Breast Pathology 2 Flashcards by Aliya Hussain

Types of miscellaneous malignant tumours of the breast?

Malignant Phyllodes tumour (sarcomatous stromal component) - the stromal component is malignant and the epithelial component is benign; the stromal part takes on the features of a sarcoma

Angiosarcoma - mainly occur post-radiotherapy

Lymphoma - breast and/or lymph nodes affected

Metastatic tumours to the breast

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Examples of metastatic tumours to the breast?

Carcinoma:
• Bronchial
• Ovarian serous carcinoma
• Clear cell carcinoma of kidney

Malignant melanoma

Soft tissue tumours:
• Leiomyosarcoma

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Definition of breast carcinoma?

Malignant tumour of breast epithelial cells that arises in the glandular epithelium of the terminal duct lobular unit (TDLU)

It is an adenocarcinoma but is referred to as breast carcinoma

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Precursor lesions of breast carcinoma?

Involve epithelial proliferation

Ductal:
• Epithelial hyperplasia of usual type, i.e: proliferation of epithelial cells that are non-neoplastic
• Columnar cell change, i.e: cells become taller and more columnar
• Atypical ductal hyperplasia
• Ductal carcinoma-in-situ (DCIS)

Lobular:
• Lobular in-situ neoplasia - can have atypical lobular hyperplasia or could be lobular carcinoma-in-situ; these are the same pathologically but are separated due to differences in the extent

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Define in-situ carcinoma?

Confined within the basement membrane of the acini and ducts

It is cytologically malignant but is non-invasive

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Classification of breast in-situ carcinoma?

Lobular

2. Ductal

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Types of lobular in-situ neoplasia?

Atypical lobular hyperplasia (ALH) - <50% of lobule involved
Lobular carcinoma-in-situ - >50% of lobule involved

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Characteristics of lobular in-situ neoplasia?

There is intra-lobular proliferation of characteristic cells, leading to:
• Small-intermediate sized nuclei
• Solid proliferation
• Intra-cytoplasmic lumens / vacuoles
• ER (oestrogen receptor) +ve
• E-cadherin -ve, on immunohistochemistry, due to deletion and mutation of the CDH1 gene on chromosome 16; this is a cell adhesion molecule and so the cells are dyscohesive

Frequently, it is multifocal and bilateral

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Occurrence of lobular in-situ neoplasia?

Often an incidental finding

Incidence decreases after menopause, due to reduced levels of circulating oestrogen

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PC of lobular in-situ neoplasia?

Not palpable or visible grossly

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Diagnosis of lobular in-situ neoplasia?

May calcify and thus be visible on mammography

But usually an incidental finding

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Issues assoc. with a diagnosis of lobular in-situ neoplasia?

Some cases picked up by core biopsy actually have a higher grade lesion on open diagnostic biopsy

8x increase in relative risk of subsequent invasive carcinoma; this risk is present with ALH but is even higher for ALH with a family history; additionally, the risk is higher with LCIS +/- a family history

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Thus, what is the significance of lobular in-situ neoplasia?

Marker of subsequent risk

Also, it is a true precursor lesion

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Management of lobular in-situ neoplasia?

If discovered on core biopsy, proceed to excision or vacuum biopsy, to exclude a higher grade lesion

If discovered on vacuum or excision biopsy:
• Follow-up
• Useful for clinical trials

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Stages/types of intraductal proliferation, i.e: ductal type precursor lesions?

Epithelial hyperplasia of usual type
Columnar cell change (lesion)
Atypical ductal hyerplasia
Ductal carcinoma-in-situ (DCIS)

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Risk assoc. with intraductal proliferation?

Progression to invasive carcinoma

Epithelial hyperplasia of usual types increases the relative risk (RR) by 2x, atypical ductal hyperplasia 4x and DCIS (low-grade) by 10x

Occurrence of DCIS?

15-20% of breast malignancies are DCIS (often picked up at breast screening)

Characteristics of DCIS?

Cytologically malignant epithelial cells are confined within the basement membrane of the duct (characteristically, it is unicentric, i.e: inv. a single duct system)

Other regions that may become involved with DCIS?

May inv. lobules (called cancerisation)

May inv. nipple skin (Paget’s disease of the nipple)

What is Paget’s disease of the nipple?

High-grade DCIS extending along the ducts to reach the epidermis of the nipple

NOTE - Paget’s is still in-situ carcinoma, i.e: it is non-invasive due to its confinement

Classification of DCIS?

