Manuel A. Castro, M.D.

, AAHIVS
Diplomate of the American Board of Internal Medicine
Certified by the American Academy of HIV Medicine

Breast

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

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. Pagets disease of the breast
5

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

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
7

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

Fibrocystic Changes
II.Proliferative fibrocytic changes

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

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)

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

10

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
11

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

12

Benign Neoplasm of Breast

11

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

12

Benign Neoplasm of Breast

1. Fibroadenoma
2. Phyllodes tumor
3. Papillomas (discussed earlier)
13

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 patients condition?
1. Papilloma of the breast
2. Fibroadenoma
3. Phyllodes tumor
4. Sclerosing adenosis
5. Comedo type ductal carcinoma in situs
6.
14

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

15

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
16

Phyllodes tumor
Arise from intralobular stroma
Mostly in the 6th decade of life
Palpable mass
Nodules of stroma covered by epithelium

17

Breast Cancer

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
16

Phyllodes tumor
Arise from intralobular stroma
Mostly in the 6th decade of life
Palpable mass
Nodules of stroma covered by epithelium

17

Breast Cancer

Clinical Manifestations
Palpable mass fix to the chest wall
DCIS has mammographic calcifications
Distortion of the architecture of the breast
18

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

19

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

20

Carcinoma of the Breast

21

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

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
21

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)

22

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

23

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

 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

26

Invasive Lobular Carcinoma

27

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.

28

Paget Disease of Breast

 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.
28

Paget Disease of Breast

29

DCIS that extends up the duct to invade skin

Presentation nipple and areola ulceration and erythema, oozing and crusting
Pagets 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.

30

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
Klinefelters syndrome

31
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

Associated with
BRCA2
Klinefelters syndrome

31
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
32
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
Pagets disease of breast

2 No mass, no calcification, lacking e-cadhesin

Lobular carcinoma in situs

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
Pagets 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
Pagets disease of breast
Male breast cancer associated with mutation of?
BRCA2

33

End

34

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