Breast Pathology Flashcards by Tim Allen

What are risk factors for locoregional recurrence in DCIS

Four most important
-age <50
-size >2cm
-grade 3
-<2mm surgical margins (less considered a positive margin)

Additional
-comedo/solid subtype
-palpable/bloody discharge
-ER/PR negative

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What are risk factors for invasive breast cancer recurrence

Patient
-age
-menopausal status
-race

Tumour
-size
-node status
-grade
-LVSI
-Genomic score
-receptor status

Treatment related
-surgical margin status (no ink on margin negative)
-systemic therapy

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What are common symptoms of papilloma and what is the cause of these symptoms

Blood discharge: due to tortion of papilloma stalk
Serous discharge: due to intermittent blockage of duct

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What is the median age of diagnosis by TCGA molecular subtypes

Luminal: older Medan age
Basal/ HER2: peak incidence in middle age. Almost half of breast cancers in younger women, 20% in older women

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What are risk factors for the development of breast cancer

Female gender
Lifetime exposure to estrogen
Age
Genetic mutation inheritance
Environmental/lifestyle factors ( less relevance)

Reduced risk
-early pregnancy aged less than 20
-prolonged breast feeding

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What proportion of breast cancers are thought to occur due to an inherited susceptibility

Quarter to one third

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What percentage of breast cancers are associated with BRCA1 or BRCA2

3-6%

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Which BRCA mutation is most commonly associated with ovarian cancer

BRCA1: 20-40% lifetime risk
BRCA2: 10-20%

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What is the typical ER profile of BRCA associated breast cancers

BRCA1: Triple negative
BRCA2: more often ER positive

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What pathway are the products of BRCA genes part of

Homologous recombination for repair of double stranded DNA breaks

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What are the response rates to chemotherapy of difference TCGA subtypes of breast cancer

Luminal A: <10% (but good response to hormone therapy)
Luminal B: 10%
HER2: good response if ER negative
Basal: 30% response

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What TCGA subtype of breast cancer is most commonly associated with Li Fraumeni syndrome

HER2+

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In triple negative breast cancer without germline BRCA1 mutation, what is the most common change to the BRCA1 gene

Epigenetic silencing

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Where are the more common metastasis sites for TNBC

Visceral sites and brain (rather than bone with luminal)

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What is the typical recurrence pattern for TNBC

Recurrence by 8 years. From 10 years recurrence is very rare

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What layer does a breast in situ carcinoma need to breach to become an invasive carcinoma

The basement membrane

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What are the microscopic features of comedo DCIS

Polymorphism of cells, high grade
Central necrosis

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What is the process that results in Paget’s disease of the breast. What is the relevance of the presence of a mass?

Malignant cells travel through ducts of breast and break through the lactiferous sinuses onto the skin of the nipple. Cause pruritis and eczema like chance ( unilateral)

If mass palpable then it is likely there is an underlying invasive breast cancer (commonly HER2+)
If no mass palpable then more likely that the underlying pathology is DCIS

What are the pathological features that distinguish LCIS from DCIS

Both form in ducts and lobules (ie the naming of them is historic and now misleading)
LCIS has the microscopic appearance of discohesive cells ( not penetrating basement membrane)
Usually have dysfunction of e-cadherin
Cells are rounded due to loss of adhesion to other cells
LCIC is not associated with Paget’s disease of the breast ie, nipple skin involvement (but does have a Pagetoid appearance within the ducts ie, discohesive cells)
LCIS is not associated with calcification

What is the natural history of LCIS, including following surgical resection

1% per year risk of invasive cancer
Ipsilateral breast only slightly more likely to be site of invasive disease
Most invasive cancers are morphologies other than lobular. 3x rate of lobular compared to general population.
It is unclear if resection of LCIS lesion lowers risk of invasive cancer
Most are ER/PR positive, so Tamoxifen is a treatment option

