Breast Path Flashcards

Question

Epithelial hyperplasia of usual type

Answer 1

Duct lumina are almost completely filled with proliferating epithelium No cytologic atypia present

Answer 2

Atypical epithelial hyperplasia increases the risk by 4 - 5 times. Epithelial hyperplasia of usual type increase risk by 1.5 -2 times. Positive family history doubles these risks

Answer 3

Includes atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) ADH is found in ~17% of biopsies performed for calcifications (more commonly is adjacent to a calcified lesion) ADH also found in fewer biopsies performed for mammographic densities or palpable lesions ALH is an incidental finding in

Answer 4

Atypical hyperplasia is a cellular proliferation resembling ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) - They lack the definitive features for a diagnosis of CIS - ALH differs from LCIS in that the cells do not fill or distend >50% of the acini in a lobule * Extension into ducts s risk of invasive carcinoma

Answer 5

Nonproliferative changes DO NOT increase the risk of cancer Proliferative disease without atypia is associated with a mild increase in risk of cancer Proliferative disease with atypia (ADH and ALH) confer a moderate increase in risk LCIS and DCIS are associated with a substantial increase in risk if left untreated (we will talk about this next). Risk may be modified by a woman’s menopausal status, family history, and time since biopsy

Answer 6

The MOST COMMON MALIGNANCY OF THE BREAST Breast cancer is the most common non-skin malignancy in ♀s A ♀ who lives to age 90 has a 1 in 8 chance of developing breast cancer -Diagnosis is expected to rise over the next 20 years because of the aging of the population -Incidence of death exceeded only by lung cancer in ♀s

Answer 7

Mammographic screening has altered the incidence of diagnosis -Screening results in increased detection of small invasive carcinomas and in situ carcinomas -After screening started, the number of cases increased and after ~10 years of screening, the mortality rate began to decline Currently, only ~20% of ♀s with breast cancer are expected to die from it

Answer 8

``` Age : Breast cancer rarely occurs prior to age 25, except in certain familial cases Incidence rises over lifetime 75% of cases occur in ♀> 50 years old Average age of diagnosis is 64 Age of menarche : There is a 20% increased risk for ♀ who reached menarche 14 yo Late menopause also increases risk ```

Answer 9

First live birth -♀ with a first full-term pregnancy at 35 yo at their first birth First-degree relatives with breast cancer -The risk increases with the number of affected first-degree relatives (mother, sister, or daughter) -Most cancers occur in ♀s without such a history -Over 87% of ♀ with a family history will not develop breast cancer NOTE: This model is not designed to calculate risk for ♀ with a high likelihood for BRCA1 or BRCA2

Answer 10

Breast biopsies -Increased risk is associated with prior breast biopsies showing atypical hyperplasia (model does not adjust for mild increase associated with proliferative breast changes without atypia) Race -Socioeconomic factors such as access to health care -Genetic factors -At age 50, the risk of developing breast cancer within the next 20 years is 1 in 15 for Caucasians, 1 in 20 for African-Americans, 1 in 26 for Asians/Pacific Islanders, and 1 in 27 for Hispanics -Overall incidence is lower in African-American women *However, more A-A ♀s

Answer 11

``` These have not been incorporated into the model owing to their rarity, difficulties in quantifying risk, or lack of definitive studies: Estrogen exposure Radiation exposure Carcinoma of the contralateral breast or endometrium Geographic influence Diet, obesity Exercise Breast-feeding Environmental toxins Tobacco ```

Answer 12

With the exception of DCIS, all other risk factors for the development of invasive breast cancer affect both breasts equally Bilateral prophylactic mastectomy can prevent development of 89% of breast cancers in ♀ who are at moderate risk owing to family history Chemoprevention is another option for ♀s who are at risk of developing invasive breast cancer -Tamoxifen is a drug that competes for binding to the estrogen receptor (ER) and has both estrogenic and antiestrogenic effects (Most widely used endocrine therapy for breast cancer). -In selected groups of ♀s, it has been shown to reduce the incidence of breast cancer Aromatase inhibitors stop the production of estrogen in post-menopausal women

