Invasive breast carcinoma - IARC

early secretory endometrium {2605}. The
oxyphilic variant has a prominent component
of large polygonal tumour cells with
abundant eosinophilic cytoplasm and
round central nuclei with pro m i n e n t
nucleoli {2258}.
Occasional tumours contain solid are a s
punctuated by tubular or round glands or
small rosette-like glands (micro g l a n d u l a r
p a t t e rn) simulating an adult granulosa
cell tumour {3206}. In contrast to Call-
Exner bodies, however, the micro g l a n d s
contain intraluminal mucin. The nuclei of
endometrioid carcinomas are usually
round and hyperc h romatic, where a s
those of granulosa cell tumours are
round, oval, or angular, pale and grooved.
Rare cases of endometrioid carcinomas
of the ovary show focal to extensive
a reas resembling Sertoli and Sert o l i -
Leydig cell tumours {2111,2466,3206}.
They contain small, well differentiated
hollow tubules, solid tubules or, rarely,
thin cords resembling sex cords. When
the stroma is luteinized, this variant may
be mistaken for a Sertoli-Leydig cell
tumour, particularly in cases in which the
patient is virilized. Nevertheless, typical
glands of endometrioid carcinoma and
squamous differentiation are each present
in 75% of the tumours, facilitating
their recognition as an endometrioid carcinoma
{3206}. Furthermore, immunostains
for alpha-inhibin are positive in
Sertoli cells but negative in the cells of
endometrioid carcinoma {1789}.
Immunoprofile
Endometrioid carcinomas are vimentin,
cytokeratin, epithelial membrane antigen,
estrogen and progesterone receptor
and B72.3 positive but alpha-inhibin
negative {1789}.
Grading
Grading of endometrioid carcinoma uses
the same criteria as endometrial adenocarcinoma
{3238} (see chapter 4).
Histogenesis
Most endometrioid carcinomas are
thought to arise from surface epithelial
inclusions, and up to 42% are accompanied
by ipsilateral ovarian or pelvic
endometriosis {676,932,1927,2489} that
may display the entire spectrum of
endometrial hyperplasia (simple, complex,
typical and atypical). Atypical ipsilateral
endometriosis occurs in up to 23%
of endometrioid carcinomas {932} and
may have a role in the evolution of some
endometrioid carcinomas {2618}.
Somatic genetics
Somatic mutations of beta-catenin
(CTNNB1) and PTEN are the most common
genetic abnormalities identified in
sporadic endometrioid carcinomas. The
incidence of CTNNB1 mutations ranges
f rom 38-50% {1909,2153}. Mutations
have been described in exon 3 (codons
32, 33, 37, and 41) and involve the phosphorylation
sequence for glycogen synthase
kinase 3β. These mutations probably
render a fraction of cellular betacatenin
insensitive to APC-mediated
down-regulation and are responsible for
its accumulation in the nuclei of the
tumour cells. Beta-catenin is immunohistochemically
detectable in carc i n o m a
cells in more than 80% of the cases.
Endometrioid carcinomas with betacatenin
mutations are characteristically
early stage tumours associated with a
good prognosis {955}.
PTEN is mutated in approximately 20% of
endometrioid ovarian tumours and in
46% of those with 10q23 loss of heterozygosity
(LOH) {2075}. PTEN mutations
occur between exons 3 to 8. The
majority of endometrioid carcinomas with
PTEN mutations are well differentiated
and stage I tumours, suggesting that in
this subset of ovarian tumours P T E N
inactivation is an early event {2075}. The
finding of 10q23 LOH and PTEN mutations
in endometriotic cysts that are adjacent
to endometrioid carcinomas with
similar genetic alterations provides additional
evidence for the precursor role of
endometriosis in ovarian carcinogenesis
{2543}.
Microsatellite instability (MI) also occurs
in sporadic endometrioid carcinomas of
the ovary although less frequently than in
uterine endometrioid carcinomas. The
reported frequency of MI in the former
tumours ranges from 12.5-19% {1055,
1909}. Like endometrial carc i n o m a s ,
many ovarian carcinomas with MI follow
the same process of MLH1 promoter
methylation and frameshift mutations at
coding mononucleotide repeat microsatellites
{1055}.
Simultaneous endometrioid
carcinomas of the ovary and
endometrium
Endometrioid carcinoma of the ovary is
associated in 15-20% of the cases with
carcinoma of the endometrium {767,822,
1479,2651,3239}. The very good prognosis
in those cases in which the tumour is
A
Fig. 2.30 Well differentiated endometrioid adenocarcinoma of the ovary. A Confluent growth of glands is evident with replacement of stroma. B Note the squamous
differentiation in the form of squamous morules and keratin pearls.
B
Surface epithelial-stromal tumours 131