Pathology--24 Breast Pathology

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Manuel A. Castro, M.D., AAHIVS
Diplomate of the American Board of Internal Medicine
Certified by the American Academy of HIV Medicine

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Breast

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Acute Mastitis
• Associated with breastfeeding
• Most common S. aureus
• Breast erythematous, painful and fever
• Localized area of inflammation
• Leading to formation of abscess
• Infiltration with neutrophils may show necrosis
• Treatment: antibiotic and continued expression of milk

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A 38 year old female presents with complaints of a painless palpable mass on her left breast.
On mammography there is a mass with calcification noted which was later removed.
The result of the biopsy shows a gray-white nodule with a chalky white foci.
Which of the following is the most likely diagnosis?
1. Acute mastitis
2. Fat necrosis of the breast
3. Fibrocystic changes of the breast
4. Sclerosing adenosis
5. Paget’s disease of the breast
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Fat Necrosis
• Painless palpable mass
• Skin thickening or retraction
• Mammographic density or calcification
• History of trauma or prior surgery
• Poorly defined gray-white nodule with chalky white foci or hemorrhagic debris
• Dystrophic calcification occurs in the breast

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A 38 year old female presents for evaluation of a breast mass. The mass is removed and
showed a mass with more than two cell lines lining the ducts and lobules.
Which of the following is the most likely diagnosis?
1. Fat necrosis of the breast
2. Epithelial hyperplasia
3. Non-proliferative fibrocystic changes
4. Sclerosing adenosis
5. Papilloma of breast
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Fibrocystic Changes
• Lumpy bumpy breast on palpation
• Dense breast with cysts on radiology
• Pathologically benign histology
I.Non-proliferative
•Three morphological components
Cysts: blue domed appearance
Fibrosis: 2nd to cyst rupture and inflammatory reaction
Adenosis: increase number of acini per lobule

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Fibrocystic Changes
II.Proliferative fibrocytic changes

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Fibrocystic Changes
• Lumpy bumpy breast on palpation
• Dense breast with cysts on radiology
• Pathologically benign histology
I.Non-proliferative
•Three morphological components
Cysts: blue domed appearance
Fibrosis: 2nd to cyst rupture and inflammatory reaction
Adenosis: increase number of acini per lobule

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Fibrocystic Changes
II.Proliferative fibrocytic changes
• Increase risk for cancer
• Density, calcifications on mammography
• Proliferation of ductal epithelium and/or stroma  without histologic feature of carcinoma
1. Epithelial hyperplasia
 More than two cell layer lining ducts or lobules (normally only two cell layers)

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Fibrocystic Changes
II. Proliferative fibrocytic changes (cont.)
2. Sclerosing adenosis
 Acini per duct double
 Risk for invasive carcinoma
 Myoepithelial cells prominent
 Lobular arrangement maintained
 Acini compressed and distorted in the center
 Acini are dilated in the periphery
 Presentation
A.Palpable mass
B.Radiologic density or calcification

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A 32 year old female presents with bloody nipple discharge. She has notice some discomfort
of her left breast for a few weeks and a few days noticed a slightly bloody discharge.
Biopsy of the lesion showed a fibromuscular core with epithelial hyperplasia as well as
apocrine metaplasia.
Which of the following is the most likely diagnosis?
1. Papilloma of breast
2. Fibroadenoma
3. Phyllodes tumor
4. Ductual carcinoma in situs
5. Invasive ductal carcinoma
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Fibrocystic Changes
II. Proliferative fibrocytic changes (cont.)
3. Papilloma
Multiple branching finger like projections
Covered by epithelial and myoepithelial cells
Central core with blood vessel
Can lead to bleeding and bloody nipple discharge
A.Most common cause of bloody nipple discharge in women 20-40
Epithelial hyperplasia and apocrine metaplasia frequent
Situated in lactiferous sinuses of nipple


