1. PATHOLOGY OF THE BREAST
Irianiwati
Dept. of Anatomical Pathology
Fac. of Medicine, GMU Yogyakarta

3. Most pathological lesions of
the breast present as a lump
or lupms.
Note the characteristic of the
Lump and the age of the patient
Discharge of the nipple occurs with some condition

6. Breast examination Characteristics of the lump:
-Well circumscribed or ill defined
-Single or multiple nodules
-Soft or firm
-Mobile or attached to skin/ underlying muscle
< 35 year, benign lumps are much more common
than carcinomas

7. Horizontal mammography
FAM
Malignant lesion
15. Breast Cancer: Horizontal Mammography

8. USG- Breast BI-RADS Categories Assassement incomplete 1 Negative 2
incomplete 1
Negative 2
Benign finding 3
Probably benign finding 4
Suspicious abnormality 5
Highly suggestive of malignancy 6
Known biopsy-proven malignancy
BI-RADS: Breast Imaging Reporting and Data System

9. Core biopsy/ histology
Core tissue is removed using a biopsy needle
Reqiures a local anesthetic and more painful

10. Fine needle aspiration cytology
Cytology reports: benign, malignant, suspicious pathology, unsatisfactory

11. Core biopsy FNAC (Histology) (Cytology)

12. Frozen section During operation Sample: Fresh tissue
Quick test ( minute )
During operation
Sample: Fresh tissue
using cryo cut (-25ᴼ C) or CO2 snow
HE staining, microscopic examination
Result: Benign/ Malignant
Frozen can determine further surgery treatment

13. Breast lesions Inflammatory, reactive tumors
Acute pyogenic mastitis, mammary duct ectasia, Fat necrosis
Proliferative disease of the breast
fibrocystic change
Benign tumors:
FAM, duct papilloma, adenoma,
soft tissue tumors
Breast carcinoma:
Non-invasive carcinomas:
ductal and lobular ca. In situ
Invasive carcinomas:
invasive duct and lobular ca.,
Tubular ca., Medullary ca.
Other types:
Paget’s disease of the nipple,
Phyllodes tumor

14. Acute pyogenic mastitis
Painfull, red swelling
fever
Non infectious: milk stasis
Infectious : staphylococcus aureus: from the baby mouth, cracks in the nipple,
localised swelling and erythema
streptococcus piogenes: widespread inflammation with systemic symptoms

15. Tuberculosis of the breast
Mistaken clinically for carcinoma
Irregular hard mass, ulcer
Granulomatous inflammation with
Caseous necrosis, epitheloid cells,
Langhans giant cell
Hematogenous process of lung tuberculosis

16. Mammary duct ectasia
Involves the larger ducts– extend to the smaller interlobular ducts
Lump or nipple discharge/retraction – mimicking carcinoma
Unknown etiology
Inflammation pattern similar to fat necrosis

17. Mammary duct ectasia/ periductal mastitis
Ductal lumen filled with foamy macrophages
and lipid material
Periductal fibrosis
Hemosiderin laden macrophages

18. Fat necrosis May result from surgery, radiation, trauma
Localised swelling +/- bruising
Clinically may mimic cancer
Resolved spontaneously but slow
FNA/ biopsy good for diagnosis
Maybe associated with microcalsification

19. Fat necrosis
Stromal calcification
Fat necrosis

20. Fat necrosis Droplet s of free fat Foamy macrophages reaction
Foreign body giant cell

21. Fibrocystic change Cystic change, apocrine metaplasia
Women of reproductive years
With florid epithelial hyperplasia: Slightly increased risk (1,5-2 %) for breast carcinoma
With atypical hyperplasia: 4% for breast carcinoma
Clinical manifestation: sometimes similar with carcinoma
Periodically discomfort hormonal influences from the
mentrual cycle --- Relative imbalance between estrogen and progesteron in each menstrual cycle

