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Systemic Pathology - Diseases of the Female Breast - Aisner/Fitzhugh

Home Get App Take Quiz Create Normal anatomy of breast Milk-producing Lobules -> duct -> Nipple. Areola. Fatty tissue. Most breast cancer arise from duct or lobule. Normal Histology of breast Lobules are the functional unit of the mammary gland. Lobules contain clusters of epithelium-lined ductules or acini. The larger duct systems (6-10) branch into smaller ducts, branch into terminal ducts, then give rise to lobules or acini. The stroma of the breast is made up of fibroconnective tissue and adipose tissue (interlobular stroma) and also contains elastic fibers around larger ducts. Terminal duct + lobule = terminal duct lobular unit or T.D.L.U. At around the age of forty, due to the decrease of estrogen, areas that are fibrous become fatty, and the lobules may atrophy, the breast becomes mostly fat; the time when mammogram monitoring starts. Histopathologic findings of breast lumps 40% fibrocystic changes 30% no disease 13% miscellaneous benign 7% fibroadenoma 10% cancer Benign changes can happen at any age. Fibrocystic changes aka fibrocystic disease Applied to changes consisting of cyst formation and fibrosis. Dilated lobules filled with secretion type material, can become large, rupture, cause inflammation and pain. Most common breast abnormality seen in premenopausal women. Consequence of the cyclic breast changes that occur normally in the menstrual cycle. Divided into proliferative and nonproliferative changes. Nonproliferative Fibrocystic Changes Often multifocal, ill-defined, bilateral changes. Diffusely increased densities and nodularity on mammography. Range from 1 to 5 cm in diameter and grossly consist of blue dome cysts (with fibrous tissue in between) filled with watery fluid. The cysts form by dilation and unfolding of lobules; The pink lining of them is apocrine metaplasia - usually benign. Fibrosis is caused by the rupture of cysts due to the irritation of the stroma by the secretory material. Proliferative Breast Disease without Atypia - Epithelial Hyperplasia Multiple layers of duct epithelium, consist of ductal and myoepithelial cells. Proliferating cells may appear as solid masses encroaching duct lumen. Proliferative Breast Disease without Atypia - Sclerosing Adenosis Proliferation of luminal spaces lined by epithelial cells and myoepithelial cells. Commonly present as mammographic calcifications, mimicking a cancer-like appearance but is actually benign. Myoepithelial cells are preserved and increased. Marked stromal fibrosis. Relationship of Fibrocystic Changes to Breast Carcinoma Fibrocystic Changes can be classified as nonproliferative or proliferative. Proliferative lesions include hyperplasia and adenosis. Minimal or no increased risk - fibrosis, cysts, apocrine metaplasia, mild epithelial hyperplasia. Slightly increased risk (1.5-2x) - moderate to florid hyperplasia without atypia, ductal papillomatosis, sclerosing adenosis. Significantly increased risk (5x) - atypical hyperplasia, whether ductal or lobular. INFLAMMATORY PROCESSES of breast Acute Mastitis Duct Ectasia (Plasma Cell Mastitis) Plasma Cell Mastitis Acute Mastitis Usually related to the first month of breast feeding. Most common organism: S. aureus access through the ducts. The breast is erythematous and painful. The tissue is infiltrated by neutrophils and may be necrotic. Duct Ectasia (Plasma Cell Mastitis) The 5th-6th decade of multiparous women. Chronic inflammation surrounding the ducts - most commonly plasma cells, Occasionally granulomas. Periareolar mass commonly associated with thick white nipple discharge and sometimes skin retraction. Dilated ducts filled with granular debris and macrophages . Fat Necrosis Painless or painful palpable mass, skin thickening or retraction, mammographic density or calcifications. Mostly associated with trauma. Acute lesions may be hemorrhagic with central areas of necrotic adipose tissue. Early acute lesions contain numerous neutrophils mixed with macrophages and giant cells. Fat necrosis of other parts of the body have the same look. TUMORS OF THE BREAST - STROMAL TUMORS AND PAPILLOMA Fibroadenoma Phyllodes Tumor Intraductal Papilloma Fibroadenoma Most common benign tumor of