breast cancer pathology

Question 1

how has breast cancer rates changed over time

Answer 1

It has decreased in the last 20 years

Question 2

breast cancer risk factors

Answer 2

Familial: BRCA1/BRCA2, Li Fraumeni syndrome (p53 mutation), Cowden syndrome (PTEN mutation), Peutz-Jeghers syndrome (STK11/LKB1 mutation). Sporadic: increasing age, young age at menarche, late menopause, hormonal, post-menopausal women, ionizing radiation, family history. Having a child earlier in life is protective

Question 3

Functions of BRCA1 and 2, and cancers associated with them

Answer 3

•Both are tumor suppressor genes which facilitate DNA damage repair (loss of function progresses to cancer). BRCA1: breast cancer, ovarian cancer. BRCA2: breast cancer (males too), ovarian cancer

Question 4

most common metastases to breast and who gets metastatic breast cancer

Answer 4

hematoogic, melanoma, lung, ovarian, kidney, prostate, stomach. • Curiously, in persons <20 yrs old metastatic lesions are more common than primary malignant lesions, but this is a very small subset of patients

Question 5

Carcinoma in-situ

Answer 5

A general concept in neoplastic pathology where neoplastic epithelial cells grow within the confines of the basement membrane. The tumor has not yet become invasive

Question 6

ductal carcinoma in situ histology

Answer 6

Clonal proliferation of epithelial cells within the ducts leaving the myoepithelial layer and basement membrane intact. Five classic histologic patterns include comedo (central necrosis), solid, cribriform (punched-out holes), papillary (large projections into the lumen) and micropapillary (small projections into the lumen)

Question 7

DCIS presentation

Answer 7

calcifications seen on mammography. Generally asymptomatic and nonpalpable

Question 8

DCIS grade

Answer 8

Comedo pattern contains central necrosis and is always high grade, other types range from low to high grade. 6. Low grades often express hormonal receptors (estrogen and progesterone), high grades often overexpress Her2/neu.

Question 9

DCIS progression and risk of recurrence

Answer 9

DCIS is associated with a significant risk of developing invasive carcinoma. Risk factors for recurrence of DCIS include (1) histologic grade, (2) extent of breast involvement (size of DCIS), (3) if the DCIS is completely excised (if the margins are negative for DCIS)

Question 10

DCIS treatment

Answer 10

Surgical excision (+/- other therapies) is curative in the vast majority of cases of tumors consisting purely of DCIS

Question 11

Pagets disease

Answer 11

Neoplastic DCIS cells grow from the ducts onto the adjacent skin without invading through the basement membrane of the ducts or skin. Clinically presents as a scaly rash on the nipple. Many have associated invasive carcinoma including 1/3 who present without an associated mass and >9/10 of those with a mass. Prognosis depends on the presence of underlying carcinoma

Question 12

Pagets histology

Answer 12

Paget cells= large cells in epidermis with clear halo

Question 13

Lobular carcinoma in situ (LCIS)

Answer 13

1. “Classic” LCIS always an incidental finding, does not form masses or calcifications. 2. Often multicentric and bilateral. 3. Patients are at a significantly increased risk for development of invasive carcinoma in both breasts (compared with DCIS were the higher risk is predominantly in the ipsalateral breast)

Question 14

LCIS histology

Answer 14

small, uniform cells with round nuclei filling the lobules and poorly adhering to adjacent cells. 5. Some recognize a “pleomorphic” variant of LCIS that behaves more aggressively and some advocate treating these similar to DCIS

Question 15

LCIS genetic alterations

Answer 15

The cells adhere to each other poorly because they have lost the function of important cell-cell adhesion molecules, chiefly e-cadherin.

Question 16

Types of atypical hyperplasia

Answer 16

Technically not yet a carcinoma, but has some histologic features of in situ carcinoma. Can resemble DCIS, termed atypical ductal hyperplasia (ADH). Can resemble LCIS, termed atypical lobular hyperplasia (ALH). Both have increased risk of invasive carcinoma

Question 17

Invasive carcinoma presentation

Answer 17

Commonly present as a palpable mass or as a mammographic abnormality. Uncommon presentations include an enlarged erythematous breast (termed “inflammatory carcinoma”) or as metastatic disease (typically an axillary lymph node). Advanced lesions fix the mass to the underlying chest wall and cause dimpling of the overlying skin.

