BREAST

PATHOLOGY
2022-2023


Professor Dr.Khitam Razzaq Al-Khafaji
 OBJECTIVES:
•  Reviewing breast architectures
•  Lis<ng examples of developmental abnormali<es
•  Enumerate the breast presen<ng symptoms of pathological
significance
•  State the inflammatory breast lesions
•  Define and classify the breast benign prolifera<ve lesions
•  Ci<ng the breast cancer epidemiological facts and risk factors
•  Lis<ng the morphological features and variants of breast cancer
•  State the stromal breast tumors
•  Evaluate the role of early breast cancer detec<on and the way to
achieve that
Normal breast
 Disorders of Development:

Supernumerary nipple

Congenital inverted
nipple
Congenital nipple inversion

Axillary breast Mssue

 Clinical PresentaMons of Breast
Diseases
•  Pain (mastalgia or mastodynia):
•  Palpable masses :
•  Nipple discharge :
Breast symptoms
 Inflammatory Disorders:
•  Acute Mas<<s:
•  the first month of breasReeding
•  Staphylococcus aureus and may cause abscess
•  May need surgical drainage
•  Fat Necrosis:
–  Palpable mass, skin thickening or retracMon
–  a history of breast trauma or prior surgery.

•  Duct Ectasia:
•  palpable periareolar mass
•  nipple secreMons and skin retracMon
•  fiVh or sixth decade of life in mulMparous women.
1- Acute Infec<ons (Pyogenic Mas<<s & Breast Abscess)

MASTITIS:

•  A local or generalized inflammaMon of the breast
•  Precipitated by lactaMon, trauma or infecMon through the ducts or nipple
abrasions.
•  Usually caused by Staph. Aureus which may invade the breast Mssue and
may progress to the formaMon of single or mulMple abscesses causing
conspicuous tenderness.
•  Less commonly may cause celluliMs.
•  If extensive necrosis occurs the destroyed breast substance will be
replaced by fibrous scar which may cause retracMon of the overlying skin
or nipple, stony hardness and axillary lymphadenopathy; changes
mimicking a malignant neoplasm.
•  Chronic inflammaMon if neglected may lead to fistula formaMon.
Trauma<c Fat Necrosis:

OVen follows trauma
Presents clinically as a firm hard mass ( in the fa]y Mssue of an
obese pendulous breast and someMmes associated with
skin retracMon.
It consists of a central focus of liquefacMve fat necrosis,
surrounded by lipid-layden macrophages and numerous
neutrophilic inflammatory infiltraMon. This is followed by
fibroblasMc proliferaMon, foreign-body giant cell
infiltraMon and ending into scar Mssue (which together
with the calcificaMon accounts for the hardness of the
lump).
Extensive fibrous reacMon may further cause nipple retracMon
and fixaMon thus simulaMng malignancy.
•  Duct Ectasia:
–  palpable periareolar mass
–  nipple secreMons and skin
retracMon
–  fiVh or sixth decade of life
in mulMparous women.
–  Chronic inflammaMon and
fibrosis
–  ectaMc duct filled with
debris
–  a firm irregular mass
•  Granulomatous Mas<<s:
•  uncommon disease that only
occurs in parous women
•  granulomas are closely
associated with lobules
•  hypersensiMvity reacMon to
anMgens expressed during
lactaMon
•  Treatment with steroids
Benign Epithelial Lesions:
 Non-prolifera<ve Breast Changes
(Fibrocys<c Changes):
•  It is not associated with an increased risk of
breast cancer: principle changes include:
1.  Cys<c change, oVen with apocrine
metaplasia
2.  fibrosis:
3.  Adenosis:
•  fibrocysMc changes:
grossly showed cysts.
Microscopically sowed
cysMc changes, apocrine
metaplasia and stromal
fibrosis
 Prolifera<ve Breast Disease Without
Atypia:
•  associated with a small
increase in the risk of
subsequent carcinoma
in either breast
(predictor of Ca.)
•  Epithelial hyperplasia.
The lumen is filled by a
heterogeneous, mixed
populaMon of luminal
and myoepithelial cell
types
 Prolifera<ve Breast Disease with
Atypia:
Atypical hyperplasia Atypical ductal hyperplasia (mic)
•  clonal proliferaMon
•  moderately increased risk of
carcinoma
1.  atypical ductal hyperplasia
cells showed atypia
(pleomorphism) yet it is
focal and inadequate to
be considered as
carcinoma in situ.
2.  atypical lobular
hyperplasia
 Clinical Significance of Benign
Epithelial Changes(risk of Ca.)
•  Without atypia 1.5- to two-fold increased risk
•  With atypia four- to five-fold increased risk.
•  Slightly more in ipsilateral breast
•  many choose careful clinical and radiologic
surveillance over intervenMon:
Carcinoma of the Breast
•  most common non-skin malignancy in women
•  is second only to lung cancer as a cause of cancer
deaths.
•  three major biologic subgroups:
–  Estrogen receptor (ER)-posi=ve, HER2-nega=ve (50%
to 65% of tumors)
–  HER2-posi=ve (10% to 20% of tumors, which may
either be ER-posiMve or ER-negaMve)
–  ER-nega=ve, HER2-nega=ve (10% to 20% of tumors).
Risk factors
Risk Factors:
•  Breast feeding. The longer women breasReed,
the greater the reducMon in risk.
•  Familial Breast Cancer: Approximately 12% of
breast cancers occur due to inheritance of an
idenMfiable suscepMbility gene or genes.
•  MutaMons in BRCA1 (on chromosome 17q21)
and BRCA2 (on chromosome 13q12.3) are
responsible for 80% to 90% of “single gene”
familial breast cancers and about 3% of all breast
cancers
 Types of Breast Carcinoma:
•  Carcinoma in Situ
»  Ductal carcinoma in situ

