The document summarizes the anatomy and histology of the normal breast as well as various benign breast conditions. It describes the lobes, ducts, lobules and stroma of the breast. It then discusses various benign breast diseases and alterations including acute mastitis, periductal mastitis, duct ectasia, fat necrosis, granulomatous mastitis and various proliferative breast diseases without atypia.

1. Dr.P.Karpagam Kiruba Rajeswari,M.B.B.S,D.C.P., Tutor in Pathology, MAPIMS.

2. ANATOMY OF BREAST Modified apocrine sweat glands . Breast parenchyma  12 to 20 lobes . Within each lobe – Lactiferous duct - branches repeatedly  leads to no. of terminal ducts  each leads to a lobule  contains multiple acini/alveoli  TDLU (TERMINAL DUCT + LOBULE) Spaces around the lobules and ducts and between the lobes are filled with fatty tissue, ligaments and connective tissue  STROMA

3. LYMPHATIC DRAINAGE OF BREAST

4. NORMAL HISTOLOGY OF THE BREAST 2 cell types – line ducts & lobules. Contractile MYOEPITHELIAL CELLS  lie on the BM  assist in milk ejection during lactation & provides structural support to the lobules EPITHELIAL CELLS  Luminal – produce milk. Epithelial & Myoepithelial cells lie on the basement membrane.

6. NORMAL HISTOLOGY OF THE BREAST 2 types of breast STROMA: INTERLOBULAR STROMA  Dense fibrous connective tissue + adipose tissue. INTRALOBULAR STROMA  Envelopes the acini + hormonally responsive fibroblast – like cells + scattered lymphocytes.

10. ACUTE MASTITIS First month of breast feeding. Cracks / fissures in the nipple  portal of entry of bacteria. Breast  erythematous,painful,fever +nt. MORPHOLOGY : Staph. Inf.  localized area of inflammation. Strep. Inf.  Diffuse, spreading. HPE : Involved breast tissue – necrotic, neutrophil infiltration. Treated with antibiotics, continuous milk expression. Rarely surgical drainage.

12. PERIDUCTAL MASTITIS Recurrent subareolar abscess/ Squamous metaplasia of lactiferous ducts/ Zuska ds. Painful erythematous subareolar mass. 90% cases – assoc. with smoking  Vit.A def./toxic substances in smoke – alters epithelial differentiation. Recurrent cases – fistula occurs. HPE : Keratinizing squamous metaplasia of ducts. Keratin shed from the cells  plugs the ductal system  dilation & rupture of duct. Periductal tissue  keratin spill  chronic granulomatous inflammatory response. Treatment: En bloc surgical removal of the involved duct, fistula. Antibiotics for secondary bacterial infection.

13. DUCT ECTASIA 5 th – 6 th decade, multiparous women. Cl.features: Poorly palpable periareolar mass, thick white secretions from nipple, skin retraction. HPE: Dilated ducts filled by granular debris  numerous lipid-laden macrophages, inspissation of breast secretions, marked periductal and interductal ( dense )infiltrate of lymphocytes and macrophages, and variable numbers of plasma cells. Eventual fibrosis  skin & nipple retraction. Principal significance  produces an irregular palpable mass - mimics the mammographic appearance of carcinoma.

14. DUCT ECTASIA Dilated duct with surrounding fibrosis and chronic inflammation. Lumen of the duct  eosinophilic secretion & markedly attenuated epithelium.

15. FAT NECROSIS Cl.features: H/o breast trauma / prior surgery. Painless palpable mass, skin thickening or retraction, a mammographic density, or calcifications. Acute lesions  hemorrhagic + central areas of liquefactive fat necrosis. Subacute lesions - areas of fat necrosis  ill-defined, firm, gray-white nodules containing small chalky-white foci or dark hemorrhagic debris. Central region of necrotic fat cells  intense neutrophilic infiltrate + macrophages. Proliferating fibroblasts + new vessels + chronic inflammatory cells surround the injured area  Giant cells, calcifications, and hemosiderin appear  focus - replaced by scar tissue.

16. FAT NECROSIS

17. GRANULOMATOUS MASTITIS Rare. CAUSES: Systemic granulomatous ds.  Sarcoidosis, Wegener’s. Granulomatous inf. d/t Mycobacteria, Fungi. GRANULOMATOUS LOBULAR MASTITIS – Parous women, confined to lobules, d/t hypersensitivity reactions to the antigens – expressed by the lobular epithelium during lactation.

