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)

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

Physiologic changes

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

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)

Developmental abnormalities

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 (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

• 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 changes

• extremely common (58% F)

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!

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 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 diagnosisbetter prognosis

Breast carcinoma - classification

• IN SITU

•INVASIVE

• DUCTAL

•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 carcinomaInvasive 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)

• 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

Invasive carcinoma

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, androgens, and other drugs (digitalis, cimetidine, spironolactone, marihuana, and tricyclic antidepressants)

Carcinoma of the male breast• uncommon < 1 % of all breast cancers