This document summarizes the normal anatomy and life cycle changes of the breast, as well as various pathologies that can affect the breast including disorders of development, inflammation, benign epithelial lesions, and breast carcinoma. It describes the clinical presentation, risk factors, classification, and histopathological features of different types of breast carcinoma such as ductal carcinoma in situ, lobular carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, and medullary carcinoma. Imaging studies and hormone receptor status that are important for prognostic and therapeutic purposes are also discussed.
This document summarizes the normal anatomy and life cycle changes of the breast, as well as various pathologies that can affect the breast including disorders of development, inflammation, benign epithelial lesions, and breast carcinoma. It describes the clinical presentation, risk factors, classification, and histopathological features of different types of breast carcinoma such as ductal carcinoma in situ, lobular carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, and medullary carcinoma. Imaging studies and hormone receptor status that are important for prognostic and therapeutic purposes are also discussed.
This document summarizes the normal anatomy and life cycle changes of the breast, as well as various pathologies that can affect the breast including disorders of development, inflammation, benign epithelial lesions, and breast carcinoma. It describes the clinical presentation, risk factors, classification, and histopathological features of different types of breast carcinoma such as ductal carcinoma in situ, lobular carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, and medullary carcinoma. Imaging studies and hormone receptor status that are important for prognostic and therapeutic purposes are also discussed.
This document summarizes the normal anatomy and life cycle changes of the breast, as well as various pathologies that can affect the breast including disorders of development, inflammation, benign epithelial lesions, and breast carcinoma. It describes the clinical presentation, risk factors, classification, and histopathological features of different types of breast carcinoma such as ductal carcinoma in situ, lobular carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma, and medullary carcinoma. Imaging studies and hormone receptor status that are important for prognostic and therapeutic purposes are also discussed.
JI CYRELLE JOY V. MALIHAN Contents Normal Anatomy and Life Cycle Changes Pathology ◦ Disorders of Development ◦ Clinical Presentation ◦ Inflammation ◦ Benign Epithelial lesions ◦ Carcinoma of the Breast Normal Morphology Lined by 2 cell types ◦ Myoepithelial cell ◦ Luminal cell
Stroma ◦ Intralobular stoma ◦ Interlobular stroma Life Cycle Changes Stage Hormonal Changes Effect Birth to Childhood Estrogen & Progesterone Presence of major ducts Life Cycle Changes Stage Hormonal Changes Effect Puberty Estrogen & Progesterone Breast Engorgement and epithelial proliferation Life Cycle Changes Stage Hormonal Effect Changes Pregnancy Estrogen & Ductal and lobular epithelium proliferates, Progestins accessory areolar glands of Montgomery become prominent Life Cycle Changes Stage Hormonal Changes Effect Lactation Estrogen & Progesterone Milk letdown Prolactin & Oxytocin Life Cycle Changes Stage Hormonal Changes Effect Menopause Estrogen & involution of the ducts and alveoli of Progesterone the breast; CT increases in density,and breast tissues are replaced by adipose tissues Disorders of Development Milkline Remnants Accessory Axillary Breast Tissue Congenital Nipple Inversion Macromastia Reconstruction or Augmentation ◦ formation of a thick fibrous capsule ◦ chronic inflammatory infiltrate of lymphocytes, macrophages, and giant cells with associated fibrosis. Clinical Presentation of Breast Diseases