•  Invasive (infiltraMve carcinoma)

•  Morphological types:
»  Ductal of No Special Type (NST) or called Not Otherwise
Specified (NOS)
»  Lobular carcinoma
»  Other variant like mucinous, medullary, apocrine, ..ect
•  Biological or called molecular types:
»  ER +ve, PR +ve,
»  Her 2 +ve
»  ER –ve, PR -ve, Her 2 –ve
 Carcinoma in Situ
•  Ductal Carcinoma in Situ (DCIS):
–  Do not break the basement membrane of 2
major types:
•  Comedo type: high grade
•  Non-comedo type: low grade
•  If untreated, women with small, low-grade
DCIS develop invasive cancer at a rate of
about 1% per year. Tumors with high-grade or
extensive DCIS are believed to have a higher
risk for progression to invasive carcinoma.
 Carcinoma in Situ
comedo non comedo cribriform
 Invasive (Infiltra<ng) Carcinoma
•  According to the morphological appearance
the majority are of (NOS) and one third
classified into certain morphological variant
that may have clinical significant

 Molecular or biological classificaMon
•  ER-PR posi<ve, HER- nega<ve (also termed
“luminal,” 50% to 65% of cancers):
•  HER2-posi<ve (approximately 20% of
cancers)
•  ER-PR nega<ve, HER2-nega<ve tumors
( triple nega<ve carcinoma), approximately
15% of cancers) (BRCA1 mutaMons )
Morphology (pathological features)
•  GROSSLY:
hard, irregular mass
graMng sound (gri]y)
when cut
of chalky-white streaks of
desmoplasMc stroma
 Microscopical features:
NOS are adenocarcinoma

moderately
well differenMated poorly differenMated
differenMated
 Correla<on between the molecular type and the
morphology:

•  ER-posi<ve, PR posi<ve carcinoma. Many

morphologic pa]erns are possible (well to
poorly differenMated). EssenMally all well
differenMated carcinomas are in this group
•  HER2-posi<ve carcinoma. The majority of
these carcinomas are poorly differenMated.
•  ER-nega<ve, PR nega<ve, HER2-nega<ve
carcinomas. Almost all of these tumors are
poorly differenMated
 Special Histologic Types
•  Lobular carcinoma
•  inflammatory carcinoma.
•  Mucinous (colloid) carcinoma
•  Tubular carcinoma
•  Papillary carcinoma,
•  medullary carcinoma.
•  Secretory carcinoma
Pathological diagnosis of breast
cancer:
 Fine needle aspiraMon cytology
•  minimally invasive,
rapid, cheap, less
painful but with
limitaMons
 Core needle biopsy (tru cut biopsy)
•  More accurate and
further diagnosMc
procedures can be
performed on the
sample
 Other surgical samples
•  Excisional biopsy of the mass
•  ConservaMve breast surgery:
•  Radical mastectomy with axillary lymph node
clearance
 PROGNOSIS
•  in situ carcinoma understandably have an
excellent prognosis
•  Once distant metastases are present, cure is
unlikely,
•  Axillary lymph node status
•  Tumor size.
•  Locally advanced disease.
•  Inflammatory carcinoma
•  Molecular subtype.
•  Special histologic types
 EARLY DETECTION OF BREAST
CANCER:
•  Age 20+
–  Self-breast examinaMon(opMonal) monthly
–  Breast clinical examinaMon every 3 years
•  Age 40+
–  Mammography annually (or biannually)
•  High Risk
–  mammography annually + MRI
 Mammography
•  Special type of low-dose x-ray imaging used to
create detailed images of the breast.
•  Currently it is the best available populaMon-
based method to detect breast cancer at an
early stage, when treatment is most effecMve
It can demonstrate microcalcificaMons smaller
than 100 μm. OVen reveals a lesion before it
is palpable by clinical examinaMon
Mammogram
Stromal Tumors:
 Fibroadenoma:
•  most common benign
neoplasm of the breast
•  composed of
fibroblasMc stroma and
epithelium-lined glands
 Phyllodes Tumor:
•  Biphasic
•  stromal element of these
tumors is more cellular
and abundant
•  oVen forming epithelium
lined leaf-like projecMons
•  increased stromal
cellularity, anaplasia, high
mitoMc acMvity, rapid
increase in size, and
infiltraMve margins
LESIONS OF THE MALE BREAST
 Gynecomas<a:
•  may occur in response to absolute or relaMve
estrogen excesses
•  cirrhosis
•  Klinefelter syndrome,
•  anabolic steroids,
•  some pharmacologic agents.
•  Physiologic gynecomasMa oVen occurs in
puberty and in extreme old age.
 Carcinoma of male breast:
•  less than 1% of that reported for women
•  diagnosed in advanced age
•  rapidly infiltrates the overlying skin and
underlying thoracic wall
•  resemble the invasive carcinomas seen in
women
•  half have spread to regional nodes or more
distant sites by the Mme they are discovered.
 Summary
•  Few developmental lesions of breast may mimic
serious lesions
•  The breast is a site of certain peculiar
inflammatory lesions
•  In atypia is present in proliferaMve lesions the risk
of CA development increases by 4-5 folds.
•  Breast cancer is the most common female cancer
and its early detecMon by screening programs
improves paMent’s survival and reduce the
medical efforts
•  Breast carcinoma and be classified according
the morphology or according to the molecular
profile regarding the expression of certain
molecules (ER & Her 2)
•  Fibroadenoma and phyllodes tumor are
stroma tumors
•  Male can also develop breast cancer
 Further readings
•  Robbins & Cotran Pathologic Basis of Disease -
8th Ed