Rivero | Robledo | Sales| Santiago L | Santiago S | Santos JR
UERM 2015B Page 1 of 8 NORMAL GROSS ANATOMY AND HISTOLOGY OF THE
BREAST The breast is composed of epithelial and stromal
components.EPITHELIAL COMPONENT
1.Lobe:Abreastofayoungfemaleiscomposedof10 lobes. Each lobe is
composed of lobules. 2.Lobules:Dependingonageandstatusofhormones
inthebody,theycanbeaslowas20lobulesper breastorupto200.Eachlobule
is composedofacini or ductal cells.3.Acini: oAKA Terminal duct
lobular unit oLined by two types of cells:
a.Cuboidalcells:innermostlayer,seen towardsthelumenandproduces
secretion b.Myoepithelialcells:outermostlayer, seen at the
periphery STROMAL COMPONENT 1.Interlobular: found in between
lobules 2.Intralobular: around each acini Figure 1. Epithelial
components of the breast: lobe, lobule and acini.Yellow arrow:
myoepithelial cells CHANGES IN THE FEMALE BREAST
Appearanceofthebreastbothonmammogramand
onhistologydependsontheageandstatusof hormones. Figure 2. Changes
in Female BreastPictureA:Inyoungerwomanwhopresentswithpalpable
lesionon breast,mammogram is not indicatedbecause itonly detects
radio dense masses. Since the breast of a young female
isalsodense,sotheresnodifferenceinlucencyonthe mammogram,so itsvery
easytomiss anytypeoflesion.The use of ultrasound is
recommended.Picture B: The density of a young woman's breast is due
to the predominanceoffibrousinterlobularstromaandscanty adipose
tissue. Picture C. In a woman who is breastfeeding, the breast will
go underlactationalchanges.Thelobulebecomesenlargedand
theacinibecomedilatedbecauseitstartsproducingmilk.
Duringlactation,progesteroneisincreasedwhichgiveriseto hyperplasia
of lobules while prolactin will produce the breast milk secretion.
Figure3.PictureD:Intheelderlyfemale,atrophicand degenerative
changes are seen. Theres atrophy and decreased
innumberoflobulesandacini,lobulesarefarapart,fibrous
tissueinbetweenlobulesisdecreasedandtheresanincrease in the adipose
tissue.PictureE:Inelderlyfemale(40-50y/o),duetoincreased
adiposetissueinthebreast,mammogramsbecomemore
radiolucentwhichcandetectnonpalpablelesionsand calcifications.
DISORDERS OF DEVELOPMENT
*Importanttorememberisyoushouldbeabletodistinguishthese disorders
of development from carcinoma. CONGENITAL NIPPLE INVERSION
Failureofthenippletoevertduringdevelopment (congenital) andmay be
unilateral A cosmetic deformity, non pathologic Can sometimes
impede lactation Cancorrectspontaneouslyduringlactationdueto
hyperplasiawhereinbreastbecomesfullandit pushes the nipple out,
everting it Inacquirednippleinversion(e.g.nipplepiercing),it
indicates malignancy (this is the main difference between
congenitalnippleinversion.Onemustbeabletoobtain history from
patient if nipple is inverted since birth) Figure 4. Nipple
inversion 5.8 PATHOLOGY OF THE BREAST Save the BREAST for last DR.
JANELYN DY-LEDESMA, DPSP JANUARY24, 2013 Rivero | Robledo |Sales|
Santiago L | Santiago S | Santos JRUERM 2015BSave the BrEaST for
last!!!Page 2 of 8 MILKLINE REMNANTS Supernumerary nipples result
from the persistence of epidermalthickeningsalongthemilkline,which
extends from the axilla to the perineum.Commonly located at the
chest Figure5.Left:Supernumerarynipple.Right:Milklinewherenipple
can arise from the axilla to the perineal area ACCESSORY AXILLARY
BREAST TISSUE Normally,thebreasttissueextendstotheaxillaor the
axillary tail of Spence
Itisonlyconsideredanaccessorybreasttissuewhen it forms a lump
Sincetheaccessorybreasttissueissimilartothe breast proper, it can
also undergo hormonal changes. It can be tender or enlarged during
menstruation and can develop a carcinoma. Figure 6. Accessory
Axillary Breast Tissue. Slight protuberance at axillary region
INFLAMMATORY DISORDERS 1.Acute Mastitis 2.Periductal Mastitis
3.Mammary Duct Ectasia 4.Fat Necrosis
5.LymphocyticMastopathy(SclerosingLymphocitic Lobulitis
6.Granulomatous Mastitis 7.Inflammatory Carcinoma 8.Pagets Disease
of the Breast Number1,2:obviouslyseenasinflammatorywiththepatient
presentingfever,erythematousswollenbreast,andtenderto
touch.Thesearecompletelybenign,canbetreatedwithantibiotics and
should not be confused with malignancy (no palpable masses).
