The document discusses normal breast anatomy and histology, as well as non-proliferative and proliferative breast conditions including fibrocystic changes, ductectasia, fat necrosis, epithelial hyperplasia, sclerosing adenosis, and papillomas. Both clinical presentations and microscopic features are described for various common breast diseases. The goal is to provide pathology residents with an overview of normal breast features and pathological lesions.

1. Breast pathology - 1
Dr.CSBR.Prasad, M.D.

2. Cases

3. Cases

4. Cases

5. Cases

6. Cases
Left image – affected breast Right image – Normal breast

7. Cases
60yo male

8. 1 2
Cases

9. Cases

10. Cases

11. Cases

12. Cases

13. Cases

14. Breast pathology

15. Mammary gland – Normal features
1. Covered by skin & subcutaneous tissue
2. Rests on pectoralis muscle
3. Pectoral fascia separates it from the pectoral muscles

16. Breast – Normal features
• Modified skin appendage.
• Composed of specialized epithelium and stroma
that gives rise to both benign and malignant
lesions.
• 6-10 major ductal system originate at the nipple.
• Keratinizing sq.epithelium of overlying skin
continues into the ducts and then abruptly changes
to a double layered cuboidal epithelium.
• Surrounding areolar skin is pigmented &
supported by smooth muscle.

17. • Normal duct system micro
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p

18. Breast – Normal features
• Morphofunctional unit of the organ is SINGLE
GLAND composed of 2major parts:
1-TDLU (secretory unit of the gland)
a-lobule
b-terminal ductule
2-Large duct system

19. Breast – Normal features
• Importance of division of mammary gland
unit into 2 major portions resides in its
relation to disease of this organs.
• TDLU (FCD, Ductal hyperplasia,
Carcinoma)
• Large duct system (Solitary papilloma,
ductectasia, rare ductal carcinomas)

20. Normal anatomy and possible
pathological lesions

21. 3910
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p

22. Histology

23. Histology
Epithelium & Stroma:
• Ducts and lobules are lined by 2 cell types
1-Myoepithelial cell lying on the BM.
2-Epithelial cells lines the lumen.
• Stroma
1-Interlobular stroma
2-Intralobular stroma (hormonally responsive)

24. Normal histology
The normal microscopic appearance of female breast tissue is shown here. There is
a larger duct to the right and lobules to the left. A collagenous stroma extends
between the structures (Interlobular – Red stars). Intralobular stroma is
hormonally responsive (Blue Stars). A variable amount of adipose tissue can be
admixed with these elements. Source: webpath

25. Normal histology
At high magnification, the appearance of a normal breast acinus is shown here. Note the
epithelial cells lining the lumen demonstrate apocrine secretion with snouting, or
cytoplasmic extrusions, into the lumen. A layer of myoepithelial cells, some of which are
slightly vacuolated, is seen just around the outside of the acinus.
Source: webpath

26. Epithelial markers
• EMA
• Milk Fat Globule Membrane antigen
• alfa-Lactalbumin
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p

27. Normal histology
An immunoperoxidase stain with antibody to actin demonstrates the
myoepithelial cell layer around the breast acinus. The myoepithelial cells are
contractile and are very sensitive to oxytocin.
Source: webpath

28. Markers for Myoepithelium
• S-100 protein
• P-Cadherin
• SMA
• Calponin
• Smooth muscle myosin-heavy chain
• Maspin
• Caldesmon
• p63
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p

29. Disorders of development
1. Milk line remnants.
2. Accessory axillary breast tissue.
3. Congenital nipple inversion.

30. Milk line remnants
“POLYTHELIA”
Epidermal thickening along the milk line
extending from axilla to perineum.

31. Milk line remnants
The classification established by Kajava in 1915 is still valid: (De Cholnoky,
1939)
1. Complete SN: Nipple + areola + glandular breast tissue
2. SN: Nipple + glandular tissue (no areola)
3. SN: Areola + glandular tissue (no nipple)
4. Aberrant glandular tissue only
5. SN: Nipple + areola + pseudomamma (fat tissue that replaces the
glandular tissue)
6. SN: Nipple only (the most common SN)
7. SN: Areola only (polythelia areolaris)
8. Patch of hair only (polythelia pilosa)

