Brea st Pathol ogy Lecturer: HaninaHibshoosh,M.D. Reading: Kumar, Cotran, Robbins, Basic Pathology, 6th Edition, pages 623- 635
Breast De velop ment • 5th week - thickening of the epidermis - milk line formation • Mammary ridges formfromaxillato groinregion • Involut ion of mam mary ridges except in chestegion, r persistanceyield supernu merarybreast (poly thelia) • 15th week - downward growth into stroma • Last mont hs of gestat canalizat ion epit helial cordstwo with formation ofion branching andof lobuloalveolar structures
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Fibro cyst ic Change s • Miscellaneous changes of breast involving ducts, lobules, and stroma • Clinical in cidence ap proximately 40 to 50% of patients, “lumps” • Pathological incid ence greater than 60 to 80% • Terminology - fibrocystic change favored over disease • Pathogenesis - reflects exaggerated changes occurring normally in the menstrual cycle
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Fibrocyst ic Disea se of Brea st 1. Fibrosis 2. Cysts 3. Apocrine Metaplasia 4. Sclerosing Adenosis 5. Papillomatosis (epithelial hyperplasia)
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Consensus Stateme nt Cancer Commit tee of th e College of Am erican P athologis ts Relative Risk for Invasive Breast Cancer Following Pathological Diagnosis of Benign Breast Disease No increased risk Hyperplasia, mild (2-4 cells) Apocrinemetaplasia Cysts (macro and micro) Ductectasia Fibroadenoma
Slightly increased risk (1.5-2x) Hyperplasia, moderate or florid (ductualand lobular) Papillomawithfibrovascularcore Adenosis( sclerosingo rflorid)
Moderately increased risk (5x) Atypical Ductaland Lobular Hyper plasia-Borderline Lesions
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Atypical Ductal Hyperplasia (ADH) Borderline lesion is defined by some as a proliferative lesion in which some of the cytologic and architectural criteria of carcinoma in situ are met but are not fully satisfied. Pageand Rogers have more recent ly published crit eriaincluding qualitative and quantitative features in the classification of ductal and lobular proliferative lesions. a) Cytologic criteria - This guideline emp hasizes the need for a populat ion of cells bearing similarity to neoplastic cells. b) Histologic or archite ctural criteria - the ductal epithelial prolifer ation predominant pattern is cribiform with secondary spaces having both punchedout regular (typical of non-comedo carcinoma in situ) and irregular borders (typical of florid hyperplasia without atypia). c) Quantitative criteria - anatomic extent of lesion . At least two basement membrane-bound spaces need to be completely involved by a cell population with the cytologic and histologic feat ures of ductalcarcinom a in situ (DCIS) for a diagnosis of DCIS . Therefore, alesion wit h a single space wit h diagnost ic features of DCIS is diagnosed as atyp ical ductal hy perplasia. Inaddition, supportfor an overall size criterion such as adv ocated by Tavassoli(2mm cumulative changes) is expressed.
