(1)
Chennai Breast Centre, Chennai, India
A detailed morphological analysis by careful scrutiny of hematoxylin and eosin-stained slides is sufficient to diagnose most breast lesions. However, many lesions defy classification by routine microscopy, by virtue of their complex morphology. The role of IHC in the diagnosis of mammary disease is growing, with the availability of increasing numbers of antibodies and technical advancements. The principal diagnostic applications of IHC include distinguishing usual epithelial hyperplasia from ADH/LG-DCIS and benign papillomas from papillary carcinoma, assessing stromal invasion, categorizing histologic subtypes, and identifying metastatic breast carcinoma. IHC also helps in confirming lymphovascular invasion.
Differentiating Usual Type Epithelial Hyperplasia (UEH) from ADH/DCIS
Most cases of usual type hyperplasia can be diagnosed on routine H and E by well-delineated histologic findings: a heterogeneous cell population, irregularly dispersed spaces, tapering bridges, and streaming. However, Florid UEH can sometimes be difficult to distinguish from ADH/DCIS. IHC can help in these situations (Table 27.1).
Table 27.1
IHC expression in intraductal epithelial proliferations
|
Marker |
UEH |
ADH |
DCIS |
LCIS |
|---|---|---|---|---|
|
34βe12 |
+ in nearly all cases |
Negative in 80–100 %cases |
Negative in 81–100 % cases |
Positive in 80–100 % cases |
|
CK5/6 |
+ in 81–100 % |
Negative in 80–92 %cases |
Negative in nearly all cases |
Negative in 83–100 % cases |
|
ER |
Negative to focal positivity |
Diffuse positivity |
Diffuse positivity |
– |
|
PR |
Negative to focal positivity |
Diffuse positivity |
Diffuse positivity |
– |
UEH is an admixture of three cell types (as is normal breast – Fig. 27.1): luminal, basal, and myoepithelial; each cell type has its own phenotype. Luminal cells express CK7, CK8, CK18, CK19; basal cells express high molecular weight cytokeratins (HMWCKs): 34βe12, CK5/6, CK14, CK17. Myoepithelial cells (MECs) markers include smooth muscle actin, calponin, and p63. MECs also stain with HMWCKs.
Fig. 27.1
Normal, luminal, myoepithelial cell layers
ADH/DCIS are composed of one cell type, in keeping with their clonal phenotype, and usually express luminal markers. A small percentage, typically high-grade DCIS, shows basal cell differentiation.
UEH is usually negative or focally positive for ER, while ADH/DCIS is often diffusely positive. A HMWCK+/ER− phenotype favors UEH, while the reverse (HMWCK−/ER+) favors ADH/DCIS. Some important caveats to the use of these markers are in apocrine DCIS, (CK5/6+, ER−, androgen receptors+), basal-type DCIS (CK5/6+, ER−), and in columnar cell lesions (benign columnar cell lesions are also ER+) (Table 27.1).
Assessing Stromal Invasion
Identifying foci of micro invasion in DCIS with lobular cancerization or involving foci of sclerosing adenosis can be difficult with routine histology. Distinguishing benign lesions with a pseudo-infiltrative pattern, such as radial scar or sclerosing adenosis, from invasive carcinoma can also be challenging. IHC can be utilized in good effect in such cases, the principle being to document extension beyond the normal anatomic barrier, the basement membrane (Table 27.2).
Table 27.2
Assessing stromal Invasion
|
Antibody |
Staining pattern |
MECs |
Myofibroblasts |
Blood vessels |
Tumorcells |
Luminal epithelial cells |
Remarks |
|---|---|---|---|---|---|---|---|
|
SMA |
Cytoplasmic |
Positive |
Positive |
Positive |
Negative |
Negative |
Highlights the architecture of small glandular proliferations, such as sclerosing adenosis |
|
SM-MHC |
Cytoplasmic |
Positive |
Weak positivity |
Positive |
Negative |
Negative |
|
|
Calponin |
Cytoplasmic |
Positive |
Positive |
Positive |
Negative |
Negative |
|
|
P63 |
Nuclear |
Positive |
Negative |
Negative |
Positivein rarecases |
Positivein rare cases
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