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Mammary gland – Normal features 1. Covered by skin & subcutaneous tissue 2. Rests on pectoralis muscle 3. Pectoral fascia separates it from the pectoral muscles
Breast – Normal features• Modified skin appendage.• Composed of specialized epithelium and stroma that gives rise to both benign and malignant lesions.• 6-10 major ductal system originate at the nipple.• Keratinizing sq.epithelium of overlying skin continues into the ducts and then abruptly changes to a double layered cuboidal epithelium.• Surrounding areolar skin is pigmented & supported by smooth muscle.
• Normal duct system microSource: Ackerman’s Surgical Pathology 9th Ed, 1765p
Breast – Normal features• Morphofunctional unit of the organ is SINGLE GLAND composed of 2major parts: 1-TDLU (secretory unit of the gland) a-lobule b-terminal ductule 2-Large duct system
Breast – Normal features• Importance of division of mammary gland unit into 2 major portions resides in its relation to disease of this organs.• TDLU (FCD, Ductal hyperplasia, Carcinoma)• Large duct system (Solitary papilloma, ductectasia, rare ductal carcinomas)
Normal anatomy and possible pathological lesions
HistologyEpithelium & Stroma:• Ducts and lobules are lined by 2 cell types 1-Myoepithelial cell lying on the BM. 2-Epithelial cells lines the lumen.• Stroma 1-Interlobular stroma 2-Intralobular stroma (hormonally responsive)
Normal histologyThe normal microscopic appearance of female breast tissue is shown here. There is a larger duct to the right and lobules to the left. A collagenous stroma extends between the structures (Interlobular – Red stars). Intralobular stroma is hormonally responsive (Blue Stars). A variable amount of adipose tissue can be admixed with these elements. Source: webpath
Normal histologyAt high magnification, the appearance of a normal breast acinus is shown here. Note the epithelial cells lining the lumen demonstrate apocrine secretion with snouting, or cytoplasmic extrusions, into the lumen. A layer of myoepithelial cells, some of which are slightly vacuolated, is seen just around the outside of the acinus. Source: webpath
Normal histologyAn immunoperoxidase stain with antibody to actin demonstrates the myoepithelial cell layer around the breast acinus. The myoepithelial cells are contractile and are very sensitive to oxytocin. Source: webpath
Markers for Myoepithelium • S-100 protein • P-Cadherin • SMA • Calponin • Smooth muscle myosin-heavy chain • Maspin • Caldesmon • p63Source: Ackerman’s Surgical Pathology 9th Ed, 1765p
Disorders of development1. Milk line remnants.2. Accessory axillary breast tissue.3. Congenital nipple inversion.
Milk line remnants “POLYTHELIA”Epidermal thickening along the milk line extending from axilla to perineum.
Milk line remnantsThe classification established by Kajava in 1915 is still valid: (De Cholnoky, 1939)1. Complete SN: Nipple + areola + glandular breast tissue2. SN: Nipple + glandular tissue (no areola)3. SN: Areola + glandular tissue (no nipple)4. Aberrant glandular tissue only5. SN: Nipple + areola + pseudomamma (fat tissue that replaces the glandular tissue)6. SN: Nipple only (the most common SN)7. SN: Areola only (polythelia areolaris)8. Patch of hair only (polythelia pilosa)
Disorders of development Accessory axillary breast tissueIn some persons normal ductal system extends into subcutaneous tissue of the chest wall and into the axillay fossa.Importance: Therapeutic mastectomy might remove the entire breast but not remove all breast epithelium.Hence cannot compeltely eliminate the risk of developing breast cancer.
Disorders of developmentAccessory axillary breast tissue
Disorders of development Congenital nipple inversionIt may be bilateral or unilateral.Importance: may be mistaken for carcinoma or inflammation.
Disorders of developmentCongenital nipple inversion
Clincal presentations PAIN• Mastalgia / mastodynia• Cyclical / non-cyclical1. Ruptured cyst2. Injury3. Infection4. Some times without any specific lesionNote: only about 10% of breast carcinoma patients presentwith pain.
