The document provides a comprehensive overview of breast pathology, detailing the anatomy of the breast and common lesions, clinical presentations, and risk factors for breast diseases including breast cancer. Key topics include types of benign tumors, classifications of breast carcinoma, diagnostic methods, and important prognostic factors. The information highlights the significance of early detection through mammographic screening and the complexities of breast cancer pathology.

1. BREAST PATHOLOGY
DR. OROMO FRANCIS OMOJO
MBBS. MD. MSc
CONSULTANT PATHOLOGIST

2. Breast Histology
- The breast is composed of six to ten ductal
systems originate at the nipple.
- Branching of the large ducts leads to the terminal
duct lobular unit which branches into cluster of
small acini to form a lobule.
- The ducts and lobules are lined by two cell
types,the epithelial and the myoepithelial
- The breast contains fibrous interlobular stroma
and myxomatous intralobular stroma.

3. Normal Breast


4. Normal Breast


5. -
***
Anatomical location Of common breast lesions
-;
-
A. Terminal duct lobular unit
:
-
1
.
Fibrocystic changes
-
2
.
Small duct papillomas
-
3
.
carcinomas
-
B.Intralobular stroma
:
-
1
.
Fibroadenoma
-
2
.
Phyllodes tumour
-
C.Large ducts and Lactiferous sinuses
:
-
1
.
Duct ectasia
-
2
.
Solitary duct papilloma
-
D. Interlobular Stroma
:
-
1
.
Fat necrosis 2. Lipoma

6. Clinical presentation of breast
diseases
- The most common symptoms are pain, palpable
mass or nipple discharge
- Pain is the most common symptom, the great
majority of painful masses are benign and about
10% of malignant lesions are painful.
- Palpable mass is the second most common symptom
and the breast masses become palpable when the
size is 2 cm.The likelihood that a palpable mass is
malignant increases with the age of the patient
- - Nipple discharge are caused mainly by solitary
ductal papilloma, cyst or carcinoma.

7. Mammographic screening
- is a tool to detect small non palpable breast
carcinomas not associated with symptoms
- -Is recommended to start at age of 40.
- Younger women usually undergo
mammography only if they are at high risk
for developing carcinoma ,like if they have
family history of breast carcinoma.

8. Inflammatory disorders
- Acute mastitis:- All cases occur during lactation due
to cracks in the nipple and the majority are caused by
Staph aureus.
- -Mammary duct ectasia:- occur in the fifth and sixth
decades of life.The patients present with periareolar
mass and nipple discharge.Microscopic examinations
shoe dilatation of major ducts suurounded by
inflammatory cells mainly plasma cells.
- Fat necrosis presents as painless mass or
mammographic calcification and can be misdiagnosed
clinically as carcinoma

9. Periductal mastitis:-
- The patients present with erythematous subareolar mas
-> 90% of patients are smokers
-Not associated with lactation
-the main histological feature is keratinizing squamous
epithelium extending to the orifices of the niple ducts
and keratin is trapped within the ducts causing
dilatation and eventual rupture of the duct and the duc
are surrounded by intense inflammatory cell ifiltrate

10. Benign tumor of the breast
Fibroadenoma
 Is the most common benign tumor of the breast
 Occurs at any age during the reproductive period
 Present usually as mobile palpable breast mass
with slight increase of size during the menstrual
cycle
 Regression occurs after menopause.
 Morphology:- Benign glands and benign stroma

11. Fibroadenoma-Gross

12. Fibroadenoma-Micr

13. Phyllodes Tumor
– Any age (45yrs) , usually large
– Encapsulated , lobulated ,soft or cystic
– Histology : - similar to fibroadenoma
- excessive stromal overgrowth
projecting into clefts, mitoses
– Majority benign , may recur,
– Features of malignancy : - stromal cellularity
- mitoses
- Rapid  size
- Extension
– Treat by local excision & simple mastectomy

15. Fibrocystic changes
 Presentation:-palpable mass , mammographic
changes or nipple discharge
 Morphological patterns:-
1. Cysts:- small or large, the lined by flat cells.
2. Fibrosis:-Rupture of the cysts lead to chronic
inflammation of the stroma and fibrosis.
3. Adenosis:- Increase in the number of the glands.

