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CARCINOMA BREAST
CLINICAL PATHOLOGY
DR MUHAMMMED MUNEER M
MS GENERAL SURGERY
SGMC & RF
TRIVANDRUM KERALA
• 63 yr old female
• Lump in the Left breast x 1 yr duration
O/e :
Lump palpable in the lower inner quadrant measuring
12x18mm
Tenderness ++
No h/o trauma
No discharge
Skin appeared normal
Multiple enlarged lymph nodes
Mammogram : BIRADS III - IV
C-5479/16
IMPRESSION
• Papillary lesion of breast with atypia
• Possibilities of Ductal carcinoma insitu /
Invasive papillary carcinoma may be ruled
out by excision biopsy
• Suggest intraoperative frozen section
examination for confirmation
FROZEN SECTION
IMPRESSION
Lumpectomy Specimen – Left breast
- Invasive cribriform carcinoma
(size 3x2.5x2.4cm)
- Modified Bloom Richardsons Grade II
- Lateral and deep resected margin are very
close 0.1cm away from the neoplasm but
inked margin is free of neoplasm
- Other margins medial,superior & inferior
margins are free of neoplasm
MRM
ESTROGEN RECEPTOR
PROGESTERONE RECEPTOR
Her 2 /neu receptor
IMPRESSION
Modified Radical Mastectomy – Left breast (post
lumpectomy)
- No residual carcinomatous focus
- Adjacent breast tissue shows a focus of DCIS
with cribriform pattern
- Rest of the breast tissue show fibroadenomatoid
change
Central Lymphnode
6/6 lymphnodes show reactive change only
HORMONE RECEPTOR STATUS
Estrogen Receptor
Proportion score = 2/3 = 4
Intensity score = 3 ( strong)
Total score = 4+3 = 7 ( POSITIVE)
Progesterone Receptor
Proportion score = 2/3 = 4
Intensity score = 3 = strong
Total score = 4+3 = 7 (POSITIVE)
HER 2/ Neu receptor
2 + equivocal – weak to moderate membrane
staining is observed in more than 10% of
tumor cells
INVASIVE CRIBRIFORM BREAST
CARCINOMA
WHO CLASSIFICATION
• Epithelial Tumors
• Invasive breast carcinoma
• Epithelial-Myoepithelial tumors
• Precursor Lesions
• Intraductal proliferative lesions
• Papillary Lesions
• Benign epithelial proliferations
• Mesenchymal tumors
• Fibroepithelial tumors
• Tumors of the nipple
• Malignant Lymphoma
• Metastatic Tumors
• Tumors of the male breast
• Clinical patterns
INVASIVE BREAST CARCINOMA
 Invasive carcinoma of no special type (NST)
 Invasive lobular carcinoma
 Tubular carcinoma
 Cribriform carcinoma
 Mucinous carcinoma
 Carcinoma with medullary features
 Carcinoma with apocrine differentiation
 Carcinoma with signet ring differentiation
 Invasive micropapillary carcinoma
 Metaplastic carcinoma of NST
 Rare types
INTRODUCTION
• Rare form of breast malignancy with an
excellent prognosis
• Grows in a pattern similar to that seen in
intraductal cribriform carcinoma
• 50% component of tubular carcinoma may be
admixed
EPIDEMIOLOGY
• 0.3 – 0.8% of breast carcinomas
• A frequency of upto 4% has been reported in
some countries
• Mean pt. age is 53-58yrs
CLINICAL FEATURES
• Tumor may present as a mass, which may be
radiologically occult
On mammography:
- Typically form a spiculate mass
- Frequently containing microcalcifications
- Multifocality is observed in 10-20% of cases
• Positive for ER in all cases & positive for PR in
69% of the cases
GROSS
• No specific gross pathologic features have
been noted
• Mean tumor size is 3.1cm
MICROSCOPY
• Pure ICC consists of an invasive cribriform
pattern in >90% of the lesion
• Tumor cells is arranged as invasive,often
angulated, islands in which well- defined
cribriform spaces are formed by arches of
cells (sieve-like pattern)
• Mucin-positive secretion bearing
microcalcifications can be present within
lumina
• Tumor cells – small to moderate in size with a
mild or moderate degree of pleomorphism
• Mitosis – rare
• DCIS generally of cribriform architecture is
frequent – 80% of cases
• Axillary LN metastases occur in 14.3% of
cases – retention of the cribriform pattern
• Invasive carcinoma with a cribriform
arrangement but associated with a
component (<50%) of tubular carcinoma is
also included in this category
• Cases with a 10-49% component of another
morphological type ( other than TC) are
regarded as mixed type
DIFFERENTIAL DIAGNOSIS
Well - differentiated neuroendocrine tumor :
Presence of intracytoplasmic argyrophilic
granules
Adenoid cystic carcinoma:
Have second population of cells as well as
intracystic secretory & basement membrane
material
Cribriform DCIS
Lack of a myoepithelial cell layer around its
invasive islands, haphazard distribution &
irregular configuration
» Carcinomas rich in osteoclast- like giant cells are
mostly seen in ICC, but such giant cells may be
seen in other types of invasive mammary
carcinoma & are not diagnostic of ICC
STAGING
HORMONE RECEPTORS
A crucial development in the treatment of
