Invasive breast carcinoma - IARC

Fig. 2.05 Serous borderline tumour. The sectioned
surface shows a solid and cystic neoplasm with
numerous papillary excrescences.
tumour pro g ression model in which
sequential accumulation of molecular
genetic alterations leading to morphologically
recognizable stages is well established
{1468}, a similar model for ovarian
s e rous carcinoma has not been proposed
because well defined precursor
lesions have not been identified.
It has been reported that even the earliest
histological serous carcinomas are
already high grade and morphologically
resemble their advanced stage counterparts
{205}. The histological similarities
are paralleled by recent molecular genetic
findings demonstrating TP53 mutations
in very small stage I serous carcinomas
and in the adjacent "dysplastic"
surface epithelium {2275}. Most studies
have shown that approximately 60% of
advanced stage ovarian serous carcinomas
have mutant TP53 {230,3095}. Thus,
although the molecular genetic findings
in these early carcinomas are preliminary,
they suggest that serous carcinoma
in its very earliest stage of development
resembles advanced stage serous carcinoma
at the molecular level. This would
support the view that there are no morphologically
recognized interm e d i a t e
steps in the progression of the conventional
type of ovarian serous carcinoma.
S e rous borderline tumours (SBTs), noninvasive
and invasive micro p a p i l l a ry
types, frequently display K R A S m u t a t i o n s
but rarely mutant T P 5 3. Increased allelic
imbalance of chromosome 5q is associated
with the pro g ression from typical
SBT to micro p a p i l l a ry SBT and incre a s e d
allelic imbalance of chromosome 1p with
the pro g ression from micro p a p i l l a ry SBT
to invasive serous carcinoma {2706}. In
contrast, K R A S mutations are very rare in
conventional serous carcinoma, but T P 5 3
mutations occur in approximately 60%.
Recently, mutations were also identified
in the BRAF gene, a downstream mediator
of KRAS. BRAF and KRAS mutations
appear to be mutually exclusive. These
mutations were only detected in low
grade ovarian serous carcinomas {2707}.
Thus, there appears to be more than one
pathway of tumorigenesis for serous carcinoma.
In one pathway, conventional
serous carcinoma, a high grade neoplasm,
develops "de novo" from the surface
epithelium of the ovary, grows rapidly
and is highly aggressive {205}.
These tumours, even at their earliest
stage, display TP53 mutations but not
KRAS mutations. In the other pathway a
SBT progresses in a "stepwise" fashion
t h rough a non-invasive micro p a p i l l a ry
stage before becoming invasive {2706}
or through microinvasion in a backg
round of typical SBT. The indolent
m i c ro p a p i l l a ry tumours frequently display
KRAS mutations, but TP53 mutations
are only rarely detected.
Genetic susceptibility
The neoplasms that develop in women
with germline B R C A 1 mutations are
mostly serous carcinomas of the ovary,
fallopian tube and peritoneum.
Prognosis and predictive factors
The overall 5-year survival is appro x i m a t e-
ly 40%; however, many of those alive at 5
years are alive with disease. Up to 85% of
cases present with widespread metastatic
disease. Survival at 5 years in this gro u p
is 10-20%. Patients with disease confined
Table 2.01
Histological criteria for the diagnosis of serous
borderline tumours.
- Epithelial hyperplasia in the form of stratification,
tufting, cribriform and micropapillary
arrangements
- Atypia (usually mild to moderate)
- Detached cell clusters
- Variable and usually minimal mitotic activity
- Absence of destructive stromal invasion
to the ovary or pelvis have a 5-year survival
of 80%. Patients with serous psamm
o c a rcinoma have a protracted clinical
course and a relatively favourable pro g-
nosis; their clinical behaviour more closely
resembles that of SBT than serous carcinoma
of the usual type.
Serous borderline tumour with
microinvasion
Definition
An ovarian serous tumour of low malignant
potential exhibiting early stromal
invasion characterized by the presence
in the stroma of individual or clusters of
neoplastic cells cytologically similar to
those of the associated non-invasive
tumour. One or more foci may be present;
none should exceed 10 mm 2 .
Synonyms
Serous tumour of low malignant potential
with microinvasion, serous tumour of borderline
malignancy with microinvasion.
Epidemiology
P resent in about 10-15% of SBTs ,
microinvasion occurs in women ranging
in age from 17-83 years with a median
age of 34.5 years {203,2867}.
Clinical features
Most symptomatic women present with a
pelvic mass or pain. About 28% of the 39
women in the 2 major series were pre g-
nant at the time of presentation {203,2867}.
Macroscopy
The macroscopic features are similar to
those of SBT without microinvasion.
Tumour spread and staging
At presentation about 60% of the neoplasms
are stage IA, 13% stage 1B, 5%
stage IC, 8% stage IIC, 10% stage III
(mostly IIIC) and 2.5% stage IV (liver
metastases).
Histopathology
The hallmark of serous borderline tumours
with microinvasion is the presence within
the tumour stroma of single cells and cell
clusters with generally abundant eosinophilic
cytoplasm morphologically identical
to those of the adjacent non-invasive tum
o u r. The microinvasive foci form microp
a p i l l a ry, solid or rarely cribriform arrangements
without or with only minimal stro m a l
or cellular reaction. These cells are often
120 Tumours of the ovary and peritoneum