1. Low grade intraductal proliferations: ADH vs DCIS
September 25, 2018
Megan L. Troxell MD/PhD

2. Histologic spectrum
UDH
ADH
LG DCIS

3. Histologic spectrum UDH ADH LG DCIS UDH ADH LG DCIS
Clinically actionable threshold for core biopsyexcision
(USA, historic)
We use criteria of Page and Rogers;
Dutch try to avoid ADH dx
Other speakers prob won’t cover ‘overtreatment’ or DCIS trials
UDH
ADH
LG DCIS
Clinically actionable threshold for margin re-excision

4. Usual Ductal Hyperplasia
1) Architecture
Irregular fenestrations; irregular bridges (twisted)
Spaces peripheral within duct (slit-like)
Uneven distribution and overlapping of nuclei
Nuclei “Streaming”
Logs in a river, school of salmon
2) Cytology
Multiple cell types, sizes, heterogeneous
Indistinct cell borders
Variable nuclear morphology, +/- grooves
Nuclei more elongated than round; normochromatic; overlapping
3) Size (any)
British: hyperplasia of the usual type

5. Usual Ductal Hyperplasia

6. Low Grade DCIS 1) Architecture 2) Cytology ‘clonal’
Round, regular spaces “punched out”
Rigid bars, >=2 cells thick
Cells polarize around spaces
2) Cytology ‘clonal’
Nuclei uniform, enlarged, round
Cells evenly spaced, nuclei non-overlapping, distinct borders, ‘tiled’
3) Size: at least 2 mm & 2 spaces

7. ADH: Atypical Ductal Hyperplasia Definition: some but not all the features of low grade DCIS
Architecture: mixed or insufficient
Cytology: mixed or insufficient
Size
<2mm even if architecture & cytology perfectADH
-- Architecture of DCIS w/o cytologyADH
-- Cytology of DCIS w/o architectureADH

8. UDH
Florid hyperplasia w/o atypia
British HUT (hyperplasia of the usual type
Page & Rogers. “ Combined Histologic & Cytologic Criteria for the Diagnosis of Mammary Atypical Ductal Hyperplasia.”
Human Pathology 1992; 23 (10):1095

9. Caveats and immunophenotype
Intermediate grade nuclei DCIS
Regardless of size or architecture
Spindle cell DCIS looks less monotonous
Large, dark nuclei; may be neuroendocrine
DDx also includes lobular neoplasia (ALH/LCIS)
Necrosis does not mandate DCIS (or ADH)
IHC doesn’t apply to columnar or apocrine
Morphology still rules; could call UDH mosaic/mosaic
If flat, columnar cell lesion (CCL)/flat epithelial atypia (FEA)/clinging DCIS
IHC stains??
CK5(6) ER
UDH
+/mosaic
Non-uniform
ADH/LG-DCIS
Negative
Diffuse+

10. UDH: CK5/6 ADH: CK5/6 ADH: ER UDH: ER
ADH: right side, same as morphologic exampleWorks for other HMWT CK also 34betaE12
Apocrine and CCL negative for CK5 (Lee); CCL +ER, apocrine -ER
Lerwill: DCIS is positive for Ecadherin and shows negative or reduced staining for cytokeratin 34bE12, while LCIS is negative for E-cadherin and positive
for cytokeratin 34bE12 (Table 2). This isn’t used [doesn’t work for ck5]
Lee says LCIS is usually CK5 neg

11. Cases Swirling; slits? Architecture? Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O-36 UDH
MONOTONOUS, ROUND, NON-OVERLAPPING?
Monotonous; non-overlapping?
Size?

12. UDH Cases Swirling; slits? Architecture? Mixed, overlapping cells?
Cytology?
O-36 UDH
UDH
Size?

13. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
DCIS if > 2mm
Monotonous; non-overlapping?
Size?

14. DCIS Architecture? Punched out; rigid? Cytology?
DCIS if >2 mm
Monotonous; non-overlapping?
Size?

15. Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Monotonous; non-overlapping?
Size?

16. ADH Architecture? Punched out; rigid? Cytology?
Monotonous; non-overlapping?
Size?
Duct partially involved

17. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Adh o-19
Monotonous; non-overlapping?
Size?

18. ADH Swirling; slits? Architecture? Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Adh o-19
Monotonous; non-overlapping?
ADH
not uniformly involved
Size?

19. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O18,21 UDH
Monotonous; non-overlapping?
Size?

20. UDH Swirling; slits? Architecture? Mixed, overlapping cells? Cytology?
O18,21 UDH
UDH
Size?

21. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Adh
Monotonous; non-overlapping?
Size?

22. ADH not uniformly involved
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Not high enough power for cytology
And papillary; right next to DCIS
Monotonous; non-overlapping?
ADH not uniformly involved
Size?

23. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O28 lobular
Monotonous; non-overlapping?
Size?

