PATHOLOGY OF THE BREAST

Lecture Outline
1. Review of Normal Anatomy and General Pathology Points
2. Benign Breast Disease
I. Non-neoplasti
II. Neoplasti
!. "verview of Breast #aner$ %pidemiology& Pathology and Prognosti 'ators
(. "ther Breast )*mo*rs
+. Pathology of the ,ale Breast
Lecture Objectives
At the end of the let*re the st*dent sho*ld -e a-le to$
1. Dis*ss the etiology and pathologi feat*res of the different forms of -enign non-neoplasti
and neoplasti -reast disease.
2. .ist the -enign -reast diseases that inrease a patient/s ris0 of developing -reast aner and
lassify these onditions aording to the degree of relative ris0.
!. "*tline the other ris0 fators predisposing to -reast aner and the inidene1prevalene of
-reast aner.
(. #lassify -reast aner into histologi s*-types and desri-e the pathologi feat*res of eah.
+. .ist the main prognosti fators for -reast aner.
Review of Normal Anatomy
)he -reast onsists of si2 to ten ma3or d*t systems4 the ma3or e2retory d*t is the latifero*s
d*t whih drains thro*gh the nipple via the latifero*s sin*s
)he latifero*s d*t divides s*essively into smaller -ranhes5the terminal d*t gives rise to
appro2. !6 aini whih form the lo-*les& the f*ntional -reast *nits4 many -reast diseases arise in
the terminal duct-lobular unit
)he d*ts and aini are lined -y ol*mnar1*-oidal epitheli*m4 a peripheral layer of
myoepitheli*m provides the ontratility neessary for the e2pression of seretions
)he -reast stroma 7 dense fi-roonnetive tiss*e 8 adipose tiss*e 9interlo-*lar stroma: and loose
stroma s*rro*nding the aini within the lo-*les 9intralo-*lar stroma:
)he -reast tiss*e responds to hormonal stim*lation e.g. d*ring the menstr*al yle and latation
and shows invol*tional1atrophi hanges at menopa*se
PathologyGeneral Points
Breast disease affets mostly women5the larger and more omple2 str*t*re of the female -reast
and sensitivity to hormonal infl*enes predisposes to a variety of diseases.
Breast diseases may present as palpa-le l*mps& pain& inflammatory masses& nipple disharges or
as non-palpa-le a-normalities deteted on -reast *ltraso*nd or mammographi sreening.
;ltraso*nd and mammography are types of radiologi imaging that allow for the detetion of
small non-palpa-le lesions not assoiated with -reast symptoms.
,ethods of pathologi diagnosis inl*de fine needle aspiration ytology 9'NA#: and inisional
or e2isional -iopsies. <oo0-wire loali=ation -iopsies or image-g*ided -iopsies are done for
lesions deteted on *ltraso*nd or mammography i.e. non-palpa-le lesions whih inl*de mass
9solid or ysti: and alifiations.
In terms of overall fre>*eny& most women who present with -reast omplaints will have -enign
lesions& however -reast aner is one of the most ommon malignanies affeting women in the
#ari--ean and the rest of the world.
