Pathology of Breast Diseases

Question 1

Inflammatory disorder of the breast:

• localized
• acute inflammation
• most common cause: Staphylococcus aureus
• less common cause: Streptococcus pyogenes (GAS)

Answer 1

Acute mastitis

Question 2

Usually cause of acute mastitis associated with suppurative inflammation that may progress to abscess (single or multiple)

Answer 2

Staphylococcus aureus

Question 3

Usually cause of acute mastitis associated with breast cellulitis

Answer 3

Streptococcus pyogenes (group A streptococci)

Question 4

Inflammatory disorder of the breast:

• mimics cancer clinically
• painless palpable mass
• usual history of breast trauma, manipulation, or prior surgery
• ill-defined, firm, gray-white modules containing small, chalky-white foci or dark hemorrhagic debris
• liquefactive necrosis with neutrophils, macrophages, and eventually giant cells, calcification, and hemosiderin, leading to fibrosis

Answer 4

Fat necrosis of the breast

Question 5

Benign epithelial lesion encompassing breast cysts, fibrosis, and adenosis

Answer 5

Fibrocystic changes of the breast

Question 6

Fibrocystic change:

• dilation of lobules
• filled with brown/blue fluid (blue-dome)
• lined with “milk of calcium” calcifications of flattened atrophic/metaplasic apocrine glands

Answer 6

Breast cyst

Question 7

Fibrocystic change:

• caused by cyst rupture, inducing inflammation

Answer 7

Breast fibrosis

Question 8

Fibrocystic change:

• increased number of acini per lobule
• columnar cell lining with flattened epithelial atypia

Answer 8

Breast adenosis

Question 9

Benign epithelial lesion encompassing epithelial hyperplasia (typical/usual ductal hyperplasia), sclerosing adenosis, complex sclerosis, papillomas, atypical ductal hyperplasia, and atypical lobular hyperplasia

Answer 9

Proliferative breast lesions without atypia

Question 10

Proliferative breast lesions without atypia:

• > 2 layers of myoepithelial cells and luminal cells (usually 1 layer each) - heterogenous cells
• irregular, peripheral, slit-like lumen
• mimics ductal carcinoma-in-situ (DCIS)

Answer 10

Epithelial hyperplasia or typical/usual ductal hyperplasia

Question 11

Proliferative breast lesions without atypia:

• acini more than doubled at the uninvolved lobules
• compression at the center due to surrounding fibrosis (solid cords or double-strands of cells in densely fibrotic stroma)
• mimics breast carcinoma

Answer 11

Sclerosing adenosis

Question 12

Proliferative breast lesions without atypia:

• papillary fronds with fibrovascular core growing within a dilated duct
• bloody nipple discharge - most common cause in women younger than 50 (when intraductal)
• develops on the lactiferous ducts or sinuses
• no known risk for cancer

Answer 12

Breast papilloma

Question 13

Proliferative breast lesions without atypia:

• COMBINATION of components of epithelial cell hyperplasia, sclerosing adenosis, and papilloma
• central nidus of entrapped glands
• radiating projections of glands and stroma, with radial sclerosing lesion (radial scar)
• mimics breast cancer

Answer 13

Complex sclerosis or complex sclerosis breast lesion

Question 14

Proliferative breast lesions without atypia:

• monomorphic cells - ductal cells only
• round, rigid lumina = cribriform/cookie-cutter appearance
• resembles DCIS but with limited (< 2mm) duct involvement
• loss of 16p and gain of 17q (also in ALH nad CIS)

Answer 14

Atypical ductal hyperplasia (ADH)

Question 15

Proliferative breast lesions without atypia:

• monomorphic round cells - lobular only - loosely cohesive (similar to LCIS and ILC), due to loss of E-cadherin
• resembles LCIS but with limited (< 50%) involvement if acini per lobule
• loss of 16p and gain of 17q (also in ADH nad CIS)

Answer 15

Atypical lobular hyperplasia (ALH)

Question 16

Most common cancer in the adult woman, with a mean age of 64 years old; also the 2nd most common cancer producing death in women (followed by lung cancer)

Answer 16

Breast carcinoma

Question 17

Benign epithelial change with the most relative risk for break cancer development

Answer 17

Carcinoma-in-situ (CIS)

(Relative risks:

• fibrocystic changes = 1.0 or 3%
• proliferative disease without atypia = 1.5-2.0 or 5-7%
• proliferative disease with atypia = 4.0-5.0 or 13-17%
• carcinoma-in-situ = 8.0-10.0 or 25-30%)

