Breast Cancer Pathology

Question 1

What is the leading cause of cancer related deaths ?

Answer 1

Lung Cancer First
Breast Cancer Second

Question 2

Why breast Cancer Incidence decreased ?

Answer 2

• Reduction in the use of HRT
• Reduction in the use of screening mammography

Question 3

The decreased mortality from breast cancer is thought to be

Answer 3

> > The result of earlier detection via mammographic screening
Decreased incidence of breast cancer
Improvements in therapy

Question 4

Noninvasive Breast Cancer

Answer 4

Two major types :
- LCIS and DCIS

Question 5

LCIS

Answer 5

• Not a neoplasm
• risk factor for the development of breast cancer

Question 6

Pleomorphic LCIS

Answer 6

• more aggressive histopathologic subtype
• marked nuclear pleomorphism
• may be associated with comedonecrosis and calcifications
• may be detected mammographically ( If calcification )
• Treated with surgical excision similar to DCIS

Question 7

Four broad types of DCIS:

Answer 7

Papillary
Cribriform
Solid
Comedo

DCIS lesions are usually of mixed morphology

Question 8

Which type more aggressive

Answer 8

lower-grade lesions :
- The papillary and cribriform types
- take longer to transform to invasive cancer

Higher-grade lesions :
- The solid and comedo types of DCIS are generally

> > DCIS can transform into an invasive cancer, usually recapitulating the morphology of the cells inside the duct.

Question 9

Why DCIS seen as calcifications on mammo

Answer 9

• Central necrosis > Coagulation and finally calcifies > tiny, pleomorphic, and linear forms of microcalcifications

Question 10

What is segmental calcifications

Answer 10

> > Entire ductal tree involved in the malignancy
Mammogram shows typical calcifications that can span from the nipple extending posteriorly into the interior of the breast

Question 11

most common form of breast cancer

Answer 11

• Invasive ductal cancer
• 50% to 70% of invasive breast cancers

> > Invasive lobular carcinoma accounts for 10% of breast cancers
Mixed ductal and lobular cancers have been increasingly recognized

Question 12

Low Grade Types of DCIS

Answer 12

• infiltrating cells form small glands lined by a single row of bland epithelium
  » tubular carcinoma
• cells may secrete copious amounts of mucin
  » mucinous or colloid tumors

Question 13

High Grades DCIS

Answer 13

• Medullary cancer
  » surrounded by an infiltrate of small mononuclear lymphocytes.
• can be Pure or medullary variant
• Hormone Receptors Negative , HER2 Negative

Question 14

Basal-like breast cancer vs Triple-negative breast cancer

Answer 14

• Basal-like breast cancer describes a specific subtype of breast cancer defined by microarray analysis,
• Triple-negative breast cancer is defined by lack of immunohistochemical detection of ER, PR, and HER-2.

Question 15

Which has bad prognosis

Answer 15

> > Basal-like breast cancer is commonly aggressive

> > Invasive lobular breast cancers carry an intermediate prognosis

> > tubular and mucinous cancers have the best overall prognosis.

Question 16

What is HER-2

Answer 16

> > This protein is the product of the erb-B2 gene and is amplified in approximately 20% of human breast cancers
Activation of tyrosine Kinase

Question 17

How to Detect Her2 ?

Answer 17

> > overexpression is measured clinically by immunohistochemistry
scale from 0 to 3+

> > fluorescence in situ hybridization
directly detects the number of HER-2–gene copies
can be used to detect gene amplification.

Question 18

Her2 Tx ?

Answer 18

> > Trastuzumab and pertuzumab are antibodies directed against the extracellular domain of the HER-2 surface receptor

Question 19

In an attempt to subclassify the disease further, investigators are turning to global assessment of

Answer 19

> > Gene expression using microarrays

Question 20

triple-negative cancers

Answer 20

> > They express proteins in common with myoepithelial cells at the base of mammary ducts and are also called basal-like cancers

> > Women who carry a deleterious mutation in BRCA1 (but not BRCA2) are much more likely to contract a basal-like cancer (triple-negative) than other subtypes

Question 21

Oncotype DX assay, a 21-gene recurrence score assay

Answer 21

> > Originally designed to predict the recurrence of ER-positive, node-negative breast cancer treated with adjuvant endocrine therapy

> > determine whether women with high-risk ER-positive breast cancer should receive adjuvant chemotherapy in addition to tamoxifen or other endocrine therapies

Question 22

MammaPrint assay

Answer 22

> > analyzes data from 70 genes to develop a risk profile.

