ihc in the diagnostic of breast disease

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    Immunohistochemistry in the

    diagnostic evaluation of breast lesions

    REVIEW ARTICLE

    Appl Immunohistochem Mol Morphol

    Volume 19, Number 6, December 2011

    David G. Hicks, MD

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    Diagnostic IHC in Breast Pathology

    1. Predicting benefit from therapeutic agents.

    2. Distinguishing true stromal invasion from

    mimics (pseudoinvasion)

    3. Distinguishing UDH from ADH/DCIS

    4. Detect subtle or minimal metastatic disease

    in sentinel lymph nodes.

    5. Classification andD. Dx for unusual lesions.

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    Normal Mammary Ductal/Lobular System

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    IHC assessment of stromal invasion:

    Antibodies that stain Myoepithelial Cells have

    been used to assess stromal invasion in:

    1. Small foci of invasion within extensive high

    grade DCIS with periductal inflammation.

    2. In situ carcinoma involving sclerosingadenosis or other complex sclerosing lesions.

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    MEC Markers

    ++++, strongly positive; +++, positive; ++, moderately positive; +, weakly positive;

    +/- equivocal; - negative.

    CK indicates cytokeratin; MEC, myoepithelial cell; SMA, smooth muscle actin;

    SMM-HC, smooth muscle myosin heavy chain.

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    Sclerosing adenosis. A, Low-power view. The lobular configuration of the lesion is

    obvious. B, Medium-power view. Note the spindle shape of the proliferating cells in the

    center of the lobule and the fibrillary quality of the cytoplasm, indicative of myoepithelial

    nature. C, Immunocytochemical stain for actin showing strong immunoreactivity in the

    myoepithelial cell component.

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    Assessment of Sentinel LN by IHC

    SLN biopsy is now the standard of care for axillary

    staging in patients with an invasive breast cancer.

    The use of cytokeratin stains to identify occult

    metastatic disease (isolated tumor cells) in LNs

    that are -ve on routine H&E is controversial, and

    the clinical significance of such findings is unclear.

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    Assessment of Sentinel LN by IHC

    Recent prospective data on clinical outcomes from

    randomized trials for recurrence and survival based

    on SLN involvement have not shown a clinical

    benefit from the IHC detection of occult disease.

    However, cytokeratin stains may be helpful in

    detecting subtle metastasis for certain primary

    tumor as metastatic lobular carcinoma, which can

    be difficult to detect by routine H&E in some cases.

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    Metastatic lobular carcinoma to an

    axillary SLN.

    The decision to perform cytokeratinstaining in SLN depends in part on

    the morphology of the primary

    tumor.

    (A) Early LN metastases from lobular

    carcinoma can be quite subtle and

    difficult to detect in standard H&E.The use of IHC staining for pan-

    cytokeratin in this LN (B) highlights

    scattered metastatic carcinoma cells

    in the subcapsular and medullary

    sinuses.

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    Assessment of Sentinel LN by IHC

    Not all epithelial cells identified in LNs by H&E or IHC

    represent metastatic carcinoma.

    Benign glandular inclusions (BGI) in LN

    s is an uncommonbut well-documented, they are often located in the

    capsule, consist of uniform cells that may contain cilia &

    may also be surrounded by myoepithelial cells.

    Axillary LNmay also contain benign epithelial cells (oftenfrom an intraductal papilloma) that have been

    iatrogenically displaced by needle core biopsy and then

    drained to regional LN.

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    Assessment of Sentinel LN by IHC

    The failure to carefully evaluate these unusual

    cases could lead to improper staging for thepatient and unnecessary therapy.

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    Assessment of Sentinel LN by IHC

    Comparison of the morphologic features of the

    SLNwith the primary tumor in the breast can

    be helpful in establishing the diagnosis of BGI.

    Using IHC to demonstrate a myoepithelial layer

    surrounding the glandular inclusion may help

    confirming the correct diagnosis.

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