Atypical Ductal Hyperplasia



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.

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