This document summarizes two breast biopsy cases of invasive ductal carcinoma and invasive lobular carcinoma. It provides details on histologic grading, immunohistochemical staining results, tumor characteristics like size and margins. It also describes lymph node sampling and definitions of treatment response. In both biopsy cases, the tumors were grade 2 with no lymphovascular invasion seen and further testing was recommended to determine biomarker status.

1. CASE PRESENTATION
Thanks to DR. BABAR YASIN
MEDICAL OFFICER
HISTOPATHOLOGY for the
preparation of this presentation

2. CASE 1

3. LEFT BREAST CORE BIOPSY

5. INVASIVE DUCTAL CARCINOMA, GRADE II
NO LYMPHO VASCULAR INVASION SEEN

6. RIGHT BREAST, CORE BIOSPY

8. INVASIVE MAMMARY CARCINOMA FOVOUR INVASIVE LOBULAR
CARCINOMA, GRADE II
NO LYMPHOVASCULAR INVASION SEEN

9. Histologic Grade (Nottingham Histologic
Score)
 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 Rate
 Score 1 (≤3 mitoses per mm2)
 Score 2 (4-7 mitoses per mm2)
 Score 3 (≥8 mitoses per mm2)

10.  Overall Grade
 Grade 1 (scores of 3, 4, or 5)
 Grade 2 (scores of 6 or 7)
 Grade 3 (scores of 8 or 9)

11. IMMUNOHISTOCHEMICAL
FEATURES
 It is recommended that hormone receptor and HER2 testing
be done on all primary invasive breast carcinomas and on
recurrent or metastatic tumors.
 If hormone receptors and HER2 are both negative on a core
biopsy, repeat testing on a subsequent specimen should be
considered, particularly when the results are discordant with
the histopathologic findings.
 Other biomarker tests (eg, Ki-67 or multigene expression
assays) are optional.

12. ER & PR
Proportion
Score
Positive Cells,
%
Intensity Intensity
Score
0 0 None 0
1 <1 Weak 1
2 1 to 10 Intermediate 2
3 11 to 33 Strong 3
4 34 to 66
5 ≥67
The Allred score combines the percentage of positive cells and the intensity of
the reaction product in most of the carcinoma. The 2 scores are added together
for a final score with 8 possible values.

13. HER2
Result Criteria
Negative
(Score 0)
No staining observed
Negative
(Score 1+)
Incomplete, faint/barely perceptible membrane staining in
>10% of invasive tumor cells
Equivocal
(Score 2+)
Incomplete and/or weak to moderate circumferential
membrane staining in >10% of invasive tumor cells
or
Complete, intense, circumferential membrane staining in
≤10% of invasive tumor cells
Positive
(Score 3+)
Complete, intense, circumferential membrane staining in
>10% of invasive tumor cells

14. Ki-67 Testing
 The percentage of Ki-67 positive tumor cells determined by
IHC is often used to stratify patients into good and poor
prognostic groups.
 ( leading edge, hot spots, overall average).

15. LEFT BREAST, CORE BIOPSY,
ER

16. PR

17. HER 2

18. Ki67

19. RIGHT BREAST, CORE BIOPSY
ER

20. PR

21. HER2

22. Ki67

24.  Luminal A
- ER-positive/ PR-positive
- HER2-negative
- Low Ki67
 Luminal B
- ER-positive/ PR-positive
- HER2-positive (or HER2-negative with high Ki67)
 Triple negative/basal-like
- ER-negative
- PR-negative
- HER2-negative
 HER2 type
- ER-negative
- PR-negative
- HER2-positive

25. Synchronous Bilateral Breast
Carcinoma
 Synchronous bilateral breast cancer is uncommon (incidence
ranges between 0.3% and 12%.) but its incidence is likely to
rise.
 This wide range is in part due to the many definitions. Some
physicians consider a contralateral cancer diagnosed within 1
year as a synchronous bilateral breast cancer. Others narrow
the definition of synchronous bilateral breast cancers to those
cancers which are diagnosed within 3 months of each other.
 In general, patients with SBBC tend to have a worse
prognosis.

