Breast Path (Bashir)

Question 1

Most breast pathology arises in the ____, the area of the breast that’s composed of a terminal duct branching into a grapelike cluster of acini

Answer 1

lobule

Question 2

Which of the following statements is FALSE?

A. The older the patient is, the more fat, and the easier it is to identify lesions on mammography

B. Ducts and acini are lined by two cell types, inner luminal epithelial cells that produce milk during lactation and outer myoepithelial cells that contract to eject it

C. Most patients that present with symptoms of breast pathology will not have cancer.

D. The most common way that patients present with breast cancer is with a palpable mass

E. Microcalcifications are an abnormal mammogram finding and may indicate the presence of tumor cells or necrotic debris

Answer 2

D. The most common presentation is an abnormal mammogram.

Question 3

What are 3 abnormal findings in the slide shown below?

Answer 3

1. tumor cells lining the duct (>2 cell layers thick)
2. necrosis present in the lumen
3. dark purple = microcalcification in the duct lumen

Question 4

this mimics breast carcinoma, usually presenting as an abnormal mammographic finding or palpable mass, and often follows a recent history of trauma or surgery

Answer 4

fat necrosis; characterized acutely by necrotic adipocytes with hemorrhage and inflammation and over time will be mixed with foamy macrophages

Question 5

Infection during breastfeeding causing erythema, pain, and fever
caused by fissures and cracks in the nipple that provide entry for S. aureus or Streptococci

Answer 5

acute mastitis

Question 6

painful, erythematous subareolar mass in smokers, in which nipple ducts undergo squamous metaplasia and keratin obstructs the ductal system leading to dilatation and rupture

Answer 6

Squamous metaplasia of lactiferous ducts
(AKA Recurrent subareolar abscess)
(AKA periductal mastitis)

*treatment is duct excision and antibiotics

Question 7

non-neoplastic enlargement of the male breast that is often painful, and is caused by an imbalance of hormones

Answer 7

gynecomastia

Question 8

most common benign breast tumor that is well-circumscribed, slow-growing and mobile, and affects women age 20-40

Answer 8

fibroadenoma

*note the stromal and epithelial proliferation (below)

Question 9

All of the following are findings associated with fibrocystic change EXCEPT:

A. Increased fibrosis in the breast parenchyma

B. Cyst formation

C. Apocrine metaplasia
D. Increased number of acini per lobule (adenosis)

E. Increased risk of developing breast carcinoma

Answer 9

E. Fibrocystic change is very common (60-80% of women) and carries no increased risk for development of carcinoma.

Question 10

Which of the following statements regarding proliferative breast disease without atypia is FALSE?

A. Variety of benign lesions that are generally well-circumscribed, but carry a slightly increased risk of invasive breast carcinoma (1.5-2X)

B. Intraductal papilloma often present with blood nipple discharge

C. ductal epithelial hyperplasia shows cytologic and architectural heterogeneity but growth is limited to 2 cell layers

D. the key histologic finding of complex sclerosing lesion/radial scar is a central core of fibroelastic stroma containing trapped glands

E. With sclerosing adneosis, the breast tissue maintains its lobular architecture

Answer 10

C. Ductal epithelial hyperplasia is characterized by growth of >2 cell layers

note: fat necrosis, sclerosing adenosis and complex sclerosing lesion/radial scar ALL mimic breast carcinoma

Question 11

Which of the following statements regarding proliferative breast disease WITH atypia is FALSE?

A. These patients are at a significant increased risk of developing breast carcinmoa (4-5x)

B. Proliferation of atypical cells shows total loss of homogeneity

C. Atypical ductal hyperplasia is most often found in biopsies done for suspicious microcalcifications in a mammogram screening

D. Atpical ductal hyperplasia differs from low grade ductal carcinoma in situ only quantitatively, in terms of the number of ducts involved

E. Atypical lobular hyperplasia is similar to lobular carcinoma in situ but fills <50% of the lobe, with loss of the e-cadherin molecule leading to poorly cohesive cells filling and expanding the acini

Answer 11

B. The opposite is true - proliferative breast disease WITH atypia is characterized by a proliferation of cells that look quite regular and organized

atypical ductal hyperplasia: solid and sheet like with cells that do not overlap making regular looking “punched out” spaces (see below)

Question 12

Which of the following statements regarding breast carcinoma is FALSE?

