General
ADH is a predictor of risk as well as a non-obligate precursor for breast cancer
Proliferative breast disease with some, but not all, features of LOW GRADE DCIS
Clonal proliferation of luminal-like cells, but lack sufficient features to be called DCIS
If you see high grade features, it makes it high grade DCIS
ADH is still confined to the ducts (maintains ME layer)
Clinical picture
Mammography shows suspicious dense area with microcalcifications
ADH diagnosis on a biopsy generally calls for a complete excision
EXCEPTION if the biopsy was for microCa++ (not a mass), there is only one 1 or 2 foci of clear-cut ADH present and post-biopsy mammogram reveals no residual Ca++ at all
Breast cancer risk
4-5x increased risk of breast cancer (60% in ipsilateral breast)
Shows loss of 16q and 17p
Higher risk if there are multiple atypical foci present or if normal regression/involutional changes are decreased in background lobular units (breast is supposed to become more fat, less glandular as you get older...seeing a lot of glands still is a bad sign)
Histology
Cluster of weird ductular structures with some myoepithelial cells still appreciated
Lacks nuclear uniformity, even spacing and well defined round secondary lumens of low grade cribriform DCIS
Epithelial cells have atypia with variation in size & shape!!
Some are enlarged & slightly hyperchromatic
ADH does NOT fill the entire ductal space and lacks the monomorphism that is seen in DCIS or LCIS.
Stains
Typically shows strong diffuse positivity with ER stain (normal ducts & lobules have a subset of positive cells)
Express LMWCK (red cytoplasm), but not HMWCK (brown cytoplasmic staining in myoepithelial cells)
(UDH should show a heterogeneous staining pattern)
HMW keratin (CK903; aslo called 34bE12) and CK5/6 are generally NEGATIVE in ADH/LG DCIS
When to call ADH:
Basically, ADH looks worse than UDH, but not bad enough to call DCIS
We want the clinician to know there is some funky stuff going on in the breast, but there just isn’t quite enough to justify calling it DCIS.
Sometimes, the duct in question may even fit all of the criteria for calling it a low grade DCIS, but pathologists may call it ADH if:
There is only a single focus present
The size is < 2mm
<3 ducts are involved
Process that run along the ductal system and undermine or replace the normal epithelium of ducts/lobules favor ADH or DCIS
HMW keratin (CK903; aslo called 34bE12) and CK5/6 are generally NEGATIVE in ADH/LG DCIS
Summary
Keep in Mind:
There is a big difference in calling something usual ductal hyperplasia (no increased risk for breast cancer) vs. atypical ductal hyperplasia (inc risk for breast cancer).
You don’t have to worry as much about whether to call something ADH vs. DCIS- these both have an increased risk for cancer.
The clear presence of well defined ME layer is reassuring in calling something benign. However, the presence/absence of myoepithelial cells is not as valuable for intraductal processes since some intraductal carcinomas retain some degree of myoepithelial cells around the periphery; these ME cells are usually attenuated or partially lost in tumor cells.