Breasts ( Mammary glands ) Structure & physiology : The breasts are originated from the skin. They resemble the sweat glands in structure & development & they are regarded as modified sweat glands. Each breast consists of lobes. Each lobe is drained by a duct that emerges at the nipple as an independent opening. The lobes are separated by interlobular connective tissue & adipose tissue. The lobes are sub-divided into lobules by layer of connective tissue & adipose tissue. Each lobe has an excretory lactiferous ducts that opens independently at the nipple. The secretory portion consists of a basement membrane, layer of myoepithelial cells & a layer of low columnar cells. In males The development is transient & is followed by involution.

In females the development continues during adolescence & reaching final development at the end of pregnancy. Mild cyclic changes involving hyperplasia followed by involution occur with each menstrual cycle. The normal development of the breast at puberty is related to an increase of oestrogen in the circulation. Also during pregnancy oestrogen plays a role in the development of the ductal portion of the glandular tissue,while progesterone is responsible for acinar development(glands). After the menopause, involutionary changes occur, with dense connective tissue gradually replacing the glandular tissue & the breast decreasing in size.

Congenital abnormalities : 1.Poly mastia : It is the presence of more than two breasts. These may occur any where along the milk- line which extends from the axilla to the groin. 2.Polythelia : It is the presence of accessory nipples.

Inflammation of the breast : 1.Acute mastitis & breast abscess : Aetiology : It is almost always associated with lactation & a cracked nipple through which staph or strepto enter to the breast tissue. Pathology : Gross : There may be generalized red,painful swelling of the breast or a localized abscess may form in a single breast lobe. Micro. : There is an acute suppurative inflammation & with abscess formation, The axillary lymph nodes are frequently swollen & show reactive hyperplasia. Results : It may result in extensive destruction & fibrous scarring of the breast if not treated early.

2.Chronic inflammatory mastitis : True chronic inflammation of the breast due to bacterial infection is uncommon. Most cases are due to incomplete resolution of acute mastitis in the lactating breast or due to chronic breast abscess. 3.Tuberculosis : It is very rare but may occur secondary to tuberculosis of the lungs. Traumatic fat necrosis of the breast : It is caused by a trauma to the breast which cause disruption of fat cells & allow the escape of fat globule into the surrounding tissue which cause foreign body giant cell reaction, foamy cells & later dense fibrous tissue. The hardness of this lesion & the fibrous reaction which may result in fixation to the surrounding tissue may be misdiagnosed as carcinoma.

Mammary duct ectasia : It is dilatation of the mammary ducts. The dilated ducts are filled with neutral fat & cellular debris leading to a pale or coloured nipple discharge. The contents of the ducts may escape to the periductal tissue & causing inflammatory response

Fibrocystic Disease It may occur at any age from puberty onwards but is common about the time of menopause & afterwards. Structural changes : It consists of : a.Fibrosis : b.Cyst formation : It occurs as a result of dilatation of ducts. The cysts are lined by flattened cuboidal epithelium. Some cysts may show metaplasia of thelining epithelial cells which become large, columnar with eosinophilic cytoplasm & it is called apocrine metaplasia. c.Adenosis : There is formation of new breast lobules as a result of proliferation of the breast epithelium of ducts & acini. There may be increase in the fibrous stroma producing distortion of the acinar pattern & eventually sclerosis. This is called sclerosing adenosis.

It is characterized by proliferation of the epithelium & connective tissue of the breast with cystic dilatation of the ducts, due to ovarian hormonal imbalance. The nature of the fibrocystic changes : The cyclic changes in the ovary, with alternating oestrogen & progesterone secretion, produce effects not only in the endometrium but also in the breasts. Thus there is overgrowth of both epithelium & stroma during the cycle with a return to normal at the end of each cycle. As aresult of hormonal imbalance either the epithelium or the stroma or both may remain in an abnormal proliferative state to produce nodular, lumpy or cystic breasts.

Proliferative Breast Diseases Without Atypia.presentation -mammographic densities or calcifications -mammographic densities or calcifications -incidental findings in biopsies -incidental findings in biopsies -nipple discharge -nipple discharge

Epitheliosis : The essential feature is increase in the thickness of the epithelium of the wall of ducts & acini due to hyperplasia of the epithelium of ducts & acini. Thus the cells are several layers in depth & the lumen may be completely obliterated by this proliferation. Fibrocystic changes is a benign condition : Adenosis & Sclerosing variants have no predisposition to carcinoma. However epitheliosis carries risk of subsequent malignant Changes.

Benign tumours : The main tumours are : 1. Fibroadenoma : It is the commonest benign tumour of the breast. It consists of both stromal & epithelial elements. Fibroadenoma is small well circumscribed rounded mass & movable.

