This document provides an overview of breast diseases, including:
- Breast anatomy and histology
- Common benign and malignant breast lesions such as fibroadenomas, phyllodes tumors, ductal carcinoma in situ, and invasive ductal carcinoma
- Risk factors, diagnostic approaches, and prognostic factors for breast cancer
It describes the clinical presentations, histopathological features, and classifications of various breast diseases.
Histopathological Interpretation of Breast Cancer.pptxMunmun Kulsum
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This lecture was prepared while opening of 'Breast Clinic' in Department of surgery , Cumilla Medical college Hospital, Cumilla, Bangladesh. This was delivered by Dr. Umme Kulsum Munmun, as a resource person in the seminar regarding opening of breast clinic.
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1. Diseases of Breast
Dr. Umme Kulsum Munmun
MD (Pathology)
Assistant Professor
Department of Pathology
Chandpur Medical College
2. • Female breast is composed of 15-
20 modified apocrine sweat
glands
• In resting adult breast, the
glandular portion is composed of
clusters of small secretory lobules
or acini ( lobular units)
• The lobules are connected by
small terminal ducts to the main
excretory or lactiferous ducts
opening into the nipple
3. The surrounding stroma is of two types : intralobular and
interlobular
Each elements are the source of both benign and malignant
lesions
before puberty – breasts in both sexes – ducts
after menopause – gradual and progressive involution
(lobular atrophy, increased fat, cystic dilatation of ducts)
4. Histology
• Two types of cells line the ducts and
lobules
Luminal cuboidal cells-
produce milk
Contractile
myoepithelial cells lie on
the basement membrane
assist in milk ejection
during lactation and
provide structural
support to the lobules
• The stroma is composed of loose
connective tissue and fat
• After menopause, the lactiferous
apparatus undergoes atrophy and
the stroma becomes more fibrous
5.
6. Clinical Presentations of Breast
Disease
The most common symptoms of disorders of breast are –
- pain
- palpable mass
- lumpiness (without a discrete mass)
- nipple discharge
7. Pain (Mastalgia or mastodynia)
May be cyclic with menses or non-cyclic
Diffuse cyclic pain may be due to premenstrual edema
Non-cyclic pain – localized to one area, caused by
ruptured cysts, physical injury and infections
Almost all painful masses are benign
10% of breast cancers present with pain
8. Palpable mass
Must be distinguished from the normal nodularity of
breast
The most common palpable lesions are cysts,
fibroadenomas and invasive carcinomas
Benign palpable masses are most common in
premenopausal women
Likelihood of a malignancy increases with age
9. Nipple Discharge
Less common
Suggests carcinoma when it is spontaneous and unilateral
Milky discharges associated with elevated prolactin levels
(pituitary adenoma, hypothyroidism or endocrine
anovulatory syndrome)
Occurs in patients taking OCP, TCA, methyldopa or
phenothiazines
Bloody or serous discharges are most commonly due to
large duct papillomas and cysts
10. Role of Mammography
Detects small, non-palpable asymptomatic breast carcinomas
Sensitivity and specificity of mammography increase with age as a
result of replacement of fibrous, radio-dense tissue of youth with the
fatty, radiolucent tissue of older women.
The principal mammographic signs of breast carcinoma are densities
and calcifications
Screening has increased the diagnosis of ductal carcinoma in situ
11.
12.
13. Disorders of Development
Milk Line remnants- supernumerary nipples or breast may
form
Accessory axillary breast tissue
Congenital nipple inversion
14. Inflammatory Disorders
Less than 1% of breast symptoms
Include-
i - Acute mastitis : during the first month of breastfeeding due to
cracks or fissures in the nipples, the breast is erythematous, painful and
fever is often present. Initially one duct system is involved, may spread to the
entire breast if untreated
ii – Squamous metaplasia of lactiferous ducts: subareolar abscess/
periductal mastitis/ Zuska disease. Presents with painful erythematous,
subareolar mass. Associated with vitamin A difficiency, smoking/toxic
substances
15. iii. Duct ectasia: fifth or sixth decades of life – palpable periareolar
mass often associated with thick, white nipple secretions and
occasionally with skin retraction.
iv. Fat necrosis: presentation closely mimics cancer, painless palpable
mass, skin thickening or retraction, mammographic densities or
calcifications
v. Lymphocytic mastopathy
vi. Granulomatous mastitis: only occurs in parous women, may be
caused by a hypersensitivity reaction to antigens expressed during
lactation.
