|
|
|
|
Gliomas
are exceptionally diverse in location, morphology,
differentiation, ease of excision and response to
postoperative therapy. Knowledge of their pathology is a
great practical aid. because it provides a conceptual
framework in which to place specific lesions, defines
reasonable expectations of surgery for each neoplasm,
and clarifies the significance of histologic diagnoses
as formulated according to current classifications. |
Astrocytic Neoplasms
Neoplasms derived from an
astrocytic lineage constitute a large and heterogeneous group.
They may be divided into two categories: (1) the fibrillary
astrocytic neoplasms (astrocytoma, anaplastic astrocytoma and
glioblastoma multiforme) and (2) a diverse group of tumor types
that warrant separation from the fibrillary astrocytic series
because of their distinctive clinicopathologic features. The
principal members of this group include the juvenile pilocytic
astrocytomas, the pleomorphic xanthoastrocytoma and the
subependymal giant cell astrocytoma.
Fibrillary Astrocytic Neoplasms
Fibrillary or fibrous
astrocytes diffusely populate the brain and are especially
prominent in the white matter, where their stellate processes
can be identified with the historically significant but
technically capricious gold impregnation of Cajal. Antibodies to
glial fibrillary acidic protein (GFAP) and the immunoperoxidase
method have been combined to bring a more specific and
predictable technique to bear on the identification of this
protein. Fibrillary astrocytes are readily seen, because their
processes are rich in the "glial"' filaments which are the
predominant site of this protein.
Grading Systems:
When neoplastically transformed, the
fibrillary astrocyte produces over 80 percent of all astrocytic
neoplasms and the majority of all gliomas. Like other gliomas.
these astrocytic neoplasms extend as a continuum from
well-differentiated lesions to anaplastic tumors. Several
grading systems have been formulated for therapeutic and
prognostic purposes. The first to be widely used was that of
Bailey and Cushing, who likened the morphology of the neoplastic
cells in these lesions to astrocytes in three stages of
embryologic development, namely, the astrocyte. the astroblast
and the spongioblast. Accordingly, the neoplasms that resembled
these cells were named in increasing order of malignancy,
astrocytoma, astroblastoma and spongioblastoma (later
glioblastoma) multiforme.
At the Mayo Clinic. meanwhile,
surgical pathologists were refining a four-tiered grading system
for carcinomas based not on resemblance to developmental
precursors, but rather on the degree of anaplasia as reflected
by such characteristics as degree of nuclear and cytoplasmic
pleomorphism, number of mitotic figures, and presence or absence
of necrosis. From this environment emerged the Kernohan system,
which divided the fibrillary astrocytomas into four grades of
increasing malignancy (astrocytoma grades 1 to 4). Shortly
thereafter, a similar scheme that also utilized cytologic and
histologic characteristics was published by Nils Ringertz, this
system differed from the Kernohan classification in having only
three grades of astrocytoma (astrocytoma, intermediate type. and
glioblastoma). Several "modified Ringertz" systems, all
retaining the basic three-tier hierarchy, subsequently emerged.
One of the most important "modifications" was a recognition of
the primacy of tumor necrosis as a prognostic factor associated
with the most malignant grade of astrocytomas (glioblastoma) and
which separated it from the intermediate-grade (anaplastic)
astrocytoma. Thus. whereas the Ringertz system permitted "very
slight" necrosis in intermediate-grade astrocytomas, such
neoplasms would be classified as glioblastomas in the modified
systems. A three-tiered classification system has been adopted
by the World Health Organization. A study by Daumas-Duport et
al. found that the Kernohan grading system accurately
distinguishes only two prognostic ally distinct groups:
low-grade astrocytomas (grades I and 2) and high-grade
astrocytomas (grades 3 and 4).
In an attempt to minimize subjectivity and
increase ease and reproducibility in grading, another method was
introduced in 1988 by Daumas-Duport et al. which is based on the
simple assessment of the presence or absence of four histologic
features: nuclear atypia, mitotic figures, microvascular
proliferation, and necrosis.