breast carcinoma has been the realization that
the presence of hormone receptors in the
tumor tissue correlates well with response to
hormone therapy & chemotherapy
• Estrogen receptor status – the most powerful
predictive marker in breast cancer
management
• Estrogen & progesterone receptors are
codependent variables
• Progesterone receptor being a weaker
predictor of response to endocrine therapy
than estrogen receptor
The two parameters evaluated in
immunohistochemical preparations of
hormone receptors are :
1. The number of tumor cell nuclei stained –
expressed as a percentage of the entire
tumor cell nuclei population
2. The intensity of the reaction
The two parameters are sometimes combined
into a scoring system :
1. Allred Scoring System
2. H
3. Quick scores
ALLRED SCORING SYSTEM
A clinical instrument based on the percentage of
cells that stain by immunohistochemistry for
- ER (on a scale of 0-5)
- Intensity of the staining (on a scale of 0-3,for a
possible total score of 8)
Stratifies a breast cancer patients ER status into
cancers that are likely to respond to hormone
therapy with tamoxifen
Proportion Score :
0 – No cells are ER+ve
1 - < 1% of cells are ER+ve
2 - 1-10% of cells are ER+ve
3 - 11-33% of cells are ER+ve
4 - 34-66% of cells are ER+ve
5 - 67-100% of cells are ER+ve
Intensity score :
0 – Negative
1 –Weak
2 – Intermediate
3 – Strong
0-1 No effect
2-3 Small (20%)chance of benefit
4-6 Moderate (50%)
7-8 Good
HER 2/neu
• Is an oncogene that encodes a transmembrane
glycoprotein with tyrosine kinase activity
known as p185 which belongs to the family of
epidermal growth factor receptors
• Its overexpression can be measured by
immunohistochemistry or FISH
MOLECULAR CLASSIFICATION
CRIBRIFORM CARCINOMA - LUMINAL A
BASAL LIKE SUBTYPE IS ASSOCIATED WITH THE WORST PROGNOSIS
PROGNOSIS & PREDICTIVE FACTORS
• The outcome for patients with ICC is
favourable 10 yr overall survival is between
90% & 100%
• The outcome for patients with mixed ICC is
less favourable than for patients with the
pure form, but better than for invasive
carcinoma NST

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Carcinoma breast clinical pathology dr mnr

  • 1. CARCINOMA BREAST CLINICAL PATHOLOGY DR MUHAMMMED MUNEER M MS GENERAL SURGERY SGMC & RF TRIVANDRUM KERALA
  • 2. • 63 yr old female • Lump in the Left breast x 1 yr duration O/e : Lump palpable in the lower inner quadrant measuring 12x18mm Tenderness ++ No h/o trauma No discharge Skin appeared normal Multiple enlarged lymph nodes Mammogram : BIRADS III - IV
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  • 6. IMPRESSION • Papillary lesion of breast with atypia • Possibilities of Ductal carcinoma insitu / Invasive papillary carcinoma may be ruled out by excision biopsy • Suggest intraoperative frozen section examination for confirmation
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  • 15. IMPRESSION Lumpectomy Specimen – Left breast - Invasive cribriform carcinoma (size 3x2.5x2.4cm) - Modified Bloom Richardsons Grade II - Lateral and deep resected margin are very close 0.1cm away from the neoplasm but inked margin is free of neoplasm - Other margins medial,superior & inferior margins are free of neoplasm
  • 16. MRM
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  • 22. Her 2 /neu receptor
  • 23. IMPRESSION Modified Radical Mastectomy – Left breast (post lumpectomy) - No residual carcinomatous focus - Adjacent breast tissue shows a focus of DCIS with cribriform pattern - Rest of the breast tissue show fibroadenomatoid change Central Lymphnode 6/6 lymphnodes show reactive change only
  • 24. HORMONE RECEPTOR STATUS Estrogen Receptor Proportion score = 2/3 = 4 Intensity score = 3 ( strong) Total score = 4+3 = 7 ( POSITIVE) Progesterone Receptor Proportion score = 2/3 = 4 Intensity score = 3 = strong Total score = 4+3 = 7 (POSITIVE)
  • 25. HER 2/ Neu receptor 2 + equivocal – weak to moderate membrane staining is observed in more than 10% of tumor cells
  • 27. WHO CLASSIFICATION • Epithelial Tumors • Invasive breast carcinoma • Epithelial-Myoepithelial tumors • Precursor Lesions • Intraductal proliferative lesions • Papillary Lesions • Benign epithelial proliferations • Mesenchymal tumors
  • 28. • Fibroepithelial tumors • Tumors of the nipple • Malignant Lymphoma • Metastatic Tumors • Tumors of the male breast • Clinical patterns
  • 29. INVASIVE BREAST CARCINOMA  Invasive carcinoma of no special type (NST)  Invasive lobular carcinoma  Tubular carcinoma  Cribriform carcinoma  Mucinous carcinoma  Carcinoma with medullary features  Carcinoma with apocrine differentiation  Carcinoma with signet ring differentiation
