BREAST DISORDERS

y y Extralobular terminal duct, lobule terminal duct Small round acini duct -> groups Histology - What lines ducts? o Single layer of cuboidal cells - More than a single layer, tumor: ABNORMAL

Developmental Disorders
Supernumeray nipples or breast respond to hormones on menstrual cycle o Occurs along the midline o Occassionally involved in cycle menstrual changes Accessory Axillary Breast Tissue o May be mistaken as metastatic breast cancer or an axillary lymph node lesion Inverted Nipple o Common o May be mistaken for nipple retraction that accompanies invasive cancer or inflammatory disease Macromastia o May be due to:  Variations in body habitus  Ununusual tissue response to hormones  May cause severe back pain Reconstruction or Augmentation o May cause  Thickening of the fibrous capsule  Silicone granuloma o Micro:  Chronic Inflammatory Infiltrate y Lymphocyte, macrophages, giantcells with fibrosis  *Round hollow objects silica y Granulomatous proliferation -

Nipple Discharge o Less common o Galactorrhea milky discharge  Prolactin adenoma  Hypothyroidism  Endocrine anovulatory syndromes  Drugs OCP, TCA, Methyldopa and Phenothiazine o Bloody or serous discharge  Large duct papilloma  Rarely associated with carcinoma

Mammographic Findings - Densities o Invasice carcinoma, fibroadenoma and cysts o DCIS rarely present as a density Calcifications o Associated with malignancy o DCIS most common (Ductal Carcinoma In Situ)

Inflammatory Breast Diseases

Acute Mastitis o Occurs during lactation o Due to nipple cracks and fissures o Etiologic agents  Staphylococcus aureus most common  Streptococcus spp. o May progress ot abscess formation o Drain lesion Fat Necrosis o Clinical Presentation  Painless palpable mass  Skin thickening or retratcion  Mammographic density or calcification o Micro:  Hemorrhage and early liquifactive necrosis of fat o Associated with trauma Preductal Mastitis o Aka. Recurrent Subareolar abscess, squamous metaplasia of lactiferous ducts, Zuska disease o Strongly associated with smoking 90% of patients o Micro  Keratinizing Mammary Duct Ectasia o Occurs in: th th  5 to 6 decade of life  Multiparous women o Clinical findings  Poorly defined palpable periareolar mass  Skin retractions  Thick, white nipple secretion

Clinical Presentation - Pain o Most common, cyclical or noncyclical, majority are benign, 10% malignant - Palpable Mass nd o 2 most common, masses do not become palpable until it reaches 2cm

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Lymphocytic Mastopathy o Single or multiple hard palpable mass o May be bilateral and appear as densities mammographically o Micro  Collagenized stroma, surrounding  DM Type 1 Granulomatous Mastitis o Rare o < 1% o Secondary to:  Systemic granulomatory disease: Wegener Granulomatous and Sarcoidosis o Infectious mycobacterial ang fungal o Seen only in parous women

Carcinoma of Breast: 1. Breast Carcinoma o Most common malignancy of the breast o Most common non-skin malignancy in women o Risk factors  70% occur in 54 years old  Menarche before 11 years old 20% increase risk of cancer  Liver birth at < 20 years old, half the risk of nulliparous women or women at the age of 35 years old at first birth o 1st degree relatives (mother, sister, daugther)  BRCA, BRCA 2 Mutations o Caucasians have high risk, African American have low risk but advanced stage compared to others. Risk factors o Estrogen exposure HRT (Increase), OCP (low) o Radiation Exposure o Carcinoma of contralateral breast or endometriosis o Obesity in <40 years old due to anovulatory cycles o Breast feeding longer duration reduces risk o Not associated with smoking