Astrocytoma
Classification and Grading Systems |
Bailey
& Cushing (1926) |
Kernohan et al.
(1949) |
Ringertz
(1950) |
Modified Ringertz |
St. Anne-Mayo
(1988) |
Univ. California, San
Francisco |
WHO
(1993) |
Astrocytoma |
Astrocytoma grade 1 |
Astrocytoma |
Astrocytoma |
Astrocytoma grade 1 |
Mildly anaplastic
astrocytoma |
Astrocytoma |
Astrocytoma grade 2 |
Astrocytoma grade 2 |
Moderately anaplastic
astrocytoma |
Astroblastoma |
|
Intermediate type |
Anaplastic astrocytoma |
Astrocytoma grade 3
|
Highly anaplastic
astrocytoma |
Anaplastic astrocytoma |
Spongioblastoma multiforme |
Astrocytoma grade 3 |
Glioblastoma multiforme |
Glioblastoma multiforme |
Astrocytoma grade
4 |
Glioblastoma multiforme |
Glioblastoma multiforme |
Astrocytoma grade
4 |
Neoplasms lacking all four variables
(exhibiting only increased cellularity) are classified
grade 1, those with one feature present are grade 2,
those with two features are grade 3, and those with
either three or four features are grade 4. Although both
the St. Anne-Mayo and the University of California, San
Francisco, grading systems have four tiers, the grade 1
astrocytomas are so comparatively rare that in practice
the vast majority of astrocytomas sort into three
grades, shows the approximate grade equivalencies among
the major grading systems.
It is obvious that specifying only a
grade without reference to the particular system
employed may lead to confusion; for example, a grade 2
neoplasm in the Kernohan system by definition does not
exhibit mitotic figures and is more similar to an
astrocytoma of the three-tiered schemes than to an
anaplastic astrocytoma. Similarly, the grade 3
astrocytoma of the Kernohan system exhibits foci of
necrosis and is by any standard a glioblastoma, whereas
the grade 3 lesion of the St. AnneMayo system
corresponds to the anaplastic astrocytoma of the
three-tiered classifications.
Proliferation Markers:
The assessment of mitotic activity as an indicator
of growth potential is an integral part of all
contemporary glioma grading systems, Newer methods for
the evaluation of tumor proliferative potential have
been introduced which offer a more sensitive and
reliable estimation of tumor growth fraction than the
time-honoured practice of counting mitotic figures,
Early studies employed tritium-labelled thymidine
incorporation into deoxyribonucleic acid (DNA), with
detection by autoradiography. Several nonradioactive,
immunohistochemical techniques utilizing novel markers
have been developed. The principal markers are (1)
Ki-67, a nuclear nonhistone protein that is expressed in
all phases of the cell cycle by actively dividing cells,
(2) proliferating cell nuclear antigen (PCNA)/cyclin, an
auxiliary protein of DNA polymerase, and (3)
bromodeoxyuridine (BUdR), a thymidine analogue that is
incorporated into DNA during the S phase. All of these
markers can be detected in tissue sections by
immunohistochemistry with specific antibodies, and the
resulting percentage of tumor cell nuclei that are
positive (the "labelling index") provides a measure of
the proliferative potential of the neoplasm. The various
techniques differ significantly with regard to technical
requirements and reproducibility.
An additional technique that may provide
an indirect measure of growth potential is the
quantitation of nucleolar organizer region-associated
argyrophilic proteins (AgNORs). These proteins are
associated with nucleolar organizer regions, which are
composed of ribosomal DNA and putatively show an
increase in number in the nuclei of actively dividing
cells. AgNORs are readily detected with a colloidal
silver stain and can be subsequently quantified. As with
the proliferation markers, correlation with tumor grade,
prognosis, and other indices of growth potential is
currently under investigation.
|
|
|
This site is non-profit directed
to medical and neurosurgical audience to share
problems and solutions for brain tumors
diagnosis and treatment modalities.
Author of the
site.
Prof. Munir A. Elias MD., PhD.
|
|
|