Invasive breast carcinoma - IARC

Lobular neoplasia
F.A. Tavassoli
R.R. Millis
W. Boecker
S.R. Lakhani
Definition
Characterized by a proliferation of generally
small and often loosely cohesive
cells, the term lobular neoplasia (LN)
refers to the entire spectrum of atypical
epithelial proliferations originating in the
terminal duct-lobular unit (TDLU), with or
without pagetoid involvement of terminal
ducts. In a minority of women after longterm
follow-up, LN constitutes a risk factor
and a nonobligatory precursor for the
subsequent development of invasive
carcinoma in either breast, of either ductal
or lobular type.
ICD-O code
Lobular carcinoma in situ (LCIS) 8520/2
Synonyms and historical annotation
The designations atypical lobular hyperplasia
(ALH) and lobular carcinoma in
situ (LCIS) have been widely used for
variable degrees of the lesion.
Two series published in 1978 {1100,
2438} concluded that the features generally
used to subdivide the lobular
changes into LCIS and ALH were not
of prognostic significance. To avoid
o v e rt reatment, Haagensen suggested
the designation lobular neoplasia (LN)
for these lesions {1100}. To emphasize
their non-invasive nature, the term lobular
intraepithelial neoplasia (LIN) has
been proposed. Based on morphological
criteria and clinical outcome, LIN has
been categorized into three grades
{338}.
Epidemiology
The frequency of LN ranges from less
than 1% {3106,3107} to 3.8 % {1099} of
all breast carcinomas. It is found in 0.5-
4% of otherwise benign breast biopsies
{2150}. Women with LN range in age
from 15 {32} to over 90 years old {2876},
but most are premenopausal.
Clinical features
The lesion is multicentric in as many as
85% of patients {2446,2876} and bilateral
in 30% {1096} to 67% {2001} of women
who had been treated by bilateral mastectomy.
No mammographic abnormalities
are recognized {2128,2273}, except
in the occasional variant of LN characterized
by calcification developing within
central necrosis {2534}.
Macroscopy
LN is not associated with any grossly
recognizable features.
Histopathology
The lesion is located within the terminal
duct-lobular unit {3091} with pagetoid
involvement of the terminal ducts evident
in as many as 75% of cases {86,1096}.
On low power examination, while lobular
architecture is maintained, the acini of
one or more lobules are expanded to
v a rying degrees by a monomorphic proliferation
of loosely cohesive, usually
small cells, with uniform round nuclei,
indistinct nucleoli, uniform chro m a t i n
and rather indistinct cell margins with
sparse cytoplasm. Necrosis and calcification
are uncommon and mitoses are infrequent.
Intracytoplasmic lumens are often
p resent but are not specific to LN {89}. In
some lesions, however, the pro l i f e r a t i n g
cells are larger and more pleomorphic or
of signet ring type. Apocrine metaplasia
occurs but the existence of endocrine
variant of LN {801} is disputed.
Two types of LN have been recognized
{1100}: Type A with the more usual morphology
described above and Type B
composed of larger, more atypical cells
with less uniform chromatin and conspicuous
nucleoli. The two cell types may
be mixed. When composed of pleomorphic
cells, the term pleomorphic LN has
been used. The neoplastic cells either
replace or displace the native epithelial
cells in the TDLU. The myoepithelial cells
may remain in their original basal location
or they may be dislodged and
admixed with the neoplastic cells. The
basement membrane is generally intact
although this is not always visible in all
sections. Pagetoid involvement of adjacent
ducts between intact overlying flattened
epithelium and underlying basement
membrane is frequent and can
result in several different patterns including
a ‘clover leaf’ or ‘necklace’ appearance
{1099}. Solid obliteration of acini
may occur, sometimes with massive distension
and central necrosis. LN may
involve a variety of lesions including sclerosing
adenosis, radial scars, papillary
lesions, fibroadenomas and collagenous
spherulosis.
Immunoprofile
LN is positive for estrogen receptor (ER)
in 60-90% of cases and in a slightly lower
p e rcentage for pro g e s t e rone re c e p t o r
(PR) {62,369,1010,2159,2483}. The classical
variety of LN is more likely to be
positive than the pleomorphic variant
{223,2683}. Unlike high grade DCIS,
h o w e v e r, classic LN rarely expre s s e s
ERBB2 or TP53 protein {62,2327a,2483,
2746}. Positivity is more likely with the
pleomorphic variant {1859,2683}. Intra-
A
Fig. 1.74 Early lobular neoplasia. A The few neoplastic lobular cells are hardly apparent on a quick examination
of the TDLU. B Double immunostaining with E-cadherin (brown) and CK34BE12 (purple) unmasks the few neoplastic
cells (purple) proliferating in this lobule. These early lesions are often missed on H&E stained sections.
B
60 Tumours of the breast