Professional Documents
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BOOBIES
Dr. Soccorro Cruz-Yanez
January 3, 2012
Histology
Mammary Lobules
- The secretory units of the breast
- Each lobule consists of a variable number of acini, or glands,
embedded within loose connective tissue and connecting to
the intralobular duct
- Each acinus is lined by two types of cells,
1. Epithelial
2. Myoepithelial
1. Epithelial or ductal cells (columnar, luminal location)
- Luminal epithelial cells overlay the myoepithelial cells.
- Only the lobular luminal cells are capable of producing
milk.
- Responsible for secretion
2. Myoepithelial (investing, basal location)
- Also known as Sentinel Cells
- When these cells are present, it indicates the presence of
a benign Lesion
- Contractile myoepithelial cells containing myofilaments lie
in a meshlike pattern on the basement membrane.
- These cells assist in milk ejection during lactation and
provide structural support to the lobules
Notes:
Functional unit of secretion of milk for nourishment of baby
Made up of several lobules of mammary breast draining
into the nipple
Drainage of lymphatic channels Disease of breast,
st
particularly malignancy, breast carcinoma: 1 line of
metastasis is regional lymph node, particular axillary node
(80-90%), internal mammary group of chain of lymph node,
particularly the inner quadrant of the breast, and
supraclavicular group of lymph node.
Lymphatic Drainage
Axillary Most common site because tumor cells in the outer
quadrant travels this drainage
Internal Mammary Where tumor cells in the Inner Quadrant
enter and travel to the intrathoracic artery
Supraclavicular If this is affected, it indicates a more
advanced stage of a disease
SECTION B
Fig. 4. Left: Active phase. Middle: Lactating phase. Right: Atrophic phase
Pathology
1 | 10
A. Imaging
- Mammography (age 40 screening mammography)
i. Densities
Most neoplasms are radiologically denser than
the intermingled normal breast tissue.
The average size of an invasive carcinoma
detected by mammography (1.1cm) is less than
half that of carcinomas detected by palpation
(2.4cm)
ii. Calcification (Malignant Heavy speckled type of
whitish calcification that are group around)
They form on secretions, necrotic debris, or
hyalinized stroma.
Ductal carcinoma in situ (DCIS) is most
commonly
detected
as
mammographic
calcifications, which are deposited in a linear,
branching pattern as the carcinoma fills the
ductal system.
- Ultrasound, MRI
B. Biopsy
- Fine Needle Aspiration
- Tissue biopsy
- Immunohistochemistry
Disorders of Development
Supernumerary Nipples Disease (Milkline remnants)
Due to persistence of epidermal thickening along the milk line,
which extends from the axilla to the perineum
2 or more nipples
can occur in both males and females
Heterotopic, hormone-responsive foci, which most commonly
come to attention as a result of painful premenstrual
enlargements
Developmental anomaly
Fig. 6. Nipple lines from the axilla to the pubic region. Also known as milk lines
SECTION B
Pathology
2 | 10
Note:
Breast tissue always extends to the axilla, and when it does
form an actual protuberance, it can be called an accessory
breast. Breasts are modified apocrine sweat glands
embryologically.
Nipple Inversion
Macromastia
Fig. 9. Macromastia
Inflammatory Conditions
Inflammatory diseases of the breast are uncommon.
Women usually present with an erythematous, swollen painful
breast
Inflammatory Disorder:
1. Acute Mastitis
2. Periductal Mastitis
3. Mammary Duct Ectasia
4. Fat Necrosis
5. Granulomatous mastitis
6. Lymphocytic Mastitis
7. Silicone Breast Implants
Note:
Periductal mastitis, mammary duct ectasia and fat
necrosis may be mistakenly clinically seen as malignancy
due to same clinical presentation like scarring and nipple
inversion.
Be sure to know the difference among the inflammatory
disorders, like how acute mastitis morphologically differ
from lymphocytic mastitis.
Acute Mastitis
Almost all cases of acute mastitis occur during the first month
of breastfeeding.