19. Benign alterations – in ducts & lobules: Detected by mammography/incidental findings in surgical specimens. Based on the risk of developing Breast Cancer – 3 groups:

20. FIBROCYSTIC CHANGE Most common benign breast condition. Primarily affects terminal duct–lobular unit (TDLU). Pathogenesis  Obscure – hormones (estrogen) -play a role. Clinical features Incidence: 10 – 20 % of adult women. Age : 25 – 45 yrs. Usually bilateral. Vague ‘lumpy’ Morphology: ‘ 3 principle changes’

21. FIBROCYSTIC CHANGE – CYSTS Dilation & unfolding of lobules  small cysts – coalesce  large cysts. Unopened cysts  turbid ,semi translucent fluid  brown/blue colour  BLUE – DOME CYSTS. Lined by flattened atrophic epithelium/metaplastic apocrine cells ( Abundant granular eosinophilic cytoplasm + round nuclei). Calcification – common. “ MILK OF CALCIUM” – Mammographers Diagnosis – confirmed – disappearance of the cyst after FNAC.

22. FIBROCYSTIC CHANGE - FIBROSIS Cysts rupture Secretory material Adjacent stroma Chronic inflammation, Fibrosis Palpable firmness of the breast

23. FIBROCYSTIC CHANGE - ADENOSIS Increase in the number of acini per lobule. Pregnancy  Normal physiologic adenosis. Nonpregnant women  adenosis - focal change. Acini – enlarged,not distorted (blunt-duct adenosis). Calcifications – occasionally - within the lumens. Acini - lined by columnar cells  benign / atypical features ( “flat epithelial atypia”)  Earliest recognizable precursor of epithelial neoplasia

24. LACTATIONAL ADENOMAS Palpable masses – pregnant/lactating women. Normal appearing breast tissue + physiological adenosis + lactational changes. Exagerrated focal response to hormones. Gross appearance: Well circumscribed mass - distinct lobular configuration, yellowish color, and marked vascularization. C/s: Gray / tan. Necrotic changes frequent. HPE: Proliferated glands lined by actively secreting cuboidal cells

26. PROLIFERATIVE BREAST DISEASE WITHOUT ATYPIA Mammographic densities, calcifications, or as incidental findings in specimens from biopsies. Found alone/assoc. with non prolif. breast changes. Lesions  proliferation of ductal epithelium and/or stroma without cytologic or architectural features suggestive of carcinoma in situ.

27. MORPHOLOGY – Epithelial hyperplasia Normal breast ducts & lobules – double layer of epithelial cells  luminal & myoepithelial layers. Epith.hyperplasia  Incidental finding - > 2 layers – luminal & myoepithelial cells  fill,distend ducts & lobules. Irregular lumens – periphery of the cellular masses.

28. Sclerosing Adenosis Palpable mass, a radiologic density, or calcifications. No. of acini per terminal duct - increased to double the number found in uninvolved lobules. Normal lobular arrangement - maintained. Acini - compressed and distorted in the central portions of the lesion & characteristically dilated at the periphery. Myoepithelial cells - prominent. NORMAL ADENOSIS

29. Complex sclerosing lesion Radial sclerosing lesion (“radial scar”) - commonly occurring benign lesion  forms - irregular masses (mimic invasive carcinoma)mammographically, grossly, and histologically. Central nidus of entrapped glands in a hyalinized stroma with long radiating projections into stroma. Radial scar – misnomer (lesions - not assoc. with prior trauma or surgery)

30. Papillomas Multiple branching fibro vascular cores, each with a connective tissue axis lined by luminal and myoepithelial cells. Growth - within a dilated duct. Epithelial hyperplasia and apocrine metaplasia - frequently present. Large duct papillomas - solitary, situated in the lactiferous sinuses of the nipple. Small duct papillomas - multiple - located deeper within the ductal system. > 80% of large duct papillomas  nipple discharge. Large papillomas  torsion of stalk  infarction  bloody discharge. Intermittent blockage and release of normal breast secretions or irritation of the duct by the papilloma  Non bloody discharge. Others  + nt as small palpable masses, or as densities or calcifications seen on mammograms

31. Atypical ductal/lobular hyperplasia  Cellular proliferation - resembles carcinoma in situ - but lacks sufficient qualitative or quantitative features for diagnosis as carcinoma.

32. ATYPICAL DUCTAL HYPERPLASIA Found in Bx specimens – done for calcifications,mammographic densities,palpable masses. Relatively monomorphic proliferation of regularly spaced cells, sometimes with cribriform spaces. Limited in extent, only partially filling ducts. Duct is filled with a mixed population of cells  oriented columnar cells at the periphery and more rounded cells within the central portion. Some of the spaces - round and regular, the peripheral spaces - irregular and slitlike  Highly Atypical.

33. ATYPICAL LOBULAR HYPERPLASIA Proliferation of cells  the cells do not fill or distend more than 50% of the acini within a lobule. Atypical lobular hyperplasia  also involves contiguous ducts through pagetoid spread ( discrete intraepidermal proliferation of cells occurring singly/ nests at all levels of the epidermis) in which atypical lobular cells lie between the ductal basement membrane and overlying normal ductal epithelial cells. A population of monomorphic small, round, loosely cohesive cells partially fill a lobule. Some intracellular lumens can be seen