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JOURNAL CLUB PRESENTATION
Thanks to my resident Dr. Babar Yasin
PLEOMORPHIC LOBULAR
CARCINOMA IN SITU
 Pauline J Carder
 Abeer M Shaaban
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.
 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.
 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.
 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.
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.
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.
CLASSICAL LOBULAR CARCINOMA IN SITU (LCIS).
A mammary lobule filled and distended by the characteristic uniform
dyscohesive lobular carcinoma cells.
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.
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.
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.
 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
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.
(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.
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
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.
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.
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.
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.
 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.
 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.

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PLCIS

  • 1. JOURNAL CLUB PRESENTATION Thanks to my resident Dr. Babar Yasin
  • 2. PLEOMORPHIC LOBULAR CARCINOMA IN SITU  Pauline J Carder  Abeer M Shaaban
  • 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.