Breast

1. Breast

2. Breastpathology • inflammations • fibrocysticchanges • - nonproliferative • - proliferative • tumors • - epithelial • - fibroepithelial

3. Inflammatorydiseases • puerperal mastitis • mammaryductectasia

4. Puerperal mastitis • occurswithin 2-3 weeksofthe start oflactation • resultofinfection via themammaryductsystem • canbesporadic (athome) orepidemic (in thehospital) • most commonorganism: Staphylococcus aureus • requires prompt antibiotictretment

5. Mammaryductectasia • unknown etiology • diffusedilatationofthe • ducts, ductalrupture • periductalinflammation • clinicalfeatures: • - spontaneousintermittentnippledischarge • - canbepain, nippleinversionorretraction • - maysimulatecarcinoma

6. Fibrocysticchanges • causesunknown - consequenceofperiodicalhormonalstimulation (estrogen predominance over progesterone) • conditionaffectingat least 50% ofwomenofchildbearingage • Clinicalfeatures: • - asymptomatic • - palpablelesion • - breastpain and/ortenderness • - canbeassociatedwithirregular menses, dysmenorrhea, ovariancysts

7. Fibrocysticchanges – relation to breastcancer • nonproliferativechange– no increased risk ofbreastcancer • usualproliferativechange– approximately 2-fold risk • atypicalproliferativechange • - atypicallobularhyperplasia – 5-fold risk • - atypicalductalhyperplasia – 3 - 5-fold risk

8. Nonproliferativefibrocysticchanges • cysts and fibrosis • most common type • usuallybilateral • no increased risk ofbreastcancer

9. Intraductalproliferativechanges • groupofcyotlogically and architecturally diverse proliferations • majority originate in theterminalduct-lobular unit • threecategories: • - usualductalhyperplasia • - atypicalductalhyperplasia • - ductalcarcinoma in situ

10. Lobularproliferativechanges • majority originate in theterminalduct-lobular unit • threecategories: • - lobularhyperplasia • - atypicallobularhyperplasia • - lobularcarcinoma in situ

11. Tumorsofthebreast • benign • malignant • epithelial • fibroepithelial • epithelial-myoepithelial • mesenchymal • tumorsofthenipple • malignantlymphoma

12. Benignepithelialtumors Papilloma Adenoma tubular lactating apocrine • intracysticorintraductal • peripheralorcentral • solitaryormultiple

13. Breastcancer

14. Breastcancer • most commoncarcinoma in women • accountingfor 23% ofallcancersglobally • incidence increasesrapidlywithage

15. Breastcancer - etiology • multifactorial: • - diet (high-calorie diet rich in animal fat and proteins) • - lackofphysicalexercise • - reproductivefactors • - infertility orfewchildren, lackofbreast-feeding • - early menarche, lateageofmanopause • - hormones • - hereditaryfactors (BRCA1, BRCA2)

16. Breastcancer – clinicalfeatures • the most commonclinical sign - palpablemass • lesscommonly: • - skin retraction • - nippleinversion • - nippledischarge • - change in theshapeorsize ofthebreast • rarely: • - enlargementoftheaxillarylymphnodes (in the absence ofany abnormality in thebreast)

17. Breastcancerprevention Primary Secondary early detection and cure breatselfexamination - monthly mammography - womenover 40 years - annual reduces the death rate from breast cancer by approximately 1/3 physicalexamination by a physician (annual) • attempts to reduce the risk of the actual development of breast cancer • bilateralmastectomy– >95% succesful • chemoprevention (tamoxifen) – 50% succesful • limit lifetime estrogen exposure (hormonaltherapyetc.) • healthy diet (low fat diet) • - weightcontrol • - cruciferousvegetables

18. Breastcancer: precursorlesions

19. Lobularneoplasia • includesatypicallobularhyperplasia and lobularcarcinoma in situ • distinctionbased on theextentofinvolvementofindividuallobularunits (LCIS - more thanhalfoftheaciniof a lobular unit are distended by neoplasticcells) • in 85% ofpatientsmulticentric • in 30-67% bilateral • Histopatology: • lobulararchitectureismaintained • aciniexpanded by a monomorphicproliferationofdyscohesivecellswithuniformroundnuclei and scantcytoplasm