Answer 13

The major risk factors for breast cancer are hormonal and genetic Hereditary breast cancer -A family history (1st degree relatives) is reported in ~13% of ♀s with breast cancer -Only 1% of ♀s have >1 affected relative which suggests a highly penetrant germline mutation -~25% of familial cancers (~3% of all breast cancers) can be attributed to 2 highly penetrant autosomal dominant genes: BRCA1 and BRCA2

Answer 14

The probablility of breast cancer associated with a mutation in these genes increases if there are multiple affected 1st degree relatives, if individuals are affected before menopause and/or have multiple cancers, if there is a case of male breast cancer, or if family members also develop ovarian cancer The general lifetime risk for ♀ carriers is 60-85% The penetrance varies with the type of mutation -BRCA1 also increases the risk for ovarian cancer (20-40%) -BRCA2 also inc risk of ovarian cancer (10-20%) but is more frequently associated with ♂ breast cancer -Also inc risk for other cancers

Answer 15

Both genes act as tumor suppressors and loss of function confers risk of malignancy BRCA1-associated tumors are more commonly poorly differentiated, do not express hormone receptors or overexpress HER2/neu (an epidermal growth factor receptor that is commonly overexpressed in breast cancer) Many other genes are also involved (e.g., p53, CHEK2) Many studies have confirmed that some of the genes (BRCA1 and p53) involved in hereditary breast cancer are also involved in sporadic cases

Answer 16

The major risk factors are related to hormone exposure: Gender Age at menarche and menopause Reproductive history Breast-feeding Exogenous estrogen -The majority of the cancers occur in postmenopausal ♀s and overexpress ER -Estrogen metabolites cause mutations or generate DNA-damaging free radicals

Answer 17

Almost all breast malignancies are ADENOCARCINOMAS | -All other types (i.e., squamous cell carcinomas, phyllodes tumors, sarcomas and lymphomas) are

Answer 18

Invasive carcinoma (synonymous with “infiltrating” carcinoma) has invaded beyond the basement membrane into the stroma -Cells might also invade into the vasculature and then the lymph nodes and distant sites -Even the smallest invasive carcinomas have some capacity to metastasize All carcinomas are thought to arise from the terminal duct lobular unit -The terms “ductal” and “lobular” do not imply a site or cell type of origin, but reflect differences in tumor cell biology, e.g., whether tumor cells express the cell adhesion protein E-cadherin or not -“Lobular” refers to carcinomas of a specific type; “ductal” to adenocarcinomas that have no other designation

Answer 19

The # of cases has risen sharply secondary to mammographic screening (15-30% of carcinomas) Among mammographically detected cancers, ~½ are DCIS Most commonly presents as mammographic calcifications -20-30% of calcifications will be associated with DCIS and must be biopsied Consists of a limited population of cells limited to ducts and lobules by the basement membrane -It is a clonal proliferation and usually involves only a single ductule -However, the cells can spread throughout ducts and lobules and produce extensive lesions involving an entire sector of the breast

Answer 20

Comedocarcinoma is characterized by solid sheets of pleomorphic cells with high grade nuclei and central necrosis Noncomedocarcinoma consists of a monomorphic population of cells with nuclear grades ranging from low to high (includes solid, cribriform, papillary, and micropapillary) Paget disease

Answer 21

The majority of cases of DCIS cannot be detected by either palpation or visual inspection of the breast Mastectomy is curative in >95% of cases Breast conservation is appropriate for most ♀s but results in a slightly higher risk of occurrence Major risk factors are grade, size, and margins

Answer 22

Always an incidental finding in a biopsy performed for another reason -LCIS is not associated with calcifications or a stromal reaction that would form a density Remains infrequent (1-6%) with or without mammographic screening Is bilateral in 20-40% of ♀s when both breasts are biopsied (compared to 10-20% for DCIS) More common in young ♀s (80-90% of cases prior to menopause) Almost always express estrogen and progesterone receptors Treatment consists of bilateral mastectomy, tamoxifen, or close clinical observation

Answer 23

In young ♀s or older ♀s not undergoing mammographic screenings, almost always presents as a palpable mass -By the time it becomes palpable, > 50% of patients will have axillary lymph node metastasis *May have lymphedema and skin changes called peau d’orange (looks like an orange peel) -If central portion of breast involved, may have nipple retraction -In older ♀s, presents as a density on mammography, and, on average, are ½ the size of a palpable cancer *

