Pathology of the breast

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 • at birthmale and female breasts • active secretion (transplacental passage of maternal hormones) bilateral breast enlargement • colostrum-like secretion ("witch's milk") • recedes several months postpartum • 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 • supernumerary breast (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 • Polythelia • 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 – disfiguration

9. Puerperal mastitis • early stages (2nd and 3rd 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 • periductalinflammation, 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 • periductalinflammation, 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) • 2nd killer among cancers (1st = lung ca) • risk factors: genetic predisposition (breast ca in close (1st 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 Ductalin situ (intraductal) Lobular in situ Ductalinvasive + other types (12) Lobular invasive

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