BENIGN BREAST DISEASE
I. Nonneo!lastic "iseases
1. Inflammation
Acute #astitis
)his is the most linially important form of mastitis4 o*rs as a ompliation of -reast-feeding
when ra0s in the nipples allow for -aterial infetion 9esp. ?taphyloo*s a*re*s& less
ommonly streptooi:
;s*ally *nilateral5a*te inflammation in the -reast an lead to a-sess formation whih is
e2>*isitely tender and painf*l
)reatment 7 s*rgial drainage 9often *nder general anesthesia: and anti-iotis
Peri$uctal #astitis %Recurrent &ubareolar Abscess'
"*rs seondary to s>*amo*s metaplasia of the lining of a latifero*s d*t 9@ related to igarette
smo0ing5A6B of affeted patients are smo0ers:4 affets -oth women and men
Ceratin -eomes entrapped leading event*ally to dilation and r*pt*re of the d*t with s*-se>*ent
hroni1gran*lomato*s inflammation4 seondary infetions with s0in -ateria an o*r
A fist*la trat an develop with re*rrent ases4 treatment involves removing the involved
d*t1trat and drainage of any assoiated a-sess
#ammary "uct (ctasia
#hiefly affets m*ltiparo*s women in the fifth and si2th deades
,ar0ed perid*tal hroni inflammation leads to destr*tion of the walls of the d*ts with
onse>*ent dilation and inspissation of seretions
Affets mainly large d*ts whih -eome filled -y lipid-laden marophages and neroti de-ris4
the *nderlying a*se of the inflammatory response is *n0nown
As the inflammation s*-sides perid*tal fi-rosis. ;s*ally presents as a poorly defined
periareolar mass that can be confused clinically with carcinoma
#an also present as a thi0& heesy nipple seretion with or witho*t the mass
,ammographi appearane an also resem-le arinoma4 arinoma m*st -e e2l*ded -y
ytologi 9'NA#: or histologi eval*ation 9-iopsy:
)at Necrosis
;nommon lesion4 ma3ority of patients give a history of tra*ma& prior s*rgial intervention or
radiation therapy
#harateri=ed initially -y a entral fo*s of neroti fat ells s*rro*nded -y foamy& lipid-laden
marophages and ne*trophils5progresses to hroni inflammation with infiltrating lymphoytes
and the formation of m*ltin*leated foreign -ody giant ells 9marophages:4 released fatty aids
an om-ine with ali*m salts to prod*e foi of alifiation
As with d*t etasia& the ma3or linial signifiane of this lesion is its possible confusion with
carcinoma when fi-rosis has reated a linially palpa-le mass or foal alifiation is seen on
mammography5'NA#1-iopsy to e2l*de malignany

2. Non-Proliferative (Fibrocystic! "han#es
Represents the sin#le most common disorder of the breast
2
"lder terminology is fi-roysti disease5more reently referred to as non-proliferative hanges
D#hangesE is generally onsidered to -e more appropriate terminology than DdiseaseE -ea*se the
alterations are present in most women and are not assoiated with any ris0 of progression or
development of aner
)ho*ght to -e a*sed -y hormonal im-alanes e.g. relative in estrogens or of progesterone&
or a-normal end-organ meta-olism of the hormones
)he main pathologi feat*res seen are$
*ystic change an$ A!ocrine meta!lasia
#ysts represent dilation of d*ts 9esp. terminal d*ts: and vary in si=e from
mirosopi to large ysts that an -e palpated
,any of the ysts will -e lined -y large polygonal ells with a-*ndant&
eosinophili ytoplasm resem-ling aporine epitheli*m of sweat glands5
apocrine metaplasia
#alifiation an o*r within the yst l*mens
A$enosis
)his is an inrease in the n*m-er of ainar *nits in the lo-*les
Aini an -e arranged in different patterns e.g. appear dilated with flattened ends
9-l*nt d*t adenosis: or t*-*lar 9t*-*lar adenosis:
)ibrosis
#ysts fre>*ently r*pt*re with the release of d*t ontents and s*-se>*ent hroni
inflammation and fi-rosis
#an present as palpa-le l*mps& nipple disharge& mammographi densities1alifiations
;s*ally diagnosed -etween the ages of 26 and (6 years4 often m*ltifoal and -ilateral prod*ing
general Dl*mpinessE of the -reast9s:
#ysts will yield lear fl*id on aspiration e.g. ompared to ysts that an develop d*ring the
latational period5galatoeles5that yield t*r-id fl*id
Benign feat*res onfirmed on 'NA# or -iopsy
$. Proliferative %isease without &typia
(!ithelial +y!er!lasia
Normal d*ts1aini are lined -y two ell layers5 epitheli*m and myoepitheli*m
%pithelial hyperplasia 7 in the n*m-er of layers of ells lining d*ts and aini
#linially signifiant hyperplasia is the presene of four or more layers of cells5so-alled
moderate or florid epithelial hyperplasia
Involved d*ts and aini are filled with overlapping& proliferating ells
N., . No atypial arhitet*ral or ytologi feat*res are present
&clerosing A$enosis
?peial type of adenosis harateri=ed -y F aini 8 stromal fi-rosis within lo-*les whih
ompresses and distorts aini
#an -e assoiated with alifiations whih may -e deteted on mammography
'. &typical (yperplasia
#ertain types of epithelial hyperplasia are harateri=ed -y the presene of atypial arhitet*ral
and1or ytologi feat*res
#an affet d*ts5atypial d*tal hyperplasia& or lo-*les5atypial lo-*lar hyperplasia
!
