Invasive breast carcinoma - IARC

IV, 6% {2233}. Patients with grade 1 and
2 tumours have a higher survival rate
than those with grade 3 tumours {1479}.
Peritoneal foreign body granulomas to
keratin found in cases of endometrioid
carcinoma with squamous differentiation
do not seem to affect the prognosis
adversely in the absence of viableappearing
tumour cells on the basis of a
small series of cases {1459}. Endometrioid
carcinomas with a mixed clear cell,
s e rous or undiff e rentiated carc i n o m a
component are reported to have a worse
prognosis {2941}.
Malignant müllerian mixed tumour
Definition
A highly aggressive neoplasm containing
malignant epithelial and mesenchymal
elements.
Synonyms
Carcinosarcoma, malignant mesodermal
mixed tumour, metaplastic carcinoma.
Epidemiology
Malignant müllerian mixed tumours
(MMMTs) are rare, representing less than
1% of ovarian malignancies. They occur
most commonly in postmenopausal
women of low parity, the median age
being around 60.
Clinical features
The clinical presentation is similar to that
of carcinoma of the ovary.
Aetiology
An increased incidence has been reported
in women who have had pelvic irradiation
{3080}.
Macroscopy
The neoplasms form large (10-20 cm
diameter), partly solid and partly cystic,
or, less commonly, solid, grey-brown, unilateral
or bilateral, bosselated masses
with foci of haemorrhage and necrosis
{479}. The sectioned surface is fleshy
and friable, and cartilage and bone may
be apparent. The tumours are bilateral in
90% of cases.
Tumour spread and staging
T h e re is extraovarian spread to the
pelvic peritoneum, omentum, pelvic
organs and regional lymph nodes in
m o re than 75% of cases at the time of
d i a g n o s i s .
Fig. 2.34 Genetic differences in concurrent endometrial and ovarian adenocarcinoma. DNA sequencing of
exon 3 of the beta-catenin(CTNNB1) gene showing a GGA to GCA change at codon 32 (Asp>His) in the ovarian
endometrioid adenocarcinoma (right, arrow). The mutation was not identified in the uterine endometrial
carcinoma (left).
Histopathology
The histological and immunoprofile are
similar to those of its uterine counterpart
and those occurring elsewhere in the
female genital system (see chapter 4).
Histogenesis
MMMT is believed to develop from the
ovarian surface epithelium or from foci of
endometriosis and, therefore, may be
regarded as a high grade carcinoma with
metaplastic sarcomatous elements. The
positive tumour response to chemotherapy
directed at ovarian carcinoma also
supports this viewpoint.
Somatic genetics
There is evidence that MMMTs are monoclonal
{26,2748} as the phenotypically
different elements share similar allelic
losses and retentions {925} and a cell
line developed from an MMMT expresses
both mesenchymal and epithelial antigens
{195}. Furt h e rm o re, a hetero g e-
neous pattern of allelic loss at a limited
number of chromosomal loci in either the
carcinomatous or sarcomatous component
of the neoplasm is consistent with
either genetic pro g ression or genetic
diversion occurring during the clonal
evolution of the tumour.
Genetic susceptibility
There is anecdotal evidence of BRCA2
mutation {2748}.
Prognosis and predictive factors
I m p roved cytoreductive surgery and
platinum based chemotherapy has
resulted in a median survival of 19
months {2715} and an overall 5-year survival
of 18-27% {120,1182}. The survivors
almost invariably have early stage disease
at the time of diagnosis, and low
stage is a statistically significant indicator
of outcome {120,436,1182,2749}. No
other histopathological factors are significant
indicators of outcome.
Adenosarcoma
Definition
A biphasic tumour characterized by a
proliferation of müllerian-type epithelium
with a benign or occasionally markedly
atypical appearance embedded in or
Fig. 2.35 Malignant müllerian mixed tumour. Poorly
differentiated glands are surrounded by spindleshaped,
rounded and multinucleated cells.
Surface epithelial-stromal tumours 133