16.  MORPHOLOGY:
A.Cysts
- Lined by epithelial and myoepithelial cells
B. Apocrine metaplasia: Lining cells have an
abundant amount of granular eosinophilic
cytoplasm
C. Fibrosis
D. Adenosis: Increase in the number of acini
per lobule
E. Mild epithelial hyperplasia: the number of
cell layers is 3-4

17. Non-proliferative fibrocystic changes(cysts,
fibrosis,adenosis)


18. Apocrine metaplasia


19. Breast carcinoma
 Is the most common malignancy of the breast and
the most common NON-skin malignancy in
females.
 Risk Factors are:
1.Age: Is rarely found in young females except in
certain familial cases.
2. Age at menarche: Women who reach menarche
younger than 11 years have increased risk
compared to women who reach menarche when
older than 14
3.First live birth: women with first pregnancy <20
years have the half risk of women over age of 35 at
their first birth

20.  First degree relative with breast cancer
Classification of breast carcinomas
1. In situ carcinomas:- neoplastic cells
limited to the ducts and lobules,no
invasion of the basement membrane
2. Invasive carcinomas

21. Carcinoma in situ
1.Ductal carcinoma in situ types are:-
- Comedo carcinoma:- high grade
characterized by central necrosis
- Solid, cribriform, papillary and
micropapillary
- 2. In situ lobular carcinoma.

22. Invasive carcinoma
- Types of invasive carcinoma:-
1.Invasive ductal carcinoma. No special type
account for 70-80% of breast carcinomas.
grossly are hard with irregular
edges.Microscopically well differentiated
tumor consist of tubules and poorly
differentiated are composed of solid sheets

23. 2. Invasive lobular carcinoma : it has a greater
incidence of bilaterality. grossly are hard and
microscopically the tumor cells grow individually
in a form of a single file (indian file)
3.medullary carcinoma; well defined mass .grossly
the tumors are soft and microscopically the tumor
cells are arranged in sheets surrounded by chronic
inflammatory cells.this tumor has better prognosis
than no special type
4. Mucinous:- Best prognosis

24. 7. Breast Carcinoma
 Is the most common malignancy of the breast
and is the leading cause of carcinoma deaths in
women
 The incidence is high in north America and
Northern Europe
 Risk factors
1.Age;-Breast cancer is rarely found before the age
of 25 except in familial cases and about 75%
of cases occur in women after age of 50
2. Age at Menarche:women who reach their
menarche when younger than 11 years of age
have a bout 20%increased risk compared to
women who reach menarche when more than
14 years of age
3. Late menopause

25. 4. First live birth: Women with a first full term
pregnancy at younger than 20 years of age
have half the risk of nulliparous women or
women over the age of 35 at their first birth
5. First degree relatives with breast cancer: the
risk of breast cancer increases with the
number of affected first degree relatives
6.Geographic variations: The risk for breast
cancer is higher in North America and
Europe than in Asia and Africa
7. Proliferative breast lesions

26. Other risk factors
1.Estrogen Exposure: postmenopausal hormonal
replacement therapy slightly increases the risk of
breast cancer.. Oral contraceptive pills are
unlikely to increase the risk
2. Carcinoma of the contralateral breast or
endometrium:-Increase the risk
3. Radiation exposure: especially at time of breast
development---Latent period is 10-15 years
5. Breast feeding: The longer the women breast-feed,
the greater is the reduction in the risk of breast
cancer
6.Tobacco: cigarette smoking is not associated with
the breast cancer

27. Pathogenesis
 The major risk factors for the development of breast cancer
are hormonal and genetic
 Genetic Factors
1.Hereditary breast cancer
- 5-10% of breast carcinomas are familial
- some familial breast cancers can be attributed to mutation in two
autosomal dominant genes:BRCA1(chr 17) and BRCA2(13)
- The general lifetime breast cancer risk for female carriers is 60-
80% and the median age at diagnosis is about 20 years earlier
compared to women without mutation in these genes
- - Mutated BRCA1 also markedly increases the risk of
developing ovarian carcinomas
2. Sporadic breast cancer
- Genetic changes have been implicated in the pathogenesis of
sporadic cancers.

