Ductal Carcinoma
In Situ
367
FIG. 11.48.
In situ carcinoma with ductal and lobular features.
A:
Carcinoma in a duct (
right
) and
distended lobular glands (
left
).
B:
Small and large cell populations are present. Microlumina have
been formed in an area composed of small cells in a duct. The lesion was immunoreactive for
E-cadherin.
quantitative descriptors of necrosis are present, focally pres-
ent, or absent. In the Van Nuys classification system, only
the “zonal” type of necrosis classifies DCIS as exhibiting
necrosis; however, occasional desquamated or individually
necrotic cells do not qualify as DCIS in this scheme.
Sneige et al.
129
studied interobserver reproducibility
among six pathologists who assessed nuclear grade, accord-
ing to Lagios’ criteria (Table 11.3), in 125 examples of DCIS.
Complete agreement on nuclear grade was reported in 43
cases (35%), and five of six pathologists agreed in 45 (36%).
The generalized kappa for distinctions between grades 1 and
2 and between 2 and 3 were 0.29 and 0.48, respectively (stan-
dard error
=
0.02). These levels of agreement were regarded
as fair and moderate by the authors. Pair-wise correlations
between individual pathologists and the consensus grade in-
cluded a range of kappa values from 0.44 to 0.76, with 5 of
6 having values greater than 0.60, representing “substantial”
agreement.
Some authors have suggested that apocrine andmicropap-
illary DCIS be listed as separate categories and not included
in a three-tiered grading scheme.
157
This proposal appears
to derive from perceived difficulty in assigning these lesions
to one of the three conventional grades because of inconsis-
tent expression of individual criteria for grading. However,
in practice, DCIS with apocrine or micropapillary features
express the same range of histologic variation as nonapo-
crine and nonmicropapillary DCIS, and separate character-
ization is not recommended. In regard to apocrine lesions,
nuclear grade is based on comparison with nuclei in usual
benign apocrine metaplasia. The distribution of architectural
patterns and necrosis is not different in apocrine and non-
apocrine DCIS. Micropapillary DCIS is subject to variations
in nuclear grade and to necrosis (illustrated in this chapter),
which do not differ from other architectural types of DCIS.
Agreement onDCIS grading has been shown to be achieved
more commonly with the Van Nuys classification system,
compared with those of Lagios and Holland.
158
Pinder et al.
159
have identified a subdivision of DCIS with “very poor prog-
nosis.” This “very high-grade” type of DCIS has high cytonu-
clear grade, solid (more than 50%) architecture, and extensive
comedo-type necrosis (more than 50%). This “novel” classifi-
cation for DCIS offered better prognostic discrimination for
ipsilateral recurrence than “cytonuclear grade” classification
alone when applied to cases assembled in a clinical trial.
159
Preliminary studies show promise in assessing the mo-
lecular “grade” of DCIS through the use of array-based com-
parative genomic hybridization (CGH) and other related
techniques. Such molecular profiling has the potential to
improve the clinical evaluation of DCIS and is becoming in-
creasingly possible.
160
Angiogenesis
Studies of the microvascular pattern of capillaries in breast
tissue from patients with DCIS have demonstrated increased
periductal vascularity associated with some but not all DCIS.
The most reliable information has been obtained from his-
tologic sections immunostained with vascular markers such
as factor VIII, CD31, or CD34. Increased microvessel size
has been observed at sites of DCIS compared with normal
breast tissue.
161
Simple hyperplasia has been shown to have
a 22-fold greater degree of microvascular density than nor-
mal ducts.
162
Neovascularization has been described around
DCIS associated with invasive lesions.
163
Periductal neo-
vascularity found around 21 (38%) of 55 examples of pure
DCIS studied by Guidi et al.
164
was not related to histologic
subtype, the presence of necrosis, proliferative index (PI),