16. Benign Epithelial Proliferations
Pathologic spectrum of seemingly related clinically benignbreast
abnormalitiy, palpably irregular and painful breasts
Classified into three groups
- non-proliferative breast changes
- proliferative breast diseases without atypia
- proliferative breast diseases with atypia
17. Non- proliferative breast changes
Non-proliferative breast changes (fibrocystic changes) include: cyst, fibrosis
and adenosis
May present with irregular lumpy area
Not associated with an increased risk for breast cancer
18. Adenosis is defined as an increased number
of acini per lobule
Preserved 2 cell layer (inner epithelial and
outer myoepithelial cells)
19. Proliferative breast disease
without atypia
Lesions characterized by proliferation of epithelial cells without
atypia
Associated with a small increase (1.5 to 2 times) in the risk of
subsequent carcinoma
Commonly detected as mammographic densities, calcifications or
as incidental findings in biopsies performed for other reasons
Also called ‘usual ductal hyperplasia’, ‘epithelial hyperplasia’,
‘epitheliosis’ etc
20. Usual Ductal Hyperplasia
The lumens are filled
with heterogenous ,
mixed population of
luminal and
myoepithelial cell types
21. Proliferative breast disease with
atypia
Associated (4 to 5 times) with moderately increased risk of
carcinoma
Includes two forms: atypical ductal hyperplasia and atypical lobular
hyperplasia
ADH is present in 5% to 17% biopsy specimens from calcifications
23. In ALH, the lobules are normal sized and still contain
identifiable lumina. This image shows the spectrum of
findings from ALH to LCIS.
• ALH is found in fewer than 5% of biopsies
• Incidental finding , no radiologic correlates
• ALH consists of cells identical to those of LCIS but the cells do not fill or
distend more than 50% of the acini within a lobule
24. Recent immunophenotypic and molecular studies indicated a
linear progression from normal epithelium through usual
hyperplasia, atypical hyperplasia and carcinoma in situ to invasive
cancer
25. Benign tumours of breast
Fibroadenoma
Tubular
adenoma
Lactating
Adenoma
Intraductal
papilloma
26. Benign tumours of breast
Fibroadenoma (stromal)
• proliferation of epithelial and stromal elements
• most common breast tumor in adolescent and young adult
women (peak age = third decade)
• well-circumscribed, freely movable, nonpainful mass
• regress with age if left untreated
• ducts distorted elongated slit-like structures
27. Tubular adenoma
• far less common than fibroadenomas
• young women, discrete, freely movable masses
• uniform sized ducts
Lactating Adenoma
• enlarging masses during lactation or pregnancy
• prominent secretory change
Intraductal papilloma
• in the mammary ducts, subareolar lactiferous ducts
• periductal inflammation, duct sclerosis
• serous or bloody nipple discharge
• fibrosis, infarction, squamous metaplasia
28. Phyllodes tumor (stromal)
• fleshy tumor, leaf-like pattern and cysts on cut
surface
• circumscribed, connective tissue and epithelial
elements (greater connective tissue cellularity
compared to fibroadenomas), 1-15 cm
• less than 1 % of breast tumors
• benign, borderline, malignant
• metastases are hematogenous
32. Ductal Carcinoma In Situ
Confined to the ductal-lobular system
No evidence of invasion through the basement membrane into the
surrounding stroma Majority are non-palpable and detected
mammographically as microcalcifications (70 - 80%)
Less frequently presents as palpable mass, nipple discharge, Paget
disease of the nipple
8-10 times higher risk for subsequent development of invasive breast
carcinoma compared to general population
33. Many morphologic variants exist:
- comedocarcinoma (High grade) and
- solid, cribriform, micropapillary, clinging etc
Papillary carcinoma is a very distinct type, arise from large ducts
Others originate in terminal duct lobular unit
34. Lobular Carcinoma in Situ (LCIS)
No specific clinical features
Most times incidental finding in biopsy for some other mass
