Breast Dr. Raid Jastania

Breast Definitions: Lactiferous ducts, Duct, Lobule, Terminal duct lobular unit Common presentations of diseases Lump, mass, pain, skin changes Mammography: fibrous thickening and calcifications Triple test: Clinical, mammography, biopsy

Rare conditions Supernumerary nipples and breast Congenital inversion of nipple Galactocele

Fibrocystic Change Present as mass or lump Hormonal related, Estrogen Types Proliferative fibrocystic change Non-proliferative fibrocystic change

Fibrocystic Change Non-Proliferative fibrocystic change Fibrosis Apocrine metaplasia

Fibrocystic Change Non-Proliferative fibrocystic change Multifocal, bilateral Nodularity, fibrosis Cysts 1-5 com, Blue dome cysts, lined by benign epithelium, myoepithelial cells present, Apocrine metaplasia Calcification

Fibrocystic Change Proliferative fibrocystic change Epithelial hyperplasia Sclerosing adenosis

Fibrocystic Change Proliferative fibrocystic change Epithelial hyperplasia Types: Ductal, Lobular Grades: Mild, moderate, severe (florid), atypcial Sclerosing adenosis

Fibrocystic Change Proliferative fibrocystic change Epithelial hyperplasia Sclerosing adenosis Hard, rubbery Fibrous stroma Proliferation of small ducts (adenosis) with marked compression of the fibrous stroma (sclerosing)

Fibrocystic Change Risk of Cancer: Family history: double the risk No Risk Non-proliferative FC, mild hyperplasia Risk of 1.5-2 x Moderate-florid hyperplasia, sclerosing adenosis, papillomatosis Risk of 5 x Atypical hyperplasia

Carcinoma Second to lung cancer as a cause of death ¼ of women with the disease die Lifetime risk is 1 in 8 women in US Increasing incidence 75% of patients are older than 50 y 5% are younger than 40 y

Carcinoma L > R (slightly) 4% bilateral Upper outer quadrant: 50% Central zone: 20% All other quadrants: 10% each

Carcinoma Classification Carcinoma In-situ Invasive carcinoma Ductal (DCIS) Lobular (LCIS) Invasive carcinoma Ductal carcinoma (Scirrhous carcinoma) Lobular carcinoma Others: medullary, colloid, tubular…

Ductal Carcinoma In-Situ DCIS Terminal duct lobular unit Large malignant cells, monotonous, within ducts Pattern Solid Cribriform Papillary Micropapillary Comedo: central necrosis

Ductal Carcinoma In-Situ DCIS Presentation Mammography: calcifications Can be palpable Prognosis: 97% survival 1/3 of cases progress to invasive cancer if untreated Recurrence in 20-25%

Lobular Carcinom In-Situ LCIS Terminal duct lobular unit Uniform, monomorphic, bland, discohesive cells, some with vacuoles (signet-ring) 1/3 will develop invasive cancer, the risk is to both sides of breast LCIS is a marker of increased risk Presentation: incidental, not palpable, no calcification

Invasive Ductal Carcinoma (NOS) or (NST) 70-80% of invasive carcinoma Associated with DCIS Hard, palpable mass, irregular borders Nipple retraction, Peau d’ orange fixation to the chest wall

Invasive Ductal Carcinoma (NOS) or (NST) Invasive adenocarcinoma Irregular glands lined by malignant cells Grading: tubular formation, nuclear grade, mitosis 2/3 ER/PR + 1/3 HER2/NEU over expression

Invasive Lobular carcinoma 20% of invasive cancer cases 2/3 are associated with LCIS Most are palpable, but can be occult More frequent multifocal, multicentric (10-20%)

Invasive Lobular carcinoma Single cells, indian file, targetoid arrangement Signet-ring cells, intracytoplasmic lumina Matastasize to serosal surfaces and CNS, ovary All ER/PR + HER2/NEU over expression is rare

Medullary Carcinoma Well circumscribed mass, pushing borders Large anaplastic cells Mixed with inflammatory cells Cases of BRCA1 show medullary carcinom-like features Lack ER/PR HER2/NEU negative

Colloid carcinoma (mucinous) Well circumscribed mass Pools of mucus Malignant cells floating in mucus ER/PR + HER2/NEU negative

Tubular carcinoma Small <1cm Irregular densities on mammography Prognosis is excellent ER/PR + HER2/NEU negative

Inflammatory Carcinoma Usually ductal carcinoma NOS Clinical: enlarged swollen, erythematous breast Cancer seen in lymphatic channels in skin Poor prognosis

Paget Diseas of nipple Extension of DCIS upto lactiferous ducts and skin of nipple 50% associated with invasive carcinoma Extramammary Paget disease Common in perineum, but can be in any site