Number3,4,5,6:classifiedasbenignandinflammatorybutoften
mistakenforcarcinomaduetopresenceofanirregularpalpable masses with
occasional nipple
dischargeNumber7,8:bothareTRUEMALIGNANTprocessbuttheywere
includedinthissectionsincetheypresentasaninflammatory
process(erythematousswollenbreastwithoccasionalnipple discharge).
They dont have a palpable mass. ACUTE MASTITIS Caused by
lactation/breastfeeding Seenonthefirstmonthofbreastfeedingwherein
nipple becomes cracked, dry and develops fissures
Staphylococcusaureusinvadesthefissuresand cracks inducing acute
mastitis Figure 7. Acute mastitis: erythematous and swollen breast
PERIDUCTAL MASTITIS AKAReccurentSubareolarAbscess,Squamous
Metaplasia of lactiferous ducts, Zuska Disease Can arise in both
male or female breast High incidence in smokers Associated with
inverted nipple Normally,thenippleislinedbykeratinproducing
squamousepithiliumwhiletheductsarelinedby cuboidal epithelium In
periductal mastitis, the ducts undergoes squamous
metaplasiawhereitproduceskeratin,keratin flakes fill up the ducts
the ducts rupture leading to
inflammation(abscessformation,secondarybacterial infection)
Note:AcuteandPeriductalMastitisaremainlyaninflammatory process
MAMMARY DUCT ECTASIA Occurs in 50-60 years old Benign inflammatory
disease Presentwithapoorlydefinedpalpableperiareolar
massthatisoften associatedwith thick,white nipple secretions and
sometimes with skin retraction Onmammogram,appearsas radiodense
image with irregular borders MORPHOLOGY Dilation of ducts, filled
with granular debris and lipid laden macrophages
Periductalandinterductaltissuecontainsdense
infiltratesoflymphocytesandmacrophages,and variable numbers of
plasma cells Fibrosismayeventuallyproduceskinandnipple retraction
(fibrous tissue pulls on the underlying skin
producingapuckering/depressionwhichcanbe mistaken for a sign of
breast cancer)
Figure8.Mammaryductectasia.Inthelaterpartofthedisease,it
producesintensefibrosissecondarytoinflammationcompressingthe
ductformingaslit-likespace.Theductsarefilledbygranulardebris that
contains numerous lipid-laden macrophages. FAT NECROSIS Associated
with history of breast trauma and surgery
Canpresentasapainlesspalpablemass,skin
thickeningorretraction,orchunkywhitelesionsin the breast
Amammographicdensity,ormammographic calcifications.
Microscopically, fat necrosis will be seen Rivero | Robledo |Sales|
Santiago L | Santiago S | Santos JRUERM 2015BSave the BrEaST for
last!!!Page 3 of 8 LYMPHOCYTIC MASTOPHATHY (SCLEROSING LYMPHOCYTIC
LOBULITIS) SeeninwomanwithType1DiabetesMellitusand other autoimmune
thyroid diseases Presentsassmallsingleormultiplehardpalpable
masses.Microscopically,itshowsacollagenizedstroma
surroundingatrophicductsandlobules.The
epithelialbasementmembraneisoftenthickened.A
prominentlymphocyticinfiltratesurroundsthe epithelium and small
blood vessels. GRANULOMATOUS MASTITIS
Canbesecondarytotuberculosis,Wegener
granulomatosisorsarcoidosiswhichproducesa granulomatous
inflammation Associatedwithpresenceofforeignbodies(leaked silicone
implants) and immunocompromised women
Thegranulomatousinflammationisconfinedtothe
lobules,suggestingthatitiscausedbya
hypersensitivityreactiontoantigensexpressedby lobular epithelium
during lactation. INFLAMMATORY CARCINOMA A TRUE malignant
tumorRarely presents as a mass
Breastappearserythematous,swollenwithnipple discharge and peau
dorange (orange peel skin) Doesntproduceamassbecausethetumorcellsis
foundwithinthedermal lymphaticswhich isnot big enough to produce a
