Breast cancer histopathology types and clinical features

1. BREAST CANCER
HISTOPATHOLOGY TYPES AND
CLINICAL FEATURES
Presentor: Dr G Santhi Priya
Moderator: Dr Rajeev
7/25/2018 Seminar

2. CONTENTS
• Introduction
• Risk factors
• Pathogenesis
• Pathways of breast cancer developement
• Clinical presentations
• Classification
7/25/2018 Seminar

3. 7/25/2018 Seminar
INTRODUCTION

4. 7/25/2018 Seminar

5. Risk factors
7/25/2018 Seminar

6. Risk factors
7/25/2018 Seminar

7. Risk factors
7/25/2018 Seminar

8. PATHOGNESIS
7/25/2018 Seminar
Most common gene
implicated in Breast
carcinoma

9. BRCA -1Breast
Cancer 1,Early
onset ( Chr.17)
BRCA-2, Breast
Cancer 2,Early
onset( Chr.13)
p53( Chr.17) CHEK2( Chr. 22)
FUNCTIONS:
• Transcription
• DNA Repair of
doublestranded
breaks
• Ubiquitination
• Transcriptional
regulation.
FUNCTIONS:
•Stability of
the human genome
•DNA double strand
break repair.
FUNCTIONS
• Cell cycle
control
• DNA replication
• DNA repair
• Apoptosis.
FUNCTIONS
• Cell cycle
checkpoint
kinase,
recognition and
repair of DNA
damage.
• Activates BRCA1
and p53 by
phosphorylation
Germline point
mutations/Deletions
of BRCA1 gene 
Hereditary breast &
ovarian cancers.
Mutations 20%
Hereditary breast
cancer, ovarian
cancer, increased
cancer risk in male
carriers.
Mutations
Sporadic breast
cancers.
 Li fraumeni
syndrome
Mutations - rare
(<5%).
Li fraumeni variant
Increase breast
cancer risk after
radiation exposure
7/25/2018 Seminar

10. PATHWAYS OF BREAST CANCER
DEVELOPEMENT
7/25/2018 Seminar

11. CLINICAL PRESENTATION
7/25/2018 Seminar
Symptoms of breast disease

12. PRESENTATIONS OF BREAST CANCER
7/25/2018 Seminar
More than half of cancers are asymptomatic and are detected by mammographic
screening and about another one third present as palpable masses—almost all
discovered by the patient

13. CLASSIFICATION
• Breast cancers are conventionally classified
into different types by
Morphological feature,
Histological features,
Tumor grade,
Proliferation status,
Lymphovascular invasion – prognostic
variables
7/25/2018 Seminar

14. WHO Classification
• EPITHELIAL TUMOURS
• MESENCHYMAL TUMOURS
• FIBROEPITHELIAL TUMOURS
• TUMOURS OF THE NIPPLE
• MALIGNANT LYMPHOMA
• METASTATIC TUMOURS
• TUMOURS OF THE MALE BREAST
7/25/2018 Seminar

15. EPITHELIAL TUMOURS
• Invasive breast carcinoma
• Epithelial–myoepithelial tumours
• Precursor lesions
• Intraductal proliferative lesions
• Papillary lesions
• Benign epithelial proliferations
7/25/2018 Seminar

16. MOLECULAR SUBTYPES
7/25/2018 Seminar

17. 7/25/2018 Seminar

18. Histopathological classification
7/25/2018 Seminar

19. DUCTAL CARCINOMA IN SITU
 Most DCIS  detected by
calcifications on mammography/
mammographic density - periductal
fibrosis surrounding a DCIS/rarely
palpable mass/ nipple
discharge/incidental finding on a
biopsy for another lesion.
 Spreads through ducts & lobules 
extensive lesions  entire sector of a
breast.
7/25/2018 Seminar

20. 7/25/2018 Seminar

21. DCIS
Characteristic
Comedo Noncomedo
Nuclear grade High Low
Estrogen receptor Negative Positive
HER2
overexpression
Present Absent
Distribution Continuous Multifocal
Necrosis Present Absent
Local recurrence High Low
Prognosis Worse Better
MORPHOLOGY
7/25/2018 Seminar

