Difference between revisions of "Invasive breast cancer"

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Ref.: <ref>PBoD NEED PAGE No.</ref>
Ref.: <ref>PBoD NEED PAGE No.</ref>


==Standard work-up==
==Standard IHC work-up==
===Overview===
*Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
*Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
**Sunnybrook uses ''CAM5.2''.
**Sunnybrook uses ''CAM5.2''.
*ER (estrogen receptor) & PR (progesterone receptor).
*ER (estrogen receptor).
**determines whether patient will get tamoxifen or other estrogen modulators.
**Positive in most breast cancers; +ve in ~75-80%.<ref>Lester. 2nd Ed. PP.241-2.</ref>
**in most breast ca ER & PR are positive.<ref>NEED REF.</ref>
*PR (progesterone receptor).
**Positive in most breast cancers; +ve in ~65-70%.<ref>Lester. 2nd Ed. PP.241-2.</ref>
*HER2/neu.
*HER2/neu.
**Positivity assoc. with a worse prognosis.
**Usually negative; -ve in 70-80%.<ref>Lester. 2nd Ed. PP.241-2.</ref>
**Determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.
**Positivity association with a worse prognosis.
**Usually negative.<ref>NEED REF.</ref>
 
 
===ER & PR scoring<ref>Lester. 2nd Ed. PP.241-2.</ref>===
*Give a percentage, i.e. 0-100%.
**Important cut points: 1% and 10%.
***0% = negative - not treated.
***<10% = low positivity - treated.
 
===HER2 scoring<ref>Lester. 2nd Ed. PP.241-2.</ref>===
{| class="wikitable"
| '''Score'''
| '''Staining intensity'''
| '''Cells stained (%)'''
| '''Membrane staining'''
| '''Management'''
| '''Percentage of cases'''
|-
| '''0'''
| nil
| <10%
| incomplete
| No HER2 blocker
| ~60%
|-
| '''1+'''
| minimum
| >10%
| incomplete
| No HER2 blocker
| ~10%
|-
| '''2+'''
| weak
| >10%
| complete
| Needs SISH
| ~10%
|-
| '''3+'''
| strong
| >10%
| complete
| HER2 blocker
| ~20%
|}
 
===Clinical===
*ER & PR status determine whether a patient will get tamoxifen or other estrogen modulators.
*HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.


==Characteristics of the subtypes==
==Characteristics of the subtypes==

Revision as of 17:35, 13 May 2010

Invasive breast cancer a very common malignancy in women.

Types of invasive breast cancer

  • Ductal also known as no specific type (NST) - 79%,  ???includes DCIS???
  • Lobular 10%,
  • Cribriform (tubular) 6%,
  • Mucinous (colloid) 2%,
  • Medullary 2%,
  • Papillary 1%,
  • Metaplastic <1%

Ref.: [1]

Standard IHC work-up

Overview

  • Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
    • Sunnybrook uses CAM5.2.
  • ER (estrogen receptor).
    • Positive in most breast cancers; +ve in ~75-80%.[2]
  • PR (progesterone receptor).
    • Positive in most breast cancers; +ve in ~65-70%.[3]
  • HER2/neu.
    • Usually negative; -ve in 70-80%.[4]
    • Positivity association with a worse prognosis.


ER & PR scoring[5]

  • Give a percentage, i.e. 0-100%.
    • Important cut points: 1% and 10%.
      • 0% = negative - not treated.
      • <10% = low positivity - treated.

HER2 scoring[6]

Score Staining intensity Cells stained (%) Membrane staining Management Percentage of cases
0 nil <10% incomplete No HER2 blocker ~60%
1+ minimum >10% incomplete No HER2 blocker ~10%
2+ weak >10% complete Needs SISH ~10%
3+ strong >10% complete HER2 blocker ~20%

Clinical

  • ER & PR status determine whether a patient will get tamoxifen or other estrogen modulators.
  • HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.

Characteristics of the subtypes

Ductal

AKA "NST" = No Specific Type.

Micro.

  • Cohesive cells - forming ducts or in sheets.
  • Nuclear pleomorphism.

Clinical

  • Typically: ER+, PR+, HER2-.

Lobular

  • "Single file" - cell line-up in a row.
    • Cell should not be cohesive -- lymphoma should briefly come to mind.
      • primary lymphoma of the breast exists... but it is extremely rare.
  • NO gland formation.
    • If it forms glands... it is more likely NST.
  • May have signet ring morphology.
  • NO desmoplastic reaction, i.e. the stroma surrounding the tumour cells should look benign and undisturbed.

Note:

  • commonly have low grade nuclear features

Subclassification:

  • Classic lobular carcinoma.
    • Low nuclear grade - NO significant variation of nucleus size.
  • Pleomorphic lobular carcinoma.
    • Significant nuclear atypia.

Note: Some pathologist grade lobular carcinoma like other types and avoid the term "pleomorphic lobular carcinoma."[7]

Medullary carcinoma

  • Some pathologists don't believe this exists.

Epidemiology:

  • Thought to have a better prognosis that no special type (NST).
  • Association with BRCA1 mutations.

Histol.

  1. Lesion has well-circumscribed border.
  2. Syncytial growth pattern = clumps of cells with poorly defined cell borders.
  3. Lymphocytic infiltrate.
  4. High nuclear grade (as per Nottingham grading system).
  5. No tubule formation.

Tubular

Epidemiology

  • Typically excellent prognosis.
  • Hormone receptors commonly present.