A. Most breast carcinomas are HER-2 positive

B. Breast cancer affects 1 in 8 women, mostly over 40

C. White women have highest incidence of breast cancer but African-American and Hispanic women have highest mortality

D. BRCA1 and BRCA2 are both autosomal dominant mutations, which carry a 65% and 45% chance of developing breast cancer, resepctively

E. High consumption of red meat is a risk factor for breast cancer

Answer 12

A. Most are HER-2 negative.

Question 13

A 33 year old woman presents with a discrete breast mass that is freely mobile. The MOST LIKELY diagnosis is:

A. Atypical ductal hyperplasia

B. Fibroadenoma

C. Intraductal papilloma

D. Abscess

Answer 13

B

Question 14

All of the following are true regarding fibrocystic change EXCEPT:

A. These women have an increased risk of developing breast cancer

B. Physical examination reveals lumpy breast tissue

C. Adenosis is seen microscopically

D. It is very common

Answer 14

A

Question 15

Which of the following statements about breast carcinoma is FALSE:

A. Mortality from breast cancer is declining

B. Physical examination may reveal a palpable mass

C. Mammographic screening is best used in women greater than 40 years of age

D. BRCA1 and 2 mutations account for 30% of breast carcinomas

Answer 15

D. Hereditary breast cancer accounts for ~12%

Question 16

What is a histologic feature of ductal hyperplasia without atypia?

A. Monotonous cells

B. Ductal cells polarized around punched out lumina

C. Ductal cells that vary in size and shape and placement

D. Regular placement of cells

Answer 16

C

Question 17

Which of the following statements regarding the development of breast cancer is FALSE?

A. The ER positive pathway is the most common pathway for the development of breast cancer

B. ER positive tumors are generally low grade “luminal” tumors

C. Histopathology of ER negative pathways for the development of breast cancer begin with flat epithelial atypia that progresses to atypical ductal hyperplasia and DCIS

D. BRCA1 mutations are included in ER negative pathways, while BRCA2 are see in ER positive pathways

E. Germline p53 mutations are seen in both ER negative and HER2 positive pathways

Answer 17

C. This is the progression seen in the ER positive pathway.

*she mentioned this was an important slide (#4 on breast path II)

Question 18

Proliferation of neoplastic epithelial cells that have not invaded beyond the basement membrane of the ductal-lobular system

Answer 18

carcinoma in situ; does not necessarily progress to invasive carcinoma but carries a 25-30% lifetime risk;

Question 19

____ disease is characterized by the spread of neoplastic cells from the ductal system into the skin of the nipple and areola, producing itchy, red, crusted, weeping lesions

Answer 19

paget disease; >95% of paget disease cases have underlying carcinoma

Question 20

grade of DCIS that shows histology very similar to atypical ductal hyperplasia, but with more extensive ductal involvement; note the monotonous regularly spaced small nuclei, inconspicuous nucleoli and rare mitoses and NO intraluminal necrosis

Answer 20

low grade DCIS

Question 21

grade of DCIS in which nuclei show marked variation in size, shape, and placement, prominent nucleoli and often abundant mitoses, and necrosis often present (AKA comedo type)

Answer 21

high grade DCIS

Question 22

grade of DCIS that shows nuclei with mild to moderate variation in size, shape, and placement, variably prominent nucleoli, mitoses and intraluminal necrosis may be present (below)

Answer 22

intermediate grade DCIS

Question 23

All of the following are true regarding the natural history and treatment of DCIS except:

A. First line treatment is mastectomy because of its 100% cure rate

B. With a partial breast excision, ~20% of women will experience recurrence

C. Partial breast excision plus radiation after surgery drops rate of recurrence to ~10%

D. Poor understanding of DCIS often results in both overtreatment and undertreatment

E. Invasive carcinoma develops in 25-30% of women with DCIS over 20-30 years time

Answer 23

A. Mastectomy does have a 100% cure rate, but this is often an overtreatment of women with DCIS

Question 24

All of the following are true regarding lobular carcinoma in situ (LCIS) except:

A. It is usually an incidental finding on a biopsy that is done for other reasons - has no specific clinical features

B. Tends to affect postmenopausal women

C. Histo is similar to atypical lobular hyperplasia but shows more extensive involvement of the breast lobules, with more than 50% of acini distended by neoplastic cells

D. Can be differentiated from low grade DCIS by E-cadherin immunohistochemistry

E. Like DCIS, LCIS is a risk factor for invasive carcinoma (25-30%); However, unlike DCIS, the risk is almost as high in the contralateral breast as in the ipsilateral breast.

Answer 24

B. Mostly affects premenopausal women, with the average age of 49

*Histo shows small poorly cohesive cells with uniform round nuclei and indistinct nucleoli that fill and distend the majority of the breast lobule (below)

Question 25

All of the folllwing regarding invasive breast cancer are true EXCEPT:

A. 1/2 of all palpable lesions are in the upper outer quadrant

B. Most common type of invasive breast cancer is invasive lobular carcinoma

C. A palpable mass, peau d’orange and nipple retratction are all concerning signs for invasive breast carcinoma

D. Not all well-circumscribed breast carcinomas are benign

E. Histologic grading of invasive breast cancer is done by the Nottingham Histologic Score which measures tubule formation, cytologic atypia and mitotic activity

Answer 25

B. This is the most common of the special types (10%). But the most common type of invasive breast cancer by far is invasive ductal carcinoma (79%)

