3. INTRODUCTION
Lobular neoplasia (introduced by Haagensen
in 1978) to defines the spectrum of
proliferative changes encompassing:
- Atypical lobular neoplasia (ALH)
- Lobular carcinoma in situ (LCIS).
Both ALH are often multifocal and bilateral.
Increased risk of developing invasive
carcinoma.
4. Recent evidence of identical molecular
changes in coexistent invasive and in situ
lesions and an over representation of
invasive lobular cancers in subsequently
developing tumours provide support for the
direct precursor model.
5. Until relatively recently, cases of atypical or
morphologically ambiguous LCIS were
referred to as ducto-lobular in situ carcinoma
“florid” LCIS or carcinoma with indeterminate
features.
6. The advent of new molecular techniques and
the introduction of more reliable IHC markers
have led to the recognition of a number of
variant subtypes permitting more precise sub
classification of problematic cases.
7. CLASSICAL LCIS
Premenopausal women (40 and 50 years of
age).
Incidence is between 0.5 and 3.8%
The acini of a lobule are filled with the
characteristic monomorphic cells leaving no
central lumina.
Lobular neoplasia is characterized by loss of
cellular cohesion.
8. TWO CELL TYPES
Type A cells: the acini are distended by
small uniform cells with bland nuclei and
scant cytoplasm
Type B cells: the cells are larger with more
cytoplasm and mild to moderate
cytological atypia.
9. CLASSICAL LOBULAR CARCINOMA IN SITU (LCIS).
A mammary lobule filled and distended by the characteristic uniform
dyscohesive lobular carcinoma cells.
10. RISK OF SUBSEQUENT INVASIVE CARCINOMA
LCIS carries a higher risk for subsequent
development of breast cancer within 15-20 years
Risk for atypical lobular hyperplasia (ALH) is half that
of LCIS
Traditionally, the increased risk was recognized to be
Three times more likely to arise within the same
breast.
LCIS is now considered both a marker of increased
risk anda non-obligate precursor of breast cancer.
11. PLEOMORPHIC LOBULAR CARCINOMA IN SITU
(PLCIS)
Relatively new entity, increasingly being
diagnosed through mammographic
screening.
Seen with invasive pleomorphic lobular
carcinoma (IPLC) in 45% cases but may also
occur as an isolated lesion.
Non-obligate precursor of invasive lobular
carcinoma.
More aggressive than conventional LCIS.
12. HISTOLOGY OF PLCIS
Cytological and architectural features of both
classic LCIS and DCIS.
solid proliferation of dyscohesive cells which fill
and distend terminal duct lobular units (TDLUs).
Intermediate or high grade nuclei but as yet
there are no consensus criteria for diagnosis.
Considerable nuclear enlargement (on average
nuclei 4 size of a lymphocyte) and nuclear
pleomorphism with a 2 to 3 fold variation in
nuclear size.
13. Eccentric nuclei, irregularities of the nuclear
membrane and oftenprominent nucleoli
Necrosis is reported in a majority of cases,
mitotic figures
Cells can appear plasmacytoid, a sub-
variant consisting almost entirely of signet
ring cells has been reported.
In the majority of cases these is coexisting
classic LCIS
E- CADHERIN NEGATIVE
14. PLEOMORPHIC APOCRINE LCIS (PALCIS)
Large dyscohesive cells with abundant
eosinophilic cytoplasm which imparts an
apocrine appearance.
The cells frequently show intracytoplasmic
vacuolation which may result in the formation
of signet ring forms.
All 10 cases in a study showed necrosis and
luminal calcification and were E-cadherin
negative and GCDFP-15 positive.
15. (a) PLCIS with central comedo necrosis and luminal calcification. It comprises large
eosinophilic cells showing cellular dyscohesion and nuclear
pleomorphism. (b) The cells are E-cadherin negative confirming the lobular nature. (c)
PLCIS comprising dyscohesive markedly pleomorphic cells with
prominent intracytoplasmic vacuoles. There is adjacent invasive lobular carcinoma. (d)
PALCIS: a solid proliferation of large apocrine cells showing
nuclear pleomorphism. Note the prominent cellular dyscohesion.
16. CLINICAL AND IMAGING FINDINGS OF PLCIS
Classic LCIS – postmenopausal
PLCIS occurring in a slightly older age group (mean
age 55 years)
PALCIS however in older population with (average
age at presentation of 60 years)
classic LCIS is typically incidental finding without a
clinical or mammographic correlate,
PLCIS usually presents as an abnormal
mammographic finding (Calcification)
The high density mammographic calcification may
appear similar to that usually associated with the
comedo necrosis of DCIS
17. BIOMARKER EXPRESSION
In contrast to classical LCIS, PLCIS is often
negative for ER and PR but shows a higher
proliferation rate as measured by Ki-67
proliferation index and increased frequency
of HER2 overexpression.
Positive for Androgen Receptor (AR) with
those showing apocrine morphology
demonstrating particularly strong positivity.
18. MOLECULAR CHARACTERISTICS
Matched PLCIS and invasive PLC show similar
genetic alterations with both showing the
hallmark features of lobular carcinomas namely
loss of chromosome 16q and 17p with gain of
1q emphasizing a close relationship with classic
lobular in situ neoplasia and suggesting clonal
evolution via a similar pathway.
PLCIS and invasive PLC however typically
display additional genetic aberrations.
19. IMMUNOHISTOCHEMICAL PROFILE OF PLCIS
(a) The lesion is ER
negative. The admixed classical LCIS is ER strongly positive. (b) Her2
positive PLCIS with adjacent negative classical LCIS.
20. MANAGEMENT IMPLICATIONS
Controversial
With conventional LCIS the risk of concurrent
invasive malignancy in a screen detected
populations may be as low as 1%
Some units advocate further non-operative
sampling by large volume mammotome rather
than immediate open surgical biopsy.
Followed by continued mammographic
surveillance if no invasive malignancy is then
found.
21. Other reports show an associated higher
grade lesions in up to 21% of classic LCIS
cases and therefore recommend a diagnostic
excision.
Core biopsies containing PLCIS are usually
categorized as B5a (as for DCIS)) rather
than B3 (as for LCIS) according to NHSBSP
guidelines.
22. Excision with clear margins is recommended
in order to remove something with a
significant potential for progression to
invasive disease. (same as DCIS)
Currently no evidence to support adjuvant
endocrine/radiotherapy.
