Invasive breast carcinoma - IARC

schema {1535,2602}. Although this classification
has been widely applied, its
reproducibility is somewhat disappointing
{240,1433}, and molecular data with
direct implications for histological diagnosis
were unavailable at the time of the
1994 classification {1956}. Nevertheless,
it remains the best available classification
and has been adopted in this new
edition.
Endometrial hyperplasias are assumed
to evolve as a progressive spectrum of
endometrial glandular alterations divided
into four separate categories by architecture
and cytology. The vast majority of
endometrial hyperplasias mimic proliferative
endometria, but rare examples
demonstrate secre t o ry features. The
entire spectrum of metaplastic changes
may be observed in hyperplastic
endometria.
Hyperplasias without atypia
Hyperplasias without atypia re p re s e n t
the exaggerated proliferative response
to an unopposed estrogenic stimulus;
the endometrium responds in a diffuse
manner with a balanced increase of both
glands and stroma. In simple hyperplasia
the glands are tubular although frequently
cystic or angular, and some even
show minor epithelial budding. The lining
is pseudostratified with cells displaying
regular, elongated nuclei lacking atypia.
In complex (adenomatous) hyperplasia
the glands display extensive complicated
architectural changes represented by
i r regular epithelial budding into both
lumina and stroma and a typical cytology
with pseudostratified but uniform, elongated
and polarized glandular nuclei;
squamous epithelial morules can be
present. There is most often a shift in the
gland to stroma ratio in favour of the
glands.
Atypical hyperplasias
The main feature which differentiates this
category from the previous one is the
atypical cytology of the glandular lining
as represented by loss of axial polarity,
unusual nuclear shapes that are often
rounded, irregularity in the nuclear membranes,
prominent nucleoli and cleared
or dense chromatin. Atypia occurs nearly
always focally.
Simple atypical hyperplasia feature s
atypical glandular cytology superimposed
on the arc h i t e c t u re of simple
hyperplasia. This pattern is extremely
unusual. The frequently found complex
atypical (adenomatous with atypia)
hyperplasia is a lesion characterized by
an increased glandular complexity with
i r regular outgrowths and cytological
atypia. There may be associated foci of
non-endometrioid differentiation such as
squamous morules. Due to the expansion
and crowding of glands, the interglandular
stroma is diminished but
remains present. Characteristic features
of adenocarcinoma are absent.
The assessment of cytological atypia is
the key problem in assigning individual
cases to one of the four different WHO
categories. Definitions of cytological
atypia are difficult to apply in the
endometrium because nuclear cytological
changes occur frequently in hormonal
imbalance, benign regeneration and
metaplasia {1619,2033}. Paradoxically,
atypical hyperplasia may exhibit more
atypical features than adenocarcinoma
{2688}, and some grade 1 invasive
endometrioid carcinomas have an
e x t remely bland cytology. Perhaps, it
would be more appropriate to consider
cytological changes in the context of
overall glandular architecture. Indeed,
architectural focality of the lesion is so
closely linked with atypia that possibly
they are inseparable. In this way, atypia
is best observed by comparison with
adjoining normal glands.
Caveat: sampling problems
The focal nature of atypical endometrial
hyperplasias may allow young women to
maintain fertility, but has the disadvantage
of possible underdiagnosis due to
incomplete sampling. The problem is
g reatest in scanty fragmented specimens,
something commonly encountered
in routine office biopsies. Clearly,
this situation is responsible for the false
negative biopsies during follow up.
Hysteroscopic direction may assist in targeting
a macroscopically apparent localized
lesion but is not a common practice
in most settings.
Contemporary approach to
endometrial hyperplasia
Poor reproducibility of the 1994 WHO
hyperplasia schema {240,1433} has led
to a proposal to reduce the number of
diagnostic classes {240}. New concepts
of pathogenesis have been incorporated
into an integrated genetic, histomorphometric
and clinical outcome model of
A
Fig. 4.18 Complex atypical hyperplasia. A There is glandular crowding with eosinophilic cytoplasm and nuclear enlargement, loss of polarity and prominent nucleoli.
On the right is a residual, non-atypical cystic gland. B The glands are tortuous with epithelial tufts (reflecting abnormal polarity) protruding into the lumens and
show cytological atypia.
B
Epithelial tumours and related lesions 229