29. Tumor Size
 Important prognostic factor.
 The single greatest dimension of the largest invasive
carcinoma is used to determine T classification.
 The best size for AJCC T classification should use
information from imaging, gross examination, and
microscopic evaluation.
 Visual determination of size is often unreliable (carcinomas
often blend into adjacent fibrous tissue). The size by
palpation of a hard mass correlates better with invasion of
tumor cells into stroma with a desmoplastic response.

31. MARGIN EVALUATION
 The specimen should be oriented in order for the pathologist
to identify specific margins.
 Sutures, Clips (Communication between surgeon &
pathologist)
A positive margin requires ink on
carcinoma.

32. Lymph Node Sampling and
Reporting
 Types of lymph nodes.
 Gross findings & sampling.
 Size of metastases
- Isolated tumor cell clusters (ITCs)
- Micrometastases
- Macrometastases

34. GROSS FINDINDS
LEFT MASTECTOMY
 Tumor bed size 3.2 x 2.4 x 2.2 cm
 3 cm from nearest postero-inferior margin
 4.5 cm from deep resection margin
 Multiple lymph nodes in axillary fat

43. OPINION
 Mucinous Adenocarcinoma
 MILLER PAYNE grade 3
 Skin & Resection margins free of tumor
 6 / 22 LNs, Positive for metastatic carcinoma
 Size of the largest metastatic deposit 0.5 cm

44. GROSS FINDINGS,
RIGHT BREAST LUMPECTOMY
AND AXILLARY CONTENT
 Tumor bed measures 3.3 x 2.4 x 2.0cm
 0.1 cm from medial resection margin
 3 cm from lateral resection margin
 1.0 cm from superior resection margin
 1.5 cm inferior resection margin
 1.2 cm from deep resection margin
 0.8 cm anterior resection margin
 Multiple lymph nodes in axillary fat

50. OPINION
 INVASIVE LOBULAR CARCINOMA, 3.3 CM
 ASSOCIATED LOBULAR CARCINOMA IN SITU
 TUMOR EXTENDS UPTO THE MEDIAL RESECTION
MARGIN
 MILLER PAYENE GRADE 3
 PERI NEURAL INVASION SEEN

51. Miller-Payne System
 Grade 1 No change or some alteration to individual malignant cells, but
no reduction in overall cellularity
 Grade 2 A minor loss of tumor cells, but overall cellularity still high; up to
30% loss
 Grade 3 Between an estimated 30% and 90% reduction in tumor cells
 Grade 4 A marked disappearance of tumor cells such that only small
clusters or widely dispersed individual cells remain; 90% loss of tumor
cells
 Grade 5 No malignant cells identifiable in sections from the site of the
tumor; only vascular fibroelastotic stroma remains, often containing
macrophages; however, ductal carcinoma in situmay be present.

52. CAP
 Treatment Effect: Response to Presurgical (Neoadjuvant) Therapy
 In the Breast
 No known presurgical therapy
 No definite response to presurgical therapy in the invasive carcinoma
 Probable or definite response to presurgical therapy in the invasive
carcinoma
 No residual invasive carcinoma is present in the breast after presurgical
therapy

 In the Lymph Nodes
 No known presurgical therapy
 No lymph nodes removed
 No definite response to presurgical therapy in metastatic carcinoma
 Probable or definite response to presurgical therapy in metastatic
carcinoma
 No lymph node metastases. Fibrous scarring, possibly related to prior
lymph node metastases with pathologic complete response
 No lymph node metastases and no prominent fibrous scarring in the
nodes

53. Completion surgery specimen
 31-03-2016
 Specimen with overlying skin and Nipple Areola comples
 A grey white area measuring 2.5x 2.0x 1.0 cm.
 Opinion:
- FIBROSIS, CHRONIC INFLAMMATION & GIANT CELL
RESPONSE
- NO RESIDUAL TUMOR SEEN