24. ALH Architecture? Nearly solid Cytology? Monotonous; non-overlapping?
O28 lobular
Monotonous; non-overlapping?
Size?

25. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O28 lobular
Monotonous; non-overlapping?
Size?

26. Not low grade nuclei: DCIS
Swirling; slits?
Architecture?
Mixed, overlapping cells?
Cytology?
O28 lobular
Not low grade nuclei: DCIS
Size?

27. Same case: DCIS
O28 lobular

28. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O28 lobular
Monotonous; non-overlapping?
Size?

29. Collagenous spherulosis
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
Mixed epi/myoepi; basement membrane matrix in center. Should be microsocopic, incidental
May be colonized by LCIS (Not here)
Collagenous spherulosis
Size?

30. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
O32-33 UDH; SKIP? Finish 6:50
Monotonous; non-overlapping?
Size?

31. UDH Swirling; slits? Architecture? Mixed, overlapping cells? Cytology?
O32-33 UDH
UDH
Size?

32. Mixed, overlapping cells?
Swirling; slits?
Architecture?
Punched out; rigid?
Mixed, overlapping cells?
Cytology?
DCIS if >2mm
Monotonous; non-overlapping?
Size?

33. DCIS Architecture? Punched out; rigid? Cytology?
DCIS if >2mm
Monotonous; non-overlapping?
Size?

34. Micropapillary pattern
May not involve uniform circumference of duct
Describe club shaped, uniform cells (if mature toward top ADH, etc)

35. Architecture Cytology Size UDH ADH DCIS LG
Swirling-streaming, irregular serpiginous slit-like spaces
Irregular nuclear shape, position, overlapping;
ill defined intercellular borders
ADH
Usually partial involvement (2+ populations)
Some cells as DCIS
Often columnar population
At least 6-7 “bothersome” cells, or 1 bar
DCIS LG
Uniform, punched out spaces, rigid bars, polarized around lumens
Uniform oval to rounded nuclei, pale cytoplasm; distinct cell borders*
2 mm and 2 ducts
*exception: spindle cell DCIS
ADH vs. DCIS: When in doubt, more benign dx appropriate

36. Oversampled 40-49 & dense breasts Oversampled atypia (real-life 4-10%)
JAMA. 2015;313:
Reported ADH rates 3-15%, study says 4-10% but absolute K patients; Agreement by experts: 90%
N=115 pathologists, each w/ 60 cases (4 unique sets) 1 H&E slide; no consult
Also analyzed most frequent participant dx for tricky cases—no change
**2 of 3 experts missing microinvasive carcinoma initially
Pathologists fromoutside of academic settings, thosewho
interpret lowerweekly volumes of breast cases and those from
small-sized practiceswere statistically significantly less likely
to agreewith the consensus-derived reference diagnosis.
Overall agreement 75.3%
Study set
Benign (UDH, CCC etc) 72
Atypia
DCIS
Invasive CA
Oversampled & dense breasts
Oversampled atypia (real-life 4-10%)

37. Concordance for all 240 cases, by category
Category is expert interpretation
Concordance for all 240 cases, by category
We show all ADH/LG DCIS to 2nd breast pathologist

38. End

39. Columnar Cell Change

40. Columnar Cell Change Variably dilated acini (cystic)
Apical snouts--not bright apocrine cytoplasm
Luminal secretions/calc (more prominent w/ atypia/hyperplasia)
Flat Epithelial Atypia (formerly Columnar Cell Change/Hyperplasia with Atypia)
Associated with synchronous ADH, DCIS, invasive carcinoma (esp tubular), lobular neoplasia
Subsequent risk ~that of ADH
(“Clinging carcinoma” Flat HIGH GRADE DCIS)

41. Columnar Cell Change Columnar Cell Change Columnar Cell Hyperplasia
Acini lined by 1-2 cell layers
Uniform, ovoid-elongated nuclei, perpendicular to BM. Nucleoli inconspicuous
Columnar Cell Hyperplasia
Stratification, tufts.
NO complexity or DCIS architecture
Nuclei as above; may be overlapping.
Flat Epithelial Atypia
Flat growth pattern, monomorphic.
Stratification OK. Cytology of LG DCIS
Round (ovoid) nuclei. enlarged, +/- nucleoli, lack polarity.
O’Malley. Mod Pathol. 19:

42. Comparative Cytologic Features
Columnar Cell
Change
Columnar Cell HP
Flat Epithelial Atypia
Dr. James
Connolly,
PNWSP 2005

43. FEA vs. apocrine epithelium
Feature
FEA
Apocrine
Apical snouts
Yes
Granular eosinophilic cytoplasm No
Hobnail cells
Psammomatous calcification
ER expression
Bcl-2 expression
From L Collins. Harvard Breast Course 2014
Apocrine
Metaplasia
FEA