28. -The normal cell must achieve seven new capabilities, to become
malignant(genomic instability, loss of apoptosis, loss of growth
inhibition, self sufficiency in growth factors, limitless replication,
angiogenesis and invasion), each of these can be achieved by a change
in one of many genes like changes in ER, P53,RAS or HER2/neu.
- Mutations in p53 can affect more than one capability
- Among the best characterized changes is overexpression of the
protooncogen ERBB2 (HER2-neu)which is amplified in 30% of cases
*Hormonal influences
-Endogenous estrogen excess plays a role
- Estrogen itself has at least two major roles in the development of breast
cancer
A. Metabolites of estrogen can cause mutations or generate DNA-
damaging free radicals
B. Via its hormonal actions , estrogen drives the proliferation of
premalignant lesions as well as cancer
-

29. ***Location of breast cancers; affects left >right breast
- 50% in the upper outer quadrant
- 15% in the upper inner quadrant
- 10% in the lower outer quadrant
- 5% in the Lower Inner quadrant
- 17% in the central region
- 3% diffuse
*** Multicentricity:-
About 13%
Mote common in in-situ lobular types (
*** Bilaterality:
- Risk of a patient with invasive cancer to develop
cancer in the other breast is 5 times that of general
population
- More in lobular carcinoma

30. Microscopic Types
 All breast cancers arise in the terminal duct lobular
unit
 Breast cancers are divided into
- Non-invasive carcinomas:malignant cells have not
penetrated the basement membranes, Insitu
ductal(intraductal carcinoma) if the malignant cells
involve predominantly the terminal ducts and insitu
lobular carcinoma,if the malignant cells affect
predominantly the acinii
- Invasive(infiltrating): malignant cells invade the
basement membranes

31. Non-invasive(in-situ carcinomas
A. Lobular carcinoma in situ
- 70% are multicentric (involving more than one
quadrant)
- 30-50% are bilateral
- Usually incidental finding
- Rare mass or calcifications
- Majority are located within 5 cm of nipple
- 20-30% of cases progress to invasive carcinoma,
Microscopically: The acini of the lobules are
completely filled by uniform malignant cells,no
necrosis

32. Insitu lobular carcinoma

33. B. Ductal carcinomas in situ
- Most frequently presents as mammographic
calcification
- It consists of malignant population of cells limited to
ducts and lobules by basement membranes
- Types of ductal carcinoma in situ (intraductal
carcinoma)
1. Comedo carcinoma-High grade
2. Solid type-Low grade
3. Cribriform type-Low grade
4. Papillary type-Low grade
5. Micropapillary type-low grade

34. Intraductal carcinoma-solid type


35. Comedo carcinoma
 Is a high grade intraductal carcinoma
 Characterized by highly pleomorphic
cells ,numerous mitoses and central
necrosis(term comedo)
 The necrotic cells commonly calcify and
detected by mammogram
 Is the most common cause of calcifications
of breast detected by mammogram
 May reach large size and become palpable
 Multicentric in 33% of case
 Bilateral in 10% of cases

36. Intraductal carcinoma-comedo
type


37.  Evolution of (DCIS)
– Not all cases develop invasive carcinoma
– Carcinoma develops after many years
– Risk is higher in comedo than in noncomedo
i.e. linked to the grade of the tumor
– Usually the invasive component is similar to
the initial intraductal tumor----invasive
component is invasive ductal carcinoma

38. Paget disease of the nipple
 Clinically: unilateral crusting pruritic lesion of the
nipple and periareolar skin mimic dermatitis
clinically
 Caused by the extension of ductal carcinoma in situ
to the lactiferous ducts and into the contiguous
nipple skin
 It is different from direct invasion of the skin by
malignant cells
 Paget disease does not affect the prognosis
 In about 60% of the cases---an underlying invasive
carcinoma will be present

39. Paget disease


40. Invasive carcinomas
 In women not undergoing mammographic
screening, invasive carcinoma almost always
present as a palpable mass
 By the time a cancer becomes palpable, over half
the patients will have axillary lymph node
metastases
 Large carcinomas may be fixed to the underlying
muscles or cause dimpling of the skin
 Lymphatics may become so involved as to block
the local area of skin drainage and causing
lymphedema of the skin breast called peau d’
orange appearance

41. Types of invasive carcinomas:
1. Invasive ductal carcinomas, , No Special type
(NOS)(schirrous carcinoma)
- accounts for 70-80% of breast cancers
- Most of these carcinomas produce desmoplastic
reaction(dense fibrosis) which replaces the normal
breast tissue , so resulting in mammographic
density and form a hard palpable mass
- Grossly ;are hard with irregular borders with gritty
sensation
- The microscopic appearance is heterogeneous
ranging from tumors with well developed tubule
formation and low grade nuclei to tumors composed
of sheets of anaplastic cells

42. Invasive ductal carcinoma-NOS

43. Invasive ductal carcinoma-NOS


44. 2.. Medullary carcinomas:
- Are common in Japan
- Microscopically: highly anaplastic cells arranged in sheets
and surrounded by dense lymphoplasmacytic infiltrate
- account for 2% of invasive carcinomas
- Grossly are well circumscribed similar to fibroadenomas
-Have better prognosis than the invasive carcinoma of no
special type
- Are negative for estrogen and progesterone receptors
3. Mucinous(colloid) carcinomas:-- Tend to occur in elderly
women
-Grow slowly
-Are positive for Estrogen and progesterone receptors
-The overall prognosis is better(if pure) than the no special type
-Grossly:The tumor is soft and
- -microscopically:the tumor cells are seen as clusters of cells
floating in mucin.