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Benign Neoplasm of Breast

2

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Fibrocystic Changes
II. Proliferative fibrocytic changes (cont.)
3. Papilloma
Multiple branching finger like projections
Covered by epithelial and myoepithelial cells
Central core with blood vessel
Can lead to bleeding and bloody nipple discharge
A.Most common cause of bloody nipple discharge in women 20-40
Epithelial hyperplasia and apocrine metaplasia frequent
Situated in lactiferous sinuses of nipple


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Benign Neoplasm of Breast

1. Fibroadenoma
2. Phyllodes tumor
3. Papillomas (discussed earlier)
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A 28 year old woman presents with a breast mass about 2 cm in diameter, rubbery and
movable. The mass was removed and showed macroscopically small slit-like spaces. On
microscopy there was proliferation of stroma, ducts and lobules without calcification or
necrosis.
Which of the following is the most likely diagnosis of this patient’s condition?
1. Papilloma of the breast
2. Fibroadenoma
3. Phyllodes tumor
4. Sclerosing adenosis
5. Comedo type ductal carcinoma in situs
6.
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Fibroadenoma

• Most common benign breast tumor in < 35 years of age
• Present with palpable mass, movable and rubbery
• Macroscopically shows small slit-like spaces
• Microscopically proliferation of benign stroma, ducts and lobules
• Stimulus cyclosporin A used in renal transplant patient
 Multiple and bilateral

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A 58 year old female presents with a palpable mass on her right breast. The mass is removed
and on microscopy showed nodules of stroma covered by epithelium, with some cellular
atypia and a leaf-like architecture. Two years after resection the mass started to grow again in
the same area
Which of the following is the most likely diagnosis?
1. Ductal carcinoma in situs
2. Invasive ductal carcinoma
3. Phyllodes tumor
4. Lobular carcinoma in situs
5. Invasive lobular carcinoma
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Phyllodes tumor
•Arise from intralobular stroma
•Mostly in the 6th decade of life
Palpable mass
Nodules of stroma covered by epithelium

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Breast Cancer

3

Which of the following is the most likely diagnosis?
1. Ductal carcinoma in situs
2. Invasive ductal carcinoma
3. Phyllodes tumor
4. Lobular carcinoma in situs
5. Invasive lobular carcinoma
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Phyllodes tumor
•Arise from intralobular stroma
•Mostly in the 6th decade of life
Palpable mass
Nodules of stroma covered by epithelium

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Breast Cancer

• Clinical Manifestations
• Palpable mass fix to the chest wall
• DCIS has mammographic calcifications
• Distortion of the architecture of the breast
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Carcinoma of the Breast

• Nipple retraction
• Skin dimpling
Infiltration of suspensory ligament
• Most common upper outer quadrant
• Gross examination
Stellate, white-tan, gritty mass
Detected exam at 2cm
Detected on MXM at 1cm




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Carcinoma of the Breast
• Affect 1 in 9 women in the US
• Most common cancer not including skin in women
• Second most common cause of cancer death in women after lung cancer


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Carcinoma of the Breast


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Risk Factors
1. Age (uncommon in young women)
In younger women tumors are
A.ER negative or
B.Human epidermal growth factor receptor (HER2/neu) positive
2. Associated with estrogen
 Menarche < 11 years
 Late menopause
 First live birth > 35 years
3. Race/ethnicity (highest non-Hispanic whites)
4. 1st degree relative with breast cancer
5. Personal history of breast or endometrial cancer
6. Prior breast biopsy revealing atypical hyperplasia

Carcinoma of the Breast
• Risks (cont.)
• Hereditary mutation of tumor suppressor genes
BRCA1, BRCA2 Genes

4

2. Associated with estrogen
 Menarche < 11 years
 Late menopause
 First live birth > 35 years
3. Race/ethnicity (highest non-Hispanic whites)
4. 1st degree relative with breast cancer
5. Personal history of breast or endometrial cancer
6. Prior breast biopsy revealing atypical hyperplasia
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Carcinoma of the Breast
• Risks (cont.)
• Hereditary mutation of tumor suppressor genes
BRCA1, BRCA2 Genes
» Help repair human DNA
– Increase risk for breast and ovary cancer
– Cancer at a younger
– BRCA2 > BRCA1 causes male breast cancer
p53 mutation (Li-Fraumeni syndrome)