Benign Epithelial Lesions

1. Fibrocytic Change (Non-Proliferative) o Lumpy Bumpy breast o Mimics carcinoma especially when solitary o Mass disappears after FNAB o Morphology  Cysts with apocrine metaplasia  Fibrosis  Aclerosis o No increase risk of cancer Fibrocytic Change (Proliferative) o Epithelial Hyperplasia  More than 2 cell layers of ductal epithelial cells  Intact myoepithelial cell layer o Scleroising Aclerosis  Increase in number of acini  May be associated with calcifications Radial Scar (Complex Sclerosing Lesion)  Stellate lesion with glands that are trapped. Papilloma  Associated with bloody nipple discharge  Multiple branching fibrovascular cores Mild risk for developing breast cancer

Ductal Carcinoma In Situ (DCIS)

Malignant ductal epithelial cells are confined to the ducts Basement membrane is intact 5 subtypes o Comedocarcinoma o Solid o Cribiform o Papillary o Micropapillary

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Paget Disease
Rare manifestation, 1-2% of cases Unilateral erythematous eruption with a scale crust Paget cells extend from DCIS into nipple skin and does not cross basement membrane Palpable mass is seen in 50-60% of cases

Lobular Carcinoma In Situ

Not associated calcifications or densities Bilateral in 20-40% More common in young women 80-90% occur prior to menopause Lacks expression of e-cadherin

Atypical Proliferative Breast Diseases

Atypical Ductal Hyperplasia Atypical Lobular Hyperplasia Resembles DCIS or LCIS but lacks sufficient features of carcinoma in situ Moderate risk for developing breast carcinoma

Invasive Carcinoma
Palpable mass most common presentation Peau d orange skin due to blockage of dermal lymphatics Nipple retractions Fired to chest wall Upper outer quadrants in 50% of cases

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10% in each remaining quadrants 20% in central or subareolar region

Prognostic Factors
DCIS better than invasive Distal metastasis Lymph node involvement o 10 year survival rate o 70-80%: no involvement o 35 40% : 1 to 3 nodes involvement o 10-15%: more than 10 lymph nodes Size: o Poor prognosis in > 2 cm Locally advanced disease Inflammatory carcinoma

Ductal (No special type) o Grossly: Ill defined mass o Tan in color Lobular Medullary Mucinous Tubular Papillary Meloplastic

Ductal (No special type)

Majority of cases: 70-80%

Tumor Grade
Grade 1 (Well differentiated) -80%, 10 year survival rate Grade 2 (Moderately differentiated) 60% Grade 3 (Poorly differentiated) 15%

Lobular Carcinoma
Similar to ductal but with a diffuse pattern Single infiltrating tumor cells (single file) Targetoid appearance May metastasize to retroperitoneum, leptomeninges, GI tract, ovaries and uterus

Lymphovascular Lesion
Proliferate rate

Breast Receptor Assays

Estrogen and Progesterone receptors o Positive assay better prognosis o Response to Tamoxifen o HER 2/ Neu (Human Epidermal Growth factor receptor 2/C-erb, B2 or neu)  Overexpression is associated with poor prognosis  Responds to chemotherapy Trastuzumab

Medullary Carcinoma
Well circumscribed Soft, fleshy consisting Morphology o Solid, synction

Mucinous (Colloid Sarcoma)

1-6% Skin growth Occurs in older women

Stromal Tumors
1. Fibroademona Benign o Most common benign lesion o Hormonally responsive o Well circumscribed and freely movable o Frequent multiple and bilateral o Mild cases for caricnoma most well established Phyllodes Tumor o Cystosarcoma phyllodes o Leaf-like pattern o Low and High Grade lesion o Treatment: Wide excision or mastectomy

Tubular Carcinoma
2% Well formed tubular Mistaken for sclerosing lesion Lacks BM Well differentiated Excellend prognosis

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Papillary Carcinoma
Better prognosis

Metaplastic carcinoma
< 1% Includes: Adenocarcinoma, Chondroid Stroma, Squamous Cell Carcinoma

Sarcomas
Angiosarcoma Rhabdomyosarcoma Liposarcoma Leiomyosarcoma

Inflammatory Carcinoma
Carcinoma extensively involving dermal lymphatics Enlarged erythematous breast Poor prognosis if present: 3-10%, 3 year survival rate