22. COMEDOCARCINOMA
 Solid sheets of pleomorphic cells
with high grade hyperchromatic
nuclei.
 Areas of central necrosis +nt.
 Necrotic cell membranes – calcify
clusters/linear & branching
microcalcifications on
mammography.
 Periductal concentric fibrosis &
chronic inflammation.
 Extensive lesions – palpable as
vague nodularity.
7/25/2018 Seminar

23. NONCOMEDO DCIS
 Monomorphic cell
population – nuclear
grades  low to high.
 CRIBRIFORM DCIS
 Intra-epithelial spaces –
evenly distributed, regular
in shape.
 COOKIE CUTTER – LIKE
• SOLID DCIS
Completely fills the
involved spaces.
7/25/2018 Seminar

24. NONCOMEDO DCIS
 PAPILLARY DCIS
 Grows into spaces along
fibrovascular cores  lack
myoepithelial cell layer.
• MICROPAPILLARY
DCIS
 Bulbous protrusions
without a fibrovascular
core arranged in complex
intraductal patterns.
 Calcifications – assoc.with
necrosis/form on
intraluminal secretions.
7/25/2018 Seminar

25. MANAGEMENT AND PROGNOSIS OF
DCIS
• MASTECTOMY for DCIS – curative  > 95 % pts.
• In ER + ve DCIS  Post- op. radiation + Tamoxifen
•  recurrence risk – low.
• Death  < 2 % DCIS.
7/25/2018 Seminar

26. LOBULAR CARCINOMA IN SITU
 Incidental biopsy finding -
no calcifications /stromal
reactions mammographic
densities.
 Bilateral - 20% to 40% .
 Young women.
 Loss of expression of E-
cadherin(transmembrane
cell adhesion protein 
cohesion of normal breast
epithelial cells).
7/25/2018 Seminar

27. LOBULAR CARCINOMA IN SITU -
MORPHOLOGY
 Dyscohesive round cells with
oval or round nuclei and
small nucleoli.
 Absence of atypia,
pleomorphism, mitoti
activity, necrosis.
 ER and PR +ve.
7/25/2018 Seminar

28. LOBULAR CARCINOMA IN SITU
 Invasive carcinoma  1% per
year.
 Both breasts - increased risk.
Risk - slightly higher in the
ipsilateral breast.
 Treatment:
• Bilateral prophylactic
mastectomy.
• Tamoxifen.
• Close clinical follow-up.
• Mammographic screening.
7/25/2018 Seminar

29. INVASIVE CARCINOMA – CLINICAL
FEATURES
 Palpable mass.
 Axillary lymph node
metastases
 Fixity to the chest wall / skin
dimpling.
 Nipple retraction
 Lymphatics - involved - block
the local area of skin drainage
 lymphedema, skin
thickening.
 Tethering of the skin to the
breast by Cooper ligaments 
peau d'orange.
 Mammography  Radiodense
mass
7/25/2018 Seminar

30. INVASIVE CARCINOMA-NST
 Majority (70% to 80%).
 Gross appearance: Most
tumors - firm to hard ,irregular
border . Less frequently - well-
circumscribed border , softer
consistency.
 When cut / scraped
characteristic grating sound
d/t small, central pinpoint foci
or streaks of chalky-white
elastotic stroma and occasional
small foci of calcification.
7/25/2018 Seminar

31. INVASIVE LOBULAR CARCINOMA
 Palpable mass/
mammographic density with
irregular borders. Sometimes
- tumor infiltrates the tissue
diffusely – little desmoplasia,
not palpable, no
mammographic density.
Metastases – difficult to
detect.
 Bilateral - 5 – 10 %.
 Biallelic loss of expression of
(CDH1,  encodes E-
cadherin) d/t mutations.
7/25/2018 Seminar

32. INVASIVE LOBULAR CARCINOMA
 Morphology: Histologic
hallmark  dyscohesive
infiltrating tumor cells, often
arranged in single file or in
loose clusters or sheets 
INDIAN FILE APPEARANCE.
 Tubule formation - absent.
 Signet-ring cells containing an
intracytoplasmic mucin droplet
are common.
 Desmoplasia - minimal or
absent
7/25/2018 Seminar