&typical features resemble but fall short of in-situ cancer
)here are no linial or radiologi feat*res that allow for diagnosis4 nee$ bio!sy
As with proliferative disease witho*t atypia& inidene has inreased with the *se of sreening
mammography and the inrease in the no. of -reast -iopsies -eing performed
II. ,enign -umours
1. Fibroadenoma
,ost ommon -enign t*mo*r of the -reast4 omposed of -oth proliferating gland*lar and stromal
elements5in a given lesion one element an predominate
Patients *s*ally present -efore age !6 years4 lassi presentation is that of a firm& mo-ile l*mp
9D-reast mo*seE:
Giant forms an o*r& espeially in yo*nger patients
Appro2. 26B of lesions are comple) fibroadenomas 5harateri=ed -y ertain speifi
histolo#ic features that have -een shown to -e linially signifiant
2. %uct Papilloma
Benign papillary epithelial t*mo*rs that o*r mainly in large d*ts
Papillae are fi-rovas*lar stal0s lined -y layers of proliferating epithelial and myoepithelial ells
with no atypial feat*res
,ost patients present with a sero*s or -loody nipple disharge
Relative Ris. for Invasive ,reast *ancer for ,enign ,reast Lesions
"ne of the most important developments in -reast pathology in reent years is the reognition
that beni#n lesions have different levels of ris* for the development of invasive breast cancer
Ris0 is often >*oted as a relative ris* i.e. what a patient/s ris0 is when ompared to someone
witho*t -reast disease.
)he magnit*de of ris0 may -e modified -y other fators e.g. menopa*sal stat*s and family
history. Not all patients& even with higher levels of ris0 however& will develop aner.
No Increased +is*
,astitis
'at nerosis
,ammary d*t etasia
Non-proliferative 9Dfi-roystiE: hanges
'i-roadenoma 9simple:
,li#htly Increased +elative +is* (1.--2 .imes!
,oderate1florid hyperplasia
?lerosing adenosis
D*t papilloma
#omple2 fi-roadenoma
/oderately Increased +elative +is* ('-- .imes!
