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

– Cystic change

– 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

• 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, 2.0-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 2.0-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

• Prolonged exogenous estrogen postmenopausally– Hormone replacement therapy

• Oral contraceptives

– Non changeable

Risk Factors

• Environmental– Geographic variations

• 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– Enlargement of male breast

– Estrogen

– Klinefelter syndrome

– Estrogen secreting tumors

– Digitalis

– Physiologic in puberty

• Carcinoma– Rare M:F ratio 1:125