33. MEDULLARY CARCINOMA
 MC - 6th decade.
 May closely mimic a benign
lesion clinically and
radiologically/ present as a
rapidly growing mass.
 MORPHOLOGY : Well –
circumscribed,soft,fleshy mass
- little desmoplasia  more
yielding on palpation and
cutting. .
7/25/2018 Seminar

34. MEDULLARY CARCINOMA - HPE
.
•Solid, syncytium-like
sheets of large cells with
vesicular, pleomorphic
nuclei, prominent
nucleoli  > 75% of the
tumor
• Frequent mitotic figures;
Moderate to marked
lymphoplasmacytic
infiltrate surrounding and
within the tumor.
Pushing (noninfiltrative)
border.
7/25/2018 Seminar

35. MEDULLARY CARCINOMA
 High nuclear grade,
aneuploidy, hormone
receptors - nt, HER2/neu
overexpression –nt.
 Lymph node metastases -
infrequent.
 Syncytial growth pattern
and pushing borders - d/t
overexpression of adhesion
molecules  intercellular
cell adhesion molecule and
E-cadherin  limit
metastatic potential.
7/25/2018 Seminar

36. MUCINOUS/COLLOID CARCINOMA
 Older women (median
age 71) grow slowly -
many years.
 Morphology: Tumor –
soft/rubbery . Consistency
& appearance of pale
gray-blue gelatin. Borders
- pushing / circumscribed.
7/25/2018 Seminar

37. MUCINOUS CARCINOMA - HPE
 Tumor cells - arranged in
clusters and small islands
within large lakes of mucin.
 Mucinous carcinomas 
diploid, well to moderately
differentiated, and ER
positive.
 Lymph node metastases -
uncommon.
 Overall prognosis is slightly
better.
7/25/2018 Seminar

38. TUBULAR CARCINOMA
 Small irregular mammographic
densities - late 40s.
 Uncommon.
 Morphology: Well-formed
tubules + nt, myoepithelial cell
layer, BM - nt  tumor cells in
direct contact with the stroma.
Apocrine snouts - typical.
Calcifications - within the
lumens.
 > 95% of all tubular carcinomas -
diploid, ER + ve,HER2/neu –ve .
 Well differentiated. Excellent
prognosis.
7/25/2018 Seminar

39. INVASIVE PAPILLARY & MICROPAPILLARY
CARCINOMA
 Rare - 1% or fewer of all
invasive cancers.
 More commonly seen in
DCIS.
 INVASIVE PAPILLARY CA.
 ER positive.
 Favorable prognosis.
 INVASIVE
MICROPAPILLARY CA.
 ER negative,HER2 positive.
 Lymph node metastases -
very common
 Prognosis is poor.
7/25/2018 Seminar

40. INFLAMMATORY CARCINOMA
 Tumors  swollen,
erythematous breast -
caused by extensive
invasion and obstruction
of dermal lymphatics by
tumor cells.
 Underlying carcinoma -
diffusely infiltrative - does
not form a discrete palpable
mass  confusion with true
inflammatory conditions a
delay in diagnosis.
 Many patients 
metastases at diagnosis /
recur rapidly.
7/25/2018 Seminar

41. 
METAPLASTIC CARCINOMA
Includes a variety of rare
types of breast cancer (<1% of
all cases)  matrix-producing
carcinomas, squamous cell
carcinomas, and carcinomas
with a prominent spindle cell
component.
 ER-PR-HER2/neu “triple
negative”.
 Lymph node metastases -
infrequent.
 Prognosis - poor.
7/25/2018 Seminar

42. References
1. Lester SC,The Breast. In Kumar V, Abbas A K, Aster J C,
Robbins and cotran patholology basis of disease. 9th ed.
Elsevier Inc: 2016. P.1043-72.
2.Rosenblum M K,Rosai J. Breast.In: Rosai J, editors. Rosai
and Ackerman's Surgical Pathology. 10th Ed. Philadelphia:
Mosby Elsevier: 2011.p1631-718
3. Li CI,Uribe DJ,Daling JR.Clinical characteristics of
different histopathologic types of breast
cancer.BJCancer.2005(93),1046-1052
4. Rakha EA, Ellis IO. Molecular profiling of breast cancer. In:
recent advances in histopathology. 24th ed. New Delhi: JP
medical publisher; 2016. 13-25.
7/25/2018 Seminar