Question 26

these are the most common genomic gains and loss in breast cancer

Answer 26

17q+ and 16q-

she said this many times

Question 27

this type of invasive breast cancer most often presents as a palpable mass or an ill defined abnormality on breast imaging, and is microscopically evident by the invastion of single cells or single file linear cords with no tubule formation

Answer 27

invasive lobular carcinoma;

these are the cancers that are poorly cohesive because of the loss of e-cadherin

Question 28

invasive lobular carcinoma (ILC) more frequenty metastasizes to the GI tract, bone, meninges and ovaries whereas invasive ductal carcinoma (IDC) most frequently metastasizes to the ____

Answer 28

lung

Question 29

invasive breast carcinoma with excellent prognosis and is characterized microscopically as a small nonpalpable spiculated mass with angulated tubules and minimal nuclear atypia

Answer 29

tubular carcinoma

Question 30

very high grade tumor with very good prognosis and tends to affect younger women (25% < 35); mimics fibroadenoma and often associated with BRCA1 mutations

Answer 30

medullary carcinoma

Question 31

All of the following are strict histologic features of medullary carinoma EXCEPT:

A. Circumscribed border

B. Lymphoplasmacytic infiltrate

C. Syncitial growth pattern

D. Cells with high grade nuclei with indistint cell borders

E. Gland formation

Answer 31

E. Note the well defined border, lymphocytic reaction and NO gland formation (below)

Question 32

tumor type that tends to present in older women, are often palpable as a slow growing mass, and histology shows tumor cells floating in abundant extracellular mucin

Answer 32

mucinous carcinoma

Question 33

Which of these is a major prognostic factor in invasive breast carcinoma?

A. Histologic grade

B. Proliferative Rate

C. Response to neoadjuvant therapy

D. ER/PR/HER2 status

E. Tumor size

Answer 33

E. All the rest are minor factors, including special subtype, lymphovascular invasion, and DNA content

*The two other major factors are those include in TNM staging: lymph node involvement and distant metastasis

Question 34

Why is it importatn to test for ER/PR/HER2 receptor status in invasive carcinomas?

Answer 34

There is a direct correlation between the level of expression of these receptors and response to hormonal therapies (e.g. tamoxifen and aromatase inhibitors)

Question 35

Which of the following subtype categories of breast carcinoma is associated with the worst prognosis?

A. Basal subtype

B. Luminal A

C. Luminal B

D. HER2

Answer 35

A. Basal subtype is triple negative, meaning it does not express ER/PR/HER2 receptors and is therefore unresponsive to those targeted therapies. Has varying response to chemo.

*Also note that in general, high grade (ie, highly proliferative) tumors respond better to chemotherapy than low grade tumors

Question 36

All of the following are true regarding invasive breast carcinoma EXCEPT:

A. Tubular carcinoma has a good prognosis

B. Medullary carcinoma presents in a younger age group and is enriched in BRCA1 mutations

C. HER2 overexpression is observed in 50% of invasive breast carcinomas

D. A patient with negative ER immunohistochemistry is unlikely to respond to hormonal therapies

Answer 36

C. Only 15-20% of tumors are HER2 positive.

Question 37

All of the following are prognostic factors in a woman with newly diagnosed invasive breast carcinoma EXCEPT:

A. Lymphovascular invasion

B. Mother and sister with breast cancer

C. Histologic grade

D. Gene expression profiling

Answer 37

B. This is more of a risk factor than a prognostic factor.

Question 38

Which of the following is false regarding DCIS:

A. Grading is based on nuclear features

B. Breast conserving surgery is the treatment of choice for most women

C. Palpable mass is the most common clinical presentation

D. Behavior is poorly understood

Answer 38

C. Most common presentation is calcifications on mammography.

Question 39

What is the relative risk of developing invasive breast carcinoma in a patient with atypical ductal hyperplasia ?

A. Relative risk 1.5 - 2.0

B. Relative risk 4.0 - 5.0

C. Relative risk 10 - 15

D. Relative risk 20 - 30

Answer 39

B. These lesion have an increased risk of invasive breast carcinoma (Relative risk 4.0-5.0; Absolute lifetime risk 25-30%)

Question 40

A 35 year old woman chooses to undergo early screening for breast cancer because she has a deleterious BRCA1 mutation and multiple first relative with breast carcinoma. All of the following are true statements EXCEPT:

A. BRCA1 associated breast carcinomas are typically poorly differentiated

B. MRI and ultrasound may be useful adjuncts to mammography in her case

C. BRCA1 associated breast carcinomas are typically positive for estrogen receptors

D. The patient has a 65% chance of developing breast cancer by age 70

E. The patient is at increased risk for developing ovarian, colonic and endometrial carcinomas

Answer 40

C. BRCA1 is associated with ER- pathways of breast cancer development.