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 |Sales| Santiago L | Santiago S | Santos JRUERM 2015BSave the 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