Atypial d*tal hyperplasia
Atypial lo-*lar hyperplasia
Gomen who are at mildly or slightly inreased ris0 for -reast aner sho*ld reeive follow-*p
are. It is now reommended that women with atypial hyperplasia reeive prophylati treatment
(
e.g. tamo2ifen in addition to aref*l follow-*p in an effort to red*e the li0elihood of aner
development
CARCINOMA OF THE BREAST
0pidemiolo#y
Breast aner is the ommonest malignany in women worldwide
Ao*nts for appro2imately 1HB of all female aners ompared with ervial aner 91+B:&
oloni aner 9AB: and aner of the stomah 9HB:
Inidene rates are highest in North Ameria& A*stralia and Gestern %*rope4 intermediate in
?o*th Ameria& the #ari--ean and %astern %*rope and lowest in #hina& Iapan and India
In Iamaia& -reast aner is the most ommon invasive t*mo*r of women
Ris. )actors
Age
)he inidene of -reast aner inreases with age4 it is *nommon -efore 2+ years -*t the
inidene inreases steadily to the time of menopa*se and slows after this
)amily +istory
Appro2imately 16B of -reast aner is d*e to inherited geneti predisposition
A woman whose first degree relative 9mother& sister or da*ghter: has had -reast aner is at an
inreased relative ris0 2 to! times ompared to other women
At least two genes that predispose to -reast aner have -een identified51+"& 1 and 2
,enign ,reast "isease
As noted previo*sly women with ertain types of -enign -reast disease are at ris0
+istory of Other *ancer
A history of aner in the other -reast or a history of ovarian or endometrial aner
+ormonal )actors
'ators assoiated with e2pos*re to inreased levels of estrogen have -een shown to inrease a
woman/s ris0 for -reast aner
)hese fators inl*de early age at menarhe& late age at menopa*se& n*lliparity& late age at first
hild--irth and post menopa*sal hormone replaement treatment
(nvironmental )actors
Dietary fators e.g. high fat inta0e and e2essive alohol ons*mption& and e2pos*re to ioni=ing
radiation have also -een proposed as ris0 fators
.he etiolo#y of breast cancer in most women is un*nown but most li*ely is due to a combination of
the ris* factors listed above i.e. #enetic2 hormonal and environmental factors
Patholo#y
+istologic *lassification
+
,reast *ancer

"uctal Lobular

Insitu %"*I&' Invasive%I"*' Insitu %L*I&' Invasive%IL*'
"uctal *arcinoma Insitu %"*I&'
Inreased inidene in ertain o*ntries related to inreased *se of mammographi sreening and
early aner detetion4 omprises appro2. +6B sreen-deteted aners
By definition these lesions are noninvasive5proliferating malignant ells within the d*t
system $o not -reah the *nderlying -asement mem-rane
%ifferent patterns an -e seen e.g. comedo 9entral nerosis!3 cribiform 9ells arranged aro*nd
Dp*nhed-o*tE spaes:4 papillary and solid 9ells fill spaes:
D#I? an -e of different #rades i.e. low& intermediate and high grade 9e.g. omedo7high:
"ften multifocal5malignant pop*lation an spread widely thro*gh the d*t system witho*t
-reahing the -asement mem-rane
Gomen with D#I? are at ris0 of re*rrent D#I? following treatment and are also at mar*ed
increased relative ris* for the development of invasive cancer 9H to 16 times: espeially in the
same affeted -reast
Lobular *arcinoma Insitu %L*I&'
Relatively *nommon lesion ompared to D#I?4 malignant proliferation of small& *niform
epithelial ells within the lo-*les whih $o not -reah the -asement mem-rane
Also at mar*ed increased relative ris* for the development of invasive cancer 9H to 16 times:&
-*t the invasive lesion an develop in either -reast i.e. ris0 is -ilateral
Invasive %Infiltrating' "uctal *arcinoma %I"*'
#ommonest form of -reast aner espeially in poorer pop*lations 9less sreening mammography
to detet early lesions s*h as D#I?:
;s*ally presents as a palpa-le l*mp 9often hard and irreg*lar: with or witho*t evidene of loal
spread e.g. tethering of the s0in& retration of the nipple& peau d4oran#e 9lymphati
