Invasive breast carcinoma - IARC

DIN terminology is used, the traditional
t e rminology should be mentioned as
well. The classification of intraductal proliferative
lesions should be viewed as an
evolving concept that may be modified
as additional molecular genetic data
become available.
Diagnostic reproducibility
Multiple studies have assessed re p roducibility
in diagnosing the range of intraductal
proliferative lesions, some with
emphasis on the borderline lesions {299,
5 0 3 , 2 1 5 5 , 2 1 5 7 , 2 4 1 1 , 2 5 7 1 , 2 7 2 3 , 2 7 2 4 } .
These studies have clearly indicated that
i n t e robserver agreement is poor when no
s t a n d a rdized criteria are used {2411}.
Although diagnostic re p roducibility is
i m p roved with the use of standardized criteria
{2571} discrepancies in diagnosis
persist in some cases, particularly in the
distinction between ADH and limited form s
of low grade DCIS. In one study, consistency
in diagnosis and classification did
not change significantly when interpre t a-
tion was confined to specific images as
c o m p a red with assessment of the entire
tissue section on a slide, reflecting inconsistencies
secondary to diff e rences in
morphological interpretation {780}. While
clinical follow-up studies have generally
demonstrated increasing levels of bre a s t
cancer risk associated with UDH, ADH
and DCIS re s p e c t i v e l y, concerns about
diagnostic re p roducibility have led some
to question the practice of utilizing these
risk estimates at the individual level {299}.
Aetiology
In general, the factors that are associated
with the development of invasive bre a s t
c a rcinoma are also associated with
i n c reased risk for the development
of intraductal proliferative lesions {1439a,
1551a,2536a}. (See section on epidemiology
of breast carc i n o m a ) .
Genetics of precursor lesions
To date, several genetic analyses have
been perf o rmed on potential pre c u r s o r
lesions of carcinoma of the breast. The
sometimes contradictory results (see
below) may be due to: (i) small number of
cases analysed, (ii) the use of diff e re n t
histological classification criteria, (iii) histomorphological
heterogeneity of both the
n o rmal and neoplastic breast tissue and
(iv) genetic hetero g e n e i t y, as identified by
either conventional cytogenetics {1175}
or by fluorescence in situ hybridization
Table 1.11
Classification of intraductal proliferative lesions.
Traditional terminology
Usual ductal hyperplasia (UDH)
Flat epithelial atypia
Atypical ductal hyperplasia (ADH)
Ductal carcinoma in situ,
low grade (DCIS grade 1)
Ductal carcinoma in situ,
intermediate grade (DCIS grade 2)
Ductal carcinoma in situ,
high grade (DCIS grade 3)
(FISH) analysis {1949}. Further evidence
for genetic heterogeneity comes from
comparative genomic hybridization
(CGH) data of microdissected tissue in
usual ductal hyperplasia (UDH), atypical
ductal hyperplasia (ADH) {135} and
DCIS {134,366}.
T h e re has been a tendency to interpre t
loss of heterozygosity as evidence for
clonal evolution and neoplastic transformation.
However, histologically norm a l
ductal epithelium closely adjacent to invasive
ductal carcinoma may share an LOH
p a t t e rn with the carcinoma, while norm a l
ducts further away in the breast do not
{671}. LOH has been re p o rted in norm a l
epithelial tissues of the breast, in association
with carcinoma and in re d u c t i o n
mammoplasties, however, the significance
of these finding remains to be evaluated
{671,1586,1945}. LOH has also been
identified in the stromal component of
in situ {1889} and invasive breast carc i n o-
ma {1545,1889}, in non-neoplastic tissue
f rom reduction mammoplasty specimens
{1568}, and in normal-appearing bre a s t
ducts {1586}. The biological significance
of these alterations are still poorly understood,
but the available data suggest that
genetic alterations may occur very early in
b reast tumorigenesis prior to detectable
morphological changes and that epithel
i a l / s t romal interactions play a role in prog
ression of mammary carc i n o m a .
Clinical features
The age range of women with intraductal
proliferative lesions is wide, spanning 7
Ductal intraepithelial neoplasia (DIN)
terminology
Usual ductal hyperplasia (UDH)
Ductal intraepithelial neoplasia,
grade 1A (DIN 1A)
Ductal intraepithelial neoplasia,
grade 1B (DIN 1B)
Ductal intraepithelial neoplasia,
grade1C (DIN 1C)
Ductal intraepithelial neoplasia,
grade 2 (DIN 2)
Ductal intraepithelial neoplasia,
grade 3 (DIN 3)
to 8 decades post adolescence. All
these lesions are extremely rare prior to
puberty; when they do occur among
infants and children, they are generally a
reflection of exogenous or abnorm a l
endogenous hormonal stimulation. The
mean age for DCIS is between 50-59
years. Though most often unilateral,
about 22% of women with DCIS in one
breast develop either in situ or invasive
c a rcinoma in the contralateral bre a s t
{3055}.
Macroscopy
A vast majority of intraductal pro l i f e r a-
tive lesions, particularly those detected
m a m m o g r a p h i c a l l y, are not evident on
m a c roscopic inspection of the specimen.
A small pro p o rtion of high grade
DCIS may be extensive enough and
with such an abundance of intraluminal
n e c rosis or associated stromal re a c t i o n
that it would present as multiple areas of
round, pale comedo necrosis or a firm ,
gritty mass.
Usual ductal hyperplasia (UDH)
Definition
A benign ductal proliferative lesion typically
characterized by secondary
lumens, and streaming of the central proliferating
cells. Although not considered
a precursor lesion, long-term follow-up of
patients with UDH suggests a slightly
elevated risk for the subsequent development
of invasive carcinoma.
64 Tumours of the breast