Question 23

Benign Phyllodes tumors

Answer 23

• average size of approximately 5 cm
• Histologically similar to fibroadenomas But
• The whorled stroma forms larger clefts lined by epithelium that resemble clusters of leaf-like structures
• stroma is more cellular
• fibroblastic cells are bland
• mitoses are infrequent

Question 24

How to Diagnose it ?

Answer 24

• mammography&raquo_space; round densities with smooth borders, indistinguishable from fibroadenomas.
• Ultrasonography may reveal a discrete structure with cystic spaces
• The diagnosis is suggested by the larger size, history of rapid growth, and occurrence in older patients.
• Cytologic analysis is unreliable

Question 25

CNB Role ?

Answer 25

CNB is preferred >> although it is difficult to classify phyllodes tumors with benign or intermediate malignant potential

Question 26

Final Diagnosis By ?

Answer 26

The final diagnosis is best made by excisional biopsy followed by careful pathologic review.

Question 27

Tx for benign and borderline ?

Answer 27

- benign phyllodes : >> similar to fibroadenoma - Borderline phyllodes : >> excision with negative margins at least 1 cm to prevent local recurrence.

Question 28

Malignant phyllodes tumors

Answer 28

- cellular atypia - high number of mitoses - stromal overgrowth

Question 29

Tx ?

Answer 29

- Complete surgical excision of the entire tumor with a margin of normal tissue is advised. - When the tumor is large with respect to the size of the breast, total mastectomy may be required

Question 30

role of radiation ?

Answer 30

- If mastectomy is performed and the margins are negative, radiation therapy is not recommended. - If the margins are concerning or close - if the tumor involves the fascia or chest wall - or if the tumor is very large (>5 cm) >> irradiation of the chest wall is considered. - If only wide local excision is performed >> adjuvant radiation therapy is recommended. - regional lymph node dissection is not required for staging or locoregional control

Question 31

Metastases from malignant phyllodes tumors occur via

Answer 31

>> hematogenous spread >> common sites of metastasis include - lung, bone, abdominal viscera, and mediastinum.

Question 32

Angiosarcoma

Answer 32

- in the breast parenchyma - or within the dermis of the breast after irradiation - develop in the upper extremity of patients with lymphedema

Question 33

Primary and Secondary Angiosarcoma

Answer 33

- Angiosarcomas arising in the absence of previous radiation therapy or surgery (primary angiosarcomas) generally form an ill-defined mass within the parenchyma of the breast. - Angiosarcomas caused by prior radiation therapy (secondary angiosarcomas) arise in the irradiated skin as purplish vascular proliferations that may go unrecognized for a period of time. - The development of angiosarcoma in the ipsilateral arm to surgery is called Stewart-Treves syndrome and is secondary to long-standing lymphedema.

Question 34

Grading of Angiosarcoma based on ?

Answer 34

- Pleomorphic nuclei - Frequent mitoses - Stacking of the endothelial cells lining neoplastic vessels - Necrosis >> Features seen in higher-grade lesions

Question 35

Diagnosis ? and Tx ?

Answer 35

- Mammography is unrevealing in most cases - surgery is performed to secure negative skin margins and usually involves a total mastectomy - Split-thickness skin graft or myocutaneous flap may be needed - Axillary dissection is not required

Question 36

After Surgery ?

Answer 36

- high risk for local recurrence - primary angiosarcoma >> radiation therapy is beneficial in locoregional treatment. >> Metastatic spread occurs hematogenously MC lungs and bone >> Adjuvant chemotherapy is generally recommended