Question 18

Type of carcinoma-in-situ:

• intact basement membrane
• disrupted lobules
• may have papillary/cribriform patterns
• necrotic with secretory activity; thus, with calcification
• divided into comedo and non-comedo types
• Paget disease of the nipple observed
• 10-20% bilateral
• variable hormonal status (usually ER-negative and HER2-positive if with Paget disease of the nipple)

Answer 18

Ductal carcinoma-in-situ (DCIS)

Question 19

Type of carcinoma-in-situ:

• intact basement membrane
• lobules intact
• WITHOUT papillary/cribriform patterns
• usually with minimal or no necrosis or secretory activity; thus, NO calcification
• nipple skin NOT involved, only Pagetoid spread seen
• 20-40% bilateral
• ER,PR-positive
• HER2-negative

Answer 19

Lobular carcinoma-in-situ (LCIS)

Question 20

Type of ductal carcinoma-in-situ involving PLEOMORPHIC cells with high-grade hyperchromatic nuclei; and central necrosis is also observed

Answer 20

Comedo DCIS

Question 21

Type of ductal carcinoma-in-situ involving MONOMORPHIC cells varying nuclear grade (low-grade to high-grade); seen with solid, cribriform, or micropapillary patterns

Answer 21

Noncomedo DCIS

(Note: In breast cancer, the “nuclear grade” refers to the evaluation of size and shape of tumor cell nuclei; another parameter of evaluation is the mitotic figures and tubule formation which both look at cell division - Nottingham score)

Question 22

Refers to the involvement of nipple skin in DCIS, seen as a unilateral erythematous eruption/rash with scaly crusts over the nipple surface with extracellular fluid seeping out of the nipple (50-60% of cases will present with palpable mass)

Answer 22

Paget disease of the nipple

Question 23

The malignant cells involved in Paget disease of the nipple, which extend from within the ductal system into the overlying nipple skin without crossing the basement membrane via the tactiferous sinuses; usually with poorly-differentiated underlying cancer that is ER-negative and HER2-positive

Answer 23

Paget cells

Question 24

Characteristic pattern of malignant cells between the basement membrane and the overlying luminal cells NOT involving the nipple skin, as seen in LCIS

Answer 24

Pagetoid spread

Question 25

Most common type of infiltrating carcinoma of the breast, developing from a carcinoma-in-situ (DCIS) with the additional loss of its formerly intact myoepithelial layer, further described: - with haphazardly disposed cells with desmoplasia - described with the Nottingham score

Answer 25

Invasive ductal carcinoma (IDC)

Question 26

Histologic scoring system for invasive ductal carcinoma that sums following parameters: - tubule formation (acinar/glandular differentiation) - nuclear pleomorphism (nuclear grade) - mitotic figures (per 10 HPF)

Answer 26

Nottingham score or: - Nottingham histologic score - Elston score/grade - Elston-Ellis modification - Scarff-Bloom-Richardson grading system - "TNM scoring"

Question 27

Type of invasive ductal carcinoma developing from this pathway: 1. normal breast tissue (ER-positive) 2. **GERMLINE BRCA2 MUTATION** 3. 1q, 16q and other chromosomal losses 4. flat epithelial atypia 5. PIK3CA mutations 6. atypial ductal hyperplasia (ADH) 7. **CRIBRIFORM DCIS** Patient groups: BRCA2 mutation carriers, older women, male breast Chemotherapy response: ~10% Late-to-intermediate relapse >10 years Long-to-intermediate survival with metastasis

Answer 27

ER-positive, HER2-negative or "luminal"

Question 28

Type of invasive ductal carcinoma developing from this pathway: 1. normal breast tissue (ER-positive or ER-negative) 2. **GERMLINE P53 MUTATION** 3. HER2 amplification 4. atypical apocrine adenosis 5. **MICROPAPILLARY DCIS** Patient groups: p53 mutation carriers, young women, most non-white women (ER-positive > ER-negative) Chemotherapy response: ~15% if ER-positive; > 30% if ER-negative Short relapse <10 years Rare survival with metastasis

Answer 28

HER2-enriched or HER2-positive | Can be either ER-positive or ER-negative, with ER-negative responding better to treatment