32. Disorders of development
Milk line remnants

33. Disorders of development
Accessory axillary breast tissue
In some persons normal ductal system extends
into subcutaneous tissue of the chest wall
and into the axillay fossa.
Importance: Therapeutic mastectomy might
remove the entire breast but not remove all
breast epithelium.
Hence cannot compeltely eliminate the risk of
developing breast cancer.

34. Disorders of development
Accessory axillary breast tissue

35. Disorders of development
Congenital nipple inversion
It may be bilateral or unilateral.
Importance: may be mistaken for carcinoma
or inflammation.

36. Disorders of development
Congenital nipple inversion

37. Clinical presentations
• Symptomatic:
1. Pain
2. Palpable mass
3. Nipple discharge
• Asymptomatic (mammography screening)
1. Densities
2. Calcifications

38. Clincal presentations
PAIN
• Mastalgia / mastodynia
• Cyclical / non-cyclical
1. Ruptured cyst
2. Injury
3. Infection
4. Some times without any specific lesion
Note: only about 10% of breast carcinoma patients present
with pain.

39. Clincal presentations
PALPABLE MASSES
• Notable points:
1. Masses must be distingusihed from the normal
nodularity of the breast.
2. Breast masses usually does not become palpable
until it’s about 2cms in diameter.
3. Likelyhood of malignancy in a papable mass
increses with age
---- <40yrs (only 10% of masses are
malignant)
---- >50yrs (about 60% of the masses are
malignant)

40. Clincal presentations
Nipple discharge
• Gains importance only if it’s
1. Spontaneous &
2. Unilateral

41. Clincal presentations
Nipple discharge
• Types of discharges:
1. Milky (>prolactin, hypothyroidism, anovulatory
cycle, OCs, M-Dopa, phenothiazines) (Not
associated with malignancy)
2. Serosanguinous (most commonly associated
with benign lesion)
3. Bloody (most commonly associated with benign
lesion – duct papillomas)

43. Acute mastitis
• Pyogenic infections
• Occurs during first few weeks of lactation
• Pathogens:
1. Staphylococcus
2. Streptococcus

44. Acute mastitis
1. Breast mass
2. Fever
3. Erythematous painful breasts
4. If not Tx it may spread to entire breast
Complictions:
---fibrous scarring
---may be mistaken for carcinoma

45. Acute mastitis
During lactation, or at other times with dermatologic conditions that allow cracks and
fissures to form in the skin of the nipple, infectious organisms can invade into breast
and result in acute inflammation, and this may progress to breast abscess formation
(Circle). The most common organism is Staphylococcus aureus. Organization with
fibrous scar formation around the abscess can mimic a carcinoma on physical
examination, by mammography, and grossly.

46. Acute mastitis
While breast-feeding the baby, the skin of the breast may become irritated and
inflamed. The skin may fissure, predisposing to infection. Acute mastitis
typically involves just one breast and is most often caused by Staphylococcus
aureus, though other bacterial organisms such as streptococci can produce this
condition, with neutrophilic infiltrates microscopically. If untreated by
antibiotic therapy, spread of infection and abscess formation can occur.

47. Granulomatous mastitis
• Chronic non-specific mastitis
Etiology:
1. Systemic granulomatous disease
(Sarcoidosis, Wegener’s)
2. Inections (TB, Fungal)
3. Silicone breast implants
4. Idiopathic (hypersensitivity to luminal
secretions)

48. Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
• Painful erythematous subareolar masses
• >90% are smokers (vit-A deficiency)
• Seen both in males and females
• Not associated with lactation

49. Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
Subareolar abscess with fistulous opening at the edge of areola

50. Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
Pathlogy:
1. Keratinization of epithelium extending to an
abnormal depth into the orifices of the nipple
ducts.
2. Keratin plugs block the ductal system and causes
dilatation & eventual rupture of the ducts.
3. Intense chronic granulomatous inflammatory
response develops to ketain spilled into
periductal tissue.

51. Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
Source: Robbins Pathologic basis of disease, 8th ed. 1125p
• 3945

52. Mammary ductectasia
• 4th to 7th decade of life.
• Usually seen in multiparous women.
• NOT assocated with cigarette smoking.
Clinically:
• Nipple discharge.
• Retraction of nipple.
• Palpable dilated ducts in the subareolar area.

53. Mammary ductectasia
• Gross:
1-Poorly defined indurated area.
2-Ropyness of the surface.
3-c/s shows dilation of one or more large
ducts containing cheesy inspissated
secretions.

54. Mammary ductectasia
• Microscopically:
1-Dilated ducts with necrotic & atrophic
epithelium
2-Lumen filled with powdery debri and foam
cells
3-Periductal & insterstitial chronic inflammaotry
cell infiltration (Ly, Plas, Histio, Giant cells)
Note: Plasma cell mastitis (when numerous plasma
cells are seen)
Obliteration mastitis (when inflammatory
scarring obliterates the lumen of the ducts)

55. Mammary ductectasia
• 3955
Source: Ackerman’s Surgical Pathology 9th Ed.

56. FAT NECROSIS
• Usually seen in obese & pendulous breasts
• Generally iniciated by trauma or prior
surgery
• It presents as painless palpable mass

57. FAT NECROSIS
• 3914

58. FAT NECROSIS
Gross:
1. Central pale cystic area of necrosis
2. Chalky white areas

59. FAT NECROSIS
• Lipid filled spaces surrounded by neutrophils, lymphocytes,
plasma cells and histiocytes having foamy cytoplasm
• FB type giant cell reaction
• Fibrosis & calcifiction

60. FAT NECROSIS
• Lipid filled spaces surrounded by neutrophils, lymphocytes,
plasma cells and histiocytes having foamy cytoplasm
• FB type giant cell reaction
• Fibrosis & calcifiction

61. Non-proliferative breast changes – FCD

62. Non-proliferative breast changes – FCD
• Form palpable masses
• Calcifications
• Spontaneous unilateral nipple discharge
• They mey disappear after FNAC

63. Non-proliferative breast changes – FCD
There are 3 principle patterns of morphologic
changes
1. Cyst formation with apocrine metaplasia
2. Fibrosis
3. Adenosis

64. Non-proliferative breast changes – FCD
CYSTS:
• Cysts form by dilation and unfolding of
lobule.
• Cystic lobules coalesce to form larger cysts.
• Cysts lined by flattened atrophic or apocrine
epithelium
• Papillary projections
• Calcification is common (‘Milk of calcium’)

65. Fibrocystic Change (FCC)
This is the gross appearance of fibrocystic changes in the breast. A 1.5 cm cyst is
noted here. This can lead to palpation of an ill-defined "lump" in the breast.
Sometimes, fibrocystic changes produce a more diffusely lumpy breast.
Source: webpath

66. Fibrocystic Change (FCC)
This is the histologic appearance of fibrocystic changes in breast. There are
cystically dilated ducts, areas of lobules that are laced with abundant
fibrous connective tissue (sclerosing adenosis), and stromal fibrosis.
There is even a small area of microcalcification seen just to the upper
right of center. No atypical changes are seen here. Source: webpath

67. Fibrocystic Change (FCC)
Another example of microscopic fibrocystic changes of the breast are shown here.
Fibrocystic changes account for the majority of "breast lumps" that are found in
women of reproductive years, particularly between age 30 and menopause.
Source: webpath