Pain (Mastalgia or Mastodynia)
◦ Cyclical or Non-cyclical
Palpable mass ◦ 50% upper outer quadrant ◦ 10% remaining quadrants ◦ 20% central or subareolar region
MRI ◦ CA with dense breasts, extent of invasion, evaluation of breast implant rupture. Inflammation Acute Mastitis ◦ erythematous painful breast ◦ Staphylococcal - localized area of acute inflammation ◦ Streptococcal - diffuse spreading infection which may be necrotic and is infiltrated by neutrophils. ◦ Tx: antibiotics and complete drainage of milk Inflammation Periductal Mastitis ◦ Recurrent Subareolar Abscess, Squamous metaplasia of lactiferous ducts ◦ Painful erythematous subareolar mass ◦ Ruptured ducts -> keratin debris ◦ Mostly smokers ◦ Tx: ◦ Surgical incision of involved duct and fistula tract ◦ Incision drainage + Antibiotic therapy Inflammation Periductal ◦ Morphology: Inflammation Mammary Duct Ectasia ◦ 5th to 6th decade of life, multiparity ◦ No association with cigarette smoking ◦ Poorly defined palpable periareolar mass
Chronic inflammation and fibrosis surround
an ectatic duct filled with inspissated debris. Inflammation Fat Necrosis ◦ Hard & painless palpable mass, skin thickening or retraction, a mammographic density or calcifications. ◦ Has history of trauma or prior surgery. ◦ Grossly: ill-defined nodule of gray-white, firm tissue containing small foci of chalky white or hemorrhagic debris. ◦ Microscopy: Necrotic fat with macrophages and neutrophilic infiltration. Benign Epithelial Lesions Non-proliferative 70% No increased risk for breast CA Has 3 principal pattern of morphologic change: ◦ Cyst ◦ dilation and unfolding of lobules ◦ Fibrosis ◦ Adenosis ◦ increase in the number of acini per lobule ◦ Enlarged & not distorted acini Proliferative disease without atypia proliferation of ductal epithelium and/or stroma without cellular abnormalities suggestive of malignancy ◦ moderate or florid epithelial hyperplasia ◦ sclerosing adenosis ◦ complex sclerosing lesions ◦ Papillomas ◦ fibroadenoma with complex features. Epithelial Hyperplasia With >2 cell layers
Lumen is filled with proliferating cells, slitlike fenestrations are
prominent at the periphery Sclerosing Adenosis Lobular unit is enlarged, and the acini are compressed and distorted by the surrounding dense stroma. Part of spectrum of FCC Complex Sclerosing Lesion Radial scar stellate lesions with central nidus of entrapped glands in a hyalinized stroma associated with prior trauma or surgery. Papillomas Small & Large duct papilloma ◦ Small type - multiple and located deeper within the ductal system; component of proliferative breast disease
Multiple branching fibrovascular cores, with a connective tissue axis lined by
luminal and myoepithelial cells. Proliferative Breast Disease with Atypia
ADH ALH
columnar cells at the periphery monomorphic small, rounded,
and more rounded cells within the loosely cohesive cells central portion; peripheral spaces are irregular and slitlike Carcinoma of the Breast Epidemiology & Incidence
• Most common non-skin malignancy Risk Factors Age ◦ 70% over 50 years of age. ◦ Average: 64 y/o
Age at Menarche ◦ <11 y/o (20%) & late menopause
First live birth
◦ < 20 y/o – half risk
First-Degree Relatives with Breast Cancer
◦ increases with the number of affected first-degree relatives Risk Factors Breast Biopsies - atypical hyperplasia Race ◦ 1 in 15 for Caucasians ◦ 1 in 20 for African Americans ◦ 1 in 26 for Asian/Pacific Islanders ◦ 1 in 27 for Hispanics
Estrogen Exposure ◦ Postmenopausal hormone replacement therapy ◦ Estrogen and progesterone vs. Estrogen Risk Factors Radiation exposure ◦ younger age and higher exposure
CAof the Contralateral Breast or Endometrium
Geographic Influence Diet ◦ reduced risk with increased β-carotene intake ◦ Cigarette smoking – High estrogen & low folate ◦ Alcoholic consumption Risk Factors Obesity ◦ Decreased risk <40 y/o due to anovulatory cycles and lower progesterone
