UDH, ADH, DCIS, and LCIS

Question 1

Differentiating ADH and low-grade DCIS

Answer 1

If cells are low-grade, you call it DCIS if:
* It fills an entire duct space
OR
* It occupies >2 mm of ductal space or at least 2 ductal profiles

If it is less than this, it is kept at ADH.

Any nuclear grade higher than low-grade (grade 1/3) makes it DCIS automatically.

Question 2

Architectural patterns of DCIS

Answer 2

Question 3

DCIS grading

Answer 3

Question 4

Answer 4

Low-grade DCIS

Note the single population of monotonous cells with uniform nuclei of smooth contour and inconspicuous nucleoli.

Question 5

Answer 5

Usual ductal hyperplasia

Note the heterogeneous cell population, variable cell size and nuclear size and shape, variable nucleoli, and haphazard arrangement.

Question 6

Architectural features of low-grade DCIS vs UDH

Answer 6

Question 7

Answer 7

Usual ductal hyperplasia

Note the irregular, slit-like spaces that are characteristic of UDH spilling into a lumenal space.

Question 8

Answer 8

Usual ductal hyperplasia

Note the thin, stretched, twisting bridges. This is as contrasted to the thick, rigid bridges of DCIS, shown on this side.

Question 9

Answer 9

Solid usual ductal hyperplasia

The lumen filling may give you pause for a moment, but these nuclei are clearly heterogeneous. This is as opposed to the homogeneous nuclei of a lumen-filling DCIS, shown on this side.

In solid UDH, the nuclei are also often found to “stream,” whereas streaming is absent in DICS.

Question 10

Answer 10

It’s definitely DCIS. Is it cribriform?

Actually no. Look closely at those spaces. They are microacini, not true cribriform lumens.

Question 11

Answer 11

Micropapillary DCIS

In addition to the nuclear features of DCIS, note the bulbous, club-like appearance of these micropapillae. This is as opposed to the tapering, tipped ends of micropapillary UDH, shown on this side.

In UDH, cells are also wider at the base and smaller at the tip, whereas in DCIS all cells are of roughly uniform size.

Question 12

Can you have UDH with necrosis?

Answer 12

YES. It is just rare.

Don’t let necrosis sway you into calling something DCIS when the other features aren’t there.

Question 13

Answer 13

UDH with squamous metaplasia

Question 14

IHC to distinguish low-grade DCIS from UDH

Answer 14

Caveat: Basal-like high grade DCIS is CK5/6 positive

Question 15

A reassuring sign that you are dealing with ADH rather than DCIS is. . .

Answer 15

. . . the retention of columnar cell morphology, which indicates that the low-grade clone is not filling the entire duct, making this ADH.

Question 16

Answer 16

The duct is partially involved with low-grade DCIS-like cells, but columnar cells are retained at the edges.

Since they do not fill the entire duct, this is just ADH.

Question 17

Answer 17

This is a gray zone.

You have two involved duct spaces, BUT it is less than 2 mm.

One could call this DCIS based on the “2 duct space” quantitative requirement alone, BUT most breast pathologists would stop at ADH.

Question 18

Quantitative thresholds for DCIS only apply for. . .

Answer 18

. . . low grade DCIS

Question 19

Haagensen LCIS cell types

Answer 19

Type A: small uniform cells with scant cytoplasm and monomorphic, round to ovoid nuclei that lack nucleoli.

Type B: larger cells with more abundant cytoplasm, slight nuclear pleomorphism and nucleoli. Can mimic “non-classical” LCIS.

Question 20

Answer 20

Classical lobular carcinoma-in-situ

Question 21

Possible patterns of E-cadherin staining in lobular breast neoplasms

Answer 21

Absent
Reduced
Cytoplasmic
Perinuclear dot-like

Question 22

ALH vs LCIS

Answer 22

ALH: Less than 50% of acini in a lobule involved

LCIS: More than 50% of acini in a lobule involved, and there should be evidence of lobule distension (compare to uninvolved lobules).

However, nowadays, we often don’t make the distinction and leave it at “non-invasive lobular neoplasm.”

Question 23

Answer 23

Non-classical LCIS

May have a “pleomorphic” (high nuclear grade, nucleus 4x lymphocyte nucleus) or “florid” (mass-forming, >40 cells across a single duct) subtype.

Shown here is a pleomorphic non-classical LCIS with apocrine and signet-ring cell features.

Usually in older women. Higher rate of proliferation compared to conventional DCIS.

Molecularly, has a more mutated genome compared to classical LCIS.

Question 24

Molecular signature of LCIS

Answer 24

Loss of 16q, gain of 1q
CDH1 mutated

Question 25

Answer 25

ALH with pagetoid growth

This is what a low-grade lobular neoplasm looks like when it behaves in a pagetoid fashion.

Question 26

MGH short guide to DCIS grading

Answer 26

Question 27

MGH short guide to invasive

Answer 27

ie, Nottingham criteria

Question 28

Assessing nuclear grade

Answer 28

First, assign two scores:
* Nuclear Size
1. Must compare to normal to appreciate slight enlargement
2. Enlargement obvious when compared to normal
3. Enlargement obvious without comparing to normal
* Nuclear Pleomorphism
1. Similar size and shape (monoclonality)
2. Noticeable variation in size and shape
3. Substantial variaton in size and shape

If the two scores agree, that is your nuclear grade. If they do not agree, consider the nucleolar and chromatin features.

Question 29

Breast mitosis score threshholds by field diameter

Answer 29

Question 30

Answer 30

DCIS grade 1 -> 2 -> 3

Question 31

“Blunt duct adenosis”

Answer 31

An old name for columnar cell change

Question 32

Answer 32

DCIS with neuroendocrine features

If it has an architectural pattern of DCIS, but the nuclei look more like UDH, consider throwing on some neuroendocrine stains.

Chromogranin is shown on this population (synapto was also positive, but out of focus on slide imaging).

Question 33

Answer 33

Columnar cell change / blunt duct adenosis

Findings common to all examples include: enlargement of the entire lobule; dilatation of the lobular glands, which exhibit a simple branching pattern often referred to as “staghorn-like”; and prominence of the myoepithelial cells.

Question 34

Answer 34

Breast hamartoma

Hamartomas form well defined nodules composed of mammary glands and connective tissues. They compress and push aside the surrounding parenchyma.

Question 35

Answer 35

Myxoid fibroadenoma

Rarely associated with Carney Complex

Question 36

Approach to neuroendocrine breast carcinomas

Answer 36

The overall ddx is:
* Papillary carcinoma with endocrine features (solid papillary carcinoma)
* Cellular mucinous carcinoma
* Neuroendocrine carcinoma (typical carcinoid-like or small cell)
* Invasive ductal carcinoma with neuroendocrine features

Question 37

Answer 37

Solid papillary carcinoma

Usually cells are rounded, but sometimes they can become elongated and streaming. The papillae are still there though.

Question 38

Answer 38

Mucinous carcinoma with neuroendocrine differentiation

Question 39

Answer 39

Small cell carcinoma of the breast

You always have to rule out metastasis, but rarely you can see in-situ small cell carcinoma, which is extremely helpful in confirming a breast primary (shown).

Question 40

Answer 40

Low-grade IDC with neuroendocrine features

Question 41

DCIS and LVI both increase the risk of. . .

Answer 41

local recurrence

Question 42

Rosen triad

Answer 42

Flat epithelial atypia
Tubular carcinoma
Lobular neoplasia

Question 43

Answer 43

Tubular carcinoma

Note how angulated the invasive glands are, and the presence of adjacent flat epithelial atypia.