Question 18

Where does invasive carcinoma usually occur

Answer 18

Carcinoma most commonly occurs in the upper outer quadrant; these tumors spread first to axillary lymph nodes. When tumors occur in the inner quadrant they preferentially spread to the internal mammary lymph nodes

Question 19

What causes inflammatory carcinoma

Answer 19

Diffuse involvement of dermal lymphatics (carries a poor prognosis)

Question 20

invasive ductal carcinoma histology

Answer 20

Well-differentiated tumors contain well formed ducts with relatively bland appearing cells infiltrating a dense fibrous stroma. Poorly-differentiated tumors have either poorly formed ducts or no duct formation in which case they are composed of irregular groupings of markedly atypical appearing cells. Sheets, nests, cords or individual cells. DCIS alos occurs in up to 80%.

Question 21

gene/ hormone expression in well vs poorly differentiated invasive ductal carcinoma

Answer 21

Well differentiated: Express hormone receptors (E and P). Poorly differentiated: less hormone receptors, tend to overexpress epidermal growth factor receptor HER2/neu

Question 22

Invasive ductal carcinoma presentation

Answer 22

firm, fibrous, rock hard mass with sharp margins.

Question 23

Invasive ductal carcinoma subgroups

Answer 23

a. Luminal A: Largest group. ER positive, HER2 negative. b. Luminal B: ER positive, HER2 positive. c. Normal breast-like: ER positive, HER2 negative just like “luminal A,” but their gene expression more closely resembles normal breast tissue. d. Basal like: ER and HER2 negative. Gene expression profile does not resemble epithelial cells, but more closely resembles myoepithelial cells and stem cells. e. HER2 positive: ER negative, HER2 positive.

Question 24

Invasive lobular carcinoma

Answer 24

second most common. Lost function of e-cadherin. Similar appearance as LCIS. individual tumor cells, sometimes in single file rows, infiltrating the stroma.

Question 25

Invasive lobular carcinoma receptors/ genes

Answer 25

1. Generally express hormone receptors and negative for HER2/neu overexpression

Question 26

metastasis of lobular and ductal invasive carcinomas

Answer 26

1. ILC tends to metastasize more frequently to CSF, G.I. tract, ovaries/uterus and peritoneum and less frequently to the lungs and pleura than ductal carcinomas

Question 27

invasive lobular carcinoma histology

Answer 27

•Tumor cells are small, uniform, round with minimal pleomorphism, evenly disbursed chromatin and no nucleoli (nuclear grade 1, like LCIS cells). Cells grow in single file (linear, single file). Cells grow in targetoid pattern of noncohesive cells encircling ducts. Cells loosely dispersed throughout fibrous matrix

Question 28

Tubular carcinoma presentation and prognosis

Answer 28

5th decade. Good prognosis

Question 29

Tbular carcinoma histology

Answer 29

Very well differentiated tumor composed of well-formed tubules and relatively bland appearing cells. Irregular angulated contours of glands. Open lumina with apocrine-like snouts and basophilic secretions
Columnar cell lesions in almost all cases with flat epithelial atypia . Desmoplastic stroma. invades fat. no basement membrane. no mitotic figures, necrosis.Very well differentiated tumor composed of well-formed tubules and relatively bland appearing cells. Irregular angulated contours of glands. Open lumina with apocrine-like snouts and basophilic secretions
Columnar cell lesions in almost all cases with flat epithelial atypia . Desmoplastic stroma. invades fat. no basement membrane. no mitotic figures, necrosis.Very well differentiated tumor composed of well-formed tubules and relatively bland appearing cells. Irregular angulated contours of glands. Open lumina with apocrine-like snouts and basophilic secretions
Columnar cell lesions in almost all cases with flat epithelial atypia . Desmoplastic stroma. invades fat. no basement membrane. no mitotic figures, necrosis.

Question 30

Tubular carcinoma hormones/ receptors

Answer 30

Almost all express hormone receptors and usually do not demonstrate HER2/neu overexpression

Question 31

Cribriform carcinoma

Answer 31

Subtype of tubular carcinoma that forms cribriform spaces in additional to well-formed tubules

Question 32

Tubular carcinoma is associated with…

Answer 32

low grade DCIS (micropapillary or cribriform)

Question 33

mucinous carcinoma presentation, histology, receptors/ genes

Answer 33

1. Often presents as a well-circumscribed mass (mimicking a benign lesion) in relatively older age groups 2. Has a striking histologic appearance with small islands of tumor cells floating in pale-blue lakes of mucin. 3. Tumors usually express hormone receptors 4. More frequent in patients with BRCA1 mutation