Histol.[8][9][10]

  • Well-formed tubules;
  • Myoepithelial cells absent,
  • +/- Cribriform spaces,
  • Apocrine snouts typical,
  • +/- Calcification,
  • Angled ducts common: "prows" - important feature (low power),
  • Looks benign to the uninitated -- IMPORTANT.

ASIDE: prow = front of a ship

DDx:

Grading breast cancer

Most common system: Nottingham (aka Scarff-Bloom-Richardson) which is based on:

  1. Nuclear grade.
    • Small, regular (1.5-2x RBC dia.) = 1.
    • Moderated variability = 2.
    • Marked variation (>2.5x RBC dia.) = 3.
  2. Tubule formation.
    • Majority of tumour - tubules >75% = 1.
    • Moderate - 10% to 75% = 2.
    • Minimal <10% = 3.
  3. Mitotic rate.
    • 0-5 mitosis/10 HPF (1.52 mm^2 --or-- 0.0152 mm^2 * 10) = 1.
    • 6-10 mitosis/10 HPF (1.52 mm^2) = 2.
    • >11 mitosis/10 HPF (1.52 mm^2) = 3.

Mnemonic: TMN = tubule formation, mitotic rate, nuclear grade.

Notes:

  • Elston & Ellis devised the system that is used.[11] They also wrote a follow-up article in 2002.[12]

Note about mitosis counting

  • One MUST adjust for the size of the field of view.
  • Most of the Resident scopes have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
  • As someone that studied engineering, I have the impression many pathologists have difficulty with the concept of sampling when mathematics is involved. Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is NOT the same as sampling ten fields, where the FOV is 0.312 mm^2. It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do not standardize the sampling area.

Calculating Nottingham score

  • Grade I = 3-5 points.
  • Grade II = 6-7 points.
  • Grade III = 8-9 points.

Notes:

  • I've found most tumours are grade II.
  • The mitotic score is usually 1/3.
  • The nuclear score is rarely 1/3 -- even in the tubular subtype.[13]

Breast IHC

  • DCIS vs LCIS:[14]
    • E-cadherin (+ve DCIS, -ve LCIS)
    • antibody 34betaE12 (+ve perinuclear LCIS, -ve DCIS)
    • CAM5.2 (peripheral stain = DCIS, perinuclear stain = LCIS)
      • CAM5.2 is against CK8
    • beta-catenin (-LCIS, +DCIS)
  • D2-40[15][16]
    • monoclonal antibody to podoplanin)
    • useful to assess lymphovascular invasion
  • ADH and DCIS[17]
    • E-cadherin.
      • Present in most epithelial cells.
      • Lost in LCIS & invasive lobular carcinoma.
    • SMMHC (smooth muscle cell myosin heavy chain).
      • Marks myoepithelial cells.

Paget's disease

General

  • Cells in the epithelium, i.e. skin, that look like they don't belong.
  • Associated with underlying breast carcinoma.[18]

Note:

  • Extra-mammary Paget's disease is not assoc. with malignancy.

Micro

Features:[18]

  • Epitheliod morphology (round/ovoid).
  • Cells nested or single.
  • Clear/pale cytoplasm key feature - may also be eosinophilic.
  • Large nucleoli.

DDx

  • Benign Toker cell hyperplasia.
  • Malignant melanoma.
  • Bowen disease.
  • Nipple duct adenoma (clinical DDx).

IHC

Panel:[18]

  • S-100 -ve, HMB-45 -ve (both typically +ve in melanoma).
  • CK7 +ve
  • CEA +ve (-ve in Bowen's disease, -ve in Toker cells).

Additional:

  • HER2/neu - usually +ve.
  • CK5/6 -ve.[19]
    • Usu. +ve in squamous cell carcinoma.

Familial breast cancer

BRCA1 vs. BRCA2[20]

  • BRCA1
    • Younger,
    • Ovarian cancer,
    • Worse types of breast cancer (e.g. triple negative breast cancer: PR-, ER-, HER2/neu-).
  • BRCA2
  • BOTH assoc. with increased risk of

Sentinel lymph node biopsy

  • CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.

See also

References

  1. ↑ PBoD NEED PAGE No.
  2. ↑ Lester. 2nd Ed. PP.241-2.
  3. ↑ Lester. 2nd Ed. PP.241-2.
  4. ↑ Lester. 2nd Ed. PP.241-2.
  5. ↑ Lester. 2nd Ed. PP.241-2.
  6. ↑ Lester. 2nd Ed. PP.241-2.
  7. ↑ MUA. Jan 22, 2009.
  8. ↑ PBoD P.1146
  9. ↑ [1]
  10. ↑ [2]
  11. ↑ PMID 12405945
  12. ↑ PMID 1757079
  13. ↑ MUA Jan, 20 2009.
  14. ↑ Yeh IT, Mies C (March 2008). "Application of immunohistochemistry to breast lesions". Arch. Pathol. Lab. Med. 132 (3): 349-58. PMID 18318578. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349.
  15. ↑ Ordóñez NG (March 2006). "Podoplanin: a novel diagnostic immunohistochemical marker". Adv Anat Pathol 13 (2): 83-8. doi:10.1097/01.pap.0000213007.48479.94. PMID 16670463.
  16. ↑ Kahn HJ, Marks A (September 2002). "A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors". Lab. Invest. 82 (9): 1255-7. PMID 12218087.
  17. ↑ Lester P.122.
  18. ↑ 18.0 18.1 18.2 http://emedicine.medscape.com/article/1101235-diagnosis
  19. ↑ RS. May 2010.
  20. ↑ PBoD P.1133
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