Pathology of Breast I: Breast Disorders PDF

Pathology of Breast I: Breast Disorders Objectives Inflammatory disease of the breast o Mammary duct ectasia o Fat necrosis o Acute mastitis o Periductal mastitis Breast benign tumor o Fibrocystic changes o Proliferative breast disorders o Stromal tumors Breast Produces milk for baby Made up of ~15...

Pathology of Breast I: Breast Disorders Objectives Inflammatory disease of the breast o Mammary duct ectasia o Fat necrosis o Acute mastitis o Periductal mastitis Breast benign tumor o Fibrocystic changes o Proliferative breast disorders o Stromal tumors Breast Produces milk for baby Made up of ~15 to 20 lobes Each lobe: multiple lobules Each lobe attached to duct Each duct drains to the nipple Lobes surrounded by stroma/fat Male breasts: Lacks glandular lobules, and Less develops ducts Terminal Duct Lobular Unit Functional unit of breast Clusters of acini within the lobule make milk Ducts drain lobule o Extralobular terminal duct: attaches to lobule o Intralobular terminal duct: duct system into lobule Breast Epithelium Lines surface of ducts and lobules Contains two layers over basement membrane o Luminal epithelial cells § Secrete milk in lobules o Myoepithelial cells § Outer layer § Contracts to expel milk outside § Respond to oxytocin Hormones Breast tissue: hormone sensitive Estrogens Normal Breast Histology o Major effect on ducts o Puberty: estrogen increases breast size in females o Menstrual cycle: cyclic increase in breast size (tenderness) o Pregnancy: increase in breast size Progesterone o Mostly acts on lobules o Growth in lobules (preparation for pregnancy/delivery) Prolactin o Essential for lactation o Increased levels in pregnancy → increases breast size Pregnancy o Growth of breast tissue o Driven by hormones o Estrogens, progesterone, and prolactin o Possibly some effect of hCG o In pregnancy no significant milk formation (inhibited by progesterone and estrogen) o Delivery: fall in hormones o Milk production occurs Breast Milk Contents Lactose Antimicrobial components o Antibodies (IgA – passive immunization) o Macrophages o Lymphocytes o Lactoferrin (anti-microbial) o Lysozymes (breaks down bacterial cell walls) 87% water 7% lactose 4% fat 1% protein Breast Feeding Benefits Benefits to child: o Low risk of infant infections (GI, pulmonary) o Long-term benefits o Reduced allergies, diabetes, obesity, asthma Benefits to mother: o Decreased risk of breast and ovarian cancer o Possible decreased risk of cardiovascular disease o Faster childbirth recovery o Reduced stress o Maternal-infant bonding o Enhanced weight loss o Longer postpartum anovulation Galactorrhea Production of milk outside lactation Common complaint: Nipple discharge Related to prolactin: o Prolactin → milk production o Dopamine (hypothalamus) inhibits Prolactin o Dopamine antagonists → INCREASES prolactin → milk production Chronic nipple (neurogenic) stimulation o Chronic stimulation = INCREASES prolactin o Example: poorly fitting bra Prolactinoma o Pituitary tumor o Galactorrhea: classic sign Drugs o Typical antipsychotics (Haldol) causes Galactorrhea Gynecomastia Enlarged breasts in men due to hormone imbalance May be physiologic May be association with galactorrhea (milk production can occur) Histology: Proliferation of ducts and stroma without lobules Occurs during: o Newborn male babies § Placental transfer of maternal estrogens § Resolves with time o Puberty in males § Some androgen to estrogen conversion § Transient o Older men (>50) § Less testosterone § More fatty tissue - convert androgen to estrogen as a result more estrogen than testosterone o Cirrhosis § Decreased liver metabolism of estrogens o Klinefelter syndrome (male 47,XXY) § Male hypogonadism (↓ testosterone) o Drugs § All have anti-androgen effects § Spironolactone (diuretic) § Cimetidine (H2 blocker) § Ketoconazole (anti-fungal) Breast Mass Change with menstrual cycle Discharge Evaluation o Mammography (microcalcifications) o Ultrasound (fluid filled cysts) o Biopsy Mammary Duct Ectasia Benign inflammatory condition o Affects older women (~50 years old) o Classically in multiparous women (multiple pregnancies) o Distension (ectasia) of subareolar ducts (nipple) Due to chronic inflammation and fibrosis o Presents as breast mass with thick, white discharge o Usually no pain, erythema o Must be differentiated from breast cancer Histology: o Periductal inflammation and dilation of ducts, with foamy histiocytes within the luminal secretions and infiltrating the wall of ducts Fat Necrosis Results from trauma o Biopsy o Surgery o Sports injury, seatbelt injury o Many women do not recall a specific trauma Benign, inflammatory process Often mimics breast cancer o May present as painless mass in breast o Often asymptomatic o Calcifications on mammogram Biopsy shows fat necrosis with inflammatory cells Histology: o Lipid-laden macrophages, multinucleated giant cells, partially necrotic adipose tissue o NO significant atypia Lactational Mastitis (acute) Occurs in women during breast feeding Trauma to skin around nipple Breast erythema, tenderness Often fever, malaise Most common infection of