ihc in the diagnostic of breast disease
TRANSCRIPT
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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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