Invasive breast carcinoma - IARC

Synonyms
Ductal intraepithelial neoplasia 1A (DIN
1A); clinging carcinoma, monomorphous
type; atypical cystic lobules; atypical lobules,
type A; atypical columnar change.
Risk of progression
Some cases of flat epithelial atypia may
progress to invasive breast cancer but
no quantitative epidemiological data are
currently available for risk estimation.
Histopathology
A flat type of epithelial atypia, this
change is characterized by replacement
of the native epithelial cells by a single
layer of mildly atypical cells often with
apical snouts, or proliferation of a monotonous
atypical cell population in the
form of stratification of uniform, cuboidal
to columnar cells generally up to 3-5 cell
layers with occasional mounding.
Arcades and micropapillary formations
a re absent or very rare. The TDLUs
involved are variably distended and may
contain secretory or floccular material
that often contains microcalcifications.
Genetic alterations
Data on genetic alterations in flat
epithelial atypia are limited. LOH has
been found in at least one locus in 70%
of cases in a study evaluating eight loci
in thirteen lesions {1889}. LOH on 11q
(D11S1311) was the most commonly
noted in 50% of the pure flat atypia,
Fig. 1.82 Flat epithelial atypia. Immunostain for
CK34βE12 shows no staining in the neoplastic cells
lining the ductules, but the residual luminal epithelial
cells adherent along the luminal surface show
intense staining.
while among seven flat atypias associated
with infiltrating carcinomas, the frequency
of LOH on 11q (D11S1311) was
57% {1889}.
Atypical ductal hyperplasia
(ADH)
Definition
A neoplastic intraductal lesion characterized
by proliferation of evenly distributed,
monomorphic cells and associated with
a moderately elevated risk for progression
to invasive breast cancer.
Synonyms
Ductal intraepithelial neoplasia 1B (DIN
1B), atypical intraductal hyperplasia.
Risk of progression
The Cancer Committee of the College of
American Pathologists has assigned
ADH a moderately increased risk (RR of
4.0-5.0) for subsequent development of
invasive breast cancer {885}. Following
a breast biopsy diagnosis of ADH, 3.7-
22% of the women develop invasive
c a rcinomas {299,733,1520,2886}. On
the other hand, ADH has also been
p resent in 2.2% {2158} to 10.5% {1688}
of controls who did not develop subsequent
carcinoma. The average interval
to the subsequent development of invasive
carcinoma is 8.3 years compare d
to 14.3 years for women with UDH
{ 2 8 8 6 } .
However, drastically different relative risk
(RR) estimations have been reported for
ADH, ranging from a low of 2.4 to a high
of 13 {412,732,1688,1775,1830,2155,
2158}. The upper values are even higher
than the RR of 8-11 suggested for DCIS
{732,885}. On the other hand, the RR of
2.4 for ADH reported in one study {1775}
is much closer to the RR of 1.9 associated
with UDH.
Histopathology
The most distinctive feature of this lesion
is the proliferation of evenly distributed,
monomorphic cells with generally ovoid
to rounded nuclei. The cells may grow in
m i c ropapillae, tufts, fronds, arc a d e s ,
rigid bridges, solid and cribriform patterns.
Cytologically, ADH corresponds to
low grade DCIS.
ADH is diagnosed when characteristic
cells coexist with patterns of UDH,
and/or there is partial involvement of
TDLU by classic morphology. There is
c u r rently no general agreement on
whether quantitative criteria should be
applied to separate ADH from low grade
DCIS. Some define the upper limit of
ADH as one or more completely involved
duct/ductular cross sections measuring
≤2 mm in aggregate, while others require
that the characteristic cytology and
architecture be present completely in two
spaces. Microcalcifications may be
absent, focal or extensive within the
lumen of involved ducts; its presence
does not impact diagnosis.
Fig. 1.81 Flat epithelial atypia. A terminal duct-lobular unit with distended acini and a floccular secretory
luminal content. The spaces are lined by one to three layers of monotonous atypical cells.
Immunoprofile
ERBB2 protein overexpression is rare in
ADH {72,1172}, in contrast to high amplification
rates in high grade DCIS, suggesting
that ERBB2 alterations are either
66 Tumours of the breast