Invasive breast carcinoma - IARC

Most melanotic tumours of the breast
re p resent metastases from malignant
melanomas originating in extra-mammary
sites {2694}. Primary melanomas may
arise anywhere in the skin of the breast,
but an origin in the nipple-areola complex
is extremely rare {2168}. The differential
diagnosis of malignant melanoma
arising in the nipple areolar region must
include Paget disease, the cells of which
may on occasion contain melanin pigment
{2544}. This is discussed in the
section on Paget disease.
Genetics
The genetic variation seen in breast cancer
as a whole is similarly reflected in
ductal NOS tumours and has until recently
proved difficult to analyse or explain.
The increasing accumulation of genetic
alterations seen with increasing grade
( d e c reasing degree of diff e re n t i a t i o n )
has been used to support the hypothesis
of a linear progression model in this type
and in invasive breast cancer as a whole.
The recent observation by a number of
groups that specific genetic lesion or
regions of alteration are associated with
histological type of cancer or related to
grade in the large ductal NOS group
does not support this view. It implies that
b reast cancer of ductal NOS type
includes a number of tumours of unrelated
genetic evolutionary pathways {365}
and that these tumours show fundamental
differences when compared to some
special type tumours including lobular
{1085} and tubular carcinoma {2476}.
F u rt h e rm o re, recent cDNA micro a r r a y
analysis has demonstrated that ductal
NOS tumours can be classified in to subtypes
on the basis of expression patterns
{2218,2756}.
Prognosis and predictive factors
Ductal NOS carcinoma forms the bulk
(50-80%) of breast cancer cases and its
p rognostic characteristics and management
are similar or slightly worse with a
35-50% 10 year survival {771} compare d
to breast cancer as a whole with aro u n d
a 55% 10 year survival. Prognosis is
influenced profoundly by the classical
p rognostic variables of histological
grade, tumour size, lymph node status
and vascular invasion (see general discussion
of prognosis and predictive factors
at the end of this chapter) and by
p redictors of therapeutic response such
as estrogen receptor and ERBB2 status.
A
Fig. 1.17 Carcinoma with choriocarcinomatous features. A,B Multinucleated tumour cells with smudged
nuclei extend their irregular, elongated cytoplasmic processes around clusters of monocytic tumour cells,
mimicking the biphasic growth pattern of choriocarcinoma. B Note the abnormal mitotic figures in this high
grade carcinoma.
Approximately 70-80% of ductal NOS
breast cancers are estrogen receptor
positive and between 15 and 30% of
cases ERBB2 positive. The management
of ductal NOS carcinomas is also influenced
by these prognostic and predictive
characteristics of the tumour as well
as focality and position in the breast.
Invasive lobular carcinoma
Definition
An invasive carcinoma usually associated
with lobular carcinoma in situ is composed
of non-cohesive cells individually
dispersed or arranged in single-file linear
pattern in a fibrous stroma.
ICD-O code 8520/3
Epidemiology
Invasive lobular carcinoma (ILC) represents
5-15% of invasive breast tumours
{725,771,1780,2541,2935,3133}. During
the last 20 years, a steady increase in its
incidence has been reported in women
over 50 {1647}, which might be attributable
to the increased use of hormone
replacement therapy {312,1648,2073}.
The mean age of patients with ILC is 1-3
years older than that of patients with infiltrating
ductal carcinoma (IDC) {2541}.
Clinical features
The majority of women present with a
palpable mass that may involve any part
of the breast although centrally located
tumours were found to be slightly more
common in patients with ILC than with
IDC {3133}. A high rate of multicentric
tumours has been reported by some
{699,1632} but this has not been found in
other series based on clinical {2541} or
B
radiological {1599} analysis (see bilateral
b reast carcinoma section). An 8-19%
incidence of contralateral tumours has
also been reported {699,725,834}, representing
an overall rate of 13.3 %. This
may be higher than that for IDC
{1241,2696}. However, no significant difference
in the rate of bilaterality was
observed in other series of cases {648,
1168,2186}. At mammography, architectural
distortion is more commonly
observed in ILC than in IDC whereas
microcalcifications are less common in
ILC {895,1780,3066}.
Macroscopy
ILC frequently present as irregular and
poorly delimited tumours which can be
d i fficult to define macro s c o p i c a l l y
because of the diffuse growth pattern of
the cell infiltrate {2696}. The mean diameter
has been reported to be slightly larger
than that of IDC in some series
{2541,2696,3133}.
Histopathology
The classical pattern of ILC {895,
1780,3066} is characterized by a proliferation
of small cells, which lack cohesion
Fig. 1.18 Macroscopy of an invasive lobular carcinoma
displays an ill defined lesion.
Invasive breast cancer
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