Hironobu SasanoTohoku University School of Medicine

Sendai, Japan

LCIS ( lobular carcinoma in situ )

Current concept and challenging issues

JBSC WHO

I. 上皮性腫瘍A. 良性腫瘍

1. 乳管内乳頭腫2. 乳管腺腫

3. 乳頭部腺腫4. 腺腫5. 腺筋上皮腫

B. 悪性腫瘍1. 非浸潤癌

a. 非浸潤性乳管癌b. 非浸潤性小葉癌

2. 浸潤癌a. 浸潤性乳管癌

a1.乳頭腺管癌a2.充実腺管癌a3.硬癌

b. 特殊型b1.粘液癌B2.髄様癌B3.浸潤性小葉癌B4.腺様嚢胞癌B5.扁平上皮癌B6.紡錘細胞癌B7.アポクリン癌B8.骨・年骨化生を伴う癌B9.管状癌B10.分泌癌B11．浸潤性微小乳頭癌B12.基質産生癌B13.その他

3. Paget病II. 結合織性および上皮性混合腫瘍

A. 線維腺腫B. 葉状腫瘍C. 癌肉腫

III. 非上皮性腫瘍A. 間質肉腫B. 軟部腫瘍C. リンパ腫および造血器腫瘍D. その他

IV. 分類不能腫瘍V. 乳腺症VI. 腫瘍性病変

A. 乳管拡張症B. 炎症性偽腫瘍C. 過誤腫D. 乳腺線維症E. 女性化乳房症

F. 副乳G. その他

1. Introduction2. Invasivecarcinomaofnospecialtype3. Specialsubtypes (略)4. Lobularneoplasia

5. Intraductal proliferativelesions• Introductionandoverview• Usualductalhyperplasia(UDH)• Columnarcelllesions (CCL)• Atypicalductalhyperplasia(ADH)

• Ductalcarcinomainsitu(DCIS)6. Microinvasive carcinoma

7. Intraductal papillarylesion• Intraductal papilloma• Intraductal papillarycarcinoma

• Encapsulatedpapillarycarcinoma• Solidpapillarycarcinoma

8. Benignepithelialproliferations• Adenosis,sclerosing adenosis andapocrine

adenosis

• Microglandular adenosis,atypicalmicroglandular adenosis andmicroglandular

adenosis withcarcinoma• Radicalscarandcomplexsclerosing lesion• Tubularadenoma

• Lactatingadenoma• Apocrineadenoma

• Ductaladenoma• Pleomorphicadenoma

9. Myoepithelial andepithelial-myoepithelial

lesions (略)10. Mesenchymaltumours (略)

11. Fibroepithelial tumours• Fibroadenoma• Phyllodes tumour

• Hamartoma12. Tumours ofthenipple

• Nippleadenoma• Syringomatous tumour• Pagetdisease

13. Lymphoidandhaematopoietic tumours (略)14. Metastasesofextramammarymalignanciesto

thebreast (略)15. Tumours ofthemalebreasｔ (略)

16. Geneticsusceptibility:inheritedsyndromes (略)

表1乳腺腫瘍の組織学的分類体系

JBCS;JapanBreastCancerSociety,WHO;World Health Organization

WHO 2012

In WHO 2004 classification

The term LCIS ( lobular

carcinoma in situ ) abolished

and all the lesions with

lobular features as

“Lobular neoplasm”

Foote FW, Stewart FW.

Lobular carcinoma in situ

: a rare form of mammary

cancer.

Am J Pathol. 1941;17:491–496

What is Lobular neoplasia (LN) ？

Any atypical epithelial proliferative lesions arising

from TDLU（terminal duct lobular unit)

Histological features in LN retain those in TDLU, i.e., small and less cohesive.

Spread as in Pagetoid spread but usually not reaching main duct of mammary

glands.

Never occur in male breast in which no lobules detected.

Why abolish ALH( atypical lobular hyperplasia) ad LCIS ( lobular

carcinoma in situ) in the new classification？

Typical ALH ( atypical lobular hyperplasia) LCIS( lobular carcinoma in situ)

Only quantitative

differences or the

areas of occupying

the lobules and no

qualitative

differences

The same cells!!

1. ALH : benign and LCIS: malignant ?

2. Very poor interobserver differences among individual pathologists.

3. The same gene expression profiles of EMT, proliferation and E

cadherin gene expression profiles

The same morphology and gene expression patterns between

ALH and LCIS. The same category in pathology diagnosis

Do we need clinically differentiate between ALH and LCIS???

How frequent LN occurs in women？Could occur in any age but most frequent in premenopausal women

1-5% among benign proliferative breast disorders.

Multiple foci in 85% and bilateral in 50% of the patients

Pivotal histological features of LN

Lobules filled with atypical small cells. In LCIS more than 50%.

The loss of E cadherin in 90%. IHC of E cadherin, α/𝛃 catenin and

p120 could be of value in differential diagnosis.

What clinicians should know on lobular neoplasia in 2018.

Subtypes of LN which clinicians should know in 2018.

Calcification detected in mammography.

Could harbor comedo necrosis.( I )

Could be diagnosed

as DCIS.

Florid type, lobular neoplasia

( II ) Pleomorphic lobular neoplasia

However, both of these lesions

had the same genetic profiles

such as the loss of E cadherin

and others as in classical

lobular neoplasia

Arch Pathol Lab Med. 2017;141:1668–1678

Florid and pleomorphic LN/LCIS are more likely associated with development

of invasive lobular carcinoma !!

(III) E carherin positive LN

1. The mixture of E cadherin positive ductal eithelium

2. Mutated E cadherin with preservation of its antigenecity

3. Mixed DCIS and lobular neoplasia

carcinoma in situ with mixed ductal and lobular features

To make sure the absence of

stromal invasion by IHC of

P63/p40/CK5/6 and…...

If no foci of stromal invasion confirmed,

those lesions in which differential diagnosis

form DCIS difficult, the above diagnosis

could be acceptable.

Difficult differential diagnosis

Whether ALH or LCIS

Lobular neoplasm is

Monoclonal

proliferation.

Recent molecular analysis revealed

Whether ALH or LCIS,

Lobular neoplasm precursors of

invasive lobular carcinoma.

Continuous gene abnormalities

????

At this juncture of 2018, we do not know which patients

of lobular neoplasm could develop into invasive LC

regardless of which methodologies to use.

Which factors to be filled out in surgical pathology

report of lobular neoplasm.

1. E cadherin positive or negative.

2. Rule out invasion using p63, CK5/6, p40 IHC.

3. Classical, florid or pleomorphic type

4. Size of the lesion on hematoxylin and eosin stained slides

5. Pagetoid spread or not in terminal ducts

6. How to describe margins….

whether the lesions with calcification

necrosis and pleomorphic LN or not

still in dispute……

What surgeons should do when receiving the

pathology diagnosis of lobular neoplasia in 2018?

1. Should recognize it as precursor lesion of invasive lobular carcinoma.

5-10 times higher in developing cancer than normal control.

2. When reporting calcification or necrosis in CNB specimens, the whole

lesion should be excised and confirm the free margins.

3. Other than #2 above, whether the lesion excised or not, could

depend on the size of the lesion and histological features of CNB

including the degree of pleomorphism and Pagetoid spread into ducts.

Intraoperative consultation

All right in the positive margins or not

but by no means whether invasive or not.