Can classify according to:
• Cytological grade, i.e: how different the cells are from the origin/parent cell; this is the most important factor
• Histological type
• Presence of necrosis

Thus, what is the significance of DCIS?

Risk factor for development of invasive breast carcinoma, as it is a precursor lesion for invasive carcinoma

NOTE - 75% progress to invasion following incisional biopsy only

Management of DCIS?

All treated SURGICALLY

Also:
• Adjuvant radiotherapy

What is microinvasive carcinoma?

High-grade DCIS with invasion of <1mm; it is RARE, due to its tight definition

Treatment of microinvasive carcinoma?

As for high-grade DCIS

Define invasive breast carcinoma?

Malignant epithelial cells that have BREACHED the basement membrane; there is infiltration of normal tissue and a risk of metastasis and death

Occurrence of invasive breast carcinoma?

Most common cancer in females; 1/8 women will develop breast cancer Incidence increases with age

Risk factors for breast carcinoma?

AGE Reproductive history: • Early menarche is a risk factor • Age of first birth - reduced risk if <30 years of age • Parity - reduced risk with more children • Breastfeeding - reduces risk • Late menopause is a risk factor NOTE - fewer menstrual cycles reduces the risk Hormones: • Endogenous • Exogenous (OCP, HRT) Previous breast disease Geography (more common in the western world) ``` Lifestyle: • Body weight - obesity is a risk factor • Physical activity is protective • Alcohol consumption (increases risk) • Diet • NSAIDs are protective • Smoking ``` Genetics - affected 1st degree relative doubles the risk

Genetic mutations assoc. with breast cancer?

BRCA1 or 2 mutation leads to a breast/ovarian tumour predisposition TP53 mutation leads to Li Fraumeni syndrome; this causes childhood sarcoma, brain, tumours, leukaemia, adrenocortical carcinoma, early-onset breast carcinoma PTEN mutation leads to Cowden's syndromes; this causes breast, GI, thyroid (benign and malignant) tumours STK11 / LKB1 mutation leads to Peutz-Jeghers syndrome; this causes breast, GI, pancreatic and ovarian tumours ATM mutation leads to ataxia telangiectasia; this causes Non-Hodgkin's lymphoma, ovarian, breast (in heterozygote carriers) tumours

Natural history of invasive breast carcinoma, in terms of TNM?

Local invasion (T): • Breast stroma • Skin • Muscles of chest wall Lymphatics (N) - regional draining lymph nodes Blood-borne (M) - bone, liver, brain, lungs, abdominal viscera, female genital tract

What are the regional draining lymph nodes for the breast?

Internal mammary nodes Intramammary nodes Sentinel nodes Axillary nodes Apical nodes Infraclavicular nodes Supraclavicular nodes Cervical nodes

Classification of invasive breast cancer?

Morphological - types and grade Gene expression profiling - has intrinsic sub-types Hormone receptor expression: • Oestrogen receptor (ER) - 80% of breast cancers are +ve • Progesterone receptor (PR) • HER2

Histopathological types of invasive breast carcinoma?

Most common are ductal (70%) and lobular (10%) Others inc, mucinous, medullary, tubular, mixed, etc

What is the grade of a tumour?

Measure of tumour differentiation

How to grade breast carcinoma?

Objective assessment of: 1. Tubular differentiation - scored 1-3 2. Nuclear pleomorphism - scored 1-3 3. Mitotic activity - scored 1-3 There are different grades: • Grade 1 - score of 3,4 or 5 • Grade 2 - score of 6 or 7 • Grade 3 - score of 8 or 9

Why is ER expression important to be aware of?

``` Predicts the response to anti-oestrogen therapy: • Oophorectomy • Tamoxifen • Aromatase inhibitors, e.g: Letrozole • GnRH antagonists ```

What is HER2?

Human Epidermal growth factor Receptor 2 - over-expression & amplification is seen in ~15% of breast cancers This predicts the response to Herceptin (AKA Trastuzamab), which is a humanised mouse monoclonal Ab that is active in HER2 +ve disease

TNM staging of breast carcinoma?

Direct invasion of adjacent tissues - T0-T4 Lymphatic spread - N0-N3 regional lymph nodes Blood-borne spread - M0-M1 distant metastasis NOTE - even with 1 +ve lymph node, prognosis worsens; it also worsens with lymphovascular invasion

Prognostic indices available for breast carcinoma?

Nottingham Prognostic Index (NPI) - uses histopathology only (grade & stage) Adjuvant! online - uses histopathology, ER and clinical factors PREDICT - uses histopathology, ER, clinical factors, HER2 and mode of detection