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Ductal Carcinoma in Situs (DCIS)
NO mass
NOT invasive
Calcification on mammography
DCIS is divided into different subtypes: comedo, cribiform, micropapillary, papillary, and
solid.
• Subtype based on architecture





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Invasive ductal carcinoma
Forms duct like structures
Most common type > 80%
Presentation as mass
Advanced causes
• Dimpling of skin
• Retraction of nipple
• Biopsy
• Duct like structure in a desmoplastic stroma
• Special subtypes
• Tubular Carcinoma
well differentiated tubules without myoepithelium
good prognosis
• Mucinous carcinoma
abundant extracellular mucin
“tumor cells floating in mucous pool”
 Older women around 70
 Good prognosis







24

Invasive ductal carcinoma
• Special subtypes
• Medullary Carcinoma
large, high-grade cells forming syncitial groups associated with lymphocytes and
plasma cells
 Well circumscribed mimicking fibroadenoma
 BRCA1

5

 Older women around 70
 Good prognosis


24

Invasive ductal carcinoma
• Special subtypes
• Medullary Carcinoma
large, high-grade cells forming syncitial groups associated with lymphocytes and
plasma cells
 Well circumscribed mimicking fibroadenoma
 BRCA1
 Good prognosis
• Inflammatory Carcinoma
In dermal lymphatics
 Presentation  inflamed swollen breast
 Blockage of lymphatics
 No discrete mass and mimicking mastitis
 Poor prognosis

25

Lobular Carcinoma in Situs (LCIS)
• Proliferation of cells in the lobules
• No invasion of the basement membrane
• No mass or calcification
• Found incidentally on biopsy
• Disorganized cell pattern lacking
• E-cadherin  adhesion protein
• Multifocal and bilateral
• Treatment  tamoxifen
• Low risk of progression

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Invasive Lobular Carcinoma






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Small bland tumor cell which forms in single file pattern
Cells with signet-ringed morphology
Usually bilateral and multifocal
No ducts  lacks E-cadherin

Prognosis
• Based on TNM
• Metastasis is the most important factor
• Metastasis to axillary LNs is most useful prognostic factor
• Sentinel lymphnode biopsy used to assess LN biopsy
• Response to treatment predictive factors
• Response to antiestrogen agents (i.e. tamoxifen)
• Receptors located in nucleous
 Estrogen receptor positive (ER)
 Progesteron receptor postitive (PR)
• Associated with response to traztuzumab
 Antibodies against HER2/neu receptor
A.Human epidermal growth factor receptor (HER2/neu)
1)Present in cell surface
• Triple negative (ER, PR, HER2/neu) poor prognosis
 Higher incidence in African Americans
A.

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Paget Disease of Breast

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• Response to antiestrogen agents (i.e. tamoxifen)
• Receptors located in nucleous
 Estrogen receptor positive (ER)
 Progesteron receptor postitive (PR)
• Associated with response to traztuzumab
 Antibodies against HER2/neu receptor
A.Human epidermal growth factor receptor (HER2/neu)
1)Present in cell surface
• Triple negative (ER, PR, HER2/neu) poor prognosis
 Higher incidence in African Americans
A.
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Paget Disease of Breast





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DCIS that extends up the duct to invade skin
Presentation  nipple and areola ulceration and erythema, oozing and crusting
Paget’s disease of breath associated with underlying carcinoma
Epidermal spread of tumor cells (Pagets cells)
 Single or multiple in the epidermis
 Clear halo surrounds the nucleus

Gynecomastia
Benign breast tissue enlargement in males
 Favor of estrogen effect over androgen
 Microscopically seen as
A. Ductal epithelial hyperplasia
B. Ductal elongation
C. Ductal branching
D. Proliferation of periductal fibroblasts
E. With increase in tissue vascularity
• Associated to
 Physiologic in adolescents
A. Can also be seen in elderly or newborn
 Klinefelter syndrome
 Hyperprolactinemic states
 Drugs: spironolactone and ketoconazole
A.


