Invasive breast carcinoma - IARC

unusual variants as well. Using this
approach many apocrine DCIS lesions
qualify as high grade, while a minority
would qualify as intermediate or, rarely,
high grade DCIS. The clear and spindle
cell DCIS are sometimes found coexistent
and continuous with typical low
grade DCIS, but often the nuclei are
moderately atypical qualifying the
lesions as intermediate grade DCIS.
High nuclear grade spindle or clear cell
DCIS is extremely rare. A vast majority of
apocrine carcinomas are ER, PR and
BCL2 negative, but androgen receptor
positive {2888}.
Proliferation
In vivo labelling with bromodeoxyuridine
(BrdU) has found no significant differences
between proliferating cell fraction
among UDH and ADH, but the proliferating
cell fraction is significantly increased
in DCIS {412}. With the Ki67 antibody, the
highest proliferating index (PI) of 13%
has been noted among the comedo
DCIS, while the PI for low grade DCIS,
cribriform type is 4.5% and for micropapillary
type, it is 0% {61}.
DNA Ploidy: Aneuploidy has been found
in 7% of UDH, 13-36% of ADH, and 30-
72% of low to high grade DCIS respectively
{408,579,792}.
Hormone receptor expression
E s t rogen plays a central role in re g u l a t i n g
the growth and diff e rentiation of bre a s t
epithelium as well as in the expression of
other genes including the pro g e s t e ro n e
receptor (PR) {72}. The presence and
concentration of the two receptors are
used, not only as a clinical index of
potential therapeutic response, but also
as markers of prognosis for invasive
b reast carcinomas {196}. Only a few
Fig. 1.91 DCIS, intermediate grade (DCIS grade 2).
This typical and most common intermediate grade
DCIS is characterized by a cribriform growth pattern
and intraluminal necrosis.
studies have evaluated estrogen re c e p t o r
(ER) in intraductal proliferative bre a s t
lesions. Among DCIS, about 75% of the
cases show ER expression {72,1399},
and an association between ER positivity
and the degree of diff e rentiation has
been described {1399}. There is agre e-
ment that nearly all examples of ADH
e x p ress high levels of ER in nearly all the
cells {72,1301,2667}. The re l a t i o n s h i p
between ER positive cell numbers and
patient age, as found in normal bre a s t
epithelium, is lost in these ADH lesions,
indicating autonomy of ER expression or
of the cells expressing the re c e p t o r
{ 2 6 6 7 } .
A
C
E
F
Fig. 1.90 Intermediate grade ductal carcinoma in situ. A Micropapillary type. The micropapillae are varied in
shape and composed of cells with moderately atypical, pleomorphic nuclei. A few apoptotic cells are present in
the lumen. B Flat type, approaching high grade DCIS. Two adjacent ductal spaces are lined by atypical cells, rare
mitotic figures and a few apoptotic nuclei. C, D Duct/part of a duct with micropapillary atypical epithelial proliferation.
Note secretory material in the lumen that should not be mixed up with comedo-type necrosis. E C l e a r
cell type. The neoplastic cells have clear cytoplasm with moderate nuclear pleomorphism. F Apocrine type with
moderate nuclear size variation. The abundant pink, granular cytoplasm suggests an apocrine cell type.
B
D
Differential diagnosis
The solid variant of low grade DCIS
may be misinterpreted as lobular neoplasia
(LN). Immunohistochemistry for
E-cadherin and CK1/5/10/14 (clone
CK34BetaE12) are helpful in separating
the two. Low grade DCIS is E-cadherin
positive in 100% of cases {337,
1090,3034} and CK34BetaE12 negative
in 92% of cases {337,1890}, whereas
lobular neoplasia (LN) is E-cadherin
negative {337,1033} and CK34BetaE12
positive in nearly all cases {337}. The
presence of individual or clusters of cells
invading the stroma (micro i n v a s i o n )
around a duct with DCIS is a frequent
source of diagnostic problems. The difficulty
is compounded by the frequent
presence of dense lymphoplasmacytic
infiltrate around the involved ducts.
Immunostains for an epithelial and myoepithelial
marker are helpful optimally in
the form of double immunostaining; the
epithelial cell marker can unmask the
haphazard distribution of the cells, while
the absence of a myoepithelial cell layer
would generally ascertain the invasive
nature of the cells in question. Despite all
Intraductal proliferative lesions
71