Chapter 7

TUMORS OF THE CENTRAL NERVOUS SYSTEM

TUMORS OF GLIAL CELLLS-B: OTHER GLIOMAS

PILOCYTIC ASTROCYTOMA-WHO GRADE I

Pilocytic astrocytoma (PA) is a biologically and histologically distinct form of astrocytoma of children and young adults and is the most frequent BT in children. Most PAs arise in the cerebellum, hypothalamus, and optic chiasm. Some arise in the cerebral hemispheres and other locations.


PA of the cerebellum

Pilocytic astrocytoma. Cerebellar cyst with solid component.


PA of the pons

Pilocytic astrocytoma of the pons.


Hypothalamic PA

Pilocytic astroctoma of the hypothalamus.

Grossly, pilocytic astrocytomas are circumscribed and often cystic with a solid mural nodule. Histologically, they are sparsely cellular tumors without anaplasia or mitoses. They have a biphasic pattern, consisting of cellular and fibrillary perivascular areas, alternating with loose microcystic zones. Some PAs are mostly compact, consisting usually of fiber-like spindle cells.


Pilocytic astrocytoma

Biphasic (cystic and solid) pilocytic astrocytoma with numerous Rosenthal fibers.


Eosinophilic granular bodies

Pilocytic astrocytoma. Granular eosinophilic bodies.


Pilocytic astrocytoma

Pilocytic astrocytoma. Spindle cells in a compact fibrillary background with numerous Rosenthal fibers.

The tumor cells often contain Rosenthal fibers and eosinophilic granular bodies. The word pilocytic (hair cell) refers to the fiber-like appearance of the tumor cells and their fibrillary stroma, but large parts of these tumors, especially in the loose areas, do not fit this description. Some PAs contain clear (oligodendroglioma-like) cells, multinucleated cells, and calcifications. PAs are highly vascular and enhance with contrast injection. Most PAs are biologically low grade and do not evolve into more malignant tumors. Surgical excision of cerebellar PA (even partial resection in some instances) sometimes results in permanent cure.

The vast majority of sporadic cerebellar and midline PAs and a smaller proportion of extracerebellar ones show activation of BRAF. This is most commonly caused by fusion of BRAF with KIAA1549, a contiguous gene on 7q34, producing a fusion gene that lacks the BRAF regulatory domain. KIAA1549:BRAF duplication/fusion activates the MAPK oncogenic signaling cascade, which is involved in the pathogenesis of PA. This BRAF alteration is not seen in PA associated with NF1. The same pathway can be activated by the V600E BRAF mutation, which is common in pleomorphic xanthoastrocytoma, ganglioglioma, and, less frequently, in other low-grade pediatric gliomas. The V600E mutation is also seen in colorectal cancer, melanoma, and thyroid carcinoma. These BRAF changes can be detected by molecular analysis. In addition to their diagnostic and prognostic value, these findings open the road for specific pharmacological interventions aiming to inhibit the activated pathways.

PLEOMORPHIC XANTHOASTROCYTOMA-WHO GRADE II


PXA

PXA. Superficial cystic mass with a solid nodule.


PXA

PXA. Cellular atypia and granular eosinophilic bodies.


PXA

PXA. The tumor cells are arranged in fascicles.


PXA

PXA. Lipidized (vacuolated) tumor cells.


PXA

PXA. Lipidized tumor cells. Oil red O stain.


PXA

PXA. Reticulin stain.

Pleomorphic xanthoastrocytoma (PXA) is a rare glioma of children and young adults. Typically, it is a superficially located, supratentorial, intra-axial cystic tumor that has a solid mural nodule. It has the tendency to invade the subarachnoid space, and, rarely, it arises in the meninges, thus mimicking the neuroimaging appearance of meningioma. The "xantho" part of the term refers to the presence of vacuolated tumor cells containing lipid droplets. The "pleomorphic" designation indicates that the tumor displays significant cellular and nuclear pleomorphism. In spite of this, PXA does not have a high proliferative index. Most PXAs are WHO grade II but may undergo malignant transformation, especially when they recur after resection. Eosinophilic granular bodies are a frequent histological marker of PXA. A network of fine collagen (reticulin) fibers permeates PXA, and lymphocytic inflammation is frequently present. Most PXAs carry the V600E BRAF mutation.

DIFFUSE MIDLINE GLIOMA


Diffuse midline glioma

DMG extending from the left thalamus to the brain stem.


Diffuse midline glioma

DMG of the pons. The pons is enlarged and wraps around the basilar artery.

Diffuse midline glioma (DMG) is a WHO grade IV glioma that affects children. It is a diffusely infiltrating astrocytic neoplasm that arises in the pons, thalamus, and other midline structures. Some of these tumors are also called “Diffuse Intrinsic Pontine Glioma” (DIPG). Pontine and medullary DMG present insidiously with brainstem signs (cranial nerve deficits, long tract signs) and progress inexorably, usually causing death in 2 years. The diagnosis is usually made by MRI which shows a large area of T1-hypointense and T2-hyperintense signal involving the pons or thalamus extensively. Biopsy is done infrequently and may be difficult to interpret, not the least because of the small sample size dictated by the location of the tumor. At autopsy, most DMGs consist of poorly differentiated glial cells that infiltrate the involved parts diffusely, leaving neurons and white matter tracts intact. This explains the mild early symptoms compared to the size of the lesion. In some cases, more aggressive features identical to glioblastoma develop. The majority of DMGs have a distinctive molecular alteration, which is a mutation at position K27 of histone coding genes. The K27M H3 mutation can be detected by immunohistochemistry.

Further Reading


Updated: October, 2016

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