Breast Pathology

PRESENTED BY
DR OWAIS
Objectives
Benign breast diseases:
● Know t h e ways that benign breast conditions can clinically present.
● Know t h e common inflammatory conditions of breast (mastitis and abscesses).
● Understand t h e pathology of fibrocystic change.
● Know t h e common benign breast tumours with special emphasis on fibroadenoma
and phyllodes tumour.
● Know t h e risk of subsequent breast cancer in women with diagnosed benign breast
lesions.
Breast cancer:
● Know t h e risk factors, classification, behavior and spread of breast cancer.
● Know t h e prognostic indicators of breast carcinoma.
 Lecture Content

1- Inflammatory
lesions
● Acute mastitis
● Periductal mastitis 2- Benign epithelial
● Mammary duct ectasia: dilated
ducts disease lesions
● Fat necrosis: due to mechanical
trauma, surgical or otherwise ● Non proliferative breast
● Lymphocytic mastopathy changes
(sclerosing lymphocytic lobulitis) ● Proliferative breast disease
seen in diabetics without atypia.
● Granulomatous mastitis
● Proliferative breast disease
with atypia

3- Stromal tumors

● Fibroadenoma
● Phyllodes tumors

5- Invasive
4- Carcinoma in situ
carcinoma
● Ductal carcinoma in situ ● Ductal carcinoma
● Lobular carcinoma in situ ● Lobular carcinoma
 Breast Inflammatory diseases
Introduction
● The functional unit of t h e breast is t h e lobule, which is
supported by intralobular stroma.
● Lined by myoepithelial and luminal cells.
● Each normal constituent is a source of Inflammatory,
benign and malignant lesions.

Mastitis
1)Acute mastitis 1 :
● Rare and may be caused by autoimmune disease, or foreign body–type reactions.
● Or Infections:
○ The only agent is Staphylococcus aureus.
○ Cause breast disease with any frequency.

Forms lactational If untreated, tissue

Gains entry via fissures
abscesses: collections of necrosis may lead to t h e
in nipple skin during t h e
neutrophils and appearance of fistula
first weeks of
associated bacteria in tracks opening onto the
breastfeeding.
fibroadipose tissue. skin.
● Symptoms include:
○ Erythema and edema, often accompanied by pain and focal tenderness.
○ Because it is rare, t h e possibility that t h e symptoms are caused by inflammatory
carcinoma should always be considered.
● Most cases are treated adequately with antibiotics and continued expression of milk.
Rarely, surgical incision and drainage is required.

2) Periductal mastitis: Recurrent subareolar abscess/ Squamous

metaplasia of lactiferous ducts, Zuska disease.
Painful erythematous subareolar mass.90% cases - assoc. with smoking
→ toxic substances in smoke alters epithelial differentiation. Recurrent
cases fistula occurs.
• HPE: Keratinizing squamous metaplasia of ducts. Keratin shed from the
cells plugs the ductal system→ dilation & rupture of duct. chronic
granulomatous inflammatory response.
• Treatment: En bloc surgical removal of the involved duct,
fistula.Antibiotics for secondary bacterial infection.

1. Most cases are treated with antibiotics and continued expression of milk.
 Intro to Breast tumors
Clinical presentation

Pain (mastalgia or mastodynia) Inflammation Nipple discharge

-Co mmo n sympto m often related to -Causes an edemato us and -May be normal when small in
menses, possibly d ue to cyclic ed ema erythemato us breast. quantity and bilateral.
and swelling. -It is rare and is mo st often caused by -The most common benign lesion
-Pain localized is usually caused by a infections, which only occur with any producing a nipple discharge is a
r up tur ed cyst or trauma to adipose frequency during lactation and
large duct papilloma.
tissue (fat necrosis). breastfeeding.
-Discharges that are spontaneous,
-Almost all painful masses are -An important mimic of
benign, b ut for unknown reasons inflammation is “inflammatory” unilateral, and bloody are of greatest
about 10% of cancers cause pain. breast carcinoma. concern for malignancy.