the female breast. Most common in 3rd decade. Sharply circumscribed, freely mobile, rubbery nodule. Diameter - 1 to 15 centimeter. Common site - Upper outer quadrant. Gray-white cut section with slit like spaces. Biopsy might be necessary, since mammography doesn't help much in young women. New growth in the glandular space of fibroblastic stromal, resembling normal stroma, and epithelial elements, surrounded and compressed or distorted by stroma. In older women the stroma becomes hyalinizedand the epithelium atrophic. Any solid breast lesion at any age has to be evaluated, via biopsy or mammography. Phyllodes Tumor Arises from intralobular stroma, stromal proliferation. Presents after 6th decade. 15% are malignant. Three Types – Benign – Low grade malignant – High grade malignant Size - from small to very large. Color - from tan to brown; higher grade lesions are hemorrhagic. Bulbous growth, hence the name (phyllodes is Greek for leaf-like). Needs to be completely excised. Histological features distinguishing phyllodes tumor from fibroadenoma In phyllodes tumor, Stromal cellularity and mitoses. Nuclear pleomorphism. Infiltrative borders. Edges of the epithelium spreading out like leaves. Intraductal Papilloma Multiple fibrovascular cores lined by ductal and myoepithelial cells grow within a dilated duct. Very common type of benign breast lesion. The tumors grow on stalks, on papillae Have some association with breast cancer, make sure the surrounding tissue doesn’t have breast cancer. Key Points-Breast Carcinoma Lifetime risk 1 in 8 75% diagnosed after the age of 50 10% are caused by inherited mutations D.C.I.S. typically found mammographically L.C.I.S. typically incidental finding L.C.I.S. can result in invasive ductal or lobular carcinoma. Mets can develop many years after initial diagnosis. Prognostic factors - tumor size, lymph node involvement, mets at presentation, tumor grade, histologic type. ER, PR, and Her2 status help determine response to treatments. Epidemiology and Risk Factors of breast carcinomas Age - Risk increases steadily after age 30, especially after menopause, and peaks at roughly 80. - 75% of women with breast cancer are older than 50. - 5% of women with breast cancer are younger than 40. Geographic variations - Risk is significantly higher in North America and Northern Europe. - Incidence and mortality are 5xs higher in the US than in Japan. - Environmental, rather than genetic. - Diet, reproductive patterns, and nursing habits. Race/Ethnicity - Highest rate is seen in white women. - Hispanics, African Americans develop more aggressive tumors at younger ages and are diagnosed at later stage. Breast Carcinoma - Classification In Situ Carcinoma - most common type picked up by mammogram, esp. D.C.I.S due to the calcification - Ductal carcinoma in situ (D.C.I.S., more) - Lobular carcinoma in situ (L.C.I.S.) Invasive carcinomas - most get ductal - Ductal carcinoma, N.O.S. (Not Otherwise Specified) • Tubular carcinoma • Colloid (mucinous) carcinoma • Medullary carcinoma • Papillary carcinoma • Metaplastic carcinoma - Lobular carcinoma • Pleomorphic lobular carcinoma Ductal Carcinoma in Situ (D.C.I.S.) Not palpable; Half of mammographically detected lesions are D.C.I.S.; calcifications are often associated. Enlarged duct just like firbrocystic disease, but filled with breast cancer changes. Malignant clonal population of cells without invasion through the basement membrane. Myoepithelial cells are present, but in diminished numbers. Can involve the Terminal Duct Lobular Units as well as larger ducts. Has five architectural sub-types and can be graded by nuclear pleomorphism. Non-comedo D.C.I.S. - D.C.I.S. without central necrosis; nuclear grades low (to high). Calcifications may be present. Comedo D.C.I.S. - a.k.a. comedocarcinoma; solid sheets of cells, central necrosis, high nuclear grade. Microinvasion - foci of tumor cells less than 1mm invading stroma, most often seen with highest grade D.C.I.S. Still curable - surgical removal and radiation therapy. Paget Disease of Breast In-situ breast cancer A form of poorly differentiated D.C.I.S. that extends from the lactiferous ducts into the skin of the nipple, causing the nipple becomes crusty, flaky, ulcerated. Involvement of epidermis by malignant cells. Only 