Dr. P. Karpagam Kiruba Rajeswari, M.B.B.S.,D.C.P.

, Tutor in Pathology, MAP MS

Most !ommon non"s#in malignan!y in women$$$

BREAST CARCINOMA RISK FACTORS

PATHOGNESIS GENETIC FACTORS

Most !ommon genes impli!ate% in Breast !ar!inoma

BRCA -1 Breast Cancer 1,Early onset ( Chr.17) &'(CT )(S* +. Trans!ription ,. D(A Repair o%ouble stran%e% brea#s .. 'bi/uitination 0. Trans!riptional regulation.

BRCA-2, Breast Cancer 2,Early onset( Chr.13) &'(CT )(S* +.Stability o- the human genome ,.D(A %ouble stran% brea# repair.

p53( Chr.17)

CHEK2( Chr. 22)

&'(CT )(S +. Cell !y!le !ontrol ,. D(A repli!ation .. D(A repair 0. Apoptosis.

&'(CT )(S +. Cell !y!le !he!#point #inase, re!ognition an% repair o- D(A %amage. ,. A!ti1ates BRCA+ an% p2. by phosphorylation

3ermline point mutations4Deletions oBRCA+ gene 5ere%itary breast 6 o1arian !an!ers.

Mutations ,78 5ere%itary breast !an!er, o1arian !an!er, in!rease% !an!er ris# in male !arriers.

Mutations Spora%i! breast !an!ers. 9i -raumeni syn%rome

Mutations " rare :;28<. 9i -raumeni 1ariant n!rease breast !an!er ris# a-ter ra%iation e=posure

HER2/neu
5uman >pi%ermal growth -a!tor Re!eptor, Member o- >rbB protein -amily. 5>R, is a !ell membrane sur-a!e"boun% re!eptor tyrosine #inase "

normally in1ol1e% in signal trans%u!tion pathways !ell growth an% %i--erentiation.

Appro=imately .7 8 o- breast !an!ers ampli-i!ation o-

the HER2/neu gene4 o1ere=pression o- its protein pro%u!t.

)1ere=pression o- this re!eptor in breast !an!er in!rease%

%isease re!urren!e an% worse prognosis.

PATHOGENESIS HORMONAL FACTORS

>=!ess 5ormonal e=posure Spora%i!

!an!ers.

Post menopausal women spora%i!

!an!ers >R positi1e.

5ormones breast growth %uring

puberty, menstrual !y!les, pregnan!y !y!les o- proli-eration !ells at ris# -or D(A %amage. present, hormones " stimulate their growth ? growth o- normal epithelial an% stromal !ells tumour %e1elopment. generate D(A"%amaging -ree ra%i!als.

- premalignant or malignant !ells are

Metabolites o- estrogen mutations 4

@ A2 8 breast malignan!ies AD>()CARC ()MAS

CLASSIFICATION BREAST CARCINOMA

NON-INVASIVE/IN

SITU CARCINOMA ntra%u!tal !ar!inoma 9obular !ar!inoma in situ

INVASIVE

Colloi% :mu!inous<

CARCINOMA n-iltrating : in1asi1e < %u!t !ar!inoma B ()S n-iltrating : in1asi1e < lobular !ar!inoma Me%ullary !ar!inoma

!ar!inoma Papillary !ar!inoma Tubular !ar!inoma A%enoi% !ysti! !ar!inoma Se!retory !ar!inoma n-lammatory !ar!inoma Car!inoma with metaplasia

PAGETS DISEASE OF THE

NIPPLE

Malignant !lonal population o- !ells limite% to %u!ts 6 lobules by the basement membrane.

DUCTAL CARCINOMA IN SITU

Most DC S %ete!te% by

calci ications on !a!!o"raphy4mammographi! %ensity " peri%u!tal -ibrosis surroun%ing a DC S4rarely palpable mass4 nipple %is!harge4in!i%ental -in%ing on a biopsy -or another lesion.
Sprea%s through %u!ts 6 lobules

e=tensi1e lesions entire se!tor o- a breast.