  • 30.  Invasive micropapillary carcinoma  Metaplastic carcinoma of NST  Rare types
  • 31. INTRODUCTION • Rare form of breast malignancy with an excellent prognosis • Grows in a pattern similar to that seen in intraductal cribriform carcinoma • 50% component of tubular carcinoma may be admixed
  • 32. EPIDEMIOLOGY • 0.3 – 0.8% of breast carcinomas • A frequency of upto 4% has been reported in some countries • Mean pt. age is 53-58yrs
  • 33. CLINICAL FEATURES • Tumor may present as a mass, which may be radiologically occult On mammography: - Typically form a spiculate mass - Frequently containing microcalcifications - Multifocality is observed in 10-20% of cases • Positive for ER in all cases & positive for PR in 69% of the cases
  • 34. GROSS • No specific gross pathologic features have been noted • Mean tumor size is 3.1cm
  • 35. MICROSCOPY • Pure ICC consists of an invasive cribriform pattern in >90% of the lesion • Tumor cells is arranged as invasive,often angulated, islands in which well- defined cribriform spaces are formed by arches of cells (sieve-like pattern) • Mucin-positive secretion bearing microcalcifications can be present within lumina
  • 36. • Tumor cells – small to moderate in size with a mild or moderate degree of pleomorphism • Mitosis – rare • DCIS generally of cribriform architecture is frequent – 80% of cases • Axillary LN metastases occur in 14.3% of cases – retention of the cribriform pattern
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  • 39. • Invasive carcinoma with a cribriform arrangement but associated with a component (<50%) of tubular carcinoma is also included in this category • Cases with a 10-49% component of another morphological type ( other than TC) are regarded as mixed type
  • 40. DIFFERENTIAL DIAGNOSIS Well - differentiated neuroendocrine tumor : Presence of intracytoplasmic argyrophilic granules Adenoid cystic carcinoma: Have second population of cells as well as intracystic secretory & basement membrane material
  • 41. Cribriform DCIS Lack of a myoepithelial cell layer around its invasive islands, haphazard distribution & irregular configuration » Carcinomas rich in osteoclast- like giant cells are mostly seen in ICC, but such giant cells may be seen in other types of invasive mammary carcinoma & are not diagnostic of ICC
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  • 45. HORMONE RECEPTORS A crucial development in the treatment of breast carcinoma has been the realization that the presence of hormone receptors in the tumor tissue correlates well with response to hormone therapy & chemotherapy
  • 46. • Estrogen receptor status – the most powerful predictive marker in breast cancer management • Estrogen & progesterone receptors are codependent variables • Progesterone receptor being a weaker predictor of response to endocrine therapy than estrogen receptor
  • 47. The two parameters evaluated in immunohistochemical preparations of hormone receptors are : 1. The number of tumor cell nuclei stained – expressed as a percentage of the entire tumor cell nuclei population 2. The intensity of the reaction
  • 48. The two parameters are sometimes combined into a scoring system : 1. Allred Scoring System 2. H 3. Quick scores
  • 49. ALLRED SCORING SYSTEM A clinical instrument based on the percentage of cells that stain by immunohistochemistry for - ER (on a scale of 0-5) - Intensity of the staining (on a scale of 0-3,for a possible total score of 8) Stratifies a breast cancer patients ER status into cancers that are likely to respond to hormone therapy with tamoxifen
  • 50. Proportion Score : 0 – No cells are ER+ve 1 - < 1% of cells are ER+ve 2 - 1-10% of cells are ER+ve 3 - 11-33% of cells are ER+ve 4 - 34-66% of cells are ER+ve 5 - 67-100% of cells are ER+ve
  • 51. Intensity score : 0 – Negative 1 –Weak 2 – Intermediate 3 – Strong 0-1 No effect 2-3 Small (20%)chance of benefit 4-6 Moderate (50%) 7-8 Good
  • 52. HER 2/neu • Is an oncogene that encodes a transmembrane glycoprotein with tyrosine kinase activity known as p185 which belongs to the family of epidermal growth factor receptors • Its overexpression can be measured by immunohistochemistry or FISH
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  • 55. MOLECULAR CLASSIFICATION CRIBRIFORM CARCINOMA - LUMINAL A BASAL LIKE SUBTYPE IS ASSOCIATED WITH THE WORST PROGNOSIS
  • 56. PROGNOSIS & PREDICTIVE FACTORS • The outcome for patients with ICC is favourable 10 yr overall survival is between 90% & 100% • The outcome for patients with mixed ICC is less favourable than for patients with the pure form, but better than for invasive carcinoma NST