Lumpiness, or a diffuse nodularity Palpable masses 1 Gynecomastia

-Can arise from proliferations of -The only co mmo n breast symptom
stromal or epithelial cells. in males.
-Throughout the breast, is usually a - Detected when they are 2-3 cm size.
-There is an increase in both stroma
result of normal glandular tissue. -Most (95%) are benign; these tend to and epithelial cells resulting from an
-When pronounced, imaging studies be r o und to oval and to have
imbalance between estrogens, which
may help to determine whether a circumscribed borders.
stimulate breast tissue, and
discrete mass is present. -In contrast, malignant tumo rs
androgens, which counteract these
usually invade across tissue planes and
have irregular borders. effects.

Mammographic screening
● Detect early, nonpalpable asymptomatic breast carcinomas before metastatic
spread has occurred.
● The average size of invasive carcinomas detected by mammography is
significantly smaller than cancers identified by palpation, and only 15% will have
metastasized to regional lymph nodes at t h e time of diagnosis.
● Generally recommended to start after age 40.
● Densities (mass):
○ Most tumors appear radiologically denser than t h e normal breast.
○ Fibroadenomas, cysts etc. can also present as densities.
● Calcifications:
○ Calcium gets deposited in secretions, necrotic debris, or hyalinized stroma.
○ It can be seen in benign and malignancy (small, irregular, numerous, &
clustered).
○ Ductal carcinoma in situ (DCIS) is most commonly detected as
mammographic calcifications. it has increased t h e diagnosis of DCIS.

1. because so me cancers grow deceptively as circumscribed masses, all palpable masses require evaluation.
 Benign epithelial lesions
1 Non proliferative Breast Changes (Fibrocystic changes)
● Most common disorder of the breast.
● No increased risk for cancer.
● Produce palpable masses, mammographic densities, nipple discharge. Cyclic pain
● Age: 20-55 years, decreases progressively after menopause.
● Thought to be due to caused by hormonal imbalances.

Histology
● Nonproliferative because t h e lesions contain 2 layers of cells (Epithelial &
myoepithelial
● Three morphological changes:

1- Cysts with apocrine metaplasia 2- Fibrosis (fibrocystic changes) 3 - Adenosis

- Cysts are lined by luminal benign - The cysts can r upt ure and cause - An increase in
flat t ened t o columnar epithelium. inflammation and fibrosis in t he number of
- With focal apocrine metaplasia: response t o t he spilled debris. acini per lobule.
cells become large and have - May produce palpable firmness - can also be
abundant eosinophilic cytoplasm. (nodularity) of t he breast. seen in
- Apocrine secretions may calcify pregnancy.
and be detected by mammography.

2 Proliferative Disease without Atypia.

● Rarely form palpable masses.
● Incidental finding; detected as small mammographic densities.
● Risk for cancer is 1.5 – 2 times normal.
● Include the following entities:

-Defined as t he presence of more than 2 Microscopy:

layers. -Both epithelial and myoepithelial cells
a- Epithelial -Range from mild, moderate to proliferate.
Hyperplasia severe/florid. -Can be seen in t he
ducts and lobules.

-Mostly as incidental microscopic finding Microscopy:

but may occasionally present as a palpable - Adenosis and stromal fibrosis in t he
mass that is mistaken clinically for cancer. lobule which leads to compression and
b- Sclerosing
-Calcification is commonly seen in t h e distortion of t he lobule.
Adenosis
lesion, so even on mammograph y it can
mimic cancer. Almost always associated
with fibrocystic changes
 Benign epithelial lesions
- Radial scars 1: are stellate lesions -Present as an irregular
c- Complex characterized by a central nidus of mammographic density.
Sclerosing entrapped glands in a hyalinized -Closely mimic an invasive
Lesion stroma. carcinoma 2 both
(Radial Scar) Nidus is surrounded by radiating arms mammographically and
of epithelium w / cysts & hyperplasia grossly.