DC S B in1ol1es lobules B a!ini

%istorte%, un-ol%e% appear as small %u!ts.

Comedoca c!noma
Soli% sheets o- pleomorphi! !ells

with high gra%e hyper!hromati! nu!lei.

Areas o- !entral ne!rosis ?nt. (e!roti! !ell membranes B !al!i-y

!lusters4linear 6 bran!hing mi!ro!al!i-i!ations on mammography.

Peri%u!tal !on!entri! -ibrosis 6

!hroni! in-lammation.
>=tensi1e lesions B palpable as

1ague no%ularity.

Noncomedo DCIS
Monomorphi! !ell

population B nu!lear gra%es low to high. CRIBRIFORM DCIS ntra"epithelial spa!es B e1enly %istribute%, regular in shape.
COOKIE CUTTER LIKE

SOLID DCIS Completely -ills the

in1ol1e% spa!es.

PAPILLARY DCIS 3rows into spa!es along

Noncomedo DCIS

-ibro1as!ular !ores la!# myoepithelial !ell layer.

MICROPAPILLARY DCIS Bulbous protrusions without

a -ibro1as!ular !ore arrange% in !omple= intra%u!tal patterns.

Cal!i-i!ations B asso!.with

ne!rosis4-orm on intraluminal se!retions.

PAGET"S DISEASE OF NIPPLE

Rare mani-estation o- breast CA. '4l erythematous eruption, Pruritus. Malignant !ells4#A$E% CE&&' >=ten%

-rom DC S within %u!tal system B 1ia la!ti-erous sinuses nipple s#in without !rossing the BM. Tumour !ells B %isrupt tight s/uamous epithelial barrier B >C& seeps out onto nipple sur-a!e oo(in" scaly cr)st. PagetCs !ells B %ete!te% by nipple B=4!ytologi!al preparation o- the e=u%ate. #alpa*le !ass 27 B D7 8 o- women E@ in+asi+e CA. ,o palpa*le !ass E@ -C.' Poorly %i--erentiate%, >R (egati1e, 5>R,4neu o1ere=p. Prognosis B %epen%s on -eatures oun%erlying Ca.

PAGET"S DISEASE OF NIPPLE

MICROIN$ASION
Area o- in1asion through

BM stroma " @ 7.+ !m.

Asso!. with

!ome%o!ar!inoma.
&ew mi!roin1asion -o!i

prognosis similar to DC S.

MANAGEMENT AND PROGNOSIS OF DCIS

MAST>CT)MF -or DC S B

/a0or ris1 actors or

!urati1e @ A2 8 pts.

Re!urren!e B rare B %4t resi%ual

DC S in %u!ts in sub!utaneous tissue B not remo1e% %uring surgery4 %4t o!!ult -o!i oin1asion not %ete!te% at %iagnosis.

rec)rrence2 +. 3ra%e ,. SiGe .. Margins

n >R ? 1e DC S Post"

op. ra%iation ? Tamo=i-en re!urren!e ris# B low.

Breast !onser1ation B !an be

%one but slightly higher ris# ore!urren!e.

Death ; , 8 DC S.

 n!i%ental biopsy -in%ing "no

LOBULAR CARCINOMA IN SITU

!al!i-i!ations 4stromal rea!tions mammographi! %ensities.

Bilateral " ,78 to 078 . Foung women. 9oss o- e=pression o- E-

ca3herin:transmembrane !ell a%hesion protein !ohesion o- normal breast epithelial !ells<.

LOBULAR CARCINOMA IN SITU % MORPHOLOG&

Dys!ohesi1e roun% !ells with

o1al or roun% nu!lei an% small nu!leoli. Absen!e o- atypia, pleomorphism, mitoti a!ti1ity, ne!rosis.
n1ol1e% a!ini B re!ogniGable

as lobules.
Mu!in"positi1e signet"ring

!ells.
>R an% PR ?1e.

LOBULAR CARCINOMA IN SITU

n1asi1e !ar!inoma +8 per

year.

Both breasts " in!rease% ris#.

Ris# " slightly higher in the ipsilateral breast.

n1asi1e !ar!inomas " lobular

type.

