UDH, ADH, DCIS, and LCIS Flashcards
Differentiating ADH and low-grade DCIS
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.
Architectural patterns of DCIS
DCIS grading
Low-grade DCIS
Note the single population of monotonous cells with uniform nuclei of smooth contour and inconspicuous nucleoli.
Usual ductal hyperplasia
Note the heterogeneous cell population, variable cell size and nuclear size and shape, variable nucleoli, and haphazard arrangement.
Architectural features of low-grade DCIS vs UDH
Usual ductal hyperplasia
Note the irregular, slit-like spaces that are characteristic of UDH spilling into a lumenal space.
Usual ductal hyperplasia
Note the thin, stretched, twisting bridges. This is as contrasted to the thick, rigid bridges of DCIS, shown on this side.
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.
It’s definitely DCIS. Is it cribriform?
Actually no. Look closely at those spaces. They are microacini, not true cribriform lumens.
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.
Can you have UDH with necrosis?
YES. It is just rare.
Don’t let necrosis sway you into calling something DCIS when the other features aren’t there.
UDH with squamous metaplasia
IHC to distinguish low-grade DCIS from UDH
Caveat: Basal-like high grade DCIS is CK5/6 positive
A reassuring sign that you are dealing with ADH rather than DCIS is. . .
. . . the retention of columnar cell morphology, which indicates that the low-grade clone is not filling the entire duct, making this ADH.
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.
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.
Quantitative thresholds for DCIS only apply for. . .
. . . low grade DCIS
Haagensen LCIS cell types
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.
Classical lobular carcinoma-in-situ
Possible patterns of E-cadherin staining in lobular breast neoplasms
Absent
Reduced
Cytoplasmic
Perinuclear dot-like
ALH vs LCIS
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.”
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.
Molecular signature of LCIS
Loss of 16q, gain of 1q
CDH1 mutated
ALH with pagetoid growth
This is what a low-grade lobular neoplasm looks like when it behaves in a pagetoid fashion.
MGH short guide to DCIS grading
MGH short guide to invasive
ie, Nottingham criteria
Assessing nuclear grade
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.
Breast mitosis score threshholds by field diameter
DCIS grade 1 -> 2 -> 3
“Blunt duct adenosis”
An old name for columnar cell change
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).
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.
Breast hamartoma
Hamartomas form well defined nodules composed of mammary glands and connective tissues. They compress and push aside the surrounding parenchyma.
Myxoid fibroadenoma
Rarely associated with Carney Complex
Approach to neuroendocrine breast carcinomas
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
Solid papillary carcinoma
Usually cells are rounded, but sometimes they can become elongated and streaming. The papillae are still there though.
Mucinous carcinoma with neuroendocrine differentiation
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).
Low-grade IDC with neuroendocrine features
DCIS and LVI both increase the risk of. . .
local recurrence
Rosen triad
Flat epithelial atypia
Tubular carcinoma
Lobular neoplasia
Tubular carcinoma
Note how angulated the invasive glands are, and the presence of adjacent flat epithelial atypia.
Clinical relevance of pleomorphic or florid LCIS variants
- More likely to be correlated with a mass
- As opposed to normal LCIS, associated with a 25-60% risk of invasive carcinoma on excision specimen - so it is an indication for excision if seen on biopsy
- WHO recommends reporting margins on excision specimens - though the clinical relevance of this is currently unknown
- More likely to be HER2 driven (classic LCIS almost never is)
Breast-type signet ring cell, with eosinophilic material in the ring
Can be seen in GI carcinomas, as the GI-type can be seen in breast, but they are more likely associated with their namesake.
