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1. Benign and malignant
breast pathology
Cecily Quinn MD, FRCPI, FRCPath
Clinical Professor, University College Dublin
Consultant Histopathologist,
Irish National Breast Screening Programme,
St. Vincent’s University Hospital, Dublin 4

2. Objectives
1. Difference between symptomatic and screen detected
2. Types of benign breast disease and significance
3. Risk factors for malignancy
4. Non-operative diagnosis, triple assessment and
multidisciplinary review meeting
5. Types of treatment including sentinel lymph node
6. Difference between in situ and invasive carcinoma
7. Ductal carcinoma in situ
8. Prognostic and predictive indices in invasive carcinoma
9. Newer tests
10. TNM classification update

3. Anatomy of the breast

4. Breast disease
Symptomatic
Lu
changes
Lump
Indrawn
nipple
Redness
Rash
Nipple
discharge
Dimpling
Symptoms Skin
changes

5. Density Nodule Calcification
Density
Breast disease
Mammographic screening

6. Benign Breast Disease
Spectrum of lesions
1. Cysts
2. Duct ectasia
3. Fibroadenoma
4. Potential for local recurrence
Phyllodes tumour
5. Increased incidence of associated malignancy
Radial scar, papilloma

7. Cyst(s)
o Fluid filled dilated breast gland (acinus)
o Often lined by apocrine epithelium
o Solitary or multiple
o May co-exist with other benign change
= fibrocystic disease

8. Cyst(s)
Clinical
oAsymptomatic
oMammographic lesion
oSymptoms
Smooth lump or lumpy area
Cyclical pain & nodularity
Management
oNo treatment
oAspiration
oMay be excised if part of a more
complex lesion

9. Duct ectasia
Pathology
•Affects breast ducts
o Duct dilatation
o Accumulation of secretions
o Periductal inflammation & fibrosis
•Peri-areolar abscess
Causes
o Smoking
o Hyperprolactinaemia
o Bacteria

10. Duct ectasia
Clinical
oNipple discharge
oLump
oPain
oCalcification
Management
oSub-areolar exploration
& removal of tissue

11. Fibroadenoma

12. Phyllodes tumour

13. Phyllodes tumour
Clinical
oMammographic lesion
oLump (1cm – 45cms)
oBenign, borderline or malignant
oPotential for local recurrence
Management
oSurveillance or excision depending
on grade

14. Radial Scar
Pathology
o Spiculate lesion with
irregular outline
o Benign tubules in sclerotic
stroma
o May mimic carcinoma,
mammographically and
pathologically
o Associated malignancy in up
to 33%

15. Radial scar
Clinical
oMammographic lesion
oLump – rare
Management
oComplete excision to
exclude malignancy

16. Papilloma
Pathology
oBenign lesion
oLocated within a duct
oSolitary or multiple
oAssociated malignancy in some cases

17. Papilloma
Clinical
oWomen in 5th and 6th
decades
oAsymptomatic
oMammographic lesion
oNipple discharge
oLump
Management
oExcise to exclude
malignancy

18. Breast cancer is the most common
cancer in WHO Europe region

19. Europe 2018
522,513 women newly diagnosed with breast cancer
(26.4% of all new cancers in women)
137,707 women died
• 1 in 8 women in EU will develop
breast cancer by age 85yrs
• Participation in screening:
o Reduces risk of dying by 41% in 10yrs
o 25% reduction in rate of advanced
breast cancer

20. Breast Cancer
• We do not know what actually causes this
common disease
• We have identified risk factors

21. Breast Cancer Risk
• Family history (20%)
Specific genetic abnormality
oBRCA1 gene – 85% risk
• Reproductive profile
Uninterrupted oestrogenic
stimulation
• Exogenous hormones
OCP, HRT

22. Breast Cancer Risk
• Lifestyle
Alcohol, diet, smoking
• Environmental
Radiation
• Sociodemographic
Residence in ‘western’
countries

23. Breast Cancer Risk
• Breast biology
oAtypical changes
oDuctal carcinoma in situ
oCancer in contralateral breast

24. Non-Operative
Breast Diagnosis

25. Triple Assessment Approach

26. Needle Core Biopsy

27. Non-Operative Breast Diagnosis
Breast: usually needle core biopsy
B1 – normal tissue or non-diagnostic
B2 – benign
B3 - heterogeneous group of lesions
May have increased incidence of associated malignancy
e.g. radial scar, papilloma
More significant pathology in vicinity e.g. CCL, ADH
Open surgical biopsy required
B4 – suspicious
B5 – malignant – in situ (B5a) or invasive (B5b)
B5b – Hormone receptor and HER2 studies

28. Non-operative
axillary lymph node diagnosis

29. Multidisciplinary Team Meeting
Non Operative Diagnosis
1. Does the pathology
diagnosis account for the
radiological lesion?
2. Review findings
Pathology
Radiology
Clinical
3. Plan treatment

30. Non-operative breast diagnosis
Guide to surgery
Wide local excision or mastectomy?
Size or extent of disease
Sentinel node biopsy or axillary clearance?