- Is a papillary t um or that arises from t h e ductal epithelium.

Large duct papillomas

(central papillomas): Small duct papillomas:

d- Papillomas - More common. -Commonly multiple and located

-Solitary and situated in t he lactiferous deeper within t he ductal system.
duct at t he nipple. -Increase t he risk of
-Patients present with bloody nipple subsequent carcinoma.
discharge. Sometimes, subareolar mass

E-Proliferative - when epithelial hyperplasia features are seen in fibrocystic disease it is called
variant of proliferative variant of fibrocystic disease
Fibrocystic
disease

3 Proliferative breast disease with atypia

● Atypical hyperplasia is a cellular proliferation.
● Risk for cancer is 4-5 times normal.
● Has some of t h e architectural and cytologic features of carcinoma in situ
but lack t h e complete criteria for that diagnosis and is categorized as:

1 Atypical ductal hyperplasia 2 Atypical lobular hyperplasia

Stromal tumors
Interlobular stroma
● Monophasic: only comprised of mesenchymal cells.
● Include benign soft tissue tumors found elsewhere in t h e body, such as
hemangiomas and lipomas.
● The only malignancy derived from this type is angiosarcoma, which may
arise in t h e breast after local radiotherapy.
1- The word "scar" refers to t h e morphologic appearance, and n o t a prior inflammation, trauma or surgery.
2- Difficult to differentiate from carcinoma.
 Stromal tumors
Intralobular stroma
● Biphasic: comprised of both stromal cells and epithelial cells.
● As t h e neoplastic proliferation of specialized lobular fibroblasts also stimulates
reactive proliferation of lobular epithelial cells.
● Two types: fibroadenoma and phyllodes tumors.

Fibroadenoma
● The most common benign tumor of female breast, Almost never malignant.
● Any age, most common before age 30.
● Classic presentation:
○ Firm, mobile lump “breast mouse”.
○ It may increase in size during pregnancy or stop growing and regress after
menopause.
● usually solitary but may be multiple and involve both breasts.
● Treatment: lumpectomy (only t h e lump is removed)

Morphology
● Gross:
○ Spherical nodules, size vary (1cm to 10cm).
○ Sharply demarcated and circumscribed
○ Freely movable and can be shelled out.
○ Cut surface: pearl-white and whorled.
● Histology:
○ Mixture of ducts and fibrous connective tissue.
○The stromal proliferation push and distort t h e
associated epithelium. Sharp borders.
Phyllodes
● Can occur at any age, but most present in t h e 40s and 50s.
● Much less common than fibroadenomas.
● Most present as large palpable masses (usually 3 to 4 c m in diameter)
● Morphology: fibroepithelial tumors, have a Phyllodes (leaflike) pattern
and a cellular stroma.
Benign phyllodes Low-grade phyllodes High-grade phyllodes

- Most (75%) of phyllodes - They t end to recur -Uncommon and they behave
tumors are benign. locally and a rarely aggressively.
metastasize. - Frequent local recurrences.
- Can metastasize to lung, bone, CNS.
 Introduction to Breast Carcinoma
Introduction
● The most common malignancy 1 and causes t h e majority of cancer deaths of women.
● Women by t h e age of 90 have a ⅛ chance of developing breast cancer.
● >95% of breast malignancies are adenocarcinomas.
● The most common location is in t h e upper outer quadrant (50%), followed by t h e
central portion (20%). About 4% of women have bilateral primary tumors or
sequentia llesions in t h e same breast.

