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Histology of intracranial tumors

Neuroepithelial tumors

The neuroepithelial tumors arise from cells that developmentally stem from primitive neuroepithelia and represent the largest group of intracranial neoplasms. Most neuroepithelial tumors show a tendency for diffuse infiltration of the brain, but only extremely rarely metastasize to other organs in the body. Glioma is a collective name for tumors that were thought to arise from tumors derived from astrocyte, oligodendrocyte or ependymal cells.

The histopathological classification system used for neuroepithelial tumors is based on similarities between the tumor cells and cells in the normal brain (6). This is based on the earlier, generally prevailing view that a tumor occurs as a consequence of changes in a normal, mature cell in the central nervous system. Tumors where the cell mainly looks like astrocytes are therefore named astrocytoma and tumors with characteristics from oligodendrocytes are named oligodendroglioma. This classification system, based on cell morphology, is now challenged by new knowledge about genetic changes in the tumor cells and tumor stem cells.

Some studies suggest that grouping the tumors with molecular genetic methods is better than a morphological grouping with regard to predicting the therapy response and survival. Recently, it was shown that stem cells are found in the brains of adults which can develop into either neurons, astrocytes or oligodendrocytes. This has led to the fact that many now believe that neuroepithelial tumors develop from neural stem cells. A stem cell has many of the same characteristics as tumor cells, e.g. the ability to proliferate, migrate and infiltrate. A stem cell will therefore require far fewer mutations in order to transform into a tumor cell than a differentiated glia cell or neuron. In the future, tumors will probably also be classified with stem cell markers and molecular genetic techniques.


MRI of patient with astrocytoma.
Click to enlarge the image.
MRI of patient with glioblastoma. Click to enlarge the image. Light microscope image of patient with glioblastoma. Click to enlarge the image.

The cells in the astrocytomas resemble astrocytes. Pilocytic astrocytoma (WHO grade I), low-grade astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV) represent subtypes of astrocytoma with increasing degree of malignancy. Glioblastoma is the most invasive, and therefore the most malignant. There is a high degree of correlation between what the histology shows and the prognosis. Glioblastoma is the most frequently occuring type of astrocytoma in adults, and can either develop from the lower-grade astrocytomas (secondary glioblastomas) or occur de novo (primary glioblastomas). Pilocytic astrocytoma is a variant of low-grade astrocytomas, as opposed to the ones above it is a well-delimited, slowly growing tumor in children and young adults with no tendency to malignant degeneration. It occurs primarily in the cerebellum, optic nerve and hypothalamus.


MRI of patient with oligodendroglioma. Click to enlarge the image. Light microscope image of oligodendroglioma, WHO grade II. Click to enlarge the image. Light microscope image of oligodendroglioma, WHO grade III. Click to enlarge the image.

These diffuse, infiltrating tumors, which have cells that look like oligodendrocytes, occur in all age groups, but most frequently between the ages of 40 and 50. They are usually localized to the cerebral hemispheres. Traditionally, it is stated that oligodendrogliomas constitute 5–10 % of all gliomas, but it is possible that they are underdiagnosed and constitute 25-30 %. Here also there is differentiation between a low and a high (anaplastic) degree of malignancy, but the correlation between the histological findings and the prognoses is not as clear as for astrocytomas.

Mixed gliomas

Mixed gliomas have elements from both of the two types of tumors mentioned above. It is important to detect any oligodendroglioma component in a glioma, since it is important in the choice of treatment.  


Ependymomas probably arise from ependymal cells in the wall of the ventricle system and the central canal of the spinal cord. The fourth ventricle is the predilection site for this type of tumor in children.

Tumors of the choroid plexus 

These are intraventricular tumors, which can infiltrate the surrounding brain tissue. Tumors can be very large and vessel-rich and often entail hydrocephalus. Most are histologically benign and are called papillomas.   

Neuroepithelial tumors with neuronal cells

The group neuronal and mixed neuronal-glial tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma and central neurocytoma) are relatively rare tumors compared with astrocytomas. They have a good prognosis, but it has been reported that gangliogliomas can become malignant. The two former types are often localized to the temporal lobes and cause epilepsy. Central neurocytoma is an intraventricular tumor of cells with neuronal differentiation. It is usually localized near the foramen of Monro and is seen most often in young adults. Approximately half of all supratentorial, intraventricular tumors in adults are neurocytomas.  