Answer 24

These include the majority of carcinomas (70-80%) that cannot be classified as any other type Recently developed techniques that examine the DNA, RNA, and proteins of carcinomas globally have provided a framework for new molecular classifications of this group of breast cancers Gene expression profiling, which can measure the relative quantities of mRNA for essentially every gene, has identified five major patterns of gene expression in the NST group: luminal A, luminal B, normal, basal-like, and HER2 positive -These molecular classes correlate with prognosis and response to therapy, and thus have taken on clinical importance

Answer 25

Commonest form of breast cancer especially in poorer populations higher sing incidence of screen- detected cancer in developed countries (usually smaller; much better prognosis) Hard, irregular palpable lump Peau d’orange (lymphatic obstruction thickening/dimpling of the skin) Paget’s disease of the nipple (ulceration/inflammation due to intraductal spread to the nipple) Tethering of the skin Retraction of the nipple Axillary mass (spread to regional lymph nodes) Distant metastasis (lung, brain, bone)

Answer 26

This is the largest group and consists of cancers that are ER positive and HER2/neu negative The majority are well- or moderately differentiated, and most occur in postmenopausal women These cancers are generally slow growing and respond well to hormonal treatments Conversely, only a small number will respond to standard chemotherapy

Answer 27

This group of cancers also expresses ER but is generally of higher grade, has a higher proliferative rate, and often overexpresses HER2/neu, and also expresses PR (progesterone receptor) They are sometimes referred to as “triple-positive cancers”, i.e., expess ER, Her2/neu, and PR They compose a major group of ER-positive cancers that are more likely to have lymph node metastases and that may respond to chemotherapy

Answer 28

This is a small group of usually well-differentiated ER-positive, HER2/neu-negative cancers characterized by the similarity of their gene expression pattern to normal tissue It is not yet clear whether or not this is a specific tumor expression pattern

Answer 29

These cancers are notable for the absence of ER, PR, and HER2/neu but the expression of markers typical of myoepithelial cells By strict definition this group is defined by their gene expression profile -Basal-like cancers are a subgroup of ER-PR-HER2/neu “triple-negative” carcinomas They are associated with an aggressive course, frequent metastasis to viscera and the brain, and a poor prognosis

Answer 30

This group comprises ER-negative carcinomas that overexpress HER2/neu protein These cancers are usually poorly differentiated, have a high proliferation rate, and are associated with a high frequency of brain metastasis

Answer 31

1 . Small nests and cords of neoplastic cells 2.Dense collagenous stroma in between cells ``` Much less common than IDC Can present with similar features More likely to be bilateral and/or multicentric (multiple lesions within the same breast) ``` 1. Indian file strands of neoplastic cells 2. Cells are small and uniform 3. Dense stroma

Answer 32

Usually present like carcinomas of NST as a palpable mass or a mammographic density Reported to have a greater incidence of bilaterality Demonstrate different metastatic patterns than other breast cancers: -Metastasize to peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries and uterus vs. lungs and pleura

Answer 33

Presents as a well circumscribed mass and may be mistaken clinically and radiogically as a fibroadenoma There can be a history of rapid explosive growth

Answer 34

Favorable histologic types (85% 5-year survival rate) -Tubular carcinoma (grade 1 intraductal), colloid or mucinous carcinoma, and papillary carcinoma Less favorable types -Medullary , invasive lobular, and invasive ductal carcinoma Least favorable type -Inflammatory breast carcinoma Staging, prognosis, and treatment

Answer 35

Tubular carcinoma - 2% of all invasive breast cancers - Generally diagnosed by mammography - Distinctive under microscope - Long-term survival aproaches 100% Mucinous (colloid) carcinoma - 3% of all invasive breast cancers - Generally confined to elderly population - Bulky, mucinous tumor with characteristic microscopic features - 5 and 10 year survival rates are 73 and 59 percent, respectively Papillary carcinoma -

