Pathology of the breast normal anatomy physiologic changes

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

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

Physiologic changes • at birth male 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)

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

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

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)

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

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

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

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 • extremely common (58% F) changes

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

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)

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

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

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

Breast carcinoma • most frequent malignant tumor in females (followed by cervix and colon) • highest incidence – developed countries (USA 84, 8/100 000 F/Y, Western Europe 64, 7/100 000 F/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

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

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

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)

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

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

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, and other drugs (digitalis, cimetidine, spironolactone, marihuana, and tricyclic antidepressants) Carcinoma of the male breast • uncommon < 1 % of all breast cancers