BREAST DISORDERS 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 cycleo Occurs along the midlineo 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 Commono 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

Lymphocyte, macrophages, giantcells with fibrosis

*Round hollow objects – “silica” Granulomatous proliferation

Clinical Presentation- Pain

o Most common, cyclical or noncyclical, majority are benign, 10% malignant

- Palpable Masso 2nd most common, masses do not become palpable

until it reaches 2cm

- Nipple Dischargeo Less commono Galactorrhea – milky discharge

Prolactin adenoma Hypothyroidism Endocrine anovulatory syndromes Drugs – OCP, TCA, Methyldopa and

Phenothiazineo Bloody or serous discharge

Large duct papilloma Rarely associated with carcinoma

Mammographic Findings- Densities

o Invasice carcinoma, fibroadenoma and cystso DCIS rarely present as a density

- Calcificationso Associated with malignancyo DCIS – most common (Ductal Carcinoma In Situ)

Inflammatory Breast Diseases- Acute Mastitis

o Occurs during lactationo Due to nipple cracks and fissureso Etiologic agents

Staphylococcus aureus –most common Streptococcus spp.

o May progress ot abscess formationo 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 diseaseo Strongly associated with smoking – 90% of patientso Micro

Keratinizing

- Mammary Duct Ectasia o Occurs in:

5th to 6th decade of life Multiparous women

o Clinical findings Poorly defined palpable periareolar mass Skin retractions

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Thick, white nipple secretion- Lymphocytic Mastopathy

o Single or multiple hard palpable masso May be bilateral and appear as densities

mammographicallyo Micro

Collagenized stroma, surrounding DM Type 1

- Granulomatous Mastitis o Rareo < 1%o Secondary to:

Systemic granulomatory disease: Wegener Granulomatous and Sarcoidosis

o Infectious – mycobacterial ang fungalo Seen only in parous women

Benign Epithelial Lesions

1. Fibrocytic Change (Non-Proliferative) o “Lumpy Bumpy” breasto Mimics carcinoma especially when solitaryo Mass disappears after FNABo Morphology

Cysts with apocrine metaplasia Fibrosis Aclerosis

o No increase risk of cancer

2. 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

o Radial Scar (Complex Sclerosing Lesion) Stellate lesion with glands that are trapped.

o Papilloma Associated with bloody nipple discharge Multiple branching fibrovascular cores

o Mild risk for developing breast cancer

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

Carcinoma of Breast:1. Breast Carcinoma

o Most common malignancy of the breasto Most common non-skin malignancy in womeno 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 factorso Estrogen exposure – HRT (Increase), OCP (low)o Radiation Exposureo Carcinoma of contralateral breast or endometriosiso Obesity in <40 years old due to anovulatory cycleso Breast feeding – longer duration reduces risko Not associated with smoking

Ductal Carcinoma In Situ (DCIS)- Malignant ductal epithelial cells are confined to the ducts- Basement membrane is intact- 5 subtypes

o Comedocarcinomao Solido Cribiformo Papillaryo Micropapillary

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

Invasive Carcinoma- Palpable mass – most common presentation- “Peau d’ orange” skin – due to blockage of dermal

lymphatics- Nipple retractions- Fired to chest wall

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- Upper outer quadrants in 50% of caseso 10% in each remaining quadrantso 20% in central or subareolar region

- Ductal (No special type)o Grossly: Ill defined masso Tan in color

- Lobular- Medullary- Mucinous- Tubular- Papillary- Meloplastic

Ductal (No special type)- Majority of cases: 70-80%

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

Medullary Carcinoma- Well circumscribed- Soft, fleshy consisting- Morphology

o Solid, synction

Mucinous (Colloid Sarcoma)- 1-6% - Skin growth- Occurs in older women

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

Papillary Carcinoma- Better prognosis

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

Cell Carcinoma

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

Prognostic Factors- DCIS better than invasive- Distal metastasis- Lymph node involvement

o 10 year survival rateo 70-80%: no involvemento 35 – 40% : 1 to 3 nodes involvemento 10-15%: more than 10 lymph nodes

