Congenital and inflammatory diseases of the breast

breast anatomy - lesions Normal breast anatomy and anatomical location of common breast lesions Breast is modified sweat gland – the largest gland of skin. Nipple - 6-10 major ductal system originates, lined by keratinizing squamous epithelium at the beginning of the ducts then abruptly changes to a double layered cuboidal epithelium. Areola – hyperpigmented skin around the nipple supported by smooth muscles. TDLU – Successive branching of the large ducts leads to the terminal duct lobular unit (TDLU) Acini (Lobule) – (Adult women) terminal branches into a grapelike cluster of small acini to form a lobule. Two cell types – Ducts and lobules are lined by low, flattened discontinuous layer of contractile cells containing myofilaments (myoepithelial cells) on the basement membrane that assist in milk ejection and maintains the normal structure and function of the lobules & BM. The second layer of epithelial cells that lines the lumen produces milk (terminal ducts and lobules) Stroma – dense fibrous connective tissue admixed with adipose tissue (interlobular stroma); lobules are enclosed by delicate myxomatous stroma (intralobular stroma) that are breast specific hormonally responsive with scattered lymphocytes PASH = Pseudoangiomatous stromal hyperplasia

Life cycle changes A: Mammogram of young women – dense white (opaque) B: Young women’s breast – density due to fibrous interlobular stroma & paucity of adipose tissue C: During pregnancy – undergo lactational changes D: Old women’s breast – small ducts & atrphic lobules in adipose tissue E: Mammogram – more radiolucent in elder’s breast Lifecycle changes. A, Mammograms in young women are typically "dense" or white in appearance. In this setting, mass-forming lesions or calcifications can be difficult to detect. B, The density of a young woman's breast is due to the predominance of fibrous interlobular stroma and the paucity of adipose tissue (normally radiolucent or black). Prior to pregnancy, the terminal duct lobular units (TDLUs) are small and are invested by loose cellular intralobular stroma. Larger ducts interconnect the TDLUs. C, During pregnancy, branching of terminal ducts results in more numerous TDLUs, and the number of acini per TDLU increases. Luminal cells within TDLUs (but not the large duct system) undergo lactational change in preparation for milk production. D, With increasing age, the TDLUs decrease in size and number, and the interlobular stroma is replaced by adipose tissue. An older woman's breast typically consists of small ducts and atrophic lobules in adipose tissue. E, Mammograms become more radiolucent (darker) with age owing to the increase in adipose tissue. Radio-dense mass-forming lesions, and calcifications become easier to detect. The cyclic changes is seen in breast tissue due to hormonal play. The breast lobules are relatively quiescent during follicular (proliferative –estrogen) phase. After ovulation due to combined effects of estrogen and rising progesterone the cell proliferation and stromal edema takes place (sense of fullness felt during premenstrual phase). The decline of estrogen and progesterone is followed by epithelial cell apoptosis and disappearance of stromal edema – regresses the lobules During pregnancy, breast assumes its complete morphological maturation and functional activity. Lobules increase in number and size to the extent of breast comprised entirely of lobules separated by a relatively scant stroma. Colostrum (high in protein) is produced immediate after delivery (birth) followed by production of milk (higher in fat & calories) within 10 days as progesterone declines. After cessation of lactation, the lobules regress and atrophy (markedly diminished breast size) After 3rd decade, long before menopause, lobules and stroma start to involute.

Congenital and inflammatory diseases of the breast Enumerate different types of inflammatory breast lesions. Enumerate the causes of inflammatory breast lesions. Describe clinical picture and management of inflammatory breast lesion. Describe the differentiation of the inflammatory breast lesion from breast cancer.

Inflammatory diseases-TYPES Uncommon – less than 1% of women with breast symptoms- 1- Acute Mastitis 2- Periductal Mastitis. 3- Mammary Duct Ectasia (plasma cell mastitis). 4- Traumatic fat necrosis. Systemic Breast Disease 5- Lymphocytic Mastopathy (autoimmune basis- scelrosing lobulitis) 6- Granulomatous Mastitis \ 7- Radiation

1- Acute mastitis- causes Cuases - Infectious agents: 1- Staph – localized area,single or multiple abscesses Acute inflammation, usually small-start at one duct Occasionally large abscess – heals by palpable scar. 2- Strep – generally spread to entire breast Pain, marked diffuse, spread of infection, swelling and tenderness Resolution rarely leaves areas of indurations. Access of bacteria to the breast 1-Through ducts- start at one duct, then spread. 2- Fissures in nipple- lactation or nipple dermatitis.