%reat!ent2 +. Bilateral prophyla!ti!

maste!tomy. ,. Tamo=i-en. .. Close !lini!al -ollow"up. 0. Mammographi! s!reening.

IN$ASI$E CARCINOMA
CLINICALFEATURES
Palpable mass A!"lla#$ l$mp% &'(e me)as)ases F"!")$ to the !hest wall 4 s#in

%impling.

N"pple #e)#a*)"'& 9ymphati!s " in1ol1e% " blo!# the

lo!al area o- s#in %rainage l$mp%e(ema, s#in thi!#ening. by Cooper ligaments pea+ (,'#a&-e. mass

Tethering o- the s#in to the breast

Mammography Ra("'(e&se

T,*e -NST. In'a(!'e Duc/a+ Ca c!noma0

Majority :H78 to I78<. G#'ss appea#a&*e. Most tumors

" -irm to har% ,irregular bor%er . 9ess -re/uently " well" !ir!ums!ribe% bor%er , so-ter !onsisten!y.
Jhen !ut 4 s!rape%

!hara!teristi! grating soun% %4t small, !entral pinpoint -o!i or strea#s o- !hal#y"white elastoti! stroma an% o!!asional small -o!i o- !al!i-i!ation.

HPE
4eat)res Tubule -ormation 5ell 3i . Ca Prominent /o3. 3i .Ca 9ess,soli% !lusters4single in-iltrating !ells 3reater nu!lear pleomorphism Present " " #oorly 3i . Ca. Ragge% nests4soli% sheets o- !ells (u!lei B enlarge%,irregular. (umerous 5igh Present (u!lei Mitoti! -igures Proli-eration rate Tumour ne!rosis Small,roun%,monom orphi! Rare " "

CARCINOMA
Palpable mass4 mammographi!

%ensity with irregular bor%ers. Sometimes " tumor in-iltrates the tissue %i--usely B little %esmoplasia, not palpable, no mammographi! %ensity. Metastases B %i--i!ult to %ete!t.

Bilateral " 2 B +7 8. Bialleli! loss o- e=pression o-

(CDH/, enco3es Eca3herin< %4t mutations.

CARCINOMA
/orpholo"y2 5istologi!

hallmar# %ys!ohesi1e in-iltrating tumor !ells, o-ten arrange% in single -ile or in loose !lusters or sheets INDIAN FILE APPEARANCE
Tubule -ormation " absent. Signet"ring !ells !ontaining an

intra!ytoplasmi! mu!in %roplet are !ommon.

Desmoplasia " minimal or absent

CARCINOMA
5ell-3i erentiate3 an3 !o3erately

3i erentiate3 carcino!as %iploi%, >R positi1e, 5>R,4neu o1ere=pression " rare

#oorly 3i erentiate3 carcino!as

aneuploi%, la!# hormone re!eptors, may o1ere=press 5>R,4neu.

Di--erent pattern o- metastasis than

other breast !an!ers. Metastasis peritoneum ,retroperitoneum, the leptomeninges :!ar!inoma meningitis<, the gastrointestinal tra!t, o1aries an% uterus.

MEDULLAR& CARCINOMA
MC " Dth %e!a%e. May !losely mimi! a benign

lesion !lini!ally an% ra%iologi!ally4 present as a rapi%ly growing mass.

MORPHOLOGY * Jell B

!ir!ums!ribe%,so-t,-leshy mass " little %esmoplasia more yiel%ing on palpation an% !utting. :me(+lla 678!arro9:).

MEDULLAR& CARCINOMA % HPE

Soli%, syn!ytium"li#e sheets o- large !ells with 1esi!ular, pleomorphi! nu!lei, prominent nu!leoli @ H28 o- the tumor ,. &re/uent mitoti! -iguresK .. Mo%erate to mar#e% lymphoplasma!yti! in-iltrate surroun%ing an% within the tumor. 0. Pushing :nonin-iltrati1e< bor%er.
+.

Poorly %i--erentiate%.