Classification
First system:
● Breast cancers are divided based on t h e expression of:
1. Hormone receptors: estrogen receptor (ER) and progesterone receptor (PR).
2. The human epidermal growth factor receptor 2 (HER2), also known as (ERBB2).
● Classified into 3 major groups:
1. ER positive (HER2 negative; 50%–65% of cancers).
2. HER2 positive (ER positive or negative; 10%–20% of cancers).
3. Triple negative (ER, PR, and HER2 negative; 10%–20% of cancers).
● These three groups show striking differences in patient characteristics, pathologic
features, treatment response, metastatic patterns, time to relapse, and outcome.
Second system 2 :
● An alternative classification system with substantial overlap relies on gene
expression profiling.
● Divides breast cancers into four major types:
1. Luminal A: are lower-grade, ER-positive, HER2 negative.
2. Luminal B: are higher-grade, ER-positive, may be HER2 positive.
3. HER2-enriched: overexpress HER2 and do n o t express ER.
4. Basal-like: The majority by gene expression profiling resemble basally located
myoepithelial cells and are ER-negative, HER2-negative.
Morphological classification:
● Classified according to whether they have penetrated t h e basement me mb r a n e .
● The main forms are as follows:
○ Noninvasive (remains within t h e basement membrane):
■ Ductal carcinoma in situ.
■ Lobular carcinoma in situ.
○ Invasive:
■ Discussed later in the slides..
1. Excluding nonmelanoma skin cancer.
2. This system is currently u sed mainly in t h e context of clinical research.
 Introduction to Breast Carcinoma
Risk factors
Age and gender Reproductive History

- Rare in women < age 25 - Early age of menarche.

- Increases in incidence rapidly after age 30 - nulliparity
-75% of women with breast cancer are > age - absence of breastfeeding,
50 - older age at first pregnancy
- 5% are < 40 (because each increases t he exposure of breast
- Incidence in m en is only 1% of that in women. epithelial cells to estrogenic stimulation)

Family history Race/Ethnicity

- Individuals with multiple affected -The highest rate of breast cancer is in women of
first-degree relatives with early-onset breast European descent, largely because of a higher
cancer are at high risk. incidence of ER-positive cancers.
-In most families, it is thought that various -Hispanic and African American women t end to
combinations of low penetrance, “weak” develop cancer at a younger age and are more
cancer genes are responsible for increased likely to develop aggressive tumors.
risk. -Such disparities are thought to result from a
-However, approximately 5% to 10% of cases combination of differences in genetics, social
occur in persons who inherit highly penetrant factors, and access to health care and are an area
germline mutations in t um or suppressor genes of intense study.
which will increase t he risk by 90%.

Geographic factors Ionizing Radiation

-High risk in t he Americas and Europe than in -Radiation to t he chest increases t h e risk of breast
Asia and Africa. cancer if exposure occurs while t h e breast is still
-Diet, reproductive patterns, and developing.
breastfeeding practices are thought to be -For example, breast cancer develops in 25% to
involved. 30% of women who underwent irradiation for
-Breast cancer rates appear to be rising in Hodgkin lymphoma in their teens and 20s, but t he
parts of t he world that are adopting Western risk for women treated later in life is n o t elevated.
habits.

Other

-Postmenopausal obesity, postmenopausal hormone replacement, mammographic density, and

alcohol consumption also have been implicated as risk factors.
-The risk associated with obesity probably is due to exposure of t he breast to estrogen produced by
adipose tissue. In keeping with this, obesity is only associated with an increased risk of tumors that
express ER.
 Carcinoma In Situ
Ductal Carcinoma In Situ
● The non-invasive proliferation of malignant cells within t h e duct system
without breaching the underlying basement membrane.
● Relative risk of development invasive carcinoma is 8-10 times normal in A

both types of carcinoma in situ.

Morphology
● Variety of histological appearance/subtypes:
B
A. Comedo: Extensive central necrosis, which produces toothpaste like
necrotic tissue with calcified debris.
■ Most frequently detected as radiologic calcifications.
■ Less commonly, t h e surrounding desmoplasia results in an
ill-defined palpable mass or a mammographic density.
■ If untreated, 100% will become invasive. C
B. Cribriform:
■ Cells forming round, regular (cookie cutter) spaces.
■ The lumens are often filled with calcifying secretory material.
C. Solid (cells fill spaces).
D. Micropapillary and papillary.
D
■ 30% of Pure cribriform/micropapillary become invasive.

