Lecture class on pathology of breast for 3rd & 4th year MBBS students based on "Robbins & Cotran: Pathologic Basis of Disease'. Images are collected from internet.

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

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

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

22. Atypical Ductal Hyperplasia

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

29. Stromal tumor
Fibroadenoma Phyllodes Tumour

30. Classification of Breast
Carcinoma
 In situ carcinoma:
- Ductal Carcinoma in situ (DCIS)
- Lobular Carcinoma in situ (LCIS)
 Invasive carcinoma:
- Invasive ductal carcinoma, not otherwise specified
- Invasive lobular carcinoma
- Tubular carcinoma
- Cribriform carcinoma
- Mucinous (Colloid) Carcinoma

31. - Medullary carcinoma
- Microinvasive carcinoma
- Papillary carcinoma
- Micropapillary carcinoma
- Apocrine carcinoma
- Metaplastic carcinoma
- Neuroendocrine carcinoma
- Inflammatory carcinoma
 Rare salivary gland type tumour:
- Acinic cell carcinoma
- Adenoid cystic carcinoma

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%

37. Invasive Ductal Carcinoma (NOS)

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

41. Microscopic (histologic) description
 Clusters / nests of tumor cells with low or intermediate nuclear
grade floating in pools of extracellular mucin

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

43. Metaplastic carcinoma

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

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

48. Tumours of Interlobular stroma
 Benign
- Lipoma
- Myofibroblastoma
- Fibromatosis
 Malignant
- Angiosarcoma
- Rhabdomyosarcoma
- Leiomayosarcoma
- Liposarcoma etc

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