22. Fibrocystic change

23. microscopic of fibrocystic change
Proliferation of TDLU
Cystic lesions, apocrine metaplasia
Epithelial cell hyperplasia:
mild: 3-4 cells layer
moderate: florid, papilomatosis, epitheliosis
Atypical hyperplasia
Chronic inflammation
Adenosis:enlargement of the lobules containing of many acini. Involve to the epithelium and myoepithelium
Sclerosing adenosis: Lobular proliferation with distorted acini and severe stromal fibrosis

24. Fibrocystic change
Cystic lesions

25. Proliferative breast lesions
Non proliferative fibrocystic change florid hyperplasia
Atypical lobular hyperplasia Atypical ductal hyperplasia

26. Sclerosing adenosis

27. Atypical hyperplasia
Epithelial hyperplasia that result in total or partial occlusion of the acini and small ducts
Abnormalities of cellular growth: disordered of cells orientation, nuclear pleomorphism, mitotic figures
Atypical ductal or lobular hyperplasia
The college of American Pathologists:
- non/ mild proliferative
- Proliferative without atypi/ florid: 1,5-2 times risk
- ductal/ lobular atypical hyperplasia: 5 times risk
- ductal/ lobular in situ ca: 8-10 times risk

28. Atypical hyperplasia
Disordered of cells orientation, nuclear pleomorphism, mitotic figures

29. Ginaecomasti Adolescence: hyperthiroidism,
tumor hypofise, adrenal, testis
Old age: treatment with stilbestrol in
prostatic cancer
Other causes: cirrosis hepatis, malnutrition
digitalization etc
Microscopic: dilated ducts, variable degree of epithelium proliferation. Edematous and myxoid stroma

30. Microscopic of Ginaecomasti
The breast tissue in men contains only ductular structures

31. Benign tumor of the breast (Fibroadenoma)
Smooth, well circumscribed
And lobulated mass
Most common in young women (3rd decades of life)
Mobile, well demarcated mass, 2-3 cm
Derived from breast lobules , have both connective tissue and epithelial element
Mostly solitery lesion, 10% multiple

32. Fibroadenoma Cytology: Monotonous of glandular epithelial
and myoepithelial cells
Histology:
Elongated duct-like structure
Surrounded by loose connective tissue

33. Phyllodes tumor
Biphasic fibroepithelial tumor. Occur at any age (median age: 45 years)
< 1% of breast tumor. Locally recurrence
Breast lump, vary in size up to as much as 45 cm in diamter
Tumor with ulceration of overlying skin
Central degeneration with surrounding solid areas

34. Phyllodes tumor
Characterized by combination of hypercellular stroma and cleft- like or cystic spaces lined by epithelium --- leaf-like pattern

35. Duct papilloma -Middle age women -Presents as blood-stained nipple
discharge
-Solitary lesion in large ducts
-Papillary structure with fibrovas-
cular core

36. Adenoma
Lactating adenoma Tubular adenoma

37. Breast carcinoma 20% of all cancer in women Risk factors:
- long interval between menarche -- menopause older age at full-term pregnancy
- obesity and high-fat diet
- family history of breast cancer
- geographic factors
- atypical hyperplasia in previous breast lesion

38. Pathogenesis of breast cancer

39. Breast cancer

40. Breast carcinoma Aetiological mechanisms:
overexposure to estrogen, underexprosure to progesteron
Early menarche, late menopause--- higher number of menstrual cycles –stimulary effect on breast epithelium
Early full-term pregnancy: high concentration of progesterone and/or prolactin proteccting against estrogen in long term.
Obesity: ability of fat cells to synthesis estrogen or to altered levels of sex hormone-binding protein levels

41. Breast carcinoma
Hormone receptors:
ER +: 70% of breast ca.
PR +: 35% of breast ca.
Important in the growth, maintenance
of breast carcinoma
- Respond to some form of hormonal
therapy
Expression of c-erb-B2/ Her-2/neu
Tend to be more aggresive than other
breast cancer type
Respond to anti Her-2/neu therapy

42. Non-invasive carcinomas
Tumor is confined to ducts or acini of the lobules.
Ductal carcinoma in situ: unilateral, in pre and post menopausal women, has several forms
Lobular carcinoma in situ: in pre menopausal women, has no clinical features, often bilateral, can be multifocal

