New definition of " ‘comedo’ ductal carcinoma in-situ"

Hi kelly:

To my layperson's knowledge, there has been no recent change in the definition of "comedo" DCIS.

In connection with linear or granular micro-calcifications, this 2014 paper by Henrot et al. (which may not be current in all aspects) notes that:

"These often easily recognised microcalcifications are frequently associated with high-grade ductal carcinoma in situ but are also, although more rarely, found in extensive low and intermediate lesions . . "

Therefore, it is true that microcalcifications are also (but not always) seen with intermediate and with low grade DCIS.

Re: "Micro-calcification is associated with necrotic cells. Necrotic cells are found in high-grade, in-situ ductal carcinoma (DCIS or 'comedo-carcinoma') and the mucin of mucin-secreting tumors."

This is not to say that microcalcifications are exclusively found in those situations, but the second sentence is perhaps poorly worded (e.g., "found in" should perhaps be revised to read "often, but not exclusively, found in").

"Necrotic cells" are found in other situations (e.g., different grades or architectural types). As this 2013 article by Bane (which may not be current in all aspects) explains:

"Two types of necrosis are identifiable.

Comedo Type

Central areas of necrosis, ghost outlines of cells and cellular debris (Figure 3).

Non-Comedo Type

Individual cell necrosis usually in the form of apoptotic cells."

In addition, because the various grading systems for DCIS include an assessment of both nuclear morphology and presence/type of necrosis, it turns out that necrosis is not limited to high grade DCIS and that not all DCIS with comedo necrosis is high grade. Per the 2013 article by Bane:

"There are three commonly referenced grading schemes for DCIS, all of which employ the assessment of nuclear grade and presence/type of necrosis with some additionally utilising cellular polarity to ascribe an overall grade [9-11]. No one system has been endorsed; however, a consensus conference and the College of American Pathologists recommend that a pathology report should include a description of nuclear grade, presence and type of necrosis, and the architectural patterns present [8,12]. Thus when we discuss the "grade" of DCIS this is now generally accepted to refer to the nuclear grade of the lesion."

For an example of one grading system, see this Stanford outline here and here.

BarredOwl

Hi kelly:

This type of layperson-oriented information can be a helpful starting point as background information, but it is not the equivalent of a grading manual.

It can be challenging to summarize complicated technical medical or scientific information in layman's terms, without losing some precision. To address all possibilities with precision, one would continually have to use caveats or wobble-words like "often, but not exclusively, found in," at the expense of simpler language. Words like "found" or "is present" do not mean "always found" or "is only present."

Note also that grading is within the area of expertise of pathologists, but "Doc" is Dr. Halls who is a Radiologist by training:

http://breast-cancer.ca

"I'm Dr. Steven Halls, MD, FRCPC, a radiologist in Canada. . . . I did breast cancer research during the first half of my career at the Cross Cancer Institute in Edmonton, along with a lot of oncologic imaging. Now in the second half my career, I work in Camrose, Alberta, Canada as a radiologist, where I continue to do mammography and breast cancer biopsies and staging and followup scanning every day."

Re the text you cited:

"Some specific diagnostic features of the different grades of DCIS:

• Comedo-type necrosis is present with high-grade (poorly differentiated) DCIS.
• Low-grade DCIS is typically diploid, estrogen and progesterone receptor-positive, with a low cell proliferative rate, and rarely shows abnormalities of the HER2/neu or p53 oncogenes.
• High-grade DCIS lacks estrogen recept and progesterone receptors, has a high proliferative rate, over-expresses the HER2 oncogene, has mutations of the p53 oncogene and is associated with angiogenesis in the surrounding breast stroma."

Re your question: "So according to the definitions given on this website, if I had DCIS displaying necrosis (not comedo type), and if the cells were ER and PR +, do I have high grade or low grade? And what about the HER2? I thought that wasn't tested for DCIS. I believe this website is fairly authoritative, so I'm surprised by the conflicting information."

The bullets are not really "definitions" of grade.

Per my prior post, current DCIS grading systems employ the assessment of [1] nuclear morphology; [2] the presence and type of necrosis; and optionally [3] cellular polarity to ascribe an overall grade. Information re at least [1] and [2] are required to assign a grade.

Currently, grading of DCIS also requires an assessment of nuclear morphology.

High grade cannot be determined solely from the presence of comedo necrosis. In fact, the Stanford outline indicates that comedo necrosis can be present in intermediate grade DCIS, if the nuclear morphology meets certain criteria. The Stanford outline also notes that high grade can exist "with or without tumor cell (comedo) necrosis." Thus, it appears that the presence of comedo necrosis is neither necessary nor sufficient to assign high grade. (Not "necessary" because DCIS can be high grade without comedo necrosis; not "sufficient" because DCIS an be intermediate grade despite comedo necrosis.)

It is true that comedo-type necrosis is often seen in high grade DCIS. But that is not the whole story, because first bullet mentions the added property of "poorly differentiated" -- a likely reference to the presence of aberrant nuclear morphology.

Various features listed in the second and third bullets are not required to assign DCIS grade, although they may be more frequently observed with either high or low grade DCIS (as determined by other criteria).

-- While highly aberrant nuclear morphology may imply a higher proliferative rate, currently, grading of DCIS does not entail any molecular assessment of "cell proliferative rate" (e.g., via Ki-67 expression).

-- Currently, ER, PR, and HER2 status are not required to assign DCIS grade. In accordance with NCCN guidelines, most institutions do not even assess HER2 status of DCIS, because it currently has no implications for clinical management.

-- p53 mutation status is not used to assign grade, and is typically only assessed in research studies.

The second and third bullets are not "definitions" of grade, but describe associations. They describe particular markers and genetic changes that may tend to be observed more often in the context of high or low grade DCIS (as determined by other criteria). As you appreciated, some are not routinely assessed by the pathologist for apparently pure DCIS (cell proliferative rate; over-expression of HER2; mutations in HER2; mutation in p53), and they are not required to assign grade.

In my layperson understanding, these additional molecular and genetic features are not absolute indicia of either low or high grade. A 2009 research paper states (emphasis added): "Low-grade DCIS is generally positive for the estrogen & progesterone receptors (ER & PR) and negative for HER2/neu, displays chromosomal losses at 16q, gains in 1q and near euploidy [10,11]. High-grade DCIS, in contrast, tends to display lack of expression of ER and PR, HER2/neu overexpression/amplification, a multitude of chromosomal changes, and aneuploidy [10,11]. Expectedly, intermediate grade DCIS displays changes that are intermediate between these two extremes [10]." Other criteria are used to assign grade. Indeed, the second bullet includes the wobble-word "typically", meaning what follows is not always the case. The third bullet needs a wobble-word (e.g., often lacks).

BarredOwl