Question 29

Type of invasive ductal carcinoma developing from this pathway: 1. normal breast tissue (ER-positive or ER-negative) 2. **GERMLINE BRCA1 MUTATION** 3. secondary p53 mutations 4. BRCA1 inactivation 5. **usually either SOLID DCIS or COMEDO DCIS** Patient groups: BRCA1 mutation carriers, young women, black women, Hispanic women Chemotherapy response: ~30 Short relapse <5 years Rarer survival with metastasis

Answer 29

ER-negative, HER2-negative or "basal-like"

Question 30

Type of infiltrating carcinoma of the breast known as the most common breast cancer to present as an occult primary breast cancer, further described: - E-cadherin or CDH1 loss - little desmoplasia - discohesive infiltrating malignant cells which may contain mucin (signet ring cells) in single file (Indian file) - usually ER-positive, HER2-negative

Answer 30

Invasive lobular carcinoma (ILC)

Question 31

Histologic pattern of malignant cells in invasive lobular carcinoma, described to be in a single file

Answer 31

Indian file pattern

Question 32

The malignant cells containing mucin, involved in invasive lobular carcinoma

Answer 32

Signet ring cells

Question 33

Type of infiltrating carcinoma, further described: - fleshy breast mass - syncitium-like solid sheets of large cells with pleomophic nuclei and prominent nucleoli - increased mitosis - lymphoplasmacytic infiltrates - "pushing borders" - usually ER-negative, HER2-negative

Answer 33

Medullary carcinoma

Question 34

Type of infiltrating carcinoma, further described: - soft/rubbery/gelatinous breast mass - mass consistency and appearance of pale grayish blue gelatin - usually ER-positive, HER2-negative

Answer 34

Mucinous carcinoma

Question 35

Type of infiltrating carcinoma, further described: - well-formed angulated tubules lined with a single layer of cells with small monomorphic nuclei - usually ER-positive, HER2-negative

Answer 35

Tubular carcinoma

Question 36

Type of infiltrating carcinoma, further described: - breast swelling with skin thickening - worst prognosis (3-year survival rate of 3-10%) - involving invasion/infiltration of the lymphatic plexus of the nipple areola - high degree of aneuploidy, typically high-grade - tumor emboli in dermal lymphatics - persistent E-cadherin expression - no particular molecular sub-type

Answer 36

Inflammatory carcinoma

Question 37

The lymphatic plexus primarily involved; invaded and infiltrated by neoplastic cells in inflammatory carcinoma

Answer 37

Sublympathic plexus of Sappey (or Sappey plexus)

Question 38

Characteristic skin thickening and dimpling appearance caused by neoplastic cell infiltration into the subareolar lymphatics as seen in inflammatory carcinoma

Answer 38

Peau d'orange

Question 39

Type of stromal tumor, further described: - benign - most common breast mass; most common benign tumor of the female breast - discrete, movable - may be painful or painless - increases in size during pregnancy - well-circumscribed, rubbery, grayish white nodules - proliferation may surround (pericanalicular) or compress (intracanalicular) epithelial component - may be further complexed with cysts (> 0.3cm), sclerosing adenosis, epithelial calcifications, and papillary apocrine change (atypical apocrine adenosis) - when complexed, may have a low risk of malignancy

Answer 39

Fibroadenoma

Question 40

The nodules of the breast fibroadenoma are further described to have slit-like spaces and these large, lobulated calcifications

Answer 40

Popcorn calcifications

Question 41

Type of stromal tumor, further described: - bulky, lobulated with cystic spaces containing leaf-like projections covered by epithelium - most common chromosomal abnormality: gains in 1q - genetic abnormality in high-grade and aggressive behavior of the tumor: HOXB13 - stromal overgrowth - infiltrative borders - high cellularity, mitosis, and nuclear pleomorphism

Answer 41

Phyllodes tumor

Question 42

Characteristic abnormality in this gene is associated with the high-grade and aggressive behavior breast stromal tumors, especially Phyllodes tumors

Answer 42

homeobox B13 (or HOXB13)

Question 43

Male breast cancer is rare, late-presenting, and would usually have a distant metastases at time of presenation; male breast cancer usually has this ER status

Answer 43

ER-positive

Question 44

Disorder in of the male breast caused by an increase in dense collagenous connective tissue and epithelial hyperplasia of the duct lining (micropapillae), sometimes but rarely with lobule formation

Answer 44

Gynecomastia

Question 45

Characteristic presentation of the hyperplasic epithelial lining in gynecomastia

Answer 45

Micropapillae (micropapillary presentation)