● Nuclear appearances:
○ Bland and monotonous: low nuclear grade.
○ Pleomorphic: high nuclear grade.
Mammography
● (E) micro-Calcifications due to calcification of necrotic debris or
secretory material.
● Mammography is specifically important here because there may n o t be a E
palpable mass, or discharge.

Treatment
● surgery: Wide local excision or mastectomy.
● Treatment with anti-estrogenic agents such as tamoxifen also is used to
decrease t h e risk of recurrence of ER-positive DCIS.

Prognosis
● The prognosis is excellent, with greater than 97% long-term survival.
● If untreated, DCIS progresses to invasive cancer in roughly ⅓ of cases,
usually in t h e same breast and quadrant as t h e earlier DCIS.
 Carcinoma In Situ
Paget disease
● Paget disease of t h e nipple is caused by t h e extension of DCIS up the
lactiferous ducts and into t h e contiguous skin of t h e nipple.
● Produce a unilateral crusting exudate over t h e nipple and areolar skin.
● The prognosis of t h e carcinoma of origin is affected by t h e presence of
paget disease and is determined by other factors.

Morphology
● Histologic hallmark: t h e infiltration of t h e epidermis by:
○ Large neoplastic ductal cells with abundant cytoplasm.
○ Pleomorphic nuclei and prominent nucleoli.
○ The cells usually stain positively for mucin.
○ Extension without crossing t h e basement membrane.
○ Palpable mass in 50% of patients

Lobular Carcinoma In Situ

● Always an incidental finding because, unlike DCIS, it is only rarely associated with
calcifications.
● Approximately ⅓ of untreated women eventually develop invasive carcinoma
(mostly lobular):
○ ⅔ may arise in t h e same breast and ⅓ in t h e contralateral breast.
○ LCIS is both a marker of an increased risk of carcinoma in both breasts and a
direct precursor of some c a n c e r s .

Morphology
● Has a uniform appearance.
● The cells are monomorphic.
● With bland, round nuclei, and are found in loosely cohesive clusters
within t h e lobules.
● The cells fill and expand t h e acini, but t h e normal structure can still
be recognized.

Treatment (Female only)

● Current treatment options include close clinical and radiologic follow-up.
● Chemoprevention with tamoxifen.
● Less commonly, bilateral prophylactic mastectomy.
 Invasive breast carcinoma
Introduction
● Invasive breast carcinoma is t u mo r that has extended across the basement
membrane.
● This permits access to lymphatics and vessels and Therefore t h e potential
to metastasize.

Classification
● Invasive ductal carcinoma: 70% to 80%. (NOS; n o t otherwise specified)
● Invasive lobular carcinoma: ~10% to 15%.
● Carcinoma with medullary features: ~5%.
● Mucinous carcinoma (colloid carcinoma): ~5%.
● Tubular carcinoma: ~5%.
● Other types.

Invasive Ductal Carcinoma

● Includes all carcinomas that cannot be subclassified into one of t h e
specialized types.
● It is associated with Ductal Carcinoma In Situs, require large excisions with
wide margins to reduce local recurrences.
● Gene expression classification:
○ 50-60% are ERpositive
○ 20% are HER2 positive
○ 15% are negative for both ER and HER2

Morphology
● Gross:
○ Firm, hard, with an irregular border.
● Cut surface:
○Gritty and shows irregular margins with stellate infiltration
(sometimes it can be soft and well demarcated).
○
In t h e center there are small foci of chalky white stroma
and occasionally calcifications.
● Histology:
○ Cells are large and pleomorphic usually within a dense stroma.
○Adenocarcinomas: so they show glandular formation but
can also be arranged in cords or sheets of cells.
○ Range from well differentiated → moderately → poorly differentiated.
 Invasive breast carcinoma
Invasive Lobular Carcinoma
● It is t h e second most common invasive breast cancer.
● It may occur alone or in combination with ductal carcinoma.