Case

49-year-old woman who has come to the doctor for evaluation of a lump in her right breast. She says she first noticed it two weeks ago while she was taking a shower. She hasn't noticed any nipple discharge, skin changes, or alteration in the lump's size. She is perimenopausal. Her mother died at age 45 from "a breast tumor." Five years previously, the patient had a biopsy of her left breast

Physical examination reveals a nontender, slightly moveable, 2 Physical examination reveals a nontender, slightly moveable, 2.0-cm mass in the upper outer quadrant of her right breast. In addition, several smaller nodules and ill-defined firm areas are present in both breasts. The nipple and skin appear normal. The lower right axilla contains a 1.5-cm moveable nodule A mammogram shows an irregular mass with stippled calcifications in the upper outer quadrant of the right breast.

Gross examination of the lumpectomy specimen shows a 2 Gross examination of the lumpectomy specimen shows a 2.0-cm, grey, scirrhous mass in the central portion of the specimen The margins of the lumpectomy specimen are free of tumor. Serial sections of the sentinal lymph node reveal metastatic ductal carcinoma ,thus, a completion axillary dissection is performed a week later, revealing 2 additional positive lymph nodes out of 15. Special studies reveal the tumor to be estrogen and progesterone receptor positive with a high proliferative rate and a diploid DNA histogram. The tumor is HER2 positive. The patient is given chemotherapy and radiotherapy.

Cancer Spread Lymph nodes 40% of cases Axillary nodes, internal mammary nodes, supacalvicular nodes Lung, liver, BM, adrenal Metastasis can be many years after the primary resection (10-15 years)

Cancer Spread Stage Size, L.N. involvement, metastasis (TNM) Poor prognostic findings Chest wall invasion, skin ulceration, inflammatory carcinoma

Cancer Spread Stage: Stage 0: DCIS, LCIS, survival 97% Stage 1: invasive <2cm, survival 87% Stage 2: invasive 2 – 5 cm, survival 75% Stage 3: invasive >5 cm + L.N., survival 46% Stage 4: metastatic disease, survival 13%

Risk Factors Environmental Host Changeable Non changeable

Risk Factors Host Changeable Non changeable Age: uncommon <30 years, increase with age till menopause Early menarche Late menopause Nulliparous

Risk Factors Host Changeable Non changeable Genetic 5-10% of cancer is related to inhereted gene Suspected in young, bilateral cancer, with ovarian tumor BRCA1, Ch 17q BRCA2, Ch 13q Li Fraumeni syndrome (P53 mutation) Cowden disease (PTEN) Ataxia-telangeictasia

Risk Factors Host Changeable Non changeable Prolonged exogenous estrogen postmenopausally Hormone replacement therapy Oral contraceptives Non changeable

Risk Factors Environmental Geographic variations Radiation Others US>Asia, Africa US 5x of Japan Radiation Early age during breast development <30y Others Obesity, high-fat diet, alcohol, smoking

Pathogenesis Genetic Overexpression of HER2/NEU (ERBB2) Found in 30% of cases Poor prognosis Amplification of Ras gene, Myc Mutations of P53, RB1

Pathogenesis Hormonal Estrogen excess (early menarche, late menopuse, nulliparity) Ovarian tumor secreting estrogen

Prognosis Tumor stage (size, LN, metastasis) Grade Type Lymphovascular invasion ER. PR. Proliferation rate Aneuploidy HER2/NEU over expression

Inflammation of Breast

Inflammation of Breast Tender, painful, Fever… Acute mastitis Nursing Staph : single, multiple Mammary duct ectasia Non bacterial, 40-50 year old Duct dilation, rupture, reactive changes Traumatic fat necrosis Mass, small, tender Fat necrosis, acute inflammation, foamy histiocytes

Fibroadenoma Most common benign tumor of the breast Young female 30y Estrogen ? Findings Discrete, freely mobile, firm, tan-white 1-10cm Pericanalicular, intracanalicular

Phyllodes Tumor Stromal tumor Usually large, leaf-like cleft and slits Most are benign Can be malignant Stromal cellularity, atypia, mitosis, invasion

Intraductal Papilloma Solitary, affect large lactiferous ducts Present: bloody nipple discharge, subareolar mass, rarely nipple retraction Findings: Dilated duct with branching tumor Papillary, double layers of cells Intraductal papillomatosis

Male Breast Gynecomastia Carcinoma Enlargement of male breast Estrogen Klinefelter syndrome Estrogen secreting tumors Digitalis Physiologic in puberty Carcinoma Rare M:F ratio 1:125