Question 34

Medullary carcinoma

Answer 34

Well circumscribed mass. Negative for horomone receptors and Her2/Neu. More frequent in patients with BRCA1 mutation

Question 35

Medullary carcinoma histology

Answer 35

(1) indistinct cell borders (aka syncytial growth) at least 75% of tumor with large pleomorphic tumor cells containing large nuclei, prominent nucleoli, numerous mitotic figures (2) Prominent lymphoplasmacytic infiltrate at periphery (T-cells and IgA plasma cells) (3) Pushing borders / well circumscribed. (4) sparse stroma, giant cells, necrosis.

Question 36

Metaplastic carcinoma

Answer 36

•Any carcinoma with nonglandular growth (ie not properties typically by epithelial or myoepithelial cells). squamous, spindle cell or heterologous (pseudosarcomatous) differentiation. arise in association with poorly differentiated ductal carcinoma more often than other types.

Question 37

Metaplastic carcinoma histology

Answer 37

Divided into squamous and pseudosarcomatous. Most typical histology is focal squamous metaplasia in an otherwise typical invasive ductal carcinoma
Divided into squamous and pseudosarcomatous. Most typical histology is focal squamous metaplasia in an otherwise typical invasive ductal carcinoma

Question 38

Spindle cell carcinoma

Answer 38

subgroup of metaplastic squamous cell carcinoma with mostly (or entirely) spindled morphology

Question 39

Sarcomas

Answer 39

May arise in most organ systems (angiosarcoma, rhabdomyosarcoma, liposarcoma, etc.). 3. Tumors derived from blood vessels, angiosarcoma and lymphangiosarcoma, are among the most common primary breast sarcomas. These can arise (1) spontaneously, (2) following radiation therapy and (3) in the setting of chronic edema (Stewart-Treves syndrome)

Question 40

Breast lymphoma

Answer 40

May occur as primary breast lesions or disseminated disease may secondarily involve the breast. Most commonly patients present with a palpable mass or masses. Of primary lesions, non-Hodgkin lymphomas (NHLs) are the most frequent, of these, Diffuse large B-cell lymphomas are the most common

Question 41

Mixed (Biphasic) of the breast

Answer 41

1. This category includes fibroadenoma (benign) and phyllodes tumors, both are composed of stromal and epithelial components and both arise from the stroma immediately surrounding the breast lobules (intralobular stroma)

Question 42

Phyllodes tumor

Answer 42

1. stromal growths covered by epithelium often forming a leaf-like appearance (“phyllo” Greek for “leaf”). Do not typically metastasize. Only the stromal part is prone to mets. Large blky mass.

Question 43

Fibroadenoma

Answer 43

cellular myxoid stroma encircling glandular/cystic spaces. Small firm mass with sharp edges.

Question 44

Phyllodes tumor vs fibroadenoma

Answer 44

Phyllodes tumors differ from fibroadenomas by: mitotic rate, overgrowth of hypercellular stromal component, infiltrative boarders

Question 45

breast cancer prognostic factors

Answer 45

Primary breast lesion characteristics (size, invasion, inflammatory carcinoma, invading skin or skeletal muscle), Regional lymph node involvement, Examination for metastatic disease

Question 46

Breast cancer staging

Answer 46

For breast carcinoma: T: Tumor size and local growth characteristics. N: Extent of lymph node involvement. M: Presence of distant metastasis

Question 47

Hormone receptor prognosis

Answer 47

Expression of estrogen and progesterone receptors portends a better prognosis. Also more likely to respond to hormonally based therapy. HER2/neu overexpression is associated with poor prognosis.

Question 48

Which carcinomas have better vs worse prognosis

Answer 48

1.Tubular, mucinous and medullary carcinoma all have better prognosis than invasive ductal carcinoma.

Question 49

compare male breast cancer to females

Answer 49

similar risk factors, BRCA2 mutations increase risk for males. Association with Klinefelters syndrome. Most often present to the clinician as a subareolar palpable mass . Same histologic types. More often involve the chest wall and skin than female cancers. Expression of estrogen receptors is more common. Men often present at higher stage but prognosis is similar to women

Question 50

breast carcinoma pathogenesis

Answer 50

Site of origin is the terminal duct lobular unit. epithelial cells progress from proliferative disease to atypical hyperplasia to carcinoma in-situ to invasive carcinoma by accumulating genetic changes.