Answer 36

Medullary carcinoma - 4% of all invasive breast cancers - Soft, hemorrhagic bulky presentation - Diagnosed microscopically (lymphocytic infiltration) - Metastases to axillary nodes in 44% - 5 and 10 year survival rates are 63 and 50 percent respectively Invasive ductal carcinoma - Most common and occurs in 78% of all invasive breast cancers. - Metastases to axillary nodes in 60% - 5 and 10 year survival rates are 54 and 38 percent respectively Invasive lobular carcinoma - 9% of all invasive breast cancers - Metastases to axillary nodes in 60% - 5 and 10 year survival rates are 50 and 32 percent respectively - Higher incidence of bilaterality

Answer 37

1. Abundant bluish staining mucin with small groups of carcinoma cells

Answer 38

The outcome varies widely Some ♀s have a normal life expectancy as those without any breast cancer Other have only a 13% chance of 5 year survival Prognosis is determined by the pathologic examination of the primary carcinoma and the axillary lymph nodes -Important for counseling patients, choosing treatment, and classifying similar patients for clinical trials

Answer 39

Breast cancer spreads through lymphatic channels to axillary lymph nodes. When axillary content is removed, all nodes are searched and embedded for microscopy

Answer 40

Invasive carcinoma vs in situ disease -By definition, in situ cannot metastasize Distant metastases - Once present, cure is unlikely, although long-term remissions and palliations can be achieved (especially for hormone responsive tumors) - Favored sites: lungs, bone, liver, adrenals, brain, and meninges

Answer 41

Local -skin, nipple , chest wall Lymphatic- lymph nodes Blood – lungs, liver, bones

Answer 42

AXILLARY LYMPH NODE STATUS IS THE MOST IMPORTANT PROGNOSTIC FACTOR FOR INVASIVE CARCINOMA (in the absence of distant metastases) Biopsy is necessary for accurate assessment With no involvement, the 10 year, disease-free survival rate is 70-80% Rate falls to 35-40% with 1-3 + nodes, and 10-15% with >10

Answer 43

Tumor size - The second most important prognostic factor - ♀s with node-negative carcinomas

Answer 44

Can be used to determine treatment regimens for ♀s with nodal invovlement and/or carcinomas >1 cm in diameter and node-free women with small carcinomas Three of these factors (estrogen receptor, progesterone receptor, and HER2/neu) are most useful as predictive factors for response to specific therapeutic agents Histologic subtypes -The 30-year survival rate of ♀s with special types of invasive carcinomas (tubular, mucinous, medullary, lobular, and papillary) is > 60% -Survival rate for NST cancers is

Answer 45

Assays use immunohistochemistry to detect receptors in the nucleus 50-85% of tumors express estrogen receptors (more commonly seen in post menopausal ♀s) -Receptor positivity yields a slightly better prognosis 80% of tumors with both ERs and PRs respond to hormonal stimulation with hormonal therapy such as tamoxifen (only ~40% of tumors with one receptor respond) Tumors with neither receptor have a

Answer 46

Human epidermal growth factor receptor or c-erb B2 or neu is a transmembrane glycoprotein involved in cell growth control Acts as a cofactor for multiple growth factors Overexpressed in 20-30% of breast carcinomas -In many studies, shown to be associated with a poor prognosis Trastuzumab (Herceptin) is a humanized monoclonal Ab developed specifically to target tumor cells and spare normal cells

Answer 47

Proliferative rate -Proliferation can be measured by a variety of means -Most reliable method to assess proliferation not yet established -High proliferation rates yield a worse prognosis DNA content -Tumors with a DNA index of 1 have a normal amount of DNA but with karyotypic changes -Aneuploid tumors have abnormal DNA indices and a slightly worse prognosis

Answer 48

The breast-specific tumors fibroadenoma and phyllodes tumor arise in the intralobular stroma -This stroma may elaborate growth factors for epithelial cells resulting in the non-neoplastic components of these tumors -Interlobular stroma is also the source of the same types of tumors found in connective tissue in other sites of the body (e.g., lipomas and angiosarcomas)

Answer 49

The MOST COMMON BENIGN TUMOR OF THE FEMALE BREAST Occurring at any age within the reproductive period of life Frequently multiple and bilateral Young ♀s present with a palpable mass and older ♀s with a mammographic density or calcifications The epithelium is hormonally responsive and may  in size during the late phase of the menstrual cycle -inc in size during lactation or infarction leading to inflammation may lead a fibroadenoma to mimic a carcinoma Grow as spherical nodules , usually sharply circumscribed, and freely movable in the surrounding breast substance