68. Fibrocystic Change (FCC)
There is prominent apocrine change of the cells lining the cysts in this example of
fibrocystic changes of breast. Note the tall, pink, columnar nature of the
epithelial cells. This appearance is benign. Source: webpath

69. Non-proliferative breast changes – FCD
FIBROSIS:
Rupture & release of secretory material into
the adjacent stroma elicit inflammation and
fibrosis.
ADENOSIS:
Increase in number of acini per lobule
‘Blunt duct adenosis’

70. Fibrocystic Change (FCC)
Prominent sclerosing adenosis, one of the features of fibrocystic changes, is demonstrated
by the appearance of a proliferation of small ducts in a fibrous stroma. Although it is
benign, the gross and mammographic appearance may mimic carcinoma, and it can be
difficult to distinguish from carcinoma on frozen section. Source: webpath

71. FCC
This mammogram demonstrates a
suspicious lesion that could be a
carcinoma or just an area of
pronounced sclerosis with
fibrocystic changes. On biopsy, this
was benign.
Source: webpath

72. PROLIFERATIVE LESIONS

73. PROLIFERATIVE LESIONS
1-without atypia
2-with atypia

74. Proliferative breast disease
without atypia
• Rarely form palpable masses
• They are often detected
---radiographically (densities, calcifications)
---in biopsies
• Proliferation of ductal epithelium & or stroma
without cellular abnormalities suggestive of
malignancy

75. Proliferative breast disease
without atypia
Entities include:
1. Florid epithelial hyperplasia
2. Sclerosing adenosis
3. Complex sclerosing lesion
4. Papillomas
5. Fibroadenomas with complex features

76. Proliferative breast disease
without atypia
EPITHELIAL HYPERPLASIA:
• Def: presence of >2 cell layers of epithelium
• >4 cell layers designates it as moderate to florid
hyperplasia
• When they fill the lumen it can be differentiated
from CIS by finding fenestrations are the
periphery of the cellular masses.

77. Proliferative breast disease
without atypia
SCLEROSING ADENOSIS:
• Increase in # of acini per terminal duct at least
twice the normal.
• Normal lobular arrangement is maintained.
• Acini are characteristically dilated at the
periphery.
• Myoepithelial cells are usually prominent.
• Sclerosis
• Calcifications are frequently present with in the
lumen of acini.

78. Proliferative breast disease
without atypia
COMPLEX SCLEROSING LESION:
• Stellate scar
• Centrally entrapped glands in hyalinized stroma
Complex sclerosing lesion include:
1. Radial scar
2. Radial scar related lesion with sclerosing
adenosis, papilloma formation
3. Epithelial hyperplasia

79. Proliferative breast disease
without atypia
PAPILLOMAS:
• Multiple branching fibrovascular cores
• Lined by luminal & myoepithelial cells
• Growth occurs within a dilated duct
• Epithelial hyperplasia and apocrine metaplasia are
frequently seen
• Large duct papillomas are single and situated
nearer to the nipple
• Small duct papillomas are multiple and located
deeper within ductal system (more prone for Ca.)

80. These breast ducts demonstrate epithelial hyperplasia. The epithelial
cells are multilayered. There is no atypia. Thus, just as with
fibrocystic changes such as fibrosis, cysts, and sclerosing adenosis,
there is no increased risk for carcinoma. Source: webpath

81. More florid ductal epithelial hyperplasia of the breast is shown here. There is a
slightly increased risk (1.5 to 2 times normal) for breast carcinoma when such
changes are present. Source: webpath

82. Proliferative breast disease
with atypia
• This includes:
1-ADH
2-ALH

83. Proliferative breast disease
with atypia - ADH

84. This is atypical ductal epithelial hyperplasia of the breast. A significantly
increased risk (5 times normal) for breast carcinoma occurs with
cytologically atypical epithelial hyperplasia.

85. Proliferative breast disease
with atypia - ALH

87. END

88. Contact:
Dr.CSBR.Prasad, M.d.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.
CSBRPRASAD@REDIFFMAIL.COM