Clincal presentations PALPABLE MASSES• Notable points:1. Masses must be distingusihed from the normal nodularity of the breast.2. Breast masses usually does not become palpable until it’s about 2cms in diameter.3. Likelyhood of malignancy in a papable mass increses with age ---- <40yrs (only 10% of masses are malignant) ---- >50yrs (about 60% of the masses are malignant)
Clincal presentations Nipple discharge• Gains importance only if it’s1. Spontaneous &2. Unilateral
Clincal presentations Nipple discharge• Types of discharges:1. Milky (>prolactin, hypothyroidism, anovulatory cycle, OCs, M-Dopa, phenothiazines) (Not associated with malignancy)2. Serosanguinous (most commonly associated with benign lesion)3. Bloody (most commonly associated with benign lesion – duct papillomas)
Acute mastitis• Pyogenic infections• Occurs during first few weeks of lactation• Pathogens:1. Staphylococcus2. Streptococcus
Acute mastitis1. Breast mass2. Fever3. Erythematous painful breasts4. If not Tx it may spread to entire breast Complictions:---fibrous scarring---may be mistaken for carcinoma
Acute mastitisDuring lactation, or at other times with dermatologic conditions that allow cracks and fissures to form in the skin of the nipple, infectious organisms can invade into breast and result in acute inflammation, and this may progress to breast abscess formation (Circle). The most common organism is Staphylococcus aureus. Organization with fibrous scar formation around the abscess can mimic a carcinoma on physical examination, by mammography, and grossly.
Acute mastitisWhile breast-feeding the baby, the skin of the breast may become irritated and inflamed. The skin may fissure, predisposing to infection. Acute mastitis typically involves just one breast and is most often caused by Staphylococcus aureus, though other bacterial organisms such as streptococci can produce this condition, with neutrophilic infiltrates microscopically. If untreated by antibiotic therapy, spread of infection and abscess formation can occur.
Periductal mastitis Recurrent sub areolar abscesses “ZUSKA disease”• Painful erythematous subareolar masses• >90% are smokers (vit-A deficiency)• Seen both in males and females• Not associated with lactation
Periductal mastitis Recurrent sub areolar abscesses “ZUSKA disease”Subareolar abscess with fistulous opening at the edge of areola
Periductal mastitis Recurrent sub areolar abscesses “ZUSKA disease”Pathlogy:1. Keratinization of epithelium extending to an abnormal depth into the orifices of the nipple ducts.2. Keratin plugs block the ductal system and causes dilatation & eventual rupture of the ducts.3. Intense chronic granulomatous inflammatory response develops to ketain spilled into periductal tissue.
Periductal mastitis Recurrent sub areolar abscesses “ZUSKA disease”Source: Robbins Pathologic basis of disease, 8th ed. 1125p • 3945
Mammary ductectasia• 4th to 7th decade of life.• Usually seen in multiparous women.• NOT assocated with cigarette smoking.Clinically:• Nipple discharge.• Retraction of nipple.• Palpable dilated ducts in the subareolar area.
Mammary ductectasia• Gross: 1-Poorly defined indurated area. 2-Ropyness of the surface. 3-c/s shows dilation of one or more large ducts containing cheesy inspissated secretions.