Other Malignancies
Lymphomas Malignancies of skin and sebaceous glands and have shafts

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Metastatic Carcinoma most common Melanoma and Lung Carcinoma frequent

Twin Placenta - Dichorionic diamnionic - Monochorionic, monoamnionic Twin-twin Transfusion - Abnormal sharing fetal circulations - Marked disparity of blood volume - May result to death Inflammation and Infections - Placentitis and Villitis - Chorioamniotitis - Funisitis - 2 routes o Ascending infection most common o Hematogenoma Toxemia - Characterized by: o HPN - Preeclampsia o Proteinuria Preeclampsia o Edema o Seizure Eclampsia o Common in primipara than multiparous women o Eclampsia DIC o Decreased uteroplaental perfusion Morphology - Placenta o Infarcts o Retroplacental hormones o Villous ischemia o Fibrinoid nd - Starts the 32 week of pregnancy - Begins early in the following o H mole o Presenting kidney disease o Preexisting hyperestrinism o Treatment  Induction delivery

Gynecomastia
Enlargement of male breast Unilateral or bilateral Indicates hyperestrinism liver cirrhosis or testicular tumor (Sertoli, Leydig ) Proliferation of ducts

Carcinoma
0-11% risk in males as compared to 13% risk in females Risk factors are similar to that in women Gynecomastia is not a risk factor Associated with BRCA 2 mutation Papillary carcinomas are more common

Gestational and Placental Diseases

Disorder of Early Pregnancy
1. Spontaneous Abortion o Occurs in 10-15% of pregnancies o Cause: Fetal or Maternal o Defective implantation most common o Infectious  Toxoplasma, Mycoplasma, Listeria, and viral o Most do not show fetal products o Chromosomal studies Ectopic Pregnancy o Fetal implantation at any site outside the uterus o Fallopian tube most common (90%) o Abnormal cavity o Intrauterine portion of Fallopian tube (Cornua) o Causes  PID with salpingitis most common  Adhesins due to appendicitis, IUD insertions o Clinical  Severe abdominal pain may lead to shock

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Disorder of Late Pregnancy

1. 2. Accessoring Placental Lobe Placenta accreta y Partial or complete absence of decidue y Placenta adhere directly to the myometrium y Causes bleeding y Placenta previa Increta deep into the myometrium Percreta through the myometrium Ancreta surface of myometrium

Gestational Trophoblastic Disease

1. Hydatidiform mole o Cystic swelling of chorionic villi with throphoblastic proliferation o Clinical Presentaion  Vaginal bleeding  Uterine size larger than for AOG  Kyawa:  High Risk: 40-50%  2 Types: Partial, Complete (swelling)

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3. Placenta Previa o Placenta implants in lower uterine segment o Cause bleeding

Complete - Fertilization by single sperm and an egg that has lost its chromosome - 46XX, 46XY (paternal)

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Partial o Fertilization of an egg with one or two sperms Feature Karyotype Villous Edema Trophoblast proliferation Complete Mole 46XX, 46 XY All villi Diffuse, circumferential Partial Mole Triploid Some Villi

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Hydatidiform Mole o Spontaneous pregnancy loss or curettage o Watery filled with grape like masses on curettage o UTZ: Snowy pattern o Serial BHCG Invasive Mole o Hydrophic chorionic villi, invades the myometrium o Pentrates uterine wall o Treatment  Hysterectomy Choriocarcinoma o Malignancy of trophoblastic cells o Rapidly invasive o Widely metastasizing  Lungs (50%) o Morphology  Abnormal proliferation of cytotrophoblast synctiotrophoblast o Treatment  Evacuation of contents  Surgery  Responds well to chemotherapy  Nongestational therapy Placental Site Trophoblastic Tumor o < 2% o Intermediate trophoblasts o Mononuclear cells with abundant cytoplasm o Human Placental Lactogen weakly immunoreactive

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