Difference between revisions of "Invasive breast cancer"

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Additional:
Additional:
*HER2/neu - usually +ve.
*HER2/neu - usually +ve.
*CK5/6 -ve.<ref>RS. May 2010.</ref>
**Usu. +ve in squamous cell carcinoma.


==Familial breast cancer==
==Familial breast cancer==

Revision as of 14:55, 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 work-up

  • Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
    • Sunnybrook uses CAM5.2.
  • ER (estrogen receptor) & PR (progesterone receptor).
    • determines whether patient will get tamoxifen or other estrogen modulators.
    • in most breast ca ER & PR are positive.[2]
  • HER2/neu.
    • Positivity assoc. with a worse prognosis.
    • Determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.
    • Usually negative.[3]

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."[4]

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.[5][6][7]

  • 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.[8] They also wrote a follow-up article in 2002.[9]

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.[10]

Breast IHC

  • DCIS vs LCIS:[11]
    • 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[12][13]
    • monoclonal antibody to podoplanin)
    • useful to assess lymphovascular invasion
  • ADH and DCIS[14]
    • 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.[15]

Note:

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

Micro

Features:[15]

  • 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:[15]

  • 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.[16]
    • Usu. +ve in squamous cell carcinoma.

Familial breast cancer

BRCA1 vs. BRCA2[17]

  • 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. NEED REF.
  3. NEED REF.
  4. MUA. Jan 22, 2009.
  5. PBoD P.1146
  6. [1]
  7. [2]
  8. PMID 12405945
  9. PMID 1757079
  10. MUA Jan, 20 2009.
  11. 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.
  12. 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.
  13. 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.
  14. Lester P.122.
  15. 15.0 15.1 15.2 http://emedicine.medscape.com/article/1101235-diagnosis
  16. RS. May 2010.
  17. PBoD P.1133