Difficulty during lactation
Associated with breaks, cracking in the skin, lactation
(mechanical trauma due to sucking of the baby) Breast is
vulnerable to bacterial infection
Big, swollen, erythematous painful breasts with pus, fever
Predominant inflammatory cells: Neutrophils inside the ducts
and stroma
SECTION B
Fig. 10. Left: Gross There is erythema and edema. Right: Histological Hallmark
Presence of many pigmented neutrophilic infiltration(yellow arrow) inside the ducts.
Periductal Mastitis
Also known as Recurrent Subareolar Abscess, Squamous
Metaplasia of lactiferous ducts, Zuska Disease
Subareolar location
Seat of inflammation is around the duct
Presents with a painful, erythematous, subareolar mass that
clinically appears to be an infectious process.
Recurrences are common
More than 90% of the afflicted are smokers
o Vitamin A deficiency associated with smoking or toxic
substances in tobacco smoke alter the differentiation of
the ductal epithelium
This condition is not associated with lactation, a specific
reproductive history, or age.
May be mistaken clinically for carcinoma due to fibrosis,
scarring, induration and nipple inversion.
Can present clinically as a malignant lesion because of
presentation
Many women with this condition have an inverted nipple, most
likely as a secondary effect of the underlying inflammation
Location is very important: Centrally beneath the nipple
Histology
- Squamous metaplasia of lactiferous duct (normally cuboidal
lining)
- Keratin trapping and duct dilatation Rupture of duct
- Chronic and granulomatous inflammation Develops once
keratin spills into the surrounding preductal tissue
- The inflammation is PERI-ductal, not Intraductal that is why
you would see the inflammatory cells surround the ducts.
Fig. 11. The key histologic feature is keratinizing squamous metaplasia of the nipple
ducts; it also shows lymphocytic infiltration around the dilated ducts(upper left).
Note:
Remember! DILATED, LYMPHOCYTE around the ducts and
METAPLASIA.
Pathology
3 | 10
Histology:
- Dilated ducts filled with granular, necrotic debris
- Necrotic, atrophic lining
- Periductal & interductal chronic granulomatous inflammation:
(+) Lymphocytes, macrophages
- Squamous metaplasia of nipple ducts is absent.
Fig. 12. Mammary Duct Ectasia, dilated ducts can be seen and atrophic lining.
Some fibrosis is appreciated.
Fat Necrosis
History of trauma, prior surgery or radiation therapy or those
with big pendulous breasts
Can present as a painless palpable mass, skin thickening or
retraction, a mammographic density, or mammographic
calcifications
Clinically simulate malignancy due to firm fibrosis occurring at
late stages of fat necrosis
The major clinical significance of this condition is its possible
confusion with breast cancer.
Histology:
- Early: Central focus of fat, necrosis, surrounded by lipid,
macrophages, inflammatory cells
- Late: Fibrosis, calcification
Lymphocytic Mastitis
Also known as Lymphocytic Mastitis/Lymphocytic
Mastopathy/ Sclerosing Lymphocytic Lobulitis
Diabetic Mastopathy
Most common in women with Type 1 DM or autoimmune
thyroid disease
Non-Bacterial etiology
Related to Inflammation
A prominent lymphocytic infiltrate surrounds the epithelium
and small blood vessels
Destruction of mammary alveolus
Single or multiple hard irregular palpable masses (The lesions
are so hard that it can be difficult to obtain tissue with needle
biopsy) Malignant clinical presentation
The major clinical significance of this condition is its possible
confusion with breast cancer.
Microscopic findings:
o Collagenized stroma
o Atrophic ducts and lobules
o Thickened BM
o Prominent lymphocytic inflammatory infiltrates
Fig. 15. Lymphocytic Mastitis, plasma cell and lymphocyte can be seen.
Pathology of Implants
Silicone Breast Implants
Fig. 13. Fat necrosis, some calcification are seen and necrosis of fat cells which
looks like ghost cell.