producing lesion such as a fibroadonoma
No specific clinical features
35. Invasive ductal carcinoma (NOS)
Most common type of invasive breast carcinoma (75 - 80%)
Lacks features of any other subtypes (i.e. is a diagnosis of exclusion)
36. Microscopic (histologic) description
Sheets, nests, cords or individual cells
Tubule formations are prominent in well differentiated tumors but absent
in poorly differentiated tumors
Tumor cells are more pleomorphic than lobular carcinoma
Calcification in 60% of cases, variable necrosis
Often DCIS (up to 80%), perineural invasion (28%)
Mitotic figures are often prominent
No myoepithelial cell lining (as seen in DCIS or benign lesions)
Angiolymphatic invasion: In 35%
38. Invasive Lobular Carcinoma
Special subtype of invasive breast carcinoma characterized by
discohesive tumor cells arranged in single files or as individual
single cells (loss of E-cadherin)
39. Mucinous Carcinoma
Rare tumor occurring in older women
Also called-
Colloid carcinoma
Mucinoid carcinoma
Gelatinous carcinoma
Mucoid carcinoma
Mucinous adenocarcinoma
Gross description
Well circumscribed mass of variable size (from < 1 cm to > 20 cm) with
gelatinous cut surface
42. Metaplastic Carcinoma
Heterogeneous group of invasive breast carcinomas characterized
by differentiation of the neoplastic epithelium towards squamous
cells or mesenchymal looking elements, including spindle,
chondroid and osseous cells
44. Molecular Classification
The diverse histologic appearances of breast carcinomas and
putative precursor lesions are the outward manifestations of the
complex genetic and epigenetic changes that drive
carcinogenesis.
For prognostic and therapeutic purposes, the molecular
classification of breast cancer is more pronounced now-a-days
There appear to be three major genetic pathways of
carcinogenesis
45.
46. Diagnostic Approaches of CA Breast
Approaches for diagnosis of CA breast
• Fine-needle aspiration cytology (FNAC)
• Core needle biopsy
• Lumpectomy
• Mastectomy
47. ER, PR , Her2 immunohistochemistry can be performed on CNB sample if
representative tissue is provided
49. Risk factors of breast carcinoma
Germline mutations
1st degree relatives with
breast cancer
Race/ethnicity
Age
Age at menarche
Age at 1st live birth
Benign breast disease
Estrogen exposure
Breast density
Radiation exposure
Carcinoma of the
contralateral breast or
endometrium
Diet
Obesity
Exercise
Breastfeeding
Environmental toxins
50. Prognostic and predictive factors
Factors related to extent of
carcinoma:
- Invasive vs in situ
- Distant metastases
- Lymph node metastases
- Tunour size
- Locally advanced disease
- Inflammatory carcinoma
- Lymphovascular invasion
Factors related to tumour
biology:
- Molecular subtype
- Special histologic
subtypes
- Histologic grade
- Proliferative rate
- Estrogen and
progesterone receptors
- HER 2
51. Familial breast cancer
Approximately 12% of breast cancers
Inheritance of gene mutations associated with breast cancer
( BRCA1, BRCA2, TP53, CHEK2)
Multiple affected first degree relatives
Early onset cancers
Multiple cancers
Family members with other specific cancers
52. Paget‘s disease of the nipple
• Result of intraepithelial spread of intraductal
carcinoma
• Large pale-staining cells within the epidermis
of the nipple
• Limited to the nipple or extend to the areola
• Pain or itching, scaling and redness, mistaken
for eczema
• Ulceration, crusting, and serous or bloody
discharge
53. Pathology of the male breast
Gynecomastia
• most common clinical and pathologic abnormality of the
male breast
• increase in subareolar tissue
• in 30 to 40 percent of adult males, both breasts are
affected in many cases
54. • associated with hyperthyroidism, cirrhosis of the liver,
chronic renal failure, chronic pulmonary disease, and
hypogonadism, use of hormones - estrogens, androgens, and
other drugs (digitalis, cimetidine, spironolactone, marihuana, and
tricyclic antidepressants)
Carcinoma of the male breast
• uncommon < 1 % of all breast cancers