Invasive breast carcinoma - IARC

A
B
C
Fig. 1.75 Lobular neoplasia. A Aggregates of loosely cohesive neoplastic cells proliferate beneath the native epithelial cell lining (pagetoid growth pattern).
B Typically, the neoplastic cells are E-cadherin negative. C Immunostain for CK34BE12 shows a polarized positive reaction in the cytoplasm.
cytoplasmic immunoreactivity for casein
has also been re p o rted {1994,2149}.
E-cadherin, commonly identified in ductal
lesions, is generally absent from both
LN and invasive lobular carc i n o m a
{ 1 8 9 2 , 2 3 3 6 } .
Grading
A three tiered grading system has been
suggested, based on the extent and
d e g ree of proliferation and/or cytological
features. Those lesions with markedly
distended acini, often with central
n e c rosis, and those composed of either
s e v e rely pleomorphic cells or pure
signet ring cells with or without acinar
distension, were designated LIN 3; they
have been re p o rted to be often associated
with invasive carcinoma {2876}.
This grading system re q u i res validation
by other centres and is not endorsed at
this time.
Differential diagnosis
Poor tissue preservation may give a false
i m p ression of loosely cohesive cells
leading to over-diagnosis of LN.
Distinction from a solid DCIS can be diff i-
cult on morphological grounds alone,
p a rticularly when DCIS remains confined
Fig. 1.76 Lobular neoplasia. CK5/6 immunohistochemistry
demonstrating the pagetoid spread of
tumour cells infiltrating the positively stained original
epithelium, leading to a reticulated staining pattern.
to the lobule without unfolding it (so
called lobular cancerization). The pre s-
ence of secondary lumina or a ro s e t t e -
like arrangement of cells indicates a ductal
lesion. In problematic cases, the
i m m u n o p rofile may be helpful. LN is typically
E-cadherin and CK 5,6 negative, but
HMW CK34BE12 positive {337}. DCIS, on
the other hand, is typically E-cadherin
positive, but CK34BE12 negative. Occasional
lesions are negative or positive for
both HMWCK34BE12 and E-cadherin
markers. Since, at present, it is uncert a i n
how these morphologically and immunohistochemically
hybrid lesions with ductal
and lobular features would behave, it is
i m p o rtant that they are recognized so that
m o re can be learned about their nature in
the future {337}.
When LN involves sclerosing adenosis or
other sclerosing lesions, it can be confused
with an invasive carcinoma. The
presence of a myoepithelial cell layer
a round the neoplastic cell clusters
excludes the possibility of an invasive
carcinoma; immunostaining for actin can
unmask the myoepithelial cells, thus
facilitating the distinction.
Presence of isolated cells invading the
stroma around a focus of LN can cause
diagnostic problems. Absence of
myoepithelial cells around the individual
cells and their haphazard distribution
accentuated by any of the epithelial
markers (optimally with double immunostaining
techniques) can help establish
the presence of stromal invasion by individual
or small clusters of neoplastic
cells.
Molecular genetics
Loss of heterozygosity (LOH) at loci frequently
observed in invasive carc i n o m a
has also been re p o rted in LN, ranging
f rom 8% on chromosome 17p to 50% on
17q {1569}. LOH on chromosome 16q,
the site of the E-cadherin gene, was
found in approximately 30%. LOH was
identified in LN associated with invasive
c a rcinoma and in pure LN, suggesting
that it may be a direct precursor of invasive
lobular cancer. Further support
for this hypothesis has come from a
re p o rt that showed LOH in 50% of LN
associated with invasive carcinoma at
markers on chromosome 11q13 {1988}.
LOH was seen in 10% of ALH and 41%
of invasive lobular carcinomas. Using
comparative genomic hybridization
(CGH), loss of chromosomal material
f rom 16p, 16q, 17p and 22q and gain
of material to 6q was identified in
equal frequency in 14 ALH and 31 LCIS
A
B
Fig. 1.77 Lobular neoplasia. A The acini are filled
and moderately distended by neoplastic cells; the
acinar outlines are retained. B Clover-leaf pattern.
This is one of the classic patterns of LN, with the
acini distended by neoplastic cells pulling away
from the intralobular segment of the terminal duct,
creating a clover-leaf or necklace appearance.
Lobular neoplasia
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