palpable lesionCannot be observed in mammogram (it is too small)
Verypoorprognosisduetotheinvolvementof lymphatics and can easily
metastasizeTumor is negative for hormone receptors Surgery,
chemotherapy and hormone therapy are not beneficial
Figure9.InflammatoryCarcinoma.Left:Breastisswollenand erythematous
Middle: peau dorange. Right: lymphatic invasion PAGETS DISEASE OF
THE BREAST Rare manifestation of breast cancer Palpable mass is
present in 50% to 60%Almost all have an underlying invasive
carcinoma Women who dont have palpable masses have Ductal Carcinoma
In Situ (DCIS)Eczematous, scaly, pruritic lesion in the nipple
Intheskinbiopsyofthenipple,thePagetcellsare
presentintheliningepitheliumofthenippleand areolar complexPresents
as calcification on mammogram Negative for Estrogen Receptor (ER)
Positive for HER2/neu, a receptor that has been used to determine
if a patient responds to
TrastuzumabTrastuzumab(Herceptin):atargettherapy antagonizing the
HER2/neu receptor; very expensive
IfpositiveforHER2/NEU,patientcantbegiven
Tamoxifen(estrogenantagonist)becauseitwillnot work on the tumor
Prognosisdependsonunderlyingfeaturesof invasive carcinoma
Figure10.TopLeft:Scalynipplelesion.TopRight:DCISarising
withintheductalsystemofthebreastcanextendupthelactiferous
ductsandintotheskinofthenipplewithoutcrossingthebasement
membrane.Themalignantcellsdisruptthenormallytightsquamous
epithelial cell barrier, allowing extracellular fluid to seep out
and form an oozingscaly crust.Bottom:Poorly differentiated, doesnt
form any tubules BENIGN EPITHELIAL LESIONS NONPROLIFERATIVE BREAST
CHANGES FIBROCYSTIC CHANGES Lumpy bumpy, rubbery, movable 30-40 y/o
Cancer risk = 3% CYSTS Formedbydilationand unfolding of lobules
Maycoalescetoform bigger cysts Linedbyflattened
atrophicepitheliumorby metaplastic apocrine cells Metaplastic
apocrine cells Abundant granular, eosinophilic cytoplasm, round
nuclei Resemblesnormal apocrineepithelium of sweat glands
Calcification common Alarming when solitary and firm!FIBROSIS
Rupturedcystrelease materialtostromachronicinflammationand fibrosis
ADENOSIS Increaseinnumberof acini per lobule Normal: pregnancy
Nonpregnant: focal change
Aciniareenlarged(blunt-ductadenosis)butNOT distorted
Linedbycolumnarcells whichmaylookbenignor haveatypicalfeatures(flat
epithelial atypia) Rivero | Robledo |Sales| Santiago L | Santiago S
| Santos JRUERM 2015BSave the BrEaST for last!!!Page 4 of 8
PROLIFERATIVE BREAST DISEASE WITHOUT ATYPIA
Proliferationofductalepitheliumand/orstroma
WITHOUTcytologicorarchitecturalfeatures suggesting carcinoma in
situ (CIS). Myoepithelial cells are PRESENT Cancer risk = 5-7%
Figure11.Normalacinilinedby2celltypes:myoepithelialand luminal cell
EPITHELIAL HYPERPLASIA Theductisdilatedandfilledwith
cells.Thereishyperplasiaofductal cells Linedby>2cell
layers(maybeboth luminaland myoepithelial) Irregularlumens
(slitlikefenestrations) at the periphery Usually incidental
SCLEROSING ADENOSIS Thelobularunitisenlarged,acini
arecompressedanddistortedby densestroma.Calcificationsare
presentwithinsomeofthelumens. Unlikecarcinomas,theaciniare
arrangedinaswirlingpattern,and theouterborderiswell-circumscribed.
>2xnumberofacini per terminal duct Normallobular arrangement
maintained Acinicompressed& distorted CENTRALLYbut dilated
PERIPHERALLY Prominent myoepithelial cells Maycompletely
compresslumensto looklikesolidcords whichmaymimic invasive
carcinoma COMPLEX SCLEROSING ADENOSIS (Radial scar)
Grosslysolidandhasirregular borders,butnotasfirmasan invasice CA.