20. Ductalcarcinoma in situ • a neoplasticproliferationofepithelialcellsconfined to themammaryductal-lobularsystem • 20-25% ofallnewlydiagnosedbreastcancers in countrieswithscreeningprogramme • Clinicalfeatures: • palpablemass • nippledischarge • Pagetdiseaseofthenipple • 80-85% ofcasesdetectedmammographically in the absence ofclinicalsymptoms • DCIS is precursor (albeit not obligate) to invasive breast cancer

21. Ductalcarcinoma in situ • Histopathology: • architecture: solid, cribriform, comedo, papillary, micropapillary • gradingbased on nuclearfeatures • - DCIS oflow / intermediate / high grade • commonmicrocalcifications

22. Invasiveductalcarcinoma • thelargestgroupofinvasivebreastcancer (50-80%) • in up to 80% ofcases, associated DCIS canbefound • Histopathology • very heterogeneous • architecture: solid, glandular, trabecular… • tumor cells: regular … highlyatypical • Grading! • based on assessmentof: • - tubule and glandformation • - nuclearpleomorphism • - mitotoccount

23. Invasivelobularcarcinoma • 5-15% ofallinvasivecarcinomas • usuallyassociatedwithlobularcarcinoma in situ • Macroscopy: • frequentlypoorlycircumsrcibedirregular tumor • difficult to definemacroscopicallybecauseofthediffusegrowthpattern • Histopathology: • noncohesivecellsindividually dispersedorarranged in a single-filelinearpattern • smallcells, infrequentmitoses

24. Breastcancer - prognosis • Prognosticfactors: • - histological type • - grade • - stage • - lymph node status • - vascularinvasion • 35-55% 10-year survival

25. Her2 – humanepidermalgrowthfactor receptor 2 • proto-oncogene (promotes cell proliferation and opposesapoptosis) • amplificationor over-expression of the ERBB2 gene occurs in approximately 20-30% of breast cancers • associatedwithworseprognosis and increaseddiseaserecurrence • most commonly used medication: Herceptin (trastuzumab)

26. Inflammatorycarcinoma • rare but very agressiveformofbreastcancer • distinctclinical and/orpathologicalfeatures • prominent geographicpattern (more common in northAfrica) • Clinicalfeatures: • rapid breastenlargement and changes in overlying skin (redness, oedema, „orange-peel“ skin) • usually no palpablemass • commondiffusefirmnessofthebreast • Histopathology: • numerousdermallymphatic tumor emboli • underlyinginvasivecarcinomaisoftenofductal type (grade 3)

27. Pagetdiseaseofthenipple • presence ofmalignantglandularepithelialcellswithinthesquamousepitheliumofthenipple • usuallyassociatedwithunderlyingcarcinoma • - invasiveductalcarcinoma (50-60%) • - ductalcarcinoma in situ (25-40%) • Clinicalfeatures: • eczematousorerythematouschangesofthenipple • maybenippledischarge, ulcerationorinversion • Histopathology: • presence ofPagetcellswithinthe epidermis

28. Fibroepithelialtumors • biphasictumorsconsistingof a proliferationofbothepithelial and stromalcomponents • fibroadenoma • phyllodes tumor • - benign • - borderline • - malignant

29. Fibroadenoma • commonbenign tumor • most frequently in women < 30 years • Clinicalfeatures: • painless, slow-growing, mobile, well-definednodule • usually up to 3 cm in diameter • maybemultiple • Macroscopy: • ovoid, well-circumscibed • cutsurfaceisgreyorwhite • Histopathology: • admixtureofstromal and epithelialproliferation

30. Phyllodes tumor • groupoftumorshistologicallyresemblingfibroadenoma • stromalhypercellularity (more cellularthan FA) • mitoses • cytologicatypia • natureof tumor borders • Clinicalfeatures: • averagesize 4-5 cm (maybe > 10 cm) • Macroscopy: • well-circumscribed • characteristicwhorledpatternresemblingleafbuds (usuallylargerlesions)