1) The document discusses the normal anatomy of the breast including ducts, lobules, and changes that occur during puberty, pregnancy, and menopause. 2) It also covers developmental abnormalities, inflammatory conditions, benign and malignant tumors of the breast including fibroadenomas, cystosarcoma phyllodes, ductal carcinoma in situ, invasive ductal carcinoma and Paget's disease of the nipple. 3) The pathology of the male breast is also summarized, mainly being gynecomastia which is a benign increase in breast tissue, and carcinoma which is rare but can occur.

1. Pathology of the breast normal anatomy physiologic changes developmental abnormalities inflammations fibrocystic changes tumors benign malignant pathology of the male breast

2. Normal anatomy before puberty – breasts in both sexes – ducts variable degrees of branching, lack lobules 15 to 25 lactiferous ducts start in the nipple – branch terminal ductal lobular unit (intralobular duct, multiple lobular ducts, ductules or acini + intralobular connective tissue) hormonally responsive

3. Physiologic changes a t birth male and female breasts active secretion ( transplacental passage of maternal hormones ) bilateral breast enlargement colostrum - like secretion ( "witch's milk" ) recedes several months postpartu m after menopause – gradual and progressive involution (lobular atrophy, increased fat, cystic dilatation of ducts)

4. Physiologic changes Macromastia diffuse enlargement of both breasts adolescence or pregnancy exaggerated response to hormonal stimulation Pubertal (Virginal) Macromastia 1669 - 23-year-old woman - breasts enlarged "overnight" to a combined weight of 104 pounds Pregnancy 1 in 100,000 pregnancies - erythematous, edematous, painful

5. Developmental abnormalities Aplasia and hypoplasia uncommon – associated with overdevelopment of the contralateral breast acquired ( irradiation – chest wall tumors ) unilateral or bilateral amastia ( absence of a nipple , breast ducts, pectoralis major muscle) – sex-linked recessive inheritance

6. Developmental abnormalities Ectopic breast s upernumerary b reast ( from ectopic breast tissue – along the milk lines ( midaxillae – normal breasts – medial groin and vulva ) 1 – 6 % of adult women , much less often in men unilateral axillary breast tissue Po lythelia areola and underlying mammary ducts Aberrant Breast beyond the usual anatomic extent (no nipple or areola )

7. Inflammatory and reactive conditions Fat necrosis can simulate carcinoma clinically and mammographically history of antecedent trauma, prior surgical intervention) histiocytes with foamy cytoplasm lipid–filled cysts fibrosis, calcifications, egg shell on mammography

8. Inflammatory and reactive conditions Hemorrhagic necrosis with coagulopathy Warfarin treatment – shortly after initiation edema , hemorrhage , necrosis ( thrombi in small blood vessels ) protein C deficiency Breast augmentation foreign materials ( shellac, glazier's putty, spun glass, epoxy resin, beeswax, and shredded silk , silicone ) thin–walled silicone bag – capsule – disfigur ation

9. Puerperal mastitis early stages (2 nd and 3 rd W) of lactation – 5% stasis of milk in distended ducts + staphylococci abscess formation (ATB, incision and drainage) Granulomatous Lobular Mastitis etiology unknown, suggests carcinoma Mammary duct ectasia periductal inflammation , duct sclerosis intermittent nipple discharge Tuberculosis less developed regions - serious condition lactating breast , innoculation via the lactiferous ducts slowly growing, solitary, painless mass

10. Benign proliferative lesions pathologic spectrum of seemingly related clinically benign breast abnormalities palpably irregular and painful breasts discrete lumps, multiple nodules, cystically dilated ducts, apocrine metaplasia, interlobular and intralobular fibrosis intraductal epithelial proliferation fibrocystic disease , fibrocystic changes extremely common (58% F)

11. Benign proliferative lesions Adenosis elongation of the terminal ductules caricature of the lobule sclerosing adenosis apocrine adenosis tubular adenosis nonpalpable lesion, recognized in mammograms microcalcifications !