43. Ductal carcinoma in situ
CK 5 expression
The ducts contain of Varying degree of nuclear pleomorphism and cytoplasm
Solid, comedo or cribriform pattern
Express high molecular weight cytikeratine (CK 5)

44. Lobular carcinoma in situ
Cellular proliferation result in formation of solid nests that expand the entire lobule
Negative expression of e-cadherin

45. Invasive breast carcinoma
Occur in pre and post menopausal women
Most are duct type
Infiltrating lobular carcinomas can be multifocal
Cells have broken through the basement membrane around the breast structure and spread into the surrounding tissue
Histological types: invasive ductal (85%), invasive lobular (10%), mucinous. tubular (2%), medullary, papillary (1%)

46. -Blokage of the local lymphatic ducts by tumor cells
Peau D’orange
- Classically seen in advancer inflammatory breast cancer
-Blokage of the local lymphatic ducts by tumor cells
-Cancer cells bloks the lymph vessels in the skin

47. Invasive ductal carcinoma
Majority of breast carcinoma
NOS : Cannot be classified as any other subtype
(tubular, papillary, medullary, mucynous etc)

48. Invasive lobular carcinoma
Tumor can be scirrhous or diffuse invasive tumor
Small, uniform cells forming strands or concentrically pattern
20% bilateral
Frequently metastasis to cerebrospinal fluid, serosal surfaces, bone marrow

49. Pagets disease of the nipple
2% of all breast cancer
Erosion of the nipple clinically resembling eczema
Associated witn underlying ductal carcinoma in situ/ invasive
Epidermis of the niplle contain of large, pale staining malignant cells

50. Paget’s disease of the nipple

51. Mucoid carcinoma tubular carcinoma
Medullary carcinoma

52. Inflammatory breast cancer
6% of all breast cancer
The most aggressive type of breast cancer
5 year survival rate < 45%
Clinic: Skin erythema and nodulairy
Pathologic: high angiogeneic, angioinvasive

53. Histological grade of breast cancer (Elston & Ellis, 1991)
Characteristic
score
Tubular formation
> 75%
10 – 75% ( moderate)
< 10% (little or none)
Nuclear pleomorphism
cell: uniform, regular, small
moderate variation
mark variation
Mitotic count
depend on the microscope field area 1 2 3
Examples of assignment of points for mitotic count for three different field areas:
Field diameter (mm) , , ,63
Field area (mm2) , , ,312
Mitotic count:
score – – – 11
score –
score > > > 23
Grade, well: scor 3 – 5, moderate: 6 – 7, poorly: 8 - 9

54. Histological diagnosis
Benign or malignant lesion
Histological type: ductal, lobular, mucinous etc
Tumor infiltration: to the nipple, fat, muscle etc
Histological grade: well, moderate, poorly
Tumor lymphovascular invasion
Lymphnode metastasis (p staging)
Infiltration of breast cancer Tumor lymphovascular Lymphnode metastasis
to the nipple invasion

55. Definition I 96 92 II 81 71 52 39 18 11 Stage 5-year Surv (%) 7-year
Tumor 2 cm or less without spread 96 92 II
Tumor 2-5cm with regional lymph node involvement but without distant metastases, OR > 5 cm in diameter without spread 81 71
III
Any size with skin/chest wall fixation, & axillary or internal mammary nodal involvement, without distant metastases 52 39 IV
Tumor of any size with or without regional spread but with evidence of distant metastases 18 11

56. Spread of Breast cancer
- Directly to the skin and muscle
Via lymphatics to axillary and other
Local lymph-nodes
Via blood stream to the lung, bone,
liver, brain

57. Prognostic factors: Type of carcinoma: ductal, Lobular, medular etc
Histological grade: well, moderate, poorly grade
Stage:TNM
Hormonal status: ER, PR
Expression of Her-2/neu
Lymphovascular invasion
Tumor cells proliferation
Angiogenesis: VEGF expression

58. Thank you