Acute Mastitis – Abscess- breast tissue is infiltrated by neutrophils and may be necrotic

2- periductal mastitis- causes is known as, subareolar abscess, squamous metaplasia of lactiferous ducts, Zuska disease. 1)Vitamin A deficiency in associated with toxic substances in tobacco smoke or smoking ↓↓ Note:- Not association with lactation Altere the differentiation of ductal epithelial

periductal mastitis: Recurrent subareolar abscess. When squamous metaplasia extends deep into a duct, keratin becomes trapped and accumulates. If the duct ruptures, the ensuing intense inflammatory response to keratin results in an erythematous painful mass. A fistula tract may burrow beneath the smooth muscle of the nipple to open at the edge of the areola. Histologic feature is keratinizing squamous metaplasia of the nipple ducts, chronic granulomatous response to keratin, +\- bacterial infections

3- Mammary duct ectasia- causes occur in the 5th or 6th decade of life, in multiparous women Chronic mastitis (non-bacterial) - inspissation of secretions in main excretory ducts Morphology: Ductal dilatation (ectasia) with ductal rupture. Dilated ropelike ducts with thick cheesy secretions Reactive changes in the surrounding breast tissue+ calcification (nipple retraction and palpable mass). Ducts filled by granular debris, sometimes containing WBCs mainly fat-laden macrophage (nipple discharge) The striking feature is prominent lymphocytic and plasma cell infiltration with occasional granulomas Mistaken for carcinoma by– retraction of overlying skin or nipple, palpable mass (even on mammogram)- nipple discharge- calcificaftion

3- Mammary duct ectasia- CHRONIC INFLAMMATION AND FIBROSIS SURROUND AN ECTATIC DUCT FILLED WITH INSPISSATED DEBRIS + INTERSTITIAL CHRONIC GRANULOMATOUS INFLAMMATORY REACTION Mammary duct ectasia. Chronic inflammation and fibrosis surround an ectatic duct filled with inspissated debris. The fibrotic response can mimic the irregular shape of malignant carcinomas on palpation or mammogram.

4 - FAT NECROSIS- causes Define as foamy macrophages infiltrating partially necrotic adipose tissue- involve adipose tissue, occ. parenchyma Traumatic fat necrosis: A) Post-traumatic fat necrosis, often in pendulous large breast (1-2 WEEKS) B) Prior surgery - Central necrotic fat cells surrounded by PMNs & mononuclear infiltrates and fat-laden macrophages. - This is enclosed later by fibrous tissue and Replaced by scar tissue or cyst + Calcification. - Skin retraction

5- LYMPHOCYTIC MASTOPATHY (SCLEROSING LYMPHOCYTIC LOBULITIS)- (Diabetic mastopathy) causes Probably immune-mediated pathogenesis (Autoimmune diseases- e.g.):- a) Type 1 (insulin-dependent) diabetes mellitus. b) Autoimmune thyroid disease Microscopy: -Diffuse dense lymphocytic infiltrates. (lobules& Small blood vessels) - Lobular atrophy. - Sclerosis: collagenized stroma surrounding atrophic ducts and lobules. - The epithelial basement membrane is thickened. Microscopically, they show collagenized stroma surrounding atrophic ducts and lobules. The epithelial basement membrane is often thickened. A prominent lymphocytic infiltrate surrounds the epithelium and small blood vessels

6- GRANULOMATOUS MASTITIS- causes Immune-mediated pathogenesis, can simulate malignancy in presentation.= (granulomatous lobulitis) 1- Systemic granulomatous diseases (e.g., Wegener granulomatosis, SLE, amyloidosis or sarcoidosis). 2- Infections- (e.g. mycobacteria or fungi, actinomycosis, Histoplasmosis)- common in immunocompromised patients. 3- Foreign objects such as breast prostheses. 4- Hypersensitivity reaction to antigens expressed by lobular epithelium during lactation (Granulomatous lobular mastitis )- uncommon.