spreadthi0ening and dimpling of the s0in:& and Pa#et4s disease of the nipple
9*leration1inflammation d*e to intrad*tal spread to the nipple:
ID# deteted -y mammography is *s*ally smaller 9m*h -etter prognosis:
#an also present with an a2illary mass 9spread to regional lymph nodes: or with evidene of
distant metastases 9e.g. l*ng& -rain& -one:
Different histolo#ic subtypes e2ist5the most ommon is scirrhous carcinoma 9also 0nown as
invasive d*tal of no speial type:. )his type is harateri=ed grossly -y an irreg*lar& hard mass
that on histology shows infiltrating l*sters of malignant epithelial ells s*rro*nded -y dense&
fi-ro*s stroma
?peial histologi types of ID# inl*de$
/edullary carcinoma5sheets of malignant ells in a dense lymphoid stroma
.ubular carcinoma5harateri=ed -y infiltrating t*-*lar str*t*res
/ucinous5colloid carcinoma5malignant ells in pools of m*in
Papillary carcinoma6papillary formations li0e papilloma 8 invasion
)he importane of reogni=ing the different types is that most of the special types carry a better
pro#nosis than the more ommon sirrho*s aner
J
Invasive %Infiltrating' Lobular *arcinoma %IL*'
,*h less ommon than its d*tal o*nterpart4 an present with similar feat*res -*t more li0ely
to -e bilateral and1or multicentric 9m*ltiple lesions within the same -reast:
#lassi histologi appearane - small& *niform ells arranged as strands within a fi-ro*s stroma
9DIndian-fileE:4 an also infiltrate aro*nd *ninvolved d*ts in D-*ll/s-eyeE pattern
,etastasi=e more fre>*ently to #?'& serosal s*rfaes and pelvi organs ompared to ID#
Pro#nostic Factors
&tage
Different staging systems e2ist e.g. the )N, and the ,anhester lassifiation5tumour si7e and
a)illary node status are important parameters. )he 16-year s*rvival rate for lymph node negative
disease is H6B vers*s !+B for t*mo*rs with positive nodes
Inflammatory carcinoma
?peifi clinical presentation K DinflammatoryE - -reast swelling and s0in thi0ening. Assoiated
with *nderlying ID# or I.# that feat*res prominent lymph-vas*lar invasion. Parti*larly poor
prognosis i.e. ! year s*rvival of !-16B
-umour Gra$e
Different grading systems also e2ist4 most pop*lar is the Bloom-Rihardson system -ased on
parameters that inl*de mitoti rate4 the higher the grade& the worse the prognosis
+istologic &ubty!es 9see ID# notes:
+ormone Rece!tors
)*mo*rs that e2press reeptors for estrogen and1or progesterone an -e treated with hormonal
manip*lation and generally have a -etter prognosis than those witho*t
#olecular #ar.ers
Newest ategory of prognosti mar0ers that an -e deteted -y imm*nohistohemistry or
mole*lar methods e.g. P#R4 inl*de -er--B2& -my and p+!

OTHER BREAST TUMOURS

Phyllo$es -umour
?tromal t*mo*r arising from the intralo-*lar stroma4 range in si=e from few m to massive
lesions and an -e linially onf*sed with fi-roadenomas
,ost are low-grade lesions that an re*r loally 9irreg*lar -order: -*t do not metastasi=e
"thers are of high-grade and e2hi-it aggressive linial -ehavio*r e.g. spread to distant sites
9these are sometimes alled ystosaroma phyllodes:
PATHOLOGY OF THE MALE BREAST
Gynecomastia
%nlargement of the male -reast related to hormonal im-alane 9rel. estrogens:
#an -e physiolo#ic5seen at p*-erty or old age& or patholo#ic5e.g. asso. with irrhosis&
f*ntional testi*lar t*mo*rs& dr*gs 9alohol& mari3*ana and ana-oli steroids:
#an -e *nilateral1-ilateral and present as diff*se enlargement or as a defined mass
L
,ost important linially as a mar0er of hyperestrinism5neoplasia needs to -e e2l*ded in
ertain ases
*arcinoma
Mery rare o*rrene4 female aner to male aner ratio appro2 166$1
Pathology and -ehavior is similar to aners seen in women altho*gh with less -reast tiss*e& s0in
involvement is more fre>*ent
N1. .he followin# lin* can provide you with additional information and ima#es for this topic8
http$11www.-reastpathology.info1
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