Tumors in the pineale body region

Pineocytomas and pineoblastomas are rare tumors arising from epiphysial tissue. Pineoblastomas are included in the PNET (Primitive Neuroectodermal Tumors) group (see medulloblastoma). Pineocytomas are better differentiated, more well-defined, and have a better prognosis than pinealoblastoma, and they are seen most often in adults. Mixed forms occur.  

Fetal tumors

Medullablastoma is an undifferentiated neuroepithelial tumor (Primitive Neuroectodermal Tumor - PNET) in the cerebellum, most often near the midline. The medullablastomas are highly malignant and display a pronounced tendency to spread in the subarachnoid space via the cerebrospinal fluid. Similar tumors in the forebrain are called supratentorial PNET and in the corpus pineale they are called pineoblastomas. 

Brain membrane tumors


MRI of patient with meningioma.
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MRI of patient with meningioma.
Click to enlarge the image.
Light microscope picture of meningioma, WHO grade II. Click to enlarge the image.

The meningiomas constitute 25 % of the primary intracranial tumors. The incidence increases steadily with age, and the majority affect women (women/men = 1.7/1). Women who have been diagnosed with a meningioma have a slightly higher incidence of breast cancer and vice-versa, probably because both tumor types can be influenced by female sex hormones. The meningiomas arise from arachnoid cells and are benign in 95 % of the patients. Radiologically, one typically sees a homogenous contrast-enhancing tumor which has a broad interface with the dura/skull and good demarcation from the brain tissue. However, the dura is normally infiltrated by the tumor, as neighboring parts of the cranium can also be. The majority of meningiomas have an arachnoidal layer between them and the brain and do not infiltrate the brain, but push it forward during growth. However, they can grow around the blood vessels and cranial nerves. This rarely occurs when the tumor grows out from the base of the skull; it can then be extremely difficult or impossible to remove. The meningiomas usually grow very slowly. Therefore, the brain can adapt to the growth of the tumor, which can explain why the patients can have tumors the size of oranges before they develop symptoms clear enough for the condition to be diagnosed. Atypical and anaplastic meningiomas have a more malignant growth pattern than the usual meningiomas, and therefore, they have a considerably worse prognosis.


This is a rare brain membrane tumor with large recurrence tendencies and with a potential for metastasizing.

Cranial nerve tumors

Vestibular Schwannoma, (formerly called acoustic neuronoma)

MRI of patient with Schwannoma.
Click to enlarge the image.
Light microscope picture of Schwannoma. Click to enlarge the image.

Schwannomas are built up of cells that look like the Schwann cells, the cells that isolate peripheral axons. The Schwannomas can occur on several cranial nerves, but in the majority of cases, are localized to one of the vestibular nerves. The earlier term acoustic neuroma is therefore doubly wrong, since the term indicates a starting point in the wrong nerve (nervus acusticus) and in the wrong cell type (nerve cell). Vestibular Schwannomas are the most common primary, infratentorial tumor in adults and constitutes 6 % of the primary intracranial tumors. They are normally diagnosed at 40–50 years of age and are more common in women than in men. Almost all vestibular Schwannomas are benign and grow slowly. They arise from the vestibular part of the 8th cranial nerve and, therefore, lie in the angle between the cerebellum and pons. In 5 % of cases, the vestibular Schwannomas are bilateral and are then usually connected to neurofibromatosis type 2. More rarely, Schwannomas occur in the 5th cranial nerve (n. trigeminus).

Primary CNS-lymphomas

Primary malignant lymphoma in the central nervous system is usually of the B-cell type. There have been reports of an increasing incidence of this type of tumor, in AIDS-patients and patients with suppressed immune system, among others.

Germinal cell tumors

Germinal cell tumors probably arise from primitive germinal cells, and the tumors are identical with those that occur in the testicles and ovaries. The tumors are most often seen in corpus pineale and in the bottom of the 3rd brain ventricle. The most common type is germinoma (corresponds to seminoma in testes and dysgerminoma in ovaries).