Exercise Breast-feeding Environmental Toxins Tobacco ◦ periductal mastitis or a subareolar abscess Etiology & Pathogenesis Hereditary Breast CA Etiology & Pathogenesis Hereditary Breast CA ◦ Increase probability ◦ multiple affected first-degree relatives ◦ affected before menopause ◦ multiple cancers ◦ male breast CA ◦ family members with ovarian CA ◦ lifetime risk: 60% to 85% ◦ Ovarian CA - BRCA 1 Etiology & Pathogenesis Sporadic Breast CA ◦ Hormone exposure ◦ Gender ◦ age at menarche and menopause ◦ reproductive history ◦ breast-feeding ◦ exogenous estrogens ◦ Postmenopausal & over express ER ◦ ER: ◦ mutations or generate DNA-damaging free radicals ◦ proliferation of premalignant lesions & CA Mechanisms of Carcinogenesis Classification of Breast Carcinoma Hormone panel ER, PR, Her2neu Both prognostic and therapeutic Hormone positive- better prognosis Hormone negative- usually more aggressive Triple negative- Younger, BRCA1 mutations Her2neu positive- More aggressive, Herceptin (trastuzumab) Carcinoma In situ Ductal Carcinoma in Situ ◦ mammographic calcifications ◦ limited to ducts and lobules by the BM ◦ myoepithelial cells are preserved with diminished in number ◦ Tx: Mastectomy ◦ Recurrence: grade, size, and margins. Paget’s disease of the nipple unilateral erythematous eruption with a scale crust extend from DCIS within the ductal system into nipple skin without crossing BM Lobular Carcinoma in situ Incidental finding Multicentric & bilateral Young women Identical to Invasive carcinoma & lack expression of e-cadherin Tx: ◦ prophylactic mastectomy ◦ Tamoxifen ◦ close clinical follow-up ◦ mammographic screening monomorphic population of small, rounded, loosely cohesive cells maintain lobular architecture Invasive Carcinoma Palpable mass Invasive Carcinoma, No Special Type firm to hard with an irregular border
tubules and nests of cells with pleomorphic cells without tubule small monomorphic nuclei invade formation infiltrate into the into the stroma adjacent stroma. Invasive Lobular Carcinoma Bilateral Post-menopausal women Well-differentiated ◦ diploid, express hormone receptors, & associated with LCIS
small, monomorphic cells with scant cytoplasm infiltrate singly in linear arrays or as small clusters of cells Medullary Carcinoma soft, fleshy & well-circumscribed mass Mistaken as fibroadenoma Better prognosis ◦ Lack HER2/neu overexpression
Characterized as: ◦ solid, syncytium-like sheets of large cells with vesicular, pleomorphic nuclei, containing prominent nucleoli and frequent mitoses ◦ lymphoplasmacytic infiltrate surrounding and within the tumor ◦ noninfiltrative border Medullary Carcinoma All are poorly differentiated DCIS is minimal or absent No lymphatic or vascular invasion
Highly pleomorphic with frequent mitoses and grow as sheets of cohesive cells. Mucinous (Colloid) Carcinoma circumscribed mass older women & grow slowly Diploid & express hormone receptors Better prognosis
small clusters of tumor cells within large pools of mucin; well circumscribed border Tubular Carcinoma Multifocal All are diploid and express hormone receptor All are well differentiated Good Prognosis
well-formed tubules lined by a single layer of well-differentiated cells Stromal Tumors Fibroadenoma ◦ most common benign tumor of breast ◦ Occurring at any age - more common <30 ◦ multiple and bilateral ◦ Young women - palpable mass ◦ Older women - mammographic density or calcifications ◦ Does not contain adipose tissue
◦ Rubbery, white, well-circumscribed mass clearly demarcated from the surrounding
yellow adipose tissue Fibroadenoma
Proliferation of intralobular stroma surrounding and often pushing and
distorting the associated epithelium Phyllodes tumor
increased stromal cellularity, cytologic atypia, and stromal overgrowth, giving
rise to the typical leaflike architecture Thank You