Answer 50

The term “cystosarcoma” phyllodes is sometimes used -The majority of these tumors behave in benign fashion and most are not cystic Can occur at any age, but most present in the 6th decade Most present as palpable masses but a few are detected mammographically Must be excised widely or with mastectomy to avoid recurrence Majority are low-grade tumors that recur locally but rarely metastasize

Answer 51

May arise from skin of the breast, sweat glands, sebaceous glands and hair shafts Tumors of the extrinsic connective tissue of the breast include the same types of benign and malignant tumors found elsewhere in the body -Malignant lesions include angiosarcoma, rhabdosarcoma, liposarcoma, leiomyosarcoma, chondrosarcoma, and osteosarcoma Lymphomas may arise in the breast or be secondarily involved Metastases usually arise from contralateral breast tumors -Most frequent nonmammary metastases are from LUNG AND MELANOMAS

Answer 52

Defined as enlargement of the male breast -Presents as a buttonlike subareolar enlargement May be unilateral or bilateral Must be differentiated from the RARE carcinoma Chiefly of importance as an indicator of hepatic cirrhosis (liver metabolizes estrogen) or a functioning testicular cancer (Leydig cell tumors or, rarely, Sertoli cell tumors)

Answer 53

The male breast is subject to hormonal influences -Gynecomastia may occur as a result of an imbalance between estrogens (which stimulate breast tissue) and androgens (which counteract these effects) It is encountered in a variety of normal and abnormal circumstances -May be found at the time of puberty, in the very aged, or at any time in adult life when there is cause for hyperestrinism *Most important is cirrhosis (liver metabolizes estrogen) *In older males, may occur owing to a relative  in adrenal estrogens as the androgenic function of the testes fails

Answer 54

Drugs -Alcohol, marijuana, heroin, antiretroviral therapy, anabolic steroids, some psychoactive agents Rarely, may occur in association with Klinefelter syndrome Presence of functioning testicular cancers (Leydig cell tumors or, rarely, Sertoli cell tumors)

Answer 55

A RARE occurrence in the male breast | Frequency ratio relative to female breast cancer is

Answer 56

Gynecomastia does not seem to be a risk factor 4-14% of cases in males are attributed to germline BRCA2 mutations -A breast cancer family with at least 1 affected male has a 60-76% chance of having a BRCA2 mutation -Male breast cancer is less commonly observed in BRCA1 families 3-8% of cases are associated with Klinefelter syndrome

Answer 57

Remarkably similar to that of ♀s The same histologic subtypes of invasive cancer are present -Although papillary carcinomas are more common and lobular carcinomas less common The expression of molecular markers is similar except that ER positivity is more common (81%of male tumors) Unlike ♀s, incidence of ER-positive tumors does not  with age Prognostic factors are similar

Answer 58

Usually present as a palpable subareolar mass (2-3 cm) Nipple discharge is common Because they are situated close to the overlying skin and chest wall, even small carcinomas can invade these structures Ulceration through skin more common in males Dissemination pattern is similar to that of females -Distant metastases to lung, brain, bone, and liver common

Answer 59

More than 90% of all breast lumps are discovered by women themselves. The majority of all breast lumps are benign. About one women in eight (12%) will develop breast cancer sometime in her life. 90% of women with breast cancer have no family history

Answer 60

It is important to evaluate breast complaints thoroughly to ensure that breast cancers, as well as benign breast lesions, are diagnosed and treated promptly. Evaluation of a woman presenting with a breast complaints requires careful assessment of symptoms and risk factors for developing breast cancer. The clinical breast exam include inspection and palpation of the breast tissue, chest wall, and regional lymph nodes. Documentation should included both positive and negative findings. Women with breast problems can present with any combination of symptoms including breast mass or thickening, breast pain, nipple discharge, or skin changes. Typically, women presenting with a suspicious breast mass who are > 30 yrs should receive a diagnostic mammogram, whereas women younger than 30 should receive a diagnostic ultrasound. Negative imaging should not stop further investigation is a suspicious lump is felt on clinical exam. Masses that are solid on ultrasound imaging require biopsy to exclude cancer and provide a histological diagnosis.

Breast Path Flashcards

(84 cards)