Mammary ductectasia• Microscopically: 1-Dilated ducts with necrotic & atrophic epithelium 2-Lumen filled with powdery debri and foam cells 3-Periductal & insterstitial chronic inflammaotry cell infiltration (Ly, Plas, Histio, Giant cells)Note: Plasma cell mastitis (when numerous plasma cells are seen) Obliteration mastitis (when inflammatory scarring obliterates the lumen of the ducts)
Non-proliferative breast changes – FCD • Form palpable masses • Calcifications • Spontaneous unilateral nipple discharge • They mey disappear after FNAC
Non-proliferative breast changes – FCDThere are 3 principle patterns of morphologic changes1. Cyst formation with apocrine metaplasia2. Fibrosis3. Adenosis
Non-proliferative breast changes – FCDCYSTS:• Cysts form by dilation and unfolding of lobule.• Cystic lobules coalesce to form larger cysts.• Cysts lined by flattened atrophic or apocrine epithelium• Papillary projections• Calcification is common (‘Milk of calcium’)
Fibrocystic Change (FCC)This is the gross appearance of fibrocystic changes in the breast. A 1.5 cm cyst is noted here. This can lead to palpation of an ill-defined "lump" in the breast. Sometimes, fibrocystic changes produce a more diffusely lumpy breast. Source: webpath
Fibrocystic Change (FCC)This is the histologic appearance of fibrocystic changes in breast. There are cystically dilated ducts, areas of lobules that are laced with abundant fibrous connective tissue (sclerosing adenosis), and stromal fibrosis. There is even a small area of microcalcification seen just to the upper right of center. No atypical changes are seen here. Source: webpath
Fibrocystic Change (FCC)Another example of microscopic fibrocystic changes of the breast are shown here. Fibrocystic changes account for the majority of "breast lumps" that are found in women of reproductive years, particularly between age 30 and menopause. Source: webpath
Fibrocystic Change (FCC)There is prominent apocrine change of the cells lining the cysts in this example of fibrocystic changes of breast. Note the tall, pink, columnar nature of the epithelial cells. This appearance is benign. Source: webpath
Non-proliferative breast changes – FCDFIBROSIS: Rupture & release of secretory material into the adjacent stroma elicit inflammation and fibrosis.ADENOSIS: Increase in number of acini per lobule ‘Blunt duct adenosis’
Fibrocystic Change (FCC)Prominent sclerosing adenosis, one of the features of fibrocystic changes, is demonstrated by the appearance of a proliferation of small ducts in a fibrous stroma. Although it is benign, the gross and mammographic appearance may mimic carcinoma, and it can be difficult to distinguish from carcinoma on frozen section. Source: webpath
FCCThis mammogram demonstrates a suspicious lesion that could be a carcinoma or just an area of pronounced sclerosis with fibrocystic changes. On biopsy, this was benign. Source: webpath
Proliferative breast disease without atypia• Rarely form palpable masses• They are often detected ---radiographically (densities, calcifications) ---in biopsies• Proliferation of ductal epithelium & or stroma without cellular abnormalities suggestive of malignancy
Proliferative breast disease without atypiaEntities include:1. Florid epithelial hyperplasia2. Sclerosing adenosis3. Complex sclerosing lesion4. Papillomas5. Fibroadenomas with complex features
Proliferative breast disease without atypiaEPITHELIAL HYPERPLASIA:• Def: presence of >2 cell layers of epithelium• >4 cell layers designates it as moderate to florid hyperplasia• When they fill the lumen it can be differentiated from CIS by finding fenestrations are the periphery of the cellular masses.
Proliferative breast disease without atypiaSCLEROSING ADENOSIS:• Increase in # of acini per terminal duct at least twice the normal.• Normal lobular arrangement is maintained.• Acini are characteristically dilated at the periphery.• Myoepithelial cells are usually prominent.• Sclerosis• Calcifications are frequently present with in the lumen of acini.
Proliferative breast disease without atypiaCOMPLEX SCLEROSING LESION:• Stellate scar• Centrally entrapped glands in hyalinized stromaComplex sclerosing lesion include:1. Radial scar2. Radial scar related lesion with sclerosing adenosis, papilloma formation3. Epithelial hyperplasia
Proliferative breast disease without atypiaPAPILLOMAS:• Multiple branching fibrovascular cores• Lined by luminal & myoepithelial cells• Growth occurs within a dilated duct• Epithelial hyperplasia and apocrine metaplasia are frequently seen• Large duct papillomas are single and situated nearer to the nipple• Small duct papillomas are multiple and located deeper within ductal system (more prone for Ca.)
These breast ducts demonstrate epithelial hyperplasia. The epithelial cells are multilayered. There is no atypia. Thus, just as with fibrocystic changes such as fibrosis, cysts, and sclerosing adenosis, there is no increased risk for carcinoma. Source: webpath
More florid ductal epithelial hyperplasia of the breast is shown here. There is a slightly increased risk (1.5 to 2 times normal) for breast carcinoma when such changes are present. Source: webpath
Proliferative breast disease with atypia • This includes: 1-ADH 2-ALH
Proliferative breast disease with atypia - ADH
This is atypical ductal epithelial hyperplasia of the breast. A significantly increased risk (5 times normal) for breast carcinoma occurs with cytologically atypical epithelial hyperplasia.
Proliferative breast disease with atypia - ALH