Glands are compressed and distorted.Only benign lesion to
formirregularmass andmimicinvasive carcinoma Hasacentralnidus
orentrappedglands inahyalinized stromawith projections containing
epitheliumwith varyingdegreesof cystformationand hyperplasia
NOTassociatedwith previoustraumaor surgery PAPILLOMAS Composedof
multiplebranching fibrovascularcores withconnective
tissueaxislinedby luminaland myoepithelial cells Growthoccursina
dilated duct (+)epithelial hyperplasiaand apocrine metaplasia
Largeduct papilloma-solitary; in lactiferous sinus of nipple;BLOODY
NIPPLE DISCHARGE Smallpapilloma multiple;located deeper;NO
DISCHARGE PROLIFERATIVE BREAST DISEASE WITH ATYPIA Resemble CIS but
lack enough features for diagnosis
Featuresofatypia:lossofstromabetweenacini,
cellularpleomorphism,hyperchromasia, increased/abnormal mitoses
Cancer risk= 13-17% ATYPICAL DUCTAL HYPERPLASIA Sameasductal
carcinoma in situ (DCIS) buthaslimitedextent andpartiallyfilling
ducts(+) myoepithelial cells More rigid cells Breast Ca risk
ATYPICAL LOBULAR HYPERPLASIA Sameaslobular carcinoma in situ (LCIS)
Cells fill < 50% of acini Mayinvolvecontiguous ductsviapagetoid
spread->atypical lobularcellsliebetween ductalcasement
membraneand overlyingnormalductal epithelial cells.
Maystaytherefora long time CARCINOMA OF THE BREAST INCIDENCE AND
RISK FACTORS Itisthemostcommonnon-skinmalignancyin women RISK
FACTORS INCLUDE 1.Ageincreaseswithage(70%occurinwomen>50 years
of age 2.AgeatMenarchethosewhoreachmenarche 10 LNs Absent IV Any
size invasive carcinoma (-) or (+) LNs Present13 BENIGN STROMAL
TUMORS FIBROADENOMA Most common benign tumor of the female breast
Occur in younger women 20s to 30s Epithelium is hormonally
responsive Can calcify with age
A:Theradiogramshowsacharacteristicallywell-circumscribedmass.B:Grossly,arubberywhite,well
circumscribedmassisclearlydemarcatedfromthe
surroundingyellowadiposetissue.C:Proliferationof
intralobularstromasurrounds,pushesanddistortsthe associated
epithelium PHYLLODES TUMOR AKACystosarcomaphylloidesmostcommonin
elderly women Distinguishedfromfibroadenomasbycellularity,
mitoticrate,nuclearpleomorphism,stromalgrowth Rivero | Robledo
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BrEaST for last!!!Page 8 of 8 and infiltrative borders
Tumorsmustbeexcisedwithwidemarginsto prevent recurrences
Phyllodestumor(leaflike).Comparedtofibroadenoma,there
isincreasedstromalcellularity,cytologicatypia,andstromal overgrowth
giving rise to typical leaflike structures BENIGN STROMAL LESIONS
Tumorsoftheinterlobularstromaofthebreastare
composedofstromalcellsw/oanaccompanying epithelial components
MALIGNANT STROMAL TUMORS Angiosarcomacanbesporadicorariseasa
complication of radiotherapy. Sporadicoccurinyoungwomenmeanageis35,
poorer prognosis Angiosarcomafromradiationexposurearisesafter 10-15
years Canalsoariseintheskinofanarmrendered
chronicallylymphedematousbypriormastectomy
andlymphnodedissection(Stewart-Treves Syndrome) Metastasis to the
lung via hematogenous route THE MALE BREAST GYNECOMASTIA
Enlargement of the male breast May be unilateral or bilateral May
occur as a result of hormonal imbalance between
estrogenwhichstimulatesbreasttissueand androgens which counteract
these effects Encountered also in liver cirrhosis
Drugssuchasalcohol,marijuana,heroin,
antiretroviraltherapy,anabolicsteroidshavealso been associated
Figure 21. Gynecomastia. Terminal ducts WITHOUT lobule formation
arelinedbyamultilayeredepitheliumwithsmallpapillarytufts. There is
typically surrounding periductal hyalinization and fibrosis.
CARCINOMA Rare occurrenceonly 1% There is a palpable subareolar
mass usually 2-3 cm in size 3-8% is associated with Klinefelters
syndrome The risk factors are similar with women
Thehistologicsubtypeisthesame,thepapillaryis more common Nipple
discharged is a common symptom
Thecarcinomaissituatedclosetotheoverlyingskin
andunderlyingthoracicwall,andevensmall
carcinomascaninvadethesestructuresandulcerate through the skin
Figure 22.Male Breast CA. remember that Gynecomastia here is NOT a
risk factor. REFERENCE Robbins and Dra. Ledesmas Lecture I see my
body as an instrument, rather than an ornament Alanis
Morissette