PATH: Breast Flashcards by Rachael Petry

What are the common symptoms of breast cancer?

Lumpiness
Pain
Palpable mass
nipple discharge

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What percentage of patients with breast cancer present with the “common” symptoms?

less than 10%

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What is the most common presentation of a woman with breast cancer?

abnormal mammogram!

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Can you diagnose a patient off of a mammogram finding?

NO! need to do biopsy to diagnose as cancer

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What cell layer is characteristically missing from breast tumors?

the myoepithelium

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What makes breast cancer tumors “rock hard”?

desmoplastic reaction (lots of intervening stroma)

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What is the progression of normal breast tissue to invasive carcinoma?

normal–> hyperplasia –> atypical hyperplasia –> carcinoma in situ –> invasive carcinoma

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What does breast hyperplasia look like?

semi-controlled proliferation of polymorphic cells with irregular spaces between (looks kind of like a glomerulus)

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What does atypical hyperplasia look like when a less controlled monomorphic sub-population takes over?

produces more uniform “cookie-cutter” spaces

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What is this cookie-cutter pattern in atypical hyperplasia called?

cribiform pattern

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What does atypical hyperplasia caused by a more aggressive subpopulation look like?

solid pattern of cell proliferation

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Is carcinoma in situ cancer?

YES (malignant transformation with cells capable of invasion and metastasis)

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List the features MORE COMMONLY SEEN in carcinoma in situ in the breast.

Necrosis
Periductal inflammation
Periductal fibrosis
Uniform hyperchromatic (darker) nuclei
Calcification
Mucin production
Loss of myoepithelial cell layer

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What is a very common pattern of DCIS? Why is it called this?

comedonecrosis pattern (necrosis in the middle of ducts looks like the comedones of acne vulagris)

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What is a more benign feature, cribiform or slit-like spaces?

slit-like spaces (DCIS from atypical hyperplasia will typically retain the cribiform pattern to some extent)

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True or false: patients with DCIS have lumpectomy and chemotherapy as major treatment.

FALSE: lumpectomy and radiation commonly done (no chemotherapy for DCIS patients); mastectomy is releatively curative but offers no survival advantage over lumpectomy and radiation

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What are some features of usual ductal hyperplasia?

heterogenous cell size, shape and orientation with poor porders (often have irregular, slit-like and PERIPHERAL lumens with stretched/twisted bridges)

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What is the difference is subsequent breast cancer risk for usual ductal versus atypical ductal hyperplasia?

usual ductal hyperplasia doubles risk

Atypical ductal hyperplasia increases risk 5 fold

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What are some features of atypical ductal hyperplasia?

small, uniform, evenly spaced cells with rounded nculei and well defined borders (will typically have regular lumens with “rigid bridges)

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Where is p63 found in the breast?

prominent in myoepithelial cells

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If you see a lack of p63 staining, what should you think of?

probably invasive!

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What “score” is used to differentiate if a breast cancer is high grade or low grade?

Nottingham Score

Tubule formaiton
Nuclear pleomorphism
Number of mitoses

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What type of mutation does a person with hereditary cancer syndromes have?

germline (ex. BRCA)

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What is it called to have a germline mutation in p53?

Li-Fraumeni syndrome (early cancer in many organs)

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What is it called to have a germline mutation in PTEN?

Cowden Syndrome (multi-organ cancers)

Where do the cells that cause BRCA-induced ovarian cancer come from?

fallopian tube

If a woman with BRCA mutations wants to preserve her fertility, what is recommended for her?

2X yearly screening for ovarian cancer with transvaginal ultrasound and serum CA-125

How common is "triple-negative" breast cancer?

15% of breast cancers

Who gets "triple-negative" breast cancer?

black women (2X more likely) and usually older, obese, and in patients who had more children at a younger age

How common are "triple-negative" breast cancers among women with BRCA1 mutations?

common, 70%

What are some characteristics of "triple-negative" breast cancer?

mostly basal-like morphology; look like basal cells; usually CK 5/6+

Where is an uncommon place for "triple-negative" breast cancer to invade?

bone (more commonly brain, lung, liver and distant LNs)

On what chromosome is HER2?

HOw do you test for HER2-positivity?

FISH for HER2a dn centromere of chromosome 17

True or false: the incidence of DCIS has rapidly declined since mammography screening become popular int he US.

FALSE: it has increased!

What mutations are common in ER+ Her2- breast cancers (luminal)?