MEDULLAR& CARCINOMA
5igh nu!lear gra%e,

aneuploi%y, hormone re!eptors " nt, 5>R,4neu o1ere=pression Bnt.

9ymph no%e metastases "

in-re/uent.

Syn!ytial growth pattern an%

pushing bor%ers " %4t o1ere=pression o- a%hesion mole!ules inter!ellular !ell a%hesion mole!ule an% >" !a%herin limit metastati! potential.

CARCINOMA
)l%er women :me%ian age

H+< grow slowly " many years.

/orpholo"y2 Tumor B

so-t4rubbery . Consisten!y 6 appearan!e o- pale gray" blue gelatin. Bor%ers " pushing 4 !ir!ums!ribe%.

HPE
Tumor !ells " arrange% in

!lusters an% small islan%s within large la#es o- mu!in.

Mu!inous !ar!inomas

%iploi%, well to mo%erately %i--erentiate%, an% >R positi1e.

9ymph no%e metastases "

un!ommon.
)1erall prognosis is slightly

better.

 Small irregular mammographi!

TUBULAR CARCINOMA

%ensities " late 07s.

'n!ommon. /orpholo"y2 Jell"-orme% tubules

? nt, myoepithelial !ell layer, BM " nt tumor !ells in %ire!t !onta!t with the stroma. Apo!rine snouts " typi!al.Cal!i-i!ations " within the lumens.
@ A28 o- all tubular !ar!inomas "

%iploi%, >R ? 1e,5>R,4neu B1e .

Jell %i--erentiate%. >=!ellent

prognosis.

IN$ASI$E PAPILLAR& 1 MICROPAPILLAR& CARCINOMA

Rare " +8 or -ewer o- all

in1asi1e !an!ers. More !ommonly seen in DC S. INVASIVE PAPILLARY CA >R positi1e. &a1orable prognosis. INVASIVE MICROPAPILLARY CA >R negati1e,5>R, positi1e. 9ymph no%e metastases " 1ery !ommon Prognosis is poor.

Tumors swollen,

INFLAMMATOR& CARCINOMA

erythematous breast " !ause% by e;tensi+e in+asion an3 o*str)ction o 3er!al ly!phatics *y t)!or cells. %i--usely in-iltrati1e " %oes not -orm a %is!rete palpable mass !on-usion with true in-lammatory !on%itions a %elay in %iagnosis. at %iagnosis 4 re!ur rapi%ly.

'n%erlying !ar!inoma "

Many patients metastases )1erall prognosis poor.

METAPLASTIC CARCINOMA
n!lu%es a 1ariety o- rare types

o- breast !an!er :;+8 o- all !ases< matri="pro%u!ing !ar!inomas, s/uamous !ell !ar!inomas, an% !ar!inomas with a prominent spin%le !ell !omponent.
>R"PR"5>R,4neu 8triple

ne"ati+e:.
9ymph no%e metastases "

in-re/uent.
Prognosis " poor.

PROGNOSTIC FACTORS % MA2OR

)ut!ome in breast CA B 1aries

wi%ely.

Major prognosti! -a!tors Prognosis B %etermine% by

pa)%'l'-"* e!am"&a)"'& '0 p#"ma#$ *a#*"&'ma 1 a!"lla#$ l$mp% &'(es

Ame#"*a& 2'"&) C'mm"))ee

'& Ca&*e# 3A2CC4 s)a-"&s$s)em %i1i%es patients into -i1e stages :) to L< !orrelate% with sur1i1al.

strongest pre%i!tors o- %eath. +< n1asi1e 1s insitu CA. ,< Distant metastasis .< 9ymph no%e metastasis 0< Tumour siGe 2< 9o!ally a%1an!e% %s. D< n-lammatory CA.

