The document discusses the staging and pathology of breast carcinoma. It covers the AJCC staging system including TNM classification of primary tumor, regional lymph nodes, and distant metastasis. It also covers histopathological classification of breast tumors including in situ carcinomas, invasive carcinomas, histological grading, hormone receptor status, and molecular subtypes. Key histopathological types described include ductal carcinoma in situ, invasive ductal carcinoma, lobular carcinoma, and special histological types.

1. Staging and Pathology of
carcinoma breast
-Dr Deepika Malik
JR – II, Dept. of Radiotherapy

2. Staging
 The AJCC ( American Joint Committee
On Cancer) staging is the most widely
used staging systems for carcinoma
breast.

3. Staging..
 Major changes in 7th edition of AJCC
manual –
1. Identified specific imaging modalities
that can be used to estimate clinical
tumor size,including mammography,
USG, MRI
2. Maintained that the term ,
“inflammatory carcinoma” be
restricted to cases with typical skin
changes involving a third or more of
skin of breast.

4. Staging..
 3. classification of isolated tumor
clusters and single cells is more
stringent. Smallclusters of cells less
than 0.2 mm or non confluent clusters
of cells( <200 cells in a single
histological lymph node are classified
as isolated tumor cells.
 4. stage I has been divided into IA and
IB
IB includes small tumors with exclusive

5. Staging..
 5. created new M0 (i+) category, --
presence of either disseminated tumor
cells or found incidently in other
tissues (such as ovaries removed
prophylactically) if not exceeding 0.2
mm.

6. Primary Tumor (T)
Classification of primary tumor are same for clinical and
pathological classification
 TX - Primary tumor cannot be assessed
 T0 - No evidence of primary tumor
 Tis- Carcinoma in situ
 Tis (DCIS) Ductal carcinoma in situ
 Tis (LCIS) Lobular carcinoma in situ
 Tis (Paget’s) Paget’s disease of the nipple NOT associated
with invasive carcinoma and/or carcinoma in situ (DCIS
and/or LCIS) in the underlying breast
Note- Paget’s disease associated with a tumor are
categorized based on the size

7. T1 - Tumor ≤ 2 cm in greatest dimension
T1mi -Tumor ≤ 1 mm in greatest dimension
T1a - Tumor > 0.1 cm but ≤ 0.5 cm in
greatest dimension
T1b- Tumor> 0.5 cm but ≤ 1 cm in greatest
dimension
T1c- Tumor > 1 cm but ≤ 2 cm in greatest
dimension

8. T2 - Tumor > 2 cm but ≤ 5 cm in greatest
dimension
T3- Tumor > 5 cm in greatest dimension

9. T4 - Tumor of any size with direct extension to the chest
wall and/or to the skin (ulceration or skin nodules)
Note: Invasion of the dermis alone does not qualify as T4
T4a- Extension to the chest wall, not including pectoralis
muscle adherence/invasion
T4b- Ulceration and/or ipsilateral satellite nodules and/or
edema (including peau d’orange) of the skin, which do not
meet the criteria for inflammatory carcinoma
T4c- Both T4a and T4b
T4d- Inflammatory carcinoma

10.  AJCC definition of inflammatory carcinoma
Staging as T4d requires these clinical features to
be present:
-diffuse erythema and edema involving a third or
more of the skin of the breast.
-Microscopically, dermal lymphatic invasion is
typically seen in this setting, however dermal
lymphatic invasion alone is NOT sufficient (nor
necessary) to diagnose inflammatory carcinoma
or stage pT4d.
 The clinical features must be present;
 if they are present but involve less than a third of the breast, AJCC states this should be staged as pT4b, not
pT4d.
 Carcinoma that ulcerates the skin is staged as pT4b.
 If the clinical features are present but dermal lymphatic invasion is not, the patient may still be classified as
inflammatory carcinoma and asT4d

11.  Regional Lymph Nodes ( N)
CLINICAL STAGING
NX- Regional lymph nodes cannot be assessed (for example,
previously removed)
N0- No regional lymph node metastases
N1- Metastases to movable ipsilateral level I, II axillary lymph
node(s)

12. N2a- Metastases in ipsilateral level I, II axillary
lymph nodes fixed to one another (matted) or to
other structures
N2b- Metastases only in clinically detected*
ipsilateral internal mammary nodes and in the
absence of clinically evident level I, II axillary lymph
node metastases

13.  N3a- Metastases in ipsilateral infraclavicular lymph node(s)
 N3b- Metastases in ipsilateral internal mammary lymph node(s)
and axillary lymph node(s)
 N3c- Metastases in ipsilateral supraclavicular lymph node

14.  PATHOLOGICAL STAGING (pN)
pNX- Regional lymph nodes cannot
be assessed (for example, previously
removed, or not removed for pathologic
study)
pN0- No regional lymph node metastasis
identified histologically

