Invasive breast carcinoma - IARC

A
B
absence of either microcalcifications or
n e c rosis does not impact the diagnosis.
UDH with necrosis, a rare event, may be
mistaken for DCIS; the diagnosis should
be based on the cytological features and
not the presence of necrotic debris. UDH
generally displays either diffuse or a
mosaic pattern of positivity with high
molecular weight cytokeratins {1963,
2126} such as CK5, CK1/5/10/14 (clone
CK34betaE12 or clone D5/16 B4); it is
also positive for E-cadherin. In UDH, the
p e rcentage of ER-positive cells was found
slightly increased compared to the norm a l
b reast {2667}. Increased levels of cyclin
D1 expression were recently described in
11-19% of UDH cases {1172,3264}.
C
Fig. 1.80 Usual ductal hyperplasia. A Florid type. The peripheral distribution of irregularly sized spaces is a
characteristic of UDH readily apparent at low magnification. B The proliferating cells may form epithelial
bridges, but the bridges are delicate and formed by spindled stretched cells. C Intensive, predominantly
solid intraductal proliferation of a heterogeneous cell population. Note spindling of the cells. Several irregular
peripheral luminal spaces. D Intraluminal proliferation with many CK5-positive and occasional CK5-
negative cells.
Synonyms
Intraductal hyperplasia, hyperplasia of
the usual type, epitheliosis, ord i n a ry
intraductal hyperplasia.
Mammography
UDH does not have a mammographic
presentation, except in rare cases with
microcalcification.
Risk of progression
Long-term follow up of patients with UDH
in one study showed that 2.6% develop
subsequent invasive carcinoma after an
average interval of over 14 years, compared
to 8.3 years for those with ADH
{2886}. In another study, the absolute risk
of a woman with UDH developing breast
cancer within 15 years was 4% {732}.
The Cancer Committee of the College of
American Pathologists has assigned
UDH a slightly increased risk (RR of 1.5-
2.0) for subsequent development of invasive
carcinoma {885}.
Histopathology
UDH is characterized by irre g u l a r l y
shaped and sized secondary lumens,
often peripherally distributed, and stre a m-
ing of the central bolus of pro l i f e r a t i n g
cells. Epithelial bridges are thin and
s t retched; nuclei are unevenly distributed.
D
In some cases, the proliferation has a
solid pattern and no secondary lumens
a re evident. Cytologically, the lesion is
composed of cells with indistinct cell margins,
variation in the tinctorial features of
the cytoplasm and variation in shape and
size of nuclei. Admixture of epithelial,
myoepithelial or metaplastic apocrine
cells is not uncommon. The presence or
Table 1.12
Usual ductal hyperplasia.
Architectural features
1. Irregular fenestrations
2. Peripheral fenestrations
3. Stretched or twisted epithelial bridges
4. Streaming
5. Uneven distribution of nuclei and overlapped
nuclei
Cellular features
1. Multiple cell types
2. Variation in appearance of epithelial cells
3. Indistinct cell margins and deviation from a
round contour
4. Variation in the appearance of nuclei
One of the most important indicators of UDH is
the presence of an admixture of two or more
cell types (epithelial, myoepithelial and/or
metaplastic apocrine cells).
Genetic alterations
A p p roximately 7% of UDH show some
d e g ree of aneuploidy. Loss of hetero z y-
gosity (LOH) for at least one locus, has
been noted in one-third of UDH {2071}.
On chromosome 11p, LOH was pre s e n t
in 10-20% of UDH cases {72,2071}.
Losses on 16q and 17p were identified in
UDH lesions without evidence of adjacent
c a rcinoma {1037} whereas no alterations
w e re re p o rted by others {301}. In UDH
adjacent to carcinoma, polysomy of chromosome
1 as well as increased signal frequencies
for the 20q13 region (typically
p resent in DCIS) were identified by FISH
{593,3100}. By CGH, UDH lesions adjacent
to carcinoma showed gain on chromosome
20q and loss on 13q in 4 of 5
cases {136}, although no alteration was
re p o rted in another study {301}. Some
recent CGH studies suggest that a prop
o rtion of UDH lesions is monoclonal
{1037,1358}, and that a subset shows
alterations similar to those observed in
ADH {1037}; however, the frequency of
genetic alterations seen in UDH using
LOH and CGH is much lower than in
ADH. TP53 protein expression has not
been demonstrated in UDH or in any
other benign proliferative lesions {1567}.
Mutations of the T P 5 3 gene are also
absent, except as inherited mutations in
Li-Fraumeni patients {72}.
Flat epithelial atypia
Definition
A presumably neoplastic intraductal
alteration characterized by replacement
of the native epithelial cells by a single or
3-5 layers of mildly atypical cells.
Intraductal proliferative lesions
65