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Male Breast Cancer
Usually seen in older adults
Subareolar mass
Usually located underneath the nipple
May produce nipple discharge
Most common type  invasive ductal carcinoma
 Very rarely lobular (no lobules in male breast)
• Associated with
 BRCA2
 Klinefelter’s syndrome






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1 •Mutation in male breast cancer

• BRCA2
•Breast tumors with calcification (3)
• Fat necrosis, Sclerosing adenosis, DCIS
•Most common cause of acute mastitis
• Breast feeding
•Most common cause of bloody nipple discharge in women 20-40

7



Associated with
 BRCA2
 Klinefelter’s syndrome

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1 •Mutation in male breast cancer

• BRCA2
•Breast tumors with calcification (3)
• Fat necrosis, Sclerosing adenosis, DCIS
•Most common cause of acute mastitis
• Breast feeding
•Most common cause of bloody nipple discharge in women 20-40
• Papilloma
•Slit-like spaces macroscopically
• Fibroadenoma
•Malignancy no mass palpable with calcification on mxm
• DCIS
•Mass with duct like structures, dimpling of skin and retraction of nipple
• Invasive ductal carcinoma
•Well differentiated tubules without myoepithelium
• IDC tubular carcinoma type
•Inflamed swollen breast with lymphatic blockage
• Inflammatory carcinoma
2 •Breast and ovary cancer associated mutation
• BRCA 1
•Most common organism in acute mastitis
• S. aureus
•Benign mass with calcification, prominent myoepithelial cells and risk for breast cancer
• Sclerosing adenosis
•Leaf-like architecture
• Pyllodes tumor
•Most common in the upper outer quadrant
• Breast cancer
•> 70 with mass with tubular cells floating in mucous
• IDC mucinous type
•Tumor cells in single file arrangement
• Invasive lobular carcinoma
•Incidental finding of disorganized cells lacking E-cadherin
• Lobular carcinoma in situs
•Ab to HER2/neu receptor
• Traztuzumab
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1 •Lack e-cadhesin

• Lobular carcinomas
•Tumor with cells in single file pattern, lacking e-cadhesin and signet-ring cells
• Invasive lobular carcinoma
•Drugs for HER2/neu positive tumors
• Traztuzumab
•Redish nipple biopsy showing cells with halo around the nucleous invading from the
basement membrane upwards
• Paget’s disease of breast

2 •No mass, no calcification, lacking e-cadhesin
• Lobular carcinoma in situs

8

1 •Lack e-cadhesin

• Lobular carcinomas
•Tumor with cells in single file pattern, lacking e-cadhesin and signet-ring cells
• Invasive lobular carcinoma
•Drugs for HER2/neu positive tumors
• Traztuzumab
•Redish nipple biopsy showing cells with halo around the nucleous invading from the
basement membrane upwards
• Paget’s disease of breast

2 •No mass, no calcification, lacking e-cadhesin
• Lobular carcinoma in situs
•Drug for estrogen and progesterone receptor positive tomors
• Tamoxifen
•Redish ulcerated nipple with calcification on mammography
• Paget’s disease of breast
•Male breast cancer associated with mutation of?
• BRCA2

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End

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Mammary Duct Ectasia

• Occurs in 5th or 6th decade in multiparous
• Poorly defined periareolar mass
• Thick white nipple secretions
• Occasionally with skin retraction
• Irregular palpable mass (mimics carcinoma)
• Morphologically
• Dilated ducts
• Inspissation of secretions
• Periductal granulomatous inflammation
• Interstitial chronic inflammatory infiltrate
• Ducts with lipid laden macrophages

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