31. William Stewart Halstead
Mastectomy

32. Breast conserving surgery
Wide local excision

33. Sentinel lymph node biopsy
The lymph node that is
most likely to harbour
metastases if patient is
LN positive
Reliable alternative to
axillary lymph node
clearance as a staging
procedure

34. Axillary lymph node clearance
• Positive lymph node fine needle aspirate
• Positive sentinel lymph node
– Depending on the size of the deposit and the
presence/absence of spread beyond the lymph
node (extranodal spread)
– Z11 trial

35. Neoadjuvant chemotherapy
Hormone monotherapy
o Extent of disease – clinical & radiology
o Patient age and/or co-morbidity
o Pandemic
o Pathology diagnosis
o Biomarker profile
Non-operative breast diagnosis
Guide to non-surgical treatment

40. Breast Cancer
Classification
In situ carcinoma
oDuctal DCIS
Invasive carcinoma
oNo special type (ductal)
oSpecial types
oInflammatory

41. Ductal carcinoma in situ
Usually screen detected
Confined to the glandular
system of the breast
Removal should be
curative
Type of surgery depends
on extent
If WLE followed by
radiotherapy
Calcification

42. Ductal carcinoma in situ
DCIS grade
Microinvasion/invasion
Extent of process
Margin status

44. ‘He will manage the cure best who has
foreseen what is to happen from the
current state of matters’
Book of Prognostics 400 BC
Hippocrates 460BC-370BC

45. • Estimation of prognosis for individual patient
• Formulation of personalised treatment plan
+
=

46. Invasive carcinoma
Tumour type
NST (no special type), pure special type, mixed
Tumour grade
Tumour size
Invasive tumour size, whole tumour size, disease extent
Lymphovascular invasion
Margin status
Lymph node status
Biomarker profile
Molecular studies – Oncotype DX, mutations etc

47. • No Special Type - ductal NST (80%)
• Special type carcinoma (15%)
• Mixed tumours (5%)

48. Invasive carcinoma
No special type
80% of breast tumours

49. • 15% breast tumours
• Grade 2 or 3
• More advanced stage at
presentation than NST
• Metastases: bone &
abdominal viscera
• Prognosis: long term
worse than NST
E-cadherin

50. Invasive lobular carcinoma
Frequently multifocal and bilateral

51. Mucinous
carcinoma
Tubular
carcinoma

52. ‘One does not
know how a
tumour is
likely to
behave until
one knows
what it is ‘

54. Tumour grade vs
survival
Consecutive series
ER pos & ER neg
LN pos & LN neg
G1 = 677
(19%)
G2 = 1383
(39%)
G3 = 1519
(42%)
•Emad A Rakha1,
•Jorge S Reis-Filho2,
•Frederick Baehner3,
•David J Dabbs4,
•Thomas Decker5,
•Vincenzo Eusebi6,
•Stephen B Fox7,
•Shu Ichihara8,
•Jocelyne Jacquemier9,
•Sunil R Lakhani10,
•José Palacios11,
•Andrea L Richardson12,
•Stuart J Schnitt13,
•Fernando C Schmitt14,
•Puay-Hoon Tan15,
•Gary M Tse16,
•Sunil Badve17 and
•Ian O Ellis1Email author
Breast Cancer
Research201012:207

55. • Guides surgery: conservation vs mastectomy
• Detection of breast tumour before 15mm
alters the course of biological progression
• Key component of TNM staging system

56. Lymph node status
Greatest predictor of
patient survival
Component of TNM
staging system
Factor in patient
selection for
chemotherapy

57. Lymph node metastases
Macrometastasis Micrometastasis
Is there spread beyond the
lymph node capsule?

58. Lymphovascular invasion
Independent marker of local & distant recurrence

59. Margin status
• Positive or “close”
radial margin predicts
local recurrence
• Further surgery may
be necessary

61. Inflammatory carcinoma
• Rare: 1-5% of all breast cancers
• Swelling, redness, dimpling
• May not form a discrete lump
• Affects younger women
• Locally advanced at diagnosis
• More aggressive

62. Inflammatory carcinoma
• Signs and symptoms are due to
blockage of lymphatic channels by
cancer cells in the skin
• Usually NST histologically
• Diagnosed, staged and managed in
accordance with usual protocols for
invasive carcinoma

63. o Hormone receptor status: ER and PR
o HER2 receptor status
o Multigene panels e.g. Oncotype DX test
o Mutational studies e.g. PIK3CA

64. Predicts response to endocrine therapy
• 80% of breast tumours are hormone receptor pos.
• > 1% staining on immunohistochemistry = positive

65. Predicts response to trastuzumab Tx
12 – 15%
breast tumours
HER2 positive
<10,000 HER2 proteins
on normal breast cell

66. Molecular classification
ER +/- PR pos, HER2 neg
low proliferation high proliferation
HER2 positive
ER, PR & HER2 neg
Perou CM, Sorlie T, Eisen MB et al. Molecular portraits
of human breast tumours. Nature 2000, 406, 747–752

67. Needle Core Biopsy

68. Surgery

69. o Further breast or axillary surgery
o Adjuvant radiotherapy
o Adjuvant endocrine therapy
o Adjuvant chemotherapy
o Immunotherapy

70. Probably YES
Lymph node positive
HER2 positive
Triple negative
Neoadjuvant or
adjuvant ?
Probably NO
Small tumour
Grade 1
Lymph node negative
ER positive
HER2 negative
Endocrine
therapy

71. Multigene panels

72. Tumour size 10 – 50mm
Grade 2 or 3
Lymph node negative or
1-3 nodes positive
ER, PR positive
HER2 negative
Value of adjuvant chemotherapy is
uncertain in this subgroup

73. • 21 gene recurrence assay
• Predicts response to chemotherapy
& likelihood of tumour recurrence

77. Thank you!