What are the 5 most common subtypes of DCIS, and which have worst prognosis

Cribriform
Papillary
Micropapillary
Solid (poor)
Comedo (poor)

What mutation do Lobular breast carcinomas often have

CDH1 (e-cadherin)

What are common metastatic sites for lobular carcinoma

Peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries, uterus

What localised reaction do lobular carcinomas often lack, making their detection more difficult

Desmoplastic reaction

Invasive breast carcinomas with medullary pattern are associated with abnormalities in what gene. How does prognosis compare to other poorly differentiated breast cancers

Associated with BRCA1. Either germline mutation or down regulation of expression. Tend to have better prognosis Associated with T-cell infiltration which may produce an anti tumour immune response

What are examples of Luminal special types of breast cancer

Lobular Mucinous Tubular Papillary

What is a common microscopic feature of lobular breast cancer

Signet ring appearance due to intracellular mucin droplets

What is the microscopic appearance of mucinous breast cancers

Clusters of cells in large lakes of mucin

What special histological types of breast cancer frequently over express HER2

Apocrine: similar appearance to cells lining sweat glands. Round nuclei, prominent nucleoli, abundant eosinophilia cytoplasm micropapillary: hollow balls of cells floating within intracellular fluid

Which special histological type of breast cancer is most associated with TNBC. What are it’s gross and histological features

Carcinoma with medullary pattern Grossly softer than others due to minimal desmoplasia Microscopically: -solid sheets of large cells with pleomorphic nuclei and prominent nucleoli -frequent mitotic figures -moderate to marked lymphoplasmacytic infiltrate -pushing, non infiltration border

What are examples of rare histological subtypes of TNBC that have favourable prognosis

Low grade adenosquamous Adenoid cystic Secretory carcinoma

What is the reason for the inflamed breast appearance in inflammatory breast cancer, and what causes the peau d’orange.

Usually NO inflammation involved. Ie stupid name. Tumour cells block lymphovascular channels, causing swelling Tethering of coopers ligaments causes the skin puckering.

What are the two types of intralobular stromal tumours of the breast

Fibroadenoma Phyllodes tumour

What is the typical presentation of a breast fibroadenoma

Women aged in 20’s and 30’s Hormone responsive with rapid growth during pregnancy Slight increased risk of invasive carcinoma

What is the typical presentation of phyllodes tumour of the breast

Median age of presentation 6th decade High grade tumours can metastasise via haematogenous spread. Node spread in very rare and node dissection contraindicated

What is the most common interlobular stromal malignant tumour of the breast

Angiosarcoma Associated with post therapy chronic angioedema of the breast and radiation therapy

What is the lifetime risk of breast cancer and ovarian cancer for BRCA1 and BRCA2 carriers respectively

Both about 70% at age 80 for breast cancer Ovarian cancer: 44% BRCA1, 17% BRCA2 (to age 80)

Is BRCA1 or BRCA2 most associated with increased cancer risk in men

BRCA2; for both breast and prostate. Breast 7% at age 70, prostate 27% at age 75, 60% at age 85

What is the histological pattern of phyllodes tumour, and how are they graded

Biphasic: epithelial and stromal elements Epithelial component usually benign Stromal component used for grading: benign, borderline, malignant Components of grading: -stromal atypia -stromal cellularity -stromal cell overgrowth -mitotic rate -tumour border -if a malignant heterologous element is present (Ie a sarcoma such as liposarcoma, chondrosarcoma, then it is automatically classified as malignant

Which subtypes of breast invasive ductal carcinoma are most favourable

Mucinous Tubular

What are components of the main grading system for invasive breast cancers

Nottingham system -tubule formation -nuclear pleomorphism -mitotic count

What receptor status are Li Fraumeni associated breast cancers often associated with

HER2 over expression

What IHCstaning can be used to distinguish between invasive and in situ breast carcinomas

Invasion is associated with loss of smooth muscle layer Therefore loss of staining of SMA