Tumors in the sellar area

Adenoma of pituitary gland

MRI of patient with pituitary adenoma. Click to enlarge the image. MRI of patient with pituitary adenoma. Click to enlarge the image. Light microscope picture of pituitary adenoma. Click to enlarge the image.

Adenomas of the pituitary gland constitute 8–10 % of intracranial tumors in surgical materials and arise from the adenohypophyse. There are large variations in the size, growth rate, clinical presentation and invasion into the surrounding tissue. The infiltration occurs first and foremost in the walls of the sellar floor (sinus cavernous). About 10 % of the adenomas of the pituitary gland are locally invasive. Metastasizing carcinomas of the pituitary gland occur but are extremely rare.
The tumors are classified according to hormone production.

  • 25–30 % are prolactin-producing (prolactinomas)
  • 20–25 % are non-hormone-producing
  • 15–20 % are growth hormone-producing
  • 10–15 % produce ACTH (Cushing's syndrome)
  • 5 % produce both prolactin and growth hormone
  • 3–5 % produce gonadotrophins (LH and FSH)
  • Tumors that produce thyreotropine-releasing hormone (TSH) are rare.

The tumors are also classified according to size.

  • Microadenoma (<10 mm)
  • Macroadenoma (≥10 mm)


Craniopharyngiomas arise from fetal remains of ductus craniopharyngeus (Rathke's pouch), and is most commonly seen in the area around the pituitary stalk and the bottom of 3rd ventricle. The tumors can have both solid and cystic components. The tumors in adults are often well-defined and extra-cerebral (papillary type).

Tumors of other origin

Capillary hemangioblastomas

MRI of patient with capillary hemgioblastoma. Click to enlarge. Photomicrograph of capillary hemangioblastoma. Click to enlarge.

These tumors constitute 1-2 % of the tumors in the central nervous system. They occur especially in fossa cranii posterior, the brain stem and spinal cord. The tumors can be solid, cystic or mixed. They are always benign. Often the tumor can only be detected by MRI examination and multiplicity is not rare. In 5-10 % of the patients, the tumor is associated with Von Hippell-Lindau syndrome (VHL), which is an autosomal dominant hereditary disease (5). VHL is associated with a number of different forms of tumor in the central nervous system, retina, kidneys, adrenal gland, pancreas and epididymis. Today gene testing can usually confirm/disprove whether capillary hemangioblastoma in a patient is part of Von Hippell-Landau disease. By negative gene testing and negative family anamnesis, the risk of tumors in other organs is small, and the follow-up of the patient should concentrate on the operated area. By negative gene testing and negative family anamnesis, it is not necessary to examine the patient's relations. By positive gene testing or family anamnesis, the patient must enter into a structured follow-up program of all risk organs, and relatives should be screened for corresponding genetic abnormalities.

Brain metastases

MRI of patient with solitary brain metastasis. Click to enlarge. MRI of patient with multiple brain metastases. Click to enlarge. Photomicrograph of metastasis from adenocarcinoma. Click to enlarge.

The incidence of brain metastases is greater than that of primary intracranial tumors, but in surgical series of brain tumors, the metastases only constitute 10-20 %. With increased dissemination of advanced radiological diagnostics, principally MRI, and more effective treatment of the primary tumor, it is to be expected that an increasing number of these metastases will be detected and treated. The primary tumor is usually localized in the bronchia, and then in the breast, skin (melanoma), digestive tract, urinary tract and genitalia, in that order. The risk of developing brain metastases varies a great deal between the various types of tumor. The patients with malignant melanomas and testicular cancer have a 50 % risk of developing brain metastases, while patients with cancer of the lung, kidney or breast have a 10-20 % risk. Patients with prostate cancer and cancer of the stomach, on the contrary, have very little risk of developing brain metastases.

The prognosis for patients with brain metastases depends, among other things, on histological type, the extent of the underlying disease, neurological-function status and the number of brain metastases. The number of brain metastases is assessed with MRI. It is currently estimated that 25 % of brain metastases are solitary, while 75 % are multiple. On an MRI, the brain metastases usually have a rounded, well-defined, homogenous appearance, are contrast uploaded and surrounded by a pronounced edema.

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