- Size:o Poor prognosis in > 2 cm

- Locally advanced disease- Inflammatory carcinoma

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

Lymphovascular Lesion- Proliferate rate

Breast Receptor Assays- Estrogen and Progesterone receptors

o Positive assay – better prognosiso Response to Tamoxifeno HER 2/ Neu (Human Epidermal Growth factor

receptor 2/C-erb, B2 or neu) Overexpression is associated with poor

prognosis Responds to chemotherapy Trastuzumab

Stromal Tumors1. Fibroademona – Benign

o Most common benign – lesiono Hormonally responsiveo Well circumscribed and freely movableo Frequent multiple and bilateralo Mild cases for caricnoma – most well established

2. Phyllodes Tumoro Cystosarcoma phyllodeso “Leaf-like” patterno Low and High Grade lesiono Treatment: Wide excision or mastectomy

Sarcomas- Angiosarcoma - Rhabdomyosarcoma- Liposarcoma- Leiomyosarcoma

Other Malignancies- Lymphomas

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- Malignancies of skin and sebaceous glands and have shafts

- Metastatic Carcinoma – most common- Melanoma and Lung Carcinoma – frequent

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 Pregnancy1. Spontaneous Abortion

o Occurs in 10-15% of pregnancieso Cause: Fetal or Maternalo Defective implantation – most commono Infectious

Toxoplasma, Mycoplasma, Listeria, and viralo Most do not show fetal productso Chromosomal studies

2. Ectopic Pregnancyo Fetal implantation at any site outside the uteruso Fallopian tube – most common (90%)o Abnormal cavityo 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

Disorder of Late Pregnancy1. Accessoring Placental Lobe2. Placenta accreta

Partial or complete absence of decidue Placenta adhere directly to the myometrium Causes bleeding Placenta previa

o Increta – deep into the myometriumo Percreta – through the myometriumo Ancreta – surface of myometrium

3. Placenta Previao Placenta implants in lower uterine segmento Cause bleeding

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 commono Hematogenoma

Toxemia- Characterized by:

o HPN - Preeclampsiao Proteinuria – Preeclampsiao Edemao Seizure – Eclampsiao Common in primipara than multiparous womeno Eclampsia – DICo Decreased uteroplaental perfusion

Morphology- Placenta

o Infarctso Retroplacental hormoneso Villous ischemiao Fibrinoid

- Starts the 32nd week of pregnancy- Begins early in the following

o H – moleo Presenting kidney diseaseo Preexisting hyperestrinismo Treatment

Induction delivery

Gestational Trophoblastic Disease1. 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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Complete- Fertilization by single sperm and an egg that has lost its

chromosome- 46XX, 46XY (paternal)- Partial

o Fertilization of an egg with one or two sperms

Feature Complete Mole Partial MoleKaryotype 46XX, 46 XY Triploid

Villous Edema All villi Some VilliTrophoblast proliferation

Diffuse, circumferential

1. Hydatidiform Mole o Spontaneous pregnancy loss or curettageo Watery filled with grape like masses on curettageo UTZ: Snowy patterno Serial BHCG

2. Invasive Mole o Hydrophic chorionic villi, invades the myometriumo Pentrates uterine wallo Treatment

Hysterectomy

3. Choriocarcinoma o Malignancy of trophoblastic cellso Rapidly invasiveo Widely metastasizing

Lungs (50%)o Morphology

Abnormal proliferation of cytotrophoblast synctiotrophoblast

o Treatment Evacuation of contents Surgery Responds well to chemotherapy Nongestational – therapy

4. Placental Site Trophoblastic Tumor o < 2%o Intermediate trophoblastso Mononuclear cells with abundant cytoplasmo Human Placental Lactogen – weakly immunoreactive

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