic syndromes


Tuberous Sclerosis (TSC)

von Hippel–Lindau Disease

Autopsy Pathology: A Manual and Atlas

Autopsy Pathology: A Manual and Atlas

Distribution of CNS Tumors

**A pilocytic astrocytoma of the cerebellum in a child. **

Glioma of the brainstem – pilocytic astrocytoma

GBM. Note the prominent vascularity as well as the area of necrosis at the left with neoplastic cells palisading around it (pseudopalisading necrosis*).

Here is an ependymoma arising from the ependymal lining of the fourth ventricle above the brainstem and bulging toward the cerebellum.

This horizontal (CT scan) section of the brain reveals a large ependymoma of the fourth ventricle.

Irregular posterior fossa mass (medulloblastoma) - near the midline of the cerebellum and extending into the fourth ventricle above the brainstem