Histopathology and
staging of breast cancer
Prof T J Stephenson
Physiological conditions
• Pregnancy and lactation
• Gynaecomastia
• Involution
Fibrocystic change
•
•
•
•
•
Adenosis
Fibrosis
Cysts
Epithelial hyperplasia (+/- atypia)
Apocrine metaplasia
Inflammatory conditions
•
•
•
•
Acute mastitis
Abscess
Duct ectasia
Fat necrosis
Benign tumours
•
•
•
•
Fibroadenoma
Adenoma
Intraduct papilloma
Connective tissue neoplasms
Fibroadenoma
• Commonest benign tumour
• Biphasic
• Very characteristic clinico-pathological
features
← Circumscribed lesion
Epithelium and stroma →
Intraduct papilloma
• Middle aged women
• Blood stained nipple discharge from
large ducts
• Typical papillary structures with
fibrovascular cores
Histological risk factors
Factor
Risk x normal
FH-
FH+
Hyperplasia
1.9
2.4
With atypia
5.3
10
DCIS
9-12
Lobular carcinoma in situ
•
•
•
•
6% of breast malignancies
Premenopausal
Impalpable
Up to ⅓ develop invasive cancer if only
biopsied
• Equal risk in both breasts, unless PLCIS
which behaves like DCIS
Ductal carcinoma in situ
• Mass / Paget’s / discharge / screening
• Different histological types / grades
• All have slightly different characteristics
Risk factors
• Female gender
• Cancer in other breast
• Long interval between menarche and
menopause
• Age at first full-term pregnancy
• Not breast feeding
• Obesity and high fat diet
• Family history
• Geographical factors
• Histological risk factors
Breast cancer
• 20% of all cancers in women, (second only to
lung)
• Commonest cancer in the UK
• Commonest cause of death in women 35 – 55
• In UK, women have 1:8 lifetime chance of
developing it (but 1:33 by 50)
• 48417 new cases per year (2009) and rising
• 11556 deaths in UK per year (2010) and falling
Insertion of guide wire
UK has worst
figures
World variations in mortality
Invasive carcinomas
Type
Invasive ductal
Invasive lobular
Mucinous
Tubular
Medullary
Papillary
Others
%
85
10
2
2
<1
<1
<1
Elston/Ellis modification of Bloom and Richardson Grading
Detailed Criteria used in Histologic Grade
Glandular (Acinar)/Tubular Differentiation
Score 1: >75% of tumor area forming glandular/tubular structures
Score 2: 10% to 75% of tumor area forming glandular/tubular structures
Score 3: <10% of tumor area forming glandular/tubular structures
Nuclear Pleomorphism
Score 1: Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines,
uniform nuclear chromatin, little variation in size
Score 2: Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size
and shape
Score 3: Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape,
occasionally with very large and bizarre forms
Mitotic Count
The mitotic count score criteria vary depending on the field diameter of the microscope used by the pathologist. The
pathologist will count how many mitotic figures are seen in 10 high power fields. Using a high power field diameter of 0.50
mm, the criteria is as follows:
Score 1: less than or equal to 7 mitoses per high power field
Score 2: 8-14 mitoses per high power field
Score 3: equal to or greater than 15 mitoses per high power field
Overall Grade
Grade 1: scores of 3, 4, or 5
Grade 2: scores of 6 or 7
Grade 3: scores of 8 or 9
Spread and Staging
•
•
•
•
Local
Intra-cavity
Lymphatic
Blood stream
Lymph drainage
TNM definitions
Primary tumor (T):
TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Tis: Carcinoma in situ;
intraductal carcinoma, lobular carcinoma in situ, or
Paget's disease of the nipple with no associated tumor.
Note: Paget's disease associated with a tumor is classified according
to the size of the tumor.
T1: Tumor 2.0 cm or less in greatest dimension
T1mic: Microinvasion 0.1 cm or less in greatest dimension
T1a: Tumor more than 0.1 but not more than 0.5 cm in greatest dimension
T1b: Tumor more than 0.5 cm but not more than 1.0 cm in greatest dimension
T1c: Tumor more than 1.0 cm but not more than 2.0 cm in greatest dimension
T2: Tumor more than 2.0 cm but not more than 5.0 cm in greatest dimension
T3: Tumor more than 5.0 cm in greatest dimension
T4: Tumor of any size with direct extension to (a) chest wall or (b) skin,
only as described below.
Note: Chest wall includes ribs, intercostal muscles, and serratus
anterior muscle but not pectoral muscle.
T4a: Extension to chest wall
T4b: Edema (including peau d'orange) or ulceration of the skin of the
breast or satellite skin nodules confined to the same breast
T4c: Both of the above (T4a and T4b)
T4d: Inflammatory carcinoma*
TNM definitions
Regional lymph nodes (N):
NX: Regional lymph nodes cannot be assessed (e.g., previously removed)
N0: No regional lymph node metastasis
N1: Metastasis to movable ipsilateral axillary lymph node(s)
N2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or
to other structures
N3: Metastasis to ipsilateral internal mammary lymph node(s)
Pathologic classification (pN):
pNX: Regional lymph nodes cannot be assessed (not removed for pathologic
study or previously removed)
pN0: No regional lymph node metastasis
pN1: Metastasis to movable ipsilateral axillary lymph node(s)
pN1a: Only micrometastasis (none larger than 0.2 cm)
pN1b: Metastasis to lymph node(s), any larger than 0.2 cm
pN1bi: Metastasis in 1 to 3 lymph nodes, any more than 0.2 cm and all
less than 2.0 cm in greatest dimension
pN1bii: Metastasis to 4 or more lymph nodes, any more than 0.2
cm and
all less than 2.0 cm in greatest dimension
pN1biii: Extension of tumor beyond the capsule of a lymph node
metastasis less than 2.0 cm in greatest dimension
pN1biv: Metastasis to a lymph node 2.0 cm or more in greatest
dimension
pN2: Metastasis to ipsilateral axillary lymph node(s) fixed to
each other
or to other structures
pN3: Metastasis to ipsilateral internal mammary lymph node(s)
TNM definitions
Distant metastasis (M):
MX: Presence of distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis present (includes metastasis to ipsilateral
supraclavicular lymph nodes)
Prognosis
• PI = 0.2(cm size) + grade (1, 2 or 3) +
LN stage* (1, 2 or 3)
* LN stage:
1 = not involved
2 = 1 – 3 nodes involved
3 = 4 or more nodes involved or level 3
Prognosis
PI
% symptomatic
patients
% 15 year
survival
<3.4
29
80
3.5 – 5.4
54
42
>5.4
17
13