Granulomatous Mastitis
Non-bacterial etiology
Idiopathic
Non-caseous type of TB
Associated with systemic granulomatous
disease,
mycobacteria, fungal infection, immunocompromized, foreign
body, hypersensitivity reaction associated with lactation
Causes include systemic granulomatous diseases that
occasionally involve the breast, and granulomatous infections
caused by mycobacteria or fungi
Most common in immunocompromised patients or adjacent to
foreign objects such as breast prostheses or nipple piercings
Granulomatous Lobular Mastitis is an uncommon breastlimited disease that only occurs in parous women
The granulomatous inflammation is confined to the lobules,
suggesting that it is caused by a hypersensitivity reaction to
antigens expressed by lobular epithelium during lactation.
Fig. 14. Granulomatous mastitis, giantcells are seen and can be mistaken for
TB therefore differentiated with an AFB stain.
SECTION B
Fig. 16. Silicone Breast Implant, the white parts are silicone that has leaked.
th
Pathology
4 | 10
o Fibrosis
As cysts rupture, chronic inflammation and scarring
fibrosis result Palpable firm breast
o Adenosis
Increase in the number of acini per lobule
The acini are line by columnar cells, which may
appear benign or show atypical features (flat epithelial
atypia)
These atypical features may be the earliest
recognizable precursor of epithelial neoplasia
o Ductal epithelial hyperplasia (ducts affected have
increased proliferative activity.
This is more worrisome due to the increased risk of
malignancy.
Sclerosing Adenosis
Increased number (to at least double the number) of distorted
and compressed acini within the lobule, CT sclerosis within
the mammary lobule
The normal lobular arrangement is maintained
Myoepithelial cells are usually prominent
Firm with induration
May be confused with Breast CA because of the CNT
proliferation
1-2 times increased risk of malignancy
Fig. 20 Sclerosing adenosis. There is connective tissue that grows inside the
adenotic lobule
Ductal Papilloma
Fig. 17. Fibrocystic Disease. There is adenosis beside the cysts. Without
hyperplasia = no risk of malignancy. With hyperplasia, high incidence of malignancy
Fig. 18. Left: Blue dome cyst which appears to be like dome, brown to blue cyst
due to leak with contamination of blood. Right: The encircled is the fibrocysts
surrounding the connective tissue and nodular upon palpation.
Fig. 21. Hyperplastic proliferation of duct which is confined in the ductal lumen
Fig. 19. Left: Normal ductal epithelium. Right: Ductal hyperplasia (more than 2
layers of cells)
SECTION B
Fig. 22. Atypical Ductal Hyperplasia. No invasion of the stroma is seen. Atypical
cells are appreciated.
Pathology
5 | 10
Phyllodes Tumor
Clinical Significance
Increase risk of carcinoma is proportional to the type of PBD
(Proliferative Breast Diseases) and presence of atypia
No risk: Adenosis, cysts, apocrine metaplasia and mild
epithelial hyperplasia
No atypia = No risk of malignancy
Type of Atypia: Mild, Moderate, Severe
Slight increase: 1.5-2 times Sclerosing adenosis, moderate
to florid epithelial hyperplasia, papillomas
Moderate increase risk: 4-5 times ADH, ALH
Fibroadenoma
Most common benign tumor of female breast
A new growth composed of fibrous and glandular tissue
More common before 30 yrs of age [previous trans says
before 20-30 yrs of age]
Morphology
o Spherical nodule, sharply circumscribed, freely movable,
palpable, soft, rubbery mass, small, demarcated, no
fixation
o VS Malignant
Irregular, thick, poorly demarcated border, firm gritty
to stony hard
o Frequently occur in the upper outer quadrant
o Size varies from 1cm to 10-15cm (giant!)
o Fibrous stromal and ductal epithelial proliferation
Gross
- Large , bulky , well circumscribed, cleft like spaces
- Hemorrhage, necrosis , cysts
Histology
- Stromal hypercellularity
- Not true sarcoma
- More fibroblastic cells within the connective tissue
- Benign glandular elements, often in canalicular slits with or
without hyperplasia
Fig. 26. Left: Gross Notice the well circumscribed, cleft-like spaces. Right:
Histology There is increased stromal cellularity, cytologic atypia, and stromal
overgrowth giving rise to the typical leaflike structure.