Clinical features
● Tend to be bilateral and multicentric.
● ⅔ of t h e cases are associated with LCIS.
● Almost all express hormone receptors, whereas HER2 overexpression is rare.
● The pattern of metastasis is unique:
○ they frequently spread to CSF, serosal surfaces, GIT, ovary, uterus, and
bone marrow.
● The amount of stromal reaction to t h e t u mo r varies:
○ Marked fibroblastic (desmoplastic) response to little to no reaction 1 .
○ therefore t h e presentation varies from a discrete mass to a subtle, diffuse
indurated area.

Morphology
● Morphologically similar to t h e t u mo r cells seen in LCIS.
● Gross: Most are firm to hard with irregular margin.
● Microscopic: Single infiltrating malignant cells, forming a
line often one cell width (called as indian file pattern).
● No tubules or papillary formation.

Medullary Carcinoma
● Special type of triple-negative cancer.
● 5% of all breast cancers.
● Typically grow as rounded masses that can be difficult to distinguish from
benign tumors on imaging.
● Seen frequently in women with germline BRCA1 mutations, but most women
with these carcinomas are n o t carriers.

Morphology
● Sheets of large anaplastic cells.
● Pronounced lymphocytic infiltrates predominantly (T cells).
● The presence of lymphocytes lead to a better response to chemotherapy
compared to poorly differentiated carcinomas without lymphoid infiltrates.

1. Clinically occult and difficult to d etect by imaging.

 Invasive breast carcinoma
Colloid Carcinoma (mucinous) Tubular Carcinoma

- ER-positive/HER2 negative - ER-positive/HER2 negative

general - produce extracellular mucin - mammography: as a small irregular mas
- may be pure, mor e mixed with ot her type

- Sharply well circumscribed

Gross - Lack fibrous stroma, slow growing
- Soft & gelatinous, glistering surface

Small islands of t umor cells and single cells - Cells are arranged in well formed tubules
Microscopy in a pool of mucin - low grade nuclei

Lumpectomy, mastectomy Lymph node metastases are rare, and t he

prognosis
prognosis is excellent

Inflammatory carcinoma
● Defined by its clinical presentation, rather than a specific morphology.
● Patients present with a swollen erythematous breast without a palpable mass.

Morphology
● The underlying invasive carcinoma is poorly differentiated and diffusely infiltrates and
obstructs dermal lymphatic spaces, causing t h e inflamed 1 appearance.

Prognosis
● Many of these tumors metastasize to distant sites.
● The overall 5-year survival is less than 50%, and lower in metastasis.
● About half express ER.
● 40% to 60% overexpress HER2.

Invasive carcinoma Grading

● Based on nuclear pleomorphism, tubule formation and proliferation 2 :
● Low grade nuclei:
○ Similar to normal cells.
○ Most form well-defined tubules,
○ Difficult to distinguish from benign lesions.
● High grade nuclei:
○ Enlarged with irregular nuclear contours.
○ Invade as solid sheets or single cells.

1.True inflammation is ab sent.

2. Proliferation is evaluated by counting mitotic figures.
 Invasive breast carcinoma
Clinical presentations
Unscreened population:
● Most breast cancers are detected as a palpable mass by t h e affected patient.
● Such carcinomas are almost all invasive and are typically at least 2 to 3 cm.
● At least ½ of these cancers will already have spread to regional lymph nodes.
● Tumor may be fixed to t h e chest wall, causing dimpling of t h e skin

Older screened populations:

● 60% of breast cancers are discovered before symptoms are present.
● About 20% are in situ carcinomas.
● Invasive carcinomas detected by screening in older women are 1to 2 cm.
● Only 15% will have metastasized to lymph nodes.

Peau d'orange:
● Lymphatics may become involved and t h e lymphatic drainage of that
area and t h e overlying skin gets blocked causing lymphedema and thickening of
the skin.
● When t h e t u mo r involves t he central portion of t h e breast,
retraction of the nipple may develop.

Prognostic factors
Biologic type
● The biologic type of cancer is evaluated by a combination of histologic
appearance, grade (including proliferative rate), expression of hormone
receptors, and expression of HER2.