1-4% of DCIS cases. Lobular Carcinoma in Situ (L.C.I.S.) Proliferation in terminal duct or lobule (T.D.L.U.) of a monomorphic population of cells. Almost always an incidental finding - not usually mammographically detected. Dyscohesive cells with oval or round nuclei and small nuclei. Underlying architecture rarely distorted. Cell adhesion protein E cadherin is lost which results in discohesion. Almost always expresses estrogen and progesterone receptors. Overexpression of Her2/neu is not observed. Indicator of high risk breast cancer of either breast, not necessarily the one found with L.C.I.S. Invasive Ductal Carcinoma, Not Otherwise Specified (NOS) Most are firm to hard - scarring around the tumor cells due to stromal reaction; most cancer induce this; not feeling the actual tumor. Scareous carcinoma - scar forming carcinoma. Tumor mass with irregular border-gritty. - Well differentiated have prominent tubule, small round nucleoli, and rare mitotic figures - Moderately differentiated may have tubules, but solid clusters or single infiltrating cells can be present. - Poorly differentiated often infiltrate as ragged nests or solid sheets of cells with enlarged nuclei. Invasive Lobular Carcinoma Bilateral and multicentric. Poorly circumscribed. Diffuse invasive pattern - single cell lineup; different look vs ductal cancer. Scarring. Loose clusters and sheets may also be seen. Loss of E-Cadherin. Metastasize to CSF, serosa, BM and solid organs. Features of Invasive Carcinomas Large tumors can extend into the skin (“peau d’orange” - skin of orange), ominous sign, clinical indication of involvement of dermal lymphatics, packed with cancer cells. Inflammatory carcinoma - Involvement of dermal lymphatics. Lymphatic Spread - axillary and internal mammary nodes. Distant metastases to virtually any site (lungs, bone, liver, adrenals, meninges are favored sites), after a very long time. BREAST CANCER GENETICS AND RECEPTORS Different locus, different allele, same phenotype BRCA1 and BRCA2 - hereditary breast and ovarian cancer. Mutations of RAS, MYC, PTEN (Cowden Syndrome), RB, p53 may be present. 95% breast cancer is not genetically linked. Molecular profiling of receptors help on selecting methods of treatment. BRCA1 60-80% risk of breast cancer by age 70. Risk of ovarian cancer - 20-40%. Chromosome 17q21. Tumor suppressor, transcriptional regulator, dsDNA repair. >500 mutations. Younger age 40-50s. Frequency of mutation - 0.1 to 0.2%. Male and female breast cancer - <20% Other associated cancers - prostate, colon, pancreas. BRCA2 60-80% risk of cancer Risk of ovarian cancer - 10-20% Chromosome 13q12.3 tumor suppressor, transcriptional regulator, DNA repair >300 mutations 50 years Frequency of mutation - 0.1 to 0.2% Higher association with male breast cancer. Other associated malignancies - prostate, pancreas, stomach, melanoma, colon. Estrogen and Progesterone Receptors 80% of double positives respond to hormone therapy, whereas only 40% of single positives respond. - E.R. positive alone cancers are less likely to respond to chemotherapy; may benefit from tamoxifen therapy. Double negative cancers are more likely to fail hormonal therapy but respond to chemotherapy. HER2/neu HER2 = Human Epidermal Growth Factor Receptor 2 Other names: neu, C-erb-B2 If have overexpression, can use herceptin. Clinical Staging of Breast Cancer Detailed history with an EMPHASIS on symptoms suggestive of metastatic disease. Physical examination - positive lymph nodes are the single most important prognostic factor. Laboratory studies (CBC, liver function tests). Imaging studies. Surgical Approaches Lumpectomy Mastectomy Lumpectomy Tumors less than 5cm (occasionally performed for larger tumors). Lobular or ductal histology. Negative margins need to be achieved. Usually cosmetically acceptable. Axillary nodes (if present) should be mobile. Mastectomy When lumpectomy is contraindicated or will result in poor cosmesis. Patients at high risk for local recurrence Prophylactic mastectomy for high risk patients with genetic predisposition.

Author neopho ID 325898 Card Set Systemic Pathology - Diseases of the Female Breast - Aisner/Fitzhugh Description Systemic Pathology - Diseases of the Female Breast - Aisner/Fitzhugh Updated 2016-11-24T17:33:59Z Show Answers