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Atypical Ductal Hyperplasia (ADH) • Incidence approximately 5% • Risk fordeveloping invasive cancer 4-5x general population • Approximately 10% of patients will dev elop canc er • Risk for cancer is bilateral • Risk greatest in first decade follow ing diagnosis • Patients with atypical ductal hyperplasia with family history have same risk asin-situ cancer group for the developm ent of 8-10x. • invasive Prognosiscancer, of atypical ductal hyperplasia associat ed cancer same as cancer lacking atypical ductal hyperplasia • ~30% of patients with ADH on needleiopsy b hav e cancer on excision
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Benign Neopla sma • Fibroadenoma • Intraductal papilloma Tumor of variable malignant potential • Cystosarcoma phyllodes
Fibroadenoma • Most common benign um t or of the fem ale breast • Usuallyappears in young women • Peak incidence in the third decade of life • A benign fibroepithelial tumor usuallysolitary be multiple with carcinoma • may Rarely associated
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Intra ducta l Papilloma • A benignpapillaryneoplasmwithin a duct • Identifiedperipherallyor centrally(nipple duct) in which case it may be associated with bloody nipple discharge • Mild n i creased risk (1.5 - 2x) of development of invasive cancer in patients with multiple peripheral intraductal papillom as
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Cystosa rcoma Phyllode s • A fibroepithelialneoplasm of variable malignant potential • Neoplastic componentis thestroma • Degenerates into a frank sarcoma with metastasis to lung and distant organs • The majoritycan be curedby complete excision • Peak incidence at 50 years of age
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Malig nant Br east Lesions • Epithelial derived tumors – Intraductal and invasive ductal carcinoma – In situ andinvasivelobularcarcinom a • Mesenchymal neoplasm (sarcoma) – Cystosarcoma phyllodes – Angiosarcoma – Others
Pathology of B reast Ca rcin oma • Most cancers (90%) show ductal epithelium differentiation • 10% referred to as lobular type • In situ and invasive components
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Ductal Carcinomas I n Situ • Neoplasticransform t ationof ductalepitheliumwithin ducts or lobules (intraductal) confined by basement membrane • Various histologic patterns: comedo, solid, cribif orm, clinging, and papillary type • May be detected byits association ith w microcalcification s • May representup to 25% of breastcarcinom a • High grade andlarge size ofhe t in situ car cinoma predicts multifocality and propensityfor invasion • Relative risk forthe develop ment of an invasive car cinoma 8-10 fold greater than the general population • Risk is primarily ipsilateral
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Paget’s Disea se of the Bre ast • In situ carcin oma of lact iferous du cts with extension to epidermis • Involving the nipple and areola • May present with nipple discharge, crustin g, or excoriation of nipple surface
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Invasive Ductal Carcinoma • An infiltrative malignant epithelial process resembling cells lining ducts--most common breast carcinoma • Classified according to histologic appearance as: 1. Carcinoma nototherwise specified -- majority 2. Special good prognosis subt ype including medullarycarcinoma,colloid (m ucinous) carcinoma, and tubular carcinoma . . . 3. Poor prognosis --inflammatory carcinoma
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Lo bul ar Carcin oma In S it u (LCI S) • Neoplastic ransform t ation of epithelial cel ls lining terminal ducts and aciniof small size –E-cadherin negative • Typically multifocal and bilateral • 6 - 9 fold increased risk for development of invasive cancer • Bilateral risk fordevelopment of invasive cancer • 3/4 of invasive cancerare of ductal type • Consideredprimarilya markerfor n i vasion
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Inva sive Lo bular Ca rcin oma • An infilt rating carcin oma resembling cells lininghe t lobules (of LCIS) • Histologically showing classical Indian “ file”pattern and targetoid“bull’s eye” pattern • Composed of elat r ivelysmall cells wit h scanty cytoplasm, sometimes vacuolated (E-cadherin negative) • Represents appr oximately 10% of breast cancer w ith a higher than usual incidence of bilaterality (approximately 20%)
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Prognost ic Fa ctor s of Brea st Ca ncer • • • • •
Size of primary tumor Lymph node involvem ent andextent Grade Histologic type To a lesser extent, estrogen/progesterone receptors, S-phase but not DNA content, C-Erb B2 andfraction ...
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Gynecomastia • Button-like subareolarswelling, bilateral, histologica lly correspondingotintraductalepithelial hyperplasia and increasedperiductal stromal cellular ity and edema • Associatedwith relative estrogen excess, cirr hosis of liver, Klinefelter’s, estrogen secreting tumor, estrogen therapy, and digitalis therapy • Physiological gy necomastiamost common in puberty and old age • No clear cutassociation with development of carcinoma
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Male Breast Ca rc ino ma • Rare, ratio of male to female breast cancer • • • •
1:125 Occurs in advanced age Identifiedin peri-nipple/areolarregion Presents in advanced stage Resembles morphologically and biologically invasive carcinomas of the female breast
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