Proliferation Expression of ER or PR Overexpression of HER2

- Evaluated by mitotic - Predicts response to anti-estrogen - Is seen in about 20% of

count. therapy. breast cancers.
- Tied to responsiveness to - The growth of hormone receptor - HER2 remains one of t he
cytotoxic chemotherapy. positive cancers can be inhibited with best-characterized
therapy and survival with distant examples of an effective
metastases is possible. therapy that is directed
- Resistance often develops in because against a tumor-specific
of mutations in t he ER gene. molecular lesion.
- In contrast, there is no therapy
available for triple negative cancers,
which are treated with chemotherapy.
 Invasive breast carcinoma
RNA expression
● RNA expression profiling is a newer method of sub classifying cancers.

Tumor stage
● Stage is a measure of t h e extent of t u mo r at t h e time of diagnosis and is
important for all biologic types of carcinoma.
● Based on features of (TNM):
● The primary tumor (T):
○ Tumors classified as T1, T2, and T3 based on t h e t u mo r size.
○ T4 tumors have ulceration of t h e skin, involvement of t h e deep muscles
of t h e chest wall, or are clinically diagnosed as inflammatory carcinoma.

● Involvement of regional lymph nodes (N):

○ Lymphatic drainage goes to one or two sentinel lymph nodes in t h e axilla
in most patients.
○ If these nodes are n o t involved, t h e remaining axillary nodes are usually
free of carcinoma.
○ Sentinel node biopsy has become t h e standard for assessing nodal
involvement, replacing more extensive lymph node dissections, which
are associated with significant morbidity.

● The presence of distant metastases (M):

○ Only detected in 5% of newly diagnosed women.
● Stages:

0 1 2
- Includes smaller
- Larger t um or size
cancers and either
- CIS or up to 3 positive
free nodes or with
- Survival rates nodes.
micro m etastases.
>95%. - Survival declines to
- Survival is ~86% at
~71% at Stage II.
10 years.

3 4
-large size, involvement
of skin or chest wall, or
- Distant metastases
by 4 or more positive
- survival is very poor
nodes.
(~11%).
-Only ~54% of patients
survive 10 years.
 Summary
Benign
Risk of Cancer Histopathology Comments
Epithelial Lesions

-Cysts with apocrine Most common disorder of

Non proliferative No risk metaplasia the breast.
- Fibrosis & Adenosis

Proliferative without atypia

Proliferation of both Defined as t he presence of

Epithelial epithelial and more than 2 layers.
Hyperplasia
myoepithelial cells

Adenosis and stromal

fibrosis with compression Incidental microscopic
Sclerosing Adenosis
finding
of t he lobule.

Central nidus of
Complex entrapped glands in a Mimic an invasive
Sclerosing 1.5 - 2 times carcinoma
hyalinized stroma.
normal

Large Duct:
Large Duct:
- Bloody nipple discharge.
- Solitary.
- Subareolar palpable mass.
- In lactiferous duct.

Papiloma
Small duct:
Small duct:
- Multiple.
- Increase t h e risk of
-Deeper within ductal
subsequent carcinoma
system.

Atypical ductal or lobular Resembling carcinoma in situ

Proliferative 4-5 times
but lack t he sufficient
without atypia normal hyperplasia.
features for that diagnosis.

Intralobular stromal tumors

-Cut surface: pearl-white and

whorled.
Most common benign tumor
Fibroadenoma -Mixture of ducts and fibrous
connective tissue.

Most present as large palpable - Phyllodes (leaflike) pattern

Phyllodes
masses and a cellular stroma.
 Summary
Breast cancer

Noninvasive

- Non-invasive proliferation of malignant cells within t he duct system.

DCIS - Histological Variants: comedo (necrotic center), Cribriform (cookie cutter).
- Micro-Calcifications is common.