Fibro-Adenoma..presents as -palpable mass in young women -palpable mass in young women -mammographic density or calcification in old women -mammographic density or calcification in old women

Micro. : 2 types : A.Pericanalicular : It consists of fibrous tissue surrounding groups of epithelial acini B.Intracanalicular : It is composed of fibrous tissue surrounding epithelial clefts which represent compressed ducts C.. Mixed

2. Duct papilloma : It occurs as a pedunculated tumour which forms within a distended duct. It consists of a branching fibro vascular stromal core covered by cuboidal epithelium. It causes blood discharge from the nipple.

Carcinoma.the most common cancer in women.risk factors -age, rare before 25 years -age, rare before 25 years -earlier menarche and later menopause -earlier menarche and later menopause -age at 1 st pregnancy -age at 1 st pregnancy -first-degree relatives with breast cancer -prior breast biopsies with atypical hyperplasia -race -first-degree relatives with breast cancer -prior breast biopsies with atypical hyperplasia -race

.additional risk factors -estrogen exposure -radiation exposure -carcinoma of the contralateral breast or endometrium -geographic influence -diet -obesity -lack of exercise -lack of breast feeding -environmental toxins -tobacco.additional risk factors -estrogen exposure -radiation exposure -carcinoma of the contralateral breast or endometrium -geographic influence -diet -obesity -lack of exercise -lack of breast feeding -environmental toxins -tobacco

.etiology and pathogenesis -major factors are genetic and hormonal -major factors are genetic and hormonal.hereditary breast cancer, affect mainly premenopausal women.hereditary breast cancer, affect mainly premenopausal women -25% are attributed to 2 autosomal dominant tumor-suppressor genes(BRCA1, BRCA2) -25% are attributed to 2 autosomal dominant tumor-suppressor genes(BRCA1, BRCA2) -other genes mutations form 10% -remaining 65% of familial breast cancers are unexplained -other genes mutations form 10% -remaining 65% of familial breast cancers are unexplained

.sporadic breast cancer, affect mainly postmenopausal women -are related to hormone exposure -majority of cancers overexpress ER.the role of estrogen in breast cancer -its metabolites can cause mutation or generate DNA-damaging free radicals -via its hormonal action, it directly stimulates proliferation of epithelial cells.sporadic breast cancer, affect mainly postmenopausal women -are related to hormone exposure -majority of cancers overexpress ER.the role of estrogen in breast cancer -its metabolites can cause mutation or generate DNA-damaging free radicals -via its hormonal action, it directly stimulates proliferation of epithelial cells

.morphology -comedocarcinoma -comedocarcinoma -solid -solid -cribriform -cribriform -papillary -papillary -micropapillary -micropapillary.many cases will progress to invasive carcinoma.mastectomy is curative in 95% of cases.many cases will progress to invasive carcinoma.mastectomy is curative in 95% of cases

Paget Disease Of The Nipple.presents as a unilateral erythematous eruption with a pruritic scaly lesion.palpable mass is present in up to 60% of cases, which almost always is associated with an underlying invasive carcinoma (poorly differentiated).malignant cells (Paget cells) extend from DCIS into nipple skin

Invasive Carcinoma.almost always presents as a palpable mass.most common histologic types -invasive carcinoma, no special type (NST) -invasive carcinoma, no special type (NST) -invasive lobular carcinoma, has a greater incidence of multi-centricity and bi-laterality -invasive lobular carcinoma, has a greater incidence of multi-centricity and bi-laterality

Spread of breast cancer : 1.Direct : It invades the breast tissue & overlying skin with ulceration & nipple retraction. It may invade the underlying muscle & chest wall. 2.Lymphatics : a.Permeation of the local dermal lymphatics by tumour cause blockage of lymphatics & oedema of the skin producing a Peau d orange. b.Dermal lymphatic invasion may produce multiple tumour nodules with thickening of skin – Cancer en cuirasse. c.Invasion of axillary lymph nodes. d.Invasion of internal mammary lymph nodes. e.Invasion of supraclavicular lymph nodes. 3.Blood : spread to lung, liver & bones.

Gynaecomastia : It is enlargement of the breast tissue of males,which is usually caused by proliferation of connective tissue & ducts of the breast. It may be unilateral or bilateral. Aetiology : 1.Endocrine disturbances : due to increase oestrogen. 2.Testicular tumours e.g. teratoma. 3.Oestrogen therapy e.g. for carcinoma of the prostate 4.Ciirrhosis : Due to failure of detoxification of oestrgen. 5.Drugs : e.g. digitalis, tricyclic compounds.