reveals identical TP53 mutations in both
gemistocytes and non-gemistocytic tu-
Fig. 1.06 Diffuse astrocytoma. Low
nuclear atypia.
change may be present, but most cells
look like one another, without the admix-
ture of gemistocytes more often seen in
reactions to injury. Pre-existing cell types
(e.g. neurons) are often entrapped.
Intraoperative diagnosis
The smear/squash technique is often
used during stereotaxic biopsies and
yields similar findings, although this
method is highly unreliable for estimating
cellularity. Many histological features are
exaggerated and amplified (e.g. nuclear
folds, abnormal chromatin pattern, and
astrocytic processes). The presence of
many round to oval nuclei with smooth
chromatin can indicate the presence of
an apparent oligodendroglial component
or (if the nuclei are less prominent) back-
ground white matter. Histologically, there
may be significant variation between tu-
mours and within the same lesion.
Growthfraction
The growth fraction as determined by the
Ki-67 proliferation index is usually < 4%.
The gemistocytic neoplastic astrocytes
show a significantly lower rate of prolif-
eration than does the intermingled small-
cell component {1046,1372,1377,1847,
2706,2812}. However, microdissection
Fig. 1.08 Diffuse astrocytoma. A Cytoplasm and cell processes show a variable extent of GFAP immunoreactivity. B The Ki-67 proliferation index is low.
20 Diffuse gliomas
mour cells {2094}. Although it has been
reported that the gemistocytic variant
may be particularly prone to progression
to anaplastic astrocytoma and glioblas-
toma {1377,2204,2273}, this does not jus-
tify a general classification as anaplastic
astrocytoma {320,2273}, nor is this im-
pression based on current molecular
cellularity and
characterization, in particular knowledge Fig. 1.07 Diffuse astrocytoma with extensive mucoid
of IDH mutation status. degeneration and cobweb-like architecture. This pattern
was previously designated protoplasmic astrocytoma.
Immunophenotype
Diffuse astrocytomas reliably express
distinction of true neoplasia from reac-
GFAP, although to various degrees and
tive gliosis {347,359}. Strong nuclear p53
not in all tumour cells. In particular, small
expression is also frequently observed,
round cells with scanty cytoplasm and
consistent with the high incidence of
processes tend not to label avidly for
TP53 mutations in diffuse astrocytoma
GFAP. In these cases, immunopositiv-
{915}. However, the use of p53 immuno-
ity may be restricted to a small perinu-
positivity to reflect TP53 mutation is not
clear rim and to admixed neoplastic cell
entirely sensitive or specific {1530,1771}.
processes in the fibrillary tumour back-
In contrast, ATRX expression is almost
ground {1292}. Vimentin is typically im-
invariably lost in the setting of ATRX mu-
munopositive as well, with a labelling pat-
tations, which also feature prominently in
tern approximating that of GFAP {995}.
diffuse astrocytoma (see Genetic profile)
The signature molecular characteristics
{361,1160,1215,2105}. ATRX typically,
of diffuse astrocytoma (see Genetic pro-
demonstrates strong nuclear expression
file) can often be demonstrated immuno-
in normal, unmutated tissue; therefore,
histochemically. For example, expression
retention of immunolabelling in non-
of R132H-mutant IDH1 (the IDH1 R132H
neoplastic vasculature and admixed
mutation accounts for about 90% of all
neuronal, glial, and microglial elements
glioma-associated IDH mutations) can
serves as a necessary internal control for
be detected using a mutation-specific
the accurate interpretation of a negative
antibody {360}. In mutant tumours, all
ATRX immunostaining pattern. Finally,
neoplastic cells typically exhibit some
consistent with its inapparent mitotic ac-
degree of cytoplasmic (stronger) and
tivity, diffuse astrocytoma nearly always
nuclear (weaker) labelling, provided the
has a Ki-67 proliferation index of < 4%
staining preparation used is technically
{492,1137,1223,2059}.
adequate {359}. For this reason, R132H-
mutant IDH1 immunohistochemistry has Cell of origin
become an invaluable diagnostic ad- The available evidence suggests that
junct, not only in the molecular stratifi- IDH-mutant and 1p/19q-codeleted oli-
cation of diffuse glioma, but also in the godendrogliomas, IDH-mutant diffuse