Invasive breast carcinoma - IARC

A
Fig. 2.31 Sertoliform endometroid carcinoma. A The tubular glands contain high grade nuclei. The luteinized
ovarian stromal cells resemble Leydig cells. B Small endometrioid glands contain luminal mucin.
(Mucicarmine stain).
limited to both organs provides strong
evidence that these neoplasms are mostly
independent primaries arising as a
result of a müllerian field effect {822}.
Less frequently, one of the carcinomas
represents a metastasis from the other
tumour.
The criteria for distinguishing metastatic
from independent primary carcinomas
rely mainly upon conventional clinicopathologic
findings, namely stage, size,
histological type and grade of the
tumours, the presence and extent of
blood vessel, tubal and myometrial invasion,
bilaterality and pattern of ovarian
involvement, coexistence with endometrial
hyperplasia or ovarian endometriosis
and, ultimately, patient follow-up {762,
2286,2978}. By paying attention to these
findings, the precise diagnosis can be
established in most cases. Occasionally,
however, the differential diagnosis may
be difficult or impossible as the tumours
may show overlapping features.
In difficult cases comparative analysis of
the immunohistochemical and DNA flow
cytometric features of the two neoplasms
may be of some help {822,2286}. The presence
of identical aneuploid DNA indexes
in two separate carcinomas suggests
B
that one of them is a metastasis from the
other {2286}. In contrast, when the two
neoplasm have diff e rent DNA indexes,
the possibility of two independent primaries
has to be considered {2286}. The latter
results, however, do not completely exclude
the metastatic nature of 1 of the tumours,
since metastatic tumours or even
d i ff e rent parts of the same tumour may
occasionally have diff e rent DNA indexes
reflecting tumour pro g ression {2728}.
Molecular pathology techniques can also
be helpful {1788}. These include LOH,
{783,923,1664,2641}, gene mutation
{923,1664,1909} and clonal X-inactivation
analyses {926}. Although LOH pattern
concordance in two separate carcinomas
is highly suggestive of a common
clonal origin (i.e. one tumour is a metastasis
from the other), the finding of different
LOH patterns does not necessarily
indicate that they represent independent
tumours. Some studies have shown varying
LOH patterns in different areas of the
same tumour as a consequence of
tumour heterogeneity {287}. Discordant
PTEN mutations and different microsatellite
instability (MI) patterns in the two
neoplasms are suggestive of independent
primary carcinomas; nevertheless,
metastatic carcinomas may also exhibit
gene mutations that differ from those of
their corresponding primary tumours as
a result of tumour progression {923}.
Alternatively, two independent primary
carcinomas may present identical gene
mutations reflecting induction of the
same genetic abnormalities by a common
carcinogenic agent acting in two
separate sites of a single anatomic
region {1786,1788}. In other words, the
genetic profile can be identical in independent
tumours and diff e rent in
metastatic carcinomas {1788}. Therefore,
clonality analysis is useful in the distinction
of independent primary carcinomas
from metastatic carcinomas provided the
diagnosis does not rely exclusively on a
single molecular result and the molecular
data are interpreted in the light of appropriate
clinical and pathologic findings
{1786,1788,2283}.
According to FIGO when the site of origin
remains in doubt after pathological
examination, the primary site of the
tumour should be determined by its initial
clinical manifestations.
Genetic susceptibility
Most endometrioid carcinomas occur
s p o r a d i c a l l y, but occasional cases
develop in families with germline mutations
in DNA mismatch repair genes,
mainly MSH2 and MLH1 (Muir-Torre syndrome)
{535}. This syndrome, thought to
be a variant of the hereditary nonpolyposis
colon cancer syndrome, is characterized
by an inherited autosomal dominant
susceptibility to develop cutaneous and
visceral neoplasms {796}.
Prognosis and predictive factors
The 5-year survival rate (FIGO) of
patients with stage I carcinoma is 78%;
stage II, 63%; stage III, 24%; and stage
A
Fig. 2.32 Endometrioid adenocarcinoma resembling a granulosa cell tumour. A Note the microglandular
pattern. B Immunostains for alpha-inhibin are positive in the luteinized stromal cells and negative in the
epithelial cells.
B
Fig. 2.33 Ovarian endometrioid carcinoma. Immunostain
for beta-catenin shows intense and diffuse
positivity.
132 Tumours of the ovary and peritoneum