45. Medullary carcinoma


46. Mucinous carcinoma


47. 5. Invasive lobular carcinomas;
- Account for 10% of breast carcinomas
--Microscopically, the tumor cells invade the stroma as
discohesive cells arranged in strands called indian files
-Are more frequently than invasive ductal
carcinomas , metastasize to cerebrospinal fluid,
peritoneun, ovary, bone marrow
4. Tubular carcinomas:-Account for 6% of
invasive carcinomas
-Rarely present as palpable masses
--Prognosis is excellent
- Lymph node metastases are rare

48. Tubular carcinoma

49. Invasive lobular carcinoma


50. 6. Mixed invasive lobular and invasive ductal
carcinomas
 INFLAMMATORY CARCINOMA:
- Clinical entity
- Edema & redness of skin of breast
- Breast swollen & tender
- Dermal lymphatics blocked by tumor cells
- Rapid clinical course

51. SPREAD of CARCINOMA
1- Local Infiltration - Nipple retraction
- Peau d’orange
- Fixation to skin & muscle
2- Lymph node in vasion related to site
Axillary , Internal mammary ,
Supraclavicular
3- Spread to opposite breast
4- Blood stream  Distant metastases
Lung,liver, bone , adrenals ,ovary , brain ….

52. Diagnosis
a.Clinical Examination
-Breast self examination
- Palpation: 60% of tumors detected by
mammogram are palpable
b. Mammography:
- Detects calcifications
- Detects extremely small tumors(1-2mm)
- Calcifications are present in 60% of breast
carcinomas and 20% of benign lesions
- Negative mammogram s do not exclude
carcinoma
- False positivity is 1%
- An average of 20% of cases suspicious by
mammograms are malignant

53. c. Cytology;
- Examination of nipple secretion:high false positive
and false negative results
- Fine needle aspiration
d. Needle core biopsy
- evaluation of tumor cytology, pattern and
invasiveness
- Definitive diagnosis is about 90%
e. Open biopsy and frozen section
-Excional biopsy if the mass is 2.5 cm or less
Incisional biosy; if the mass >.2.5 cm
Frozen section:false positive is zero, false negative is
1% and deferred answers in 5% of cases

54. Prognostic Factors
Major prognostic factors:
A. Invasive or insitu carcinoma
- Most patients with DCIS with adequately treated DCIS
will be cured
B.Distant metastases: once distant metastases are present, cure
is unlikely, although long term remissions can be achieved
especially for women with hormone responsive tumors
C.. Lymph node metastases: Axillary lymph node status is the
most important prognostic factor in the absence of distant
metastases. The number of involved lymph nodes if < or >
4
C. Tumor size: is the second most important prognostic factor
and its independent from lymph node status, however the
risk of axillary lymph node metastases increases with
increasing size
- Women with tumors , 1 cm with no lymph node metastases
have a prognosis similar to women without breast cancer

55. D. Locally advanced disease: tumors invading into the skin
and skeletal muscles are associated with concurrent or
subsequent distant metastases
E. Inflammatory carcinoma: bad prognosis
**** Minor prognostic factors
a. Histological subtype:
- Excellent prognosis:pure tubular and pure mucinous
- good prognosis:classic invasive lobular and medullary
- Poor prognosis; Invasive ductal carcinoma, NOS
b. Tumor grade
Predictive Factors
1. ER and PR receptors:; Women with hormone receptor
positive cancers have a slightly better prognosis than
hormone receptor-negative tumors.Evaluation of hormone
receptors is important to determine the response to
hormonal therapy(Tamoxifen)

56. 2.HER2/neu status;Many studies have shown that
overexpression of HER2/neu is associated with poor
prognosis.Evaluation of HER2-neu status is
important to determine the response to Herceptin
*** Breast Cancer In Males
- male breast Ca:female breast cancer is 1:100
- 8% are associated with Klinfelter syndrome
- Most cases are invasive ductal carcinoma
- Most present as subareolar masses
- Carcinoma is close to overlying skin and thoracic
wall,so even small carcinomas can invade these
structures