Granulomatous Lobular Mastopathy

Inflammatory dis-clinical features 1- Mastitis – development of cracks and fissures in the nipples, erythematous and painful, and fever  single or multiple abscesses. 2- Periductal Mastitis- painful erythematous subareolar mass+ a fistula tract of the smooth muscle of the nipple and opens onto the skin 3- Mammary Duct Ectasia (plasma cell mastitis). poorly defined palpable periareolar mass,+ a\w thick, white nipple secretions and sometimes with skin retraction + No pain or erythematous 4- Traumatic fat necrosis- painless palpable mass, skin thickening or retraction, a mammographic density or calcifications. 5- Lymphocytic Mastopathy- LOBULAR (autoimmune basis), single or multiple hard palpable masses, may be bilateral, so hard lesion. 6- Granulomatous Mastitis- immunocompromised patients or adjacent to foreign objects + hypersensitivity reaction

management of inflammatory breast lesion. Diagnosis: clinical examination, US, MG, FNAC, tissue biopsy Management: according to the type and etiology Acute mastitis, Mammary duct ectasia and breast abscess A)- ;Frequent nursing and massaging of the breast(keep it empty) B) - Appropriate antibiotics. C) Incision and drainage. Fat necrosis A) Using warm compresses B) Analgesics (ibuprofen,aspirin) C) FANC drainage of oil d) Lumpectomy if mass persist. LYMPHOCYTIC MASTOPATHY Surgery (often recur) Granulomatous mastitis- systemic antibiotics, anti TB, steroids, immunosuppressive - methotrexate, surgery

Describe the differentiation of the inflammatory breast lesion from breast cancer Age, sex, clinical presenting symptoms, signs& durations. Nipple bloody discharge, Nipple pain. Examination findings: Breast mass (localized, involve X quadrants, size), firm\hard, with irregular margins Skin: irritation, dimpling, redness, pseduo-orange, ulcer. Nipple:retraction, depression, irritations, redness scaling. Corresponding axilla- enlarged lymph nodes, accessory. Examination of other breast

Asymmetrical & distortion Breast ca- skin changes Breast ca- skin changes

Life cycle changes A: Mammogram of young women – dense white (opaque) B: Young women’s breast – density due to fibrous interlobular stroma & paucity of adipose tissue C: During pregnancy – undergo lactational changes D: Old women’s breast – small ducts & atrphic lobules in adipose tissue E: Mammogram – more radiolucent in elder’s breast Lifecycle changes. A, Mammograms in young women are typically "dense" or white in appearance. In this setting, mass-forming lesions or calcifications can be difficult to detect. B, The density of a young woman's breast is due to the predominance of fibrous interlobular stroma and the paucity of adipose tissue (normally radiolucent or black). Prior to pregnancy, the terminal duct lobular units (TDLUs) are small and are invested by loose cellular intralobular stroma. Larger ducts interconnect the TDLUs. C, During pregnancy, branching of terminal ducts results in more numerous TDLUs, and the number of acini per TDLU increases. Luminal cells within TDLUs (but not the large duct system) undergo lactational change in preparation for milk production. D, With increasing age, the TDLUs decrease in size and number, and the interlobular stroma is replaced by adipose tissue. An older woman's breast typically consists of small ducts and atrophic lobules in adipose tissue. E, Mammograms become more radiolucent (darker) with age owing to the increase in adipose tissue. Radio-dense mass-forming lesions, and calcifications become easier to detect. The cyclic changes is seen in breast tissue due to hormonal play. The breast lobules are relatively quiescent during follicular (proliferative –estrogen) phase. After ovulation due to combined effects of estrogen and rising progesterone the cell proliferation and stromal edema takes place (sense of fullness felt during premenstrual phase). The decline of estrogen and progesterone is followed by epithelial cell apoptosis and disappearance of stromal edema – regresses the lobules During pregnancy, breast assumes its complete morphological maturation and functional activity. Lobules increase in number and size to the extent of breast comprised entirely of lobules separated by a relatively scant stroma. Colostrum (high in protein) is produced immediate after delivery (birth) followed by production of milk (higher in fat & calories) within 10 days as progesterone declines. After cessation of lactation, the lobules regress and atrophy (markedly diminished breast size) After 3rd decade, long before menopause, lobules and stroma start to involute.

Developmental disorders Supernumerary nipples or breast: Mildline remnants – extends from axilla to perineum Axillary breast: Normal ductal system extends into chest wall & axilla. Congenital Nipple Inversion: Failure to evert during development, may be unilateral; may be confused with acquired causes that may give rise to inversion sometimes – like in cases of invasive breast cancer or inflammatory diseases of nipple (recurrent subareolar abscess or duct ectasia). Macromastia: One cause is an unusual tissue response to hormonal changes during puberty  massive rapid breast growth (Juvenile hypertrophy)