S. Aureus Usual treatment: dicloxacillin or cephalexin Mother should continue nursing Can progress to abscess requiring drainage Histo: o Acute gland inflammation o Erythema overlying infectious focus Periductal Mastitis Squamous Metaplasia of Lactiferous Ducts Inflammation of subareolar ducts More than 90% cases occur in female smokers o Smoking toxic to subareolar ducts o Smoking may cause relative vitamin A deficiency in ducts Cells produce keratin and block the duct resulting in inflammation Inflammation → squamous metaplasia Fibrocystic Changes Group of breast changes/lesions All are Benign o Non-proliferative o Not associated with risk of cancer Occur in ages 25-45 years Must be distinguished from breast cancer Changes: o Simple cysts § Occur in terminal duct lobular unit § Fluid-filled, round cysts § Filled with dark fluid § Cyst looks blue dome on gross exam o Fibrosis § Cyst rupture→ inflammation →fibrosis o Apocrine metaplasia § Also called “benign epithelial alteration” § Alterations to lobular epithelial cells § Take on the appearance of apocrine (gland) cells Proliferative Breast Disorders Proliferation of epithelial cells Benign No atypia Small increase in risk of breast cancer Key types: o Epithelial hyperplasia o Sclerosing adenosis o Intraductal papilloma Epithelial Hyperplasia Normally, ducts/lobules: o double-layer epithelium o Luminal cells o Myoepithelial cells Epithelial Hyperplasia: o INCREASED luminal/myoepithelial cells o Distended ducts or lobules o Lumen filled with cluster of cells Sclerosing Adenosis Increased number of compressed acini Dense stroma May result in calcifications Increased risk for invasive carcinoma Intraductal Papilloma Benign breast lesion Abnormal proliferation of the epithelial cells lining the breast ducts o Proliferation of normal epithelial cells o Develop in ducts or lactiferous sinuses Ages 35 to 55 Present with bloody/serous discharge Small mass near the nipple Cells grown in “finger-like” projections Stromal Tumors Neoplastic epithelial/mesenchymal lesions Stromal tumors o Fibroadenoma o Phyllodes Tumor Both arise from intralobular stroma Stromal growth may trigger epithelial proliferation Fibroadenoma Most common benign breast tumor Masses of fibrous and glandular tissue Compressed epithelial lined spaces Hypoechoic on ultrasound Occurs ages 15 to 35 years Hormone sensitive o Increased size in menstrual/pregnancy o Decrease in size after menopause Well-defined, solid, mobile mass in lobules Not usually require treatment Can be removed surgically Different Types of Fibroadenomas Juvenile Complex Giant Young adolescent women Fibrocystic-like changes Massive Hx of rapid growth Apocrine changes > 10 cm Epithelial/stromal hyperplasia Sclerosing adenosis Cyst formation Simple No malignancy risk High malignancy risk Malignancy in Fibroadenomas seen in: Complex Fibroadenomas Fibroadenomas in older women Fibroadenoma in women w family hx of breast carcinoma Phyllodes Tumor Stromal fibroepithelial tumor o Benign (usually), borderline, malignant o Both epithelial and stromal tissue grow rapidly o Low-grade forms similar to fibroadenomas o High-grade variants can metastasize Usually present in older women (>60 years) Phyllodes = Greek word “leaf-like” Leaf-like growths of stroma covered by epithelial cells Histology: Characteristic long clefts and myxoid cellular stroma Breast Disorders Summary Inflammatory o Mammary duct ectasia (white discharge) o Fat necrosis (trauma) o Mastitis (erythema, tenderness) Fibrocystic changes o Cysts o Fibrosis o Apocrine metaplasia o Benign Proliferative breast disorders o Epithelial hyperplasia, sclerosis adenosis, papilloma o Associated with increased cancer risk o Not usually precursors of cancer Stromal tumors o Fibroadenoma (fibrous and glandular) o Phyllodes tumor (fibroepithelial stroma) Quiz 1. a. b. c. d. c Mammary duct ectasia is characterized by which of the following microscopic findings? Epithelial proliferation that fills and distends the terminal duct lobular units Infiltrating ductal proliferation with desmoplastic stromal response Periductal inflammation and dilation of ducts, with foamy histiocytes within the luminal secretions and infiltrating the wall of ducts Proliferation of both stromal and glandular elements 2. a. b. c. d. a The _____ begins at the extralobular terminal duct and extends to the terminal ductules TDLU (terminal duct lobular unit) Lobule Acini Lactiferous sinus 3. a. b. c. d. b _____ duct openings are found on the surface of the nipple. 5 to 10 15 to 20 20 to 25 25 to 35 4. _____, a hormone produced by the anterior lobe of the pituitary gland, is essential for lactation when other essential hormones are present. Estrogen Prolactin Progesterone Testosterone a. b. c. d. b 5. a. b. c. d. a The most common type of bladder cancer? Urothelial cancers Squamous cell carcinoma Small-cell carcinoma Adenocarcinoma 6. a. b. c. d. a What is the biggest risk factor for bladder cancer? Smoking Female Human papilloma virus Radiation 7. a. b. c. d. c At which stage does bladder cancer spread into nearby organs or lymph nodes or in the pelvic nodes? Stage I Stage II Stage III Stage IV