Criteria of Malignancy:
o Stromal cell atypia
Mitosis
Pleomorphism
Nuclear atypia
o Cellular stroma overrunning epithelial component
o Infiltrative borders vs pushing borders
Clinical Behavior
o Tendency for local recurrence
o Malignant PT, metastasis by hematogenous route
Breast Carcinoma
Carcinoma of the breast is the most common non-skin
malignancy in women
The majority of carcinomas are estrogen-positive (ER)
positive.
Fig. 24. Left: Gross White circumscribed tumor in the middle. Right:
Mammography showing calcification
Risk Factors
SECTION B
Pathology
6 | 10
Age at Menarche
o Those <11 years of age have a 20% increased risk
compared to women who reach menarche when >14
years of age
o Late menopause also increases risk.
Age at First Live Birth
o Women with a first full-term pregnancy at <20 years old.
Race / ethnicity: Highest among white americans
Estrogen exposure Hormonal Replacement Therapy 1.2 to
1.7 increase risk
Oral Contraceptive use
High breast radio density
Radiation exposure
Carcinoma of contra lateral breast Ca ( 1 % ) and ovarian
Ca
Diet:
o Increase risk: Alcohol, fat
o Decrease risk: Caffeine
o Post menopausal Obesity
Exercise: Protective factor
Breast feeding --. Lower risk
Environmental Toxins (pesticides)
Tobacco
Etiopathogenesis
The major risk factors for the development of breast cancer
are hormonal, radiation and genetic
Breast cancers can therefore be divided into sporadic cases,
probably related to hormonal exposure, and hereditary cases,
associated with germline mutations.
Hormonal factors
o Hyperestrenism, endogenous and exogenous
Environmental factors
o Radiation
o Diet: Fat, moderate alcohol consumption
Increasing age
Proliferative breast disease
CA in contralateral breast
Parity
o Decreased parity Higher risk
o When the woman is pregnant, theres an interruption in
estrogen production there less risk for breast CA
Obesity
Genetic factors
o Gene line mutations in BRCA1 and BRCA2, p53,
Autosomal inherited
o sSngle gene mutation of breast susceptible cancer
gene: BRCA1 and BRCA2, p53
o BRCA1 : 17q21
Increase risk of developing ovarian CA
Poorly differentiated , triple negative IHC
(-) ER, Estrogen, Progesterone, HER2
Poor prognosis, alternative hormonal treatment is not
an option
o BRCA2: 13q12-13
Associated carcinoma
Ovarian(lesser extent), prostate, pancreatic stomach
CA
Poorly differentiated, more often ER positive.
Amenable for hormonal treatment
o Germline mutation of p53 (17p13.1)
Associated with Li-Fraumeni syndrome with sarcoma,
lymphoma, leukemia, brain tumors
Sporadic breast cancer
o Major risk factors related to hormone exposure
o Usually post-menopausal and are ER +
o Well-differentiated
SECTION B
15 30 %
80 %
20 %
70-85 %
79 %
10 %
6%
2%
2%
1%
Features of Atypia
Note:
The asterisked items, are more suspicious than the nonasterisked items. Intraductal NECROSIS is the most suspicious
feature of all.
Pathology
7 | 10
B. Non-comedo DCIS
Consists of a monomorphic population of cells with nuclear
grades ranging from low to high
Solid without necrosis
Morphologic variants:
o Cribriform DCIS
o Solid DCIS
o Papillary DCIS
o Micropapillary DCIS
Fig. 29. LCIS: A whole lobule filled with monotonous cells of the same type can be
called LCIS, or lobular carcinoma in situ.