- Incidental finding.
LCIS - ⅓ of women eventually develop invasive carcinoma.
- Rarely associated with Calcifications

Invasive

-Includes all carcinomas that cannot be subclassified into one of t he specialized

Invasive Ductal types.
Carcinoma - Associated with DCIS.
- 50-60% are ER positive.

- Tend to be bilateral and multicentric.

Invasive Lobular
- Unique metastatic pattern, to CSF, GIT, ovary, uterus and bone marrow.
Carcinoma
- Single file invasion of stroma.

-Triple negative cancer presenting as a rounded mass.

Medullary
- Associated with BRCA1 germline mutations.
Carcinoma
- Sheets of large anaplastic cells associated with lymphocytic infiltrates (T cells).

Colloid -ER positive, HER2 negative.

(Mucinous) - Produces abundant amounts of extracellular mucin.
Carcinoma - Soft and gelatinous.

-ER positive, HER2 negative.

Tubular
- Detected on mammography as a small irregular mass.
carcinoma
- Cells are arranged in well formed tubules, with low grade nuclei.

-Defined by clinical presentation, swollen erythematous breast without a palpable

mass.
Inflammatory
- Metastasize to distant sites.
carcinomas
- 50% are ER positive, 40-60% overexpress HER2.
- Cause inflamed appearance.
 Quiz

1)Which of the following is the most common 5)A 52-year-old woman was diagnosed with
benign tumor of the female breast? breast cancer. Upon examination of the tumor,
A) Phyllodes t um or it was soft, sharply circumscribed, and lacked
B) Papiloma fibrous stroma. It also had small islands of
C) Fibroadenoma tumor cells and single tumor cells floating in
D) LCIS pools of extracellular mucin. The most likely
diagnosis is:
2)A 52-year-old woman presents with a 3 A) Invasive ductal carcinoma
month history of a palpable breast mass. B) Medullary carcinoma
Physical examination confirms a 1-cm nodule in C) Colloid carcinoma
the upper outer quadrant of the right breast. A D) Intraductal carcinoma
biopsy shows small cuboidal cells with round
nuclei and prominent nucleoli. The cells are 6)A 40-year-old woman noticed a red, scaly
arranged in single cell columns between appearance on her left nipple and surrounding
strands of connective tissue. What is the most areola. On histological examination of the
likely diagnosis? nipple, there was infiltration of the epidermis
A) Acute mastitis with abscess by large neoplastic ductal cells with abundant
B) Invasive lobular carcinoma cytoplasm, pleomorphism, and prominent
C) Fibroadenoma nucleoli. The cells stain positive for mucin?
D) Intraductal carcinoma What is the most likely diagnosis?
A) Ductal carcinoma in-situ
3)A 48-year-old woman has noticed a red, scaly B) Fibroadenoma
area of skin on her left breast that has grown C) Fibrocystic change
slightly larger over the past 4 months. On D) Paget’s disease of t he breast
physical examination, there is a 1-cm area of E) Granulomatous mastitis
eczematous skin adjacent to the areola. The
figure shows the microscopic appearance of the 7)A 35-year-old nulliparous woman presents
skin biopsy specimen. What is the most likely with swollen breasts that are nodular upon
diagnosis? palpation. A mammogram shows foci of
A) Paget disease of t he breast calcification in both breasts. A breast biopsy
B) Fat necrosis reveals cystic duct dilation and ductal epithelial
C) Apocrine metaplasia hyperplasia without atypia. What is the
D) Lobular carcinoma in situ appropriate diagnosis?
A) Fibrocystic change
4)A 38-year-old woman feels a lump in her B) Fibroadenoma
right breast. Examination of the cross-section C) Ductal carcinoma in situ
showed a firm mass with gritty margins and D) Granulomatous mastitis
stellate infiltration, and small foci of chalky
white stroma. The most likely diagnosis is:
A) Invasive ductal carcinoma
B) Invasive lobular carcinoma
C) Fibroadenoma
D) Intraductal carcinoma
6) D
3) A
4) A
5) C
2) B

7) A
1)C
Thank You!