15. pN0(i−) - No regional lymph node metastases histologically,
negative IHC
pN0(i+)- Malignant cells in regional lymph node(s) no
greater than 0.2 mm (detected by H&E or IHC)
pN0(mol−)- No regional lymph node metastases
histologically, negative molecular findings (RT-PCR)
pN0(mol+) - Positive molecular findings (RT-PCR)**, but
no regional lymph node metastases detected by histology
or IHC

16. pN1mi- Micrometastases (greater than 0.2 mm
and/or more than 200 cells, but none greater than 2.0
mm)
pN1a - Metastases in 1–3 axillary lymph nodes, at
least one metastasis greater than 2.0 mm
pN1b- Metastases in internal mammary nodes with
micrometastases or macrometastases detected by
sentinel lymph node biopsy but not clinically
detected***
pN1c- Metastases in 1–3 axillary lymph nodes and in
internal mammary lymph nodes with
micrometastases or macrometastases detected by
sentinel lymph node biopsy but not clinically
detected

17. pN2-
pN2a- Metastases in 4–9 axillary lymph nodes (at least
one tumor deposit greater than 2.0 mm)
pN2b- Metastases in clinically detected internal
mammary lymph nodes in the absence of axillary
lymph node

18. pN3a -Metastases in >=10 axillary lymph nodes (at least
one tumor deposit greater than 2.0 mm);
or metastases to the infraclavicular (level III
axillary lymph) nodes
pN3b- Metastases in clinically detected ipsilateral
internal mammary lymph nodes in the presence of one
or more positive axillary lymph nodes;
or >3 axillary lymph nodes and in internal
mammary lymph nodes with micrometastases or
macrometastases detected by sentinel lymph node
biopsy but not clinically detected***
pN3c Metastases in ipsilateral supraclavicular lymph
nodes

19. Distant Metastases (M)
 M0- No clinical or radiographic evidence of
distant metastases
 cM0(i+) No clinical or radiographic evidence of
distant metastases, but deposits of molecularly or
microscopically detected tumor cells in
circulating blood, bone marrow, or other
nonregional nodal tissue that are < 0.2 mm in a
patient without symptoms or signs of metastases
 M1- Distant detectable metastases as determined
by classic clinical and radiographic means
and/or histologically proven larger than 0.2 mm

20. Group staging

22. Pathological classification of
carcinoma breast
 WHO classification
 AJCC histopathological classification
of breast tumors

23. AJCC on Cancer
histopathological classification of
breast tumors
In situ carcinomas
NOS
Intraductal (in
situ)
Paget's disease
and intraductal
Invasive carcinomas
NOS
Ductal
Inflammatory
Medullary, NOS
Medullary with lymphoid stroma
Mucinous
Papillary (predominantly micropapillary
pattern)
Tubular
Lobular
Paget's disease
Undifferentiated
Squamous cell
Adenoid cystic
Secretory
Cribriform
NOS, not otherwise specified

24. Microinvasive carcinoma
 Definition- extension of cancer cells beyond the
basement membrane into the adjacent tissues
with no focus more than 0.1 cm in greatest
dimension.
 Staged as T1mic, a subset of T1 breast cancer.
 Note- when there are multiple foci of
microinvasion,
- the size of only the largest focus is used
to classify the microinvasion
- the sizes of the individual foci should not
be added together.

25. Carcinoma in situ
 Neoplastic population of cells limited
to ducts and lobules by basement
membrane.
 Does not invade into lymphatics, blood
vessels and cannot metastasize.

26.  Ductal carcinoma in situ
- malignant population of cells limited to
ducts and lobules by basement
membrane.
- Is a clonal proliferation and usually
involves only a single ductal system.
- However cells can spread through
ducts and lobules--- acini get distorted
and give appearance of small ducts.

27.  Majority of DCIS cannot be detected
on visual inspection or palpation.
 Sometimes when associated with
periductal fibrosis --- thickening of
tissue.
 Many cases of DCIS progress to
invasive carcinoma.

28. Paget’s disease and intraducat
carcinoma IS
 Rare, 1-2 % of breast cancer
 Malignant cells called as paget cells
extend from DCIS to nipple skin
without crossing basement
membrane.
 Tumor cells disrupt the normal
epithelial barrier and this allows
extracellular fluid to seep out on nipple

29. Invasive (infiltrating)
carcinoma
 Neoplastic population of cells invade
beyond the basement membrane into
stroma .
 May also invade vasculature, reach
regional lymph nodes and also
metastasize

30. Invasive (infiltrating) ductal
carcinoma (IDC)
 most common type of breast cancer
 comprising more than 50% of all
cases.
 appears as solid cords or groups of
ductal tumor cells varying in size and
cytoplasmic content and degree of
differentiation

31. Invasive (infiltrating) ductal carcinoma
of the breast

32. Inflammatory carcinoma
 Clinical presentation of carcinoma
involving extensively dermal
lymphatics resulting in large
erythematous breast
 Typically does not form a discrete
palpable mass
 This results in confusion with
inflammatory breast conditions and
delay in diagnosis.
 Staged as T4d.