Inflitrating Ductal CA
Also known as Invasive carcinoma, No Special Type
(NST/Invasive Ductal Carcinoma)
70 80 % of breast carcinoma
Originates from ducts with invasion into stroma
May have pronounced desmoplasia (Fibrosis) Scirrhous
carcinoma
Most carcinomas induce a marked increase in dense, fibrous
desmoplastic stroma, giving the tumor a hard consistency on
palpation and replace fat, resulting in a mammographic
density (scirrhous carcinoma)
Classification of DCIS
Based on cyto-nuclear
grade and
architectural growth pattern and necrosis
Grading Classification:
o High grade DCIS Grade 3
o Intermediate grade DCIS Grade 2
o Low grade DCIS Grade 1
o Increase grade Increase necrosis
o Low grade More Solid
High grade DCIS
Intermed
grade DCIS
Nuclear
changes in
between
Punctate
necrosis
differentiation
SECTION B
Pathology
8 | 10
Inflitrating Lobular CA
Bilaterality ( 5 10 % )
Multicentric
Diffusely invasive pattern
Frequent metastasis to CSF, serosal surfaces, ovary , uterus
and bone marrow
Greater incidence of bilaterality
Increasing incidence in postmenopausal women
Multicentric: May involve all breast quadrants
Usually present as a palpable mass or mammographic
density
have a diffusely invasive pattern without prominent
desmoplasia
Have a different pattern of metastasis than other breast
cancers
o Metastasis tends to occur to the peritoneum and
retroperitoneum,
the
leptomeninges
(carcinoma
meningitis), GIT, and the ovaries and uterus
In some cases, metastatic lobular carcinoma may be
mistaken for signet ring carcinoma of the GIT, which it closely
resembles
Histologic hallmark: Pattern of single infiltrating tumor cells,
often only one cell in width (in the form of a single file) or in
loose clusters or sheets
Fig. 32. Left: Soft, well circumscribed, pale gray-blue gelatinous consistency. Right:
The tumor cells are seen as clusters and small islands of cells within large lakes of
mucin that push into the adjacent stroma
Tubular Carcinoma
Good carcinoma
Typically detected as irregular mammographic densities
Occur in women in late 40s
All are well-differentiated
Excellent prognosis
Consist exclusively of well-formed tubules and are sometimes
mistaken for benign sclerosing lesions
A myoepithelial cell layer is absent, and tumor cells are in
direct contact with stroma
Frequently associated with ALH, LCIS, or low grade DCIS
Axillary metastases occur in fewer than 100% of cases unless
multiple foci of invasion are present. This subtype is important
to recognize because of its excellent prognosis
Fig. 31. Indian File pattern: Like Indians dancing side by side in a single line
Medullary Carcinoma
th
Fig. 32. Medullary Carcinoma. Left: Gross. Right: Histology. Highly pleomorphic
with lymphocytic infiltrates surrounding the tumor cells (important characteristic of
this carcinoma)
Characterized by:
o Solid, syncytium-like sheets of large cells with vesicular,
pleomorphic nuclei, and prominent nucleoli, which
compose more than 75% of the tumor mass
o Frequent mitotic figures
o Moderate to marked lymphoplasmacytic infiltrate
surrounding and within the tumor
o pushing(noninfiltrative) border
All medullary carcinomas are poorly differentiated
Mucinous (Colloid) CA
Tends to occur in older women (Median age is 71 yrs )
Soft, well circumscribed , gelatinous consistency
Better prognosis compared to NOS carcinoma - Good
carcinoma
Usually ER positive
Unusual type of breast CA
SECTION B
Inflammatory Carcinoma
The term inflammatory carcinoma is reserved for tumors that
present with a swollen, erythematous breast
Very aggressive! Youll be dead within months
Involves dermal lymphatics
Usually has a diffuse infiltrative pattern and typically does not
form a discrete palpable mass
Common presentation like mastitis
Ulcerated, red, weeping, eczematoid, skin trophic changes
Fig. 34. Left: Inflammatory carcinoma with its classic Peau dorange appearance.
Right: Lymphatic Invasion in axillary node
Pathology
9 | 10
Fig. 36. Left: Skin ulceration. Right: Skin ulcerations with palpable axillary lymph
nodes.
SECTION B
REFERENCES
1. Dra. Yanezs Lecture and PPT
2. 2013B trans
3. Robbins and Cotrans
Pathology
10 | 10