'ta"e 7

%2 #ri!ary Cancer DC S or 9C S n1asi1e !ar!inoma M, !m n1asi1e !ar!inoma @, !m

&y!ph ,o3es (&,s) (o metastases (o metastases (o metastases

/2 -istant /etastasis Absent Absent Absent Absent Absent Absent Absent

5-<ear ')r+i+al (=) A, IH H2

n1asi1e !ar!inoma + to . positi1e 9(s ;2 !m n1asi1e !ar!inoma + to . positi1e 9(s @2 !m Any siGe in1asi1e !ar!inoma N0 positi1e 9(s

0D

n1asi1e !ar!inoma 7 to @+7 positi1e with s#in or !hest 9(s. wall in1ol1ement or in-lammatory !ar!inoma L Any siGe in1asi1e !ar!inoma (egati1e or positi1e lymph no%es

Present

+.

MINOR

FIBROADENOMA
MC benign tumor " , n% 6 . r%

%e!a%e.Multiple, bilateral. Foung women palpable mass. )l%er women mammographi! %ensity 4 !al!i-i!ations. >pithelium B hormonally reponsi1e in!rease in siGe %uring la!tation !ompli!ate% by in-lammation, in-ar!tion mimi!s CA. Stroma " %ensely hyaliniGe% a-ter menopause "may !al!i-y. &ar"e lo*)late3 (8popcorn:) calci ications !hara!teristi! mammographi! appearan!e. '!all calci ications " !lustere% "re/uire biopsy to e=!lu%e !ar!inoma.

GROSS: Spherical, sharply circumscribed, rubbery, grayish white, freely movable nodules -bulge above the surrounding tissue and contain slitlike spaces. < 1 cm large tumors.

FIBROADENOMA % HPE
'tro!a B %eli!ate,

!ellular,my=oi%"resembles normal intralobular stroma. Epitheli)! " surroun%e% by stroma " !ompresse% 6 %istorte% by it. Ris# o- malignan!y asso!. with Co!ple; i*roa3eno!as !ysts @ 7.. !m. in siGe, s!lerosing a%enosis, epithelial !al!i-i!ations, papillary apo!rine !hange.

FIBROADENOMA % T&PES
.,%RACA,A&.C>&AR #ER.CA,A&.C>&AR

n pericanalic)lar histologi! pattern, the "lan3s !aintain their ro)n3 or o+al pro iles. There is no pro"nostic or clinical si"ni icance atta!he% to the peri!anali!ular an% intra!anali!ular patterns. Both may be seen within the same lesion.

PH&LLODES TUMOUR Phyllodes

leaf-like Arise -rom intralobular stroma.
Any age, most B Dth %e!a%e. Majority palpable masses, -ew

-oun% by mammography. Misnomer.

Cystosarcoma phyllodes MORPHOLOGY . &ew !ms. to

massi1e lesions in1ol1ing the entire breast 9arger lesions bulbous protrusions %4t the presen!e o- no%ules oproli-erating stroma !o1ere% by epithelium . Some tumors " protrusions e=ten% into a !ysti! spa!e.

PH&LLODES TUMOUR
HPE. 3reater !ellularity,

mitoti! rate, nu!lear pleomorphism, stromal o1ergrowth, an% in-iltrati1e bor%ers.

Re!ur lo!ally, rare metastases. Majority 9ow"gra%e lesions

Rare 5igh"gra%e lesions.

Phyllo%es tumors " e=!ise% with

wi%e margins 4 maste!tomy to a1oi% lo!al re!urren!es.

NORMAL MALE BREAST

Consists o- the nipple an%

a ru%imentary %u!t system en%ing in terminal bu%s without lobule -ormation.

G&NAECOMASTIA
>nlargement o- male breast. Puberty41ery age%4hyperestrinism. Cirrhosis o- li1er, n!rease% a%renal

estrogens as an%rogeni! -un!tions o- testis -ail in 1ery age%, Drugs B al!ohol, marijuana, heroin, ART, anaboli! steroi%s use% by atheletes 6 bo%y buil%ers, Kline-elter syn%rome.

D4t imbalan!e between estrogens,

stimulate breast tissue an% an%rogens whi!h !ountera!t these e--e!ts

'nilateral or bilateral Button"li#e subareolar enlargement.

Morphology : ncrease in dense collagenous connective tissue, marked micropapillary epithelial hyperplasia of the duct lining. ndividual epithelial cells fairly regular, columnar to cuboidal cells with regular nuclei. !obule formation is rare.