34. Medullary carcinomas
 Composed of cords and masses of
large cells with reticular pleomorphic
nuclei with prominent nucleoli
 Scant fibrous stroma, prominent
lymphoid infiltrate.
 Microscopically and grossly well
circumscribed.
 Prognosis in general is better than
other types.
 More common in young females.

35. Medullary carcinoma breast

36. Mucinous (colloid) carcinoma
 Exremely soft tumor
 Tumor cells seen as clusters and small
islands of cells within large flakes of
mucin.
 Slow growing
 Rare lymphatic invasion
 Overall prognosis is better than with IDC

38. Invasive Papillary carcinoma
 Growth of tumor cell clusters in
prominent clear spaces resembling
dilated angiolymphatic vessels.
 Rare, <1 % of invasive breast
carcinomas.

39. Invasive papillary carcinoma
breast

40. Tubular carcinoma breast
 Composed of tubular structures lined
by a single layer of well differentiated
epithelium
 Axillary metastasis is rare
 Exelllent prognosis.

41. Tubular carcinoma

42. Lobular invasive carcinoma
 Cells appear singly or in small clusters
 Aggressive , multicenric
 Prone for distant metastasis.

43. Metaplastic carcinoma breast
 Relatively rare
 Wide variety of rare types of breast
cancer including adenocarcinoma ,
SCC,and carcinomas with prominent
spindle component , difficult to
distinguish from sarcomas.

44. Adenoid cystic carcinoma
 Rare in breast
 Prognosis is good.

45. Cystosarcoma phylloides
 Usually benign
 Large tumors
 Usually encapsulated
 Frequently develop from preexisting
fibromas and have a long initial period
of slow growth followed by sudden ,
rapid increase in size.

46. Primary breast lymphomas
 Rare, 0.4-0.5%
 Lymphoepithelial lesions in ducts and
lobules,
 Frequent vascular invasion

47. Histological grading of breast
tumors
 The grade of a breast cancer is
representative of the "aggressive
potential" of the tumor
 "low grade" cancers tend to be less
aggressive than "high grade" cancers.
 Determining the grade is thus very
important, and the clinicians use this
information to help guide the treatment
options for patients.

48.  Nottingham Histologic Score system (the Elston-
Ellis modification of Scarff-Bloom-Richardson
grading system)
 In this scoring system, there are three factors
that the pathologists take into consideration:
-the amount of gland formation ("differentiation"
or how well the tumor cells try to recreate normal
glands)
-the nuclear features ("pleomorphism“ )
-the mitotic activity (how much the tumor cells are
dividing)
Each of these features is scored from 1-3, and then
each score is added to give a final total score
ranging from 3-9.

49. 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

50. 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

51. Mitotic Count
 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 are as follows:
 Score 1: less than or equal to 7 mitoses
per 10 high power fields
 Score 2: 8-14 mitoses per 10 high power
fields
 Score 3: equal to or greater than 15
mitoses per 10 high power fields

52.  Grade 1( well diff) tumors - score of 3-
5
 Grade 2 (mod diff) -score of 6-7
 Grade 3 (poorly diff) - score of 8-9

53. Hormone regulation
 The degree of exposure to estrogen is a
well-established risk factor for
developing ER-positive breast cancer.
 Estrogen is a steroid hormone that has a
profound proliferative effect on normal
human mammary epithelium through its
activation of ER
 ER is overexpressed in as many as 70%
of breast cancers.
 Carcinoma breast patients with hormonal
receptors have a significantly higher
survival rate.

55. Molecular subtypes

56. Model histopathological report
(WHO guidelines, 2006)
 For invasive carcinoma
 Laterality of breast and procedure
 Histological type
 Histological grade
 Margins of resection-
- state if tumor is at the margin
-if not at margin , distance from
margin to be specified.

57.  Lymph node status
number of nodes removed
number of nodes positive
perinodal extension into fat +/-
• Lymphovascular invasion
• Size of tumor- maximum diameter
• ER/PR/Her2Neu status

58.  For DCIS
 Laterality of breast and procedure
 Grade
 Necrosis- +/-
 Architectural type- cribriform,
micropapillary,solid, comedo, papillary,
mixed
 Margins
 Size

59. Model histopathology report (
TMH, 2009)
• Tumour size (all 3 dimensions)
• Tumour type
• Tumour grade (Modified Richardson Bloom
Score)
• Presence of extensive intraductal carcinoma
(EIC)
• Lymphovascular embolisation
• Cut Margin status (gross positive/ focal
positive/ negative) in case of lumpectomy or
wide excision
• No. of positive/total axillary lymph node
dissected Receptor status: ER and PgR (by
IHC )

60.  Thankyou