Invasive breast carcinoma - IARC

Fig. 4.19 Endometrial polyp. The glands are cystic
and contain mucoid material, the stroma is fibrous,
and the vessels are prominent.
premalignant disease {1956,1958} (see
section on genetics of endometrial carcinoma
and precursor lesions).The clinical
relevance of the model, however, has yet
to be established.
Endometrial polyp
Definition
A benign nodular protrusion above the
endometrial surface consisting of
endometrial glands and stroma that is
typically at least focally fibrous and contains
thick-walled blood vessels.
Histopathology
Histologically, they are pedunculated or
sessile lesions with a fibrous stroma in
which characteristic thick-walled, tortuous,
dilated blood vessels are found. The
glandular component is patchily distributed
and shows dilated, occasionally
crowded glands lined with an atrophic
epithelium, although rarely cyclic activity
may be observed. Rare cases of atypical
Fig. 4.21 Uterine tamoxifen-related lesion.Thickened
myometrium in a 69 year old patient with subendometrial
cysts and a polyp (arrow).
Fig. 4.20 Endometrial polyp with complex hyperplasia.
Note the foci of crowded, convoluted glands in
an atrophic endometrial polyp.
stromal cells have been documented in
endometrial polyps {2834}, similar to
those seen in polyps of the lower female
genital system. Polyps can be differentiated
from polypoid hyperplasias due to
the distinctive stromal and vascular features
of the former. Atypical hyperplasias
and malignant tumours including adenocarcinomas
of endometrioid and other
types such as serous, as well as sarcomas
and mixed tumours {2675} can be
found arising in polyps.
Somatic genetics
Endometrial polyps constitute benign
monoclonal proliferations of mesenchyme
{891} and frequently show kary o t y p i c
a b n o rmalities of chromosomal re g i o n s
6p21 and 12q15 {2854}, sites in which the
H M G I C and H M G I Y genes are located.
Prognosis and predictive factors
Polyp resection or polypectomy are the
t reatments of choice with few re c u r-
rences reported {2928}.
Tamoxifen-related lesions
Definition
Lesions that develop in the endometrium
in patients undergoing long term tamoxifen
therapy.
Epidemiology
Patients undergoing long term tamoxifen
treatment often have enlarged uteri and
frequently show endometrial cysts; up to
25% have endometrial polyps {531}.
Macroscopy
Tamoxifen-related polyps differ from noniatrogenic
endometrial polyps in that they
are larger, sessile with a wide implantation
base in the fundus and frequently
show a honeycomb appearance.
Histopathology
H i s t o l o g i c a l l y, the diff e rential feature s
with normal endometrial polyps include
the bizarre stellate shape of glands and
the frequent epithelial (mucinous, ciliated,
eosinophilic, microglandular) and
s t romal (smooth muscle) metaplasias
{665,1437,2558}. There is often a
periglandular stromal condensation
(cambium layer). Malignant transformation
occurs in up to 3% of cases, and
endometrioid adenocarcinoma is the
most frequent type. However, other types
of malignant neoplasm such as serous
c a rcinoma and carc i n o s a rcoma may
develop in this setting.
Somatic genetics
Despite these histological differences,
the cytogenetic profile of tamoxifen-related
polyps is identical to non-iatrogenic
polyps {609}.
Genetics of endometrial
carcinoma and precancer
Genotype and histotype
Endometrial adenocarcinoma is characterized
by the abrogation of PTEN or
T P 53
tumour suppressor pathways,
respectively, for the endometrioid (type I)
and non-endometrioid (type II, including
serous and clear cell types) clinicopathological
subgroups {2647}. Deletion
and/or mutation of the PTEN and TP53
genes themselves are early events with
w i d e s p read distribution in advanced
tumours and a presence in the earliest
Fig. 4.22 TP53 mutations in endometrial carcinoma.
Left: Wild type sequence in an endometrioid carcinoma:
Exon 8 mutations in two serous carcinomas
(arrows). Middle: GTT > TTT; Val > Phe (codon 274).
R i g h t : CGT > CAT; Arg > His (codon 273).
230 Tumours of the uterine corpus