Germline BRCA2 mutations (1q gain and 16q loss), PIK3CA mutations (leads to atypical ductal lyperplasia before DCIS)

What mutations are common in Her2 positive cancers?

Germline TP53 mutations HER2 amplification (leads to atypical apocrine adenosis before DCIS)

What mutations are common in ER-, HER3- breast cancers (basal-like)?

Germline BRCA1 mutaitons TP53 mutation BRCA1 inactivation

What is stage 1 breast cancer?

invasive carcinoma <2cm | No mets or only micromets

What is stage 2 breast cancer?

invasive carcinoma >5cm invasive with 1-3 postive LNs | invasive carcinoma > 2cm but less than or equal to 5cm with 0-3 positive lymph nodes

What is stage 3 breast cancer?

invasive carcinoma >5cm (Negative or positive LNs) Any size invasive carcinoma (>/= 4 positive LNs) invasive carcinoma with skin or chest wall involvement or inflammatory carcinoma (negative or positive LNs)

What is stage 4 breast cancer?

any size invasive carcinoma with negative or positive LNs

In what type of breast cancer is "indian filing" or infiltrating single file characteristic?

lobular breast cancer

What is the most common type of breast cancer to present as an occult primary?

lobular breast cancer

What is the histological hallmark of lobular breast cancer?

presence of discohesive infiltrating tumor cells (often including signet-ring cells containing intracytoplasmic droplets)

Do you commonly see tubule formation with lobular breast cancer?

What are masses of lobular breast cancer like?

hard irregular masses (but can be diffuse pattern with minimal desmoplasia that is difficult to palpate or detect)

What is a benign epithelial neoplasm growing within a dilated duct (composed or multiple branching fibrovascular cores)?

papilloma

Where are large duct papillomas usually found?

lactiferous sinuses of nipple (usually solitary)

Where are small duct papillomas usually found?

deeper in the ductal system (usually multiple)

What is the characteristic symptom of a papilloma?

80% have nipple discharge (that can be bloody if stalk undergoes torsion)

What is the word for a breast stromal neoplasm that is commonly multiple and bilateral in 20-40 year old women?

fibroadenomas

What is the microscopic characteristic of fibroadenomas?

slit-like spaces that are compressed by normal looking stroma

How do fibroadenomas differ between old women and younger girls?

in older women, the stroma becomes densely hyalinized and the epithelium becomes atropic

Why do fibroadenomas get bigger durign pregnancy?

because the epithelial component is hormonally responsive

Are fibroadenomas ALWAYS benign?

NO- very small chance of malignancy

What is a breast stromal neoplasm?

Phyllodes tumor

Who gets Phyllodes tumors?

rare, more likely in Latinas (50-60 yo)

What causes a Phyllodes tumor to have a higher tumor grade and more aggressive behavior?

gains of chromosome 1q, increased chromosomal aberrations and overexpression of HOXb13

When viewed in 2D, what does a phyllodes tumor look like?

leaves

Do Phyllodes tumor usually metastasize?

no they metastasize rarely, but the do invade locally

What distinguishes a Phyllodes tumor from a fibroadenoma?

higher cellularity, higher mitotic rate, nuclear pleomorphism, stromal overgrowth and infiltrative borders

What is the "only" sarcoma that occurs in the breast?

angiosarcoma (SUPER UNCOMMON)

Who gets angiosarcomas?

women who had radiation to breast skin 5-10 years prior

What is sclerosing adenosis?

something that looks like adenocarcinoma but is not

What are some characteristics of sclerosing adenosis?

increased acini number compressed/distorted in certral portion of the lesion (arranged in swirling pattern and the outer border is well-circumscribed) Stromal fibrosis that compresses lumens to create appearance of solid cords or double strands of cells

What is fibrocystic changes of the breats?

benign, non-proliferative cysts with assoicated fibrosis (that makes breasts lumpy and bumpy on palpation)

What do unopened cysts of fibrocystic change contain?

semi-translucent fluid of a brown or blue color called "blue-dome cysts"

Are fibrocystic changes associated with an increased risk of breast cancer?

What are the most common causes of fat necrosis?

breast trauma or prior surgery

What is the pathogenesis of fat necrosis?

Hemorrhagic --> central areas of liqueactive necrosis with neutrophils and macrophages--> proliferating fibroblasts and chronic inflammatory cells surround area--> giant cells, calcificaiton and hemosiderin--> scar tissue or fibrous tissue walls off lesion