12. Benign tumors Fibroadenoma proliferation of epithelial and stromal elements most common breast tumor in adolescent and young adult women (peak age = third decade) higher incidence in black patients well-circumscribed, freely movable, nonpainful mass regress with age if left untreated ducts distorted elongated slit-like structures - intracanalicular pattern , ducts not compressed pericanalicular growth pattern (little practical value)

13. Tubular adenoma far less common than fibroadenomas young women, discrete, freely movable masses uniform sized ducts Lactating Adenoma enlarging masses during lactation or pregnancy prominent secretory change Intraductal papilloma in the mammary ducts, subareolar lactiferous ducts periductal inflammation , duct sclerosis serous or bloody nipple discharge fibrosis, infarction, squamous metaplasia

14. Cystosarcoma phyllodes ( phyllodes tumor) initial description - over 150 years ago - fleshy tumor, leaf-like pattern and cysts on cut surface circumscribed, connective tissue and epithelial elements (× fibroadenomas = greater connective tissue cellularity), 1-15 cm less than 1 % of breast tumors benign, malignant metastases are hematogenous low grade high grade

15. Proliferative changes ductal and lobular hyperplasia atypical ductal and lobular hyperplasia higher risk for the cancer than "normal" population associated w. microcalcifications (!mammography!) incidental histological finding atypical hyperplasia = precancerous lesion

16. Breast carcinoma most frequent malignant tumor in females (followed by cervix and colon) highest incidence – developed countries (USA 84,8/100 000F/Y, Western Europe 64,7/100 000F/Y) 2 nd killer among cancers (1 st = lung ca) risk factors: genetic predisposition (breast ca in close (1 st degree) relatives), proliferative changes, early menarche, late menopause, history of ca (breast, ovary, endometrium) importance of preventive controls ! – early diagnosis better prognosis

17. Breast carcinoma - classification IN SITU INVASIVE DUCTAL LOBULAR Ductal in situ (intraductal) Lobular in situ Ductal invasive Lobular invasive + other types (12)

18. Carcinoma in situ preinvasive - does not form a palpable tumor not detected clinically (only X-ray – screening !!!) multicentricity and bilaterality (namely LCIS) continuum : bland hyperplasia - increasing atypism - carcinoma in situ no metastatic spread (basement membrane) risk of invasion depending on grade

19. Invasive carcinoma Invasive ductal carcinoma largest group ( 65 to 80 % of mammary carcinomas ) mid to late fifties stellate , white, firm (desmoplasia) less often circumscribed , soft (medullary ca) hormonally dependent (estrogen, progesterone) Invasive lobular carcinoma uniform cells , infiltrative growth ( linear arrangement - indian file pattern)

20. Invasive carcinoma other types: tubular, mucinous, medullary, inflammatory – together about 10 % of breast ca metastases: regional lymph nodes (axillary, parasternal), lungs, liver, bone marrow, brain treatment: surgery (radical – mastectomy, breast conserving surgery – lumpectomy), radiotherapy antihormonal therapy (Tamoxifen) chemotherapy

21. Paget‘s disease of the nipple result of intraepithelial spread of intraductal carcinoma large pale-staining cells within the epidermis of the nipple limited to the nipple or extend to the areola pain or itching, scaling and redness , mistaken for eczema ulceration, crusting, and serous or bloody discharge

22. Pathology of the male breast Gynecomastia most common clinical and pathologic abnormality of the male breast increase in subareolar tissue in 30 to 40 percent of adult males , both breasts are affected in many cases associated with hyperthyroidism, cirrhosis of the liver, chronic renal failure, chronic pulmonary disease, and hypogonadism, use of hormones - estrogens, androgens, and other drugs (digitalis, cimetidine, spironolactone, marihuana, and tricyclic antidepressants) Carcinoma of the male breast uncommon < 1 % of all breast cancers