Breakout Group A Summary and Recomendations with Group Discussion: Pathology, Molecular Profiling, Prognosis

SLIDES & TRANSCRIPTS
Tuesday, June 18

Breakout Group A Summary and Recomendations with Group Discussion: Pathology, Molecular Profiling, Prognosis

Sharon W. Weiss, MD

Slide 1:

DR. WEISS: Thank you very much. Jonathan Fletcher and I were co-chairing breakout group one, which, as you recall, were the pathology issues, molecular profiling, and prognosis.

Now, I had a few reservations about being in a group that had so many pathologists in one area, but it turned out to be on the whole a very functional group, and I think we enjoyed ourselves.

Special thanks, I think, are in order to Raph Pollock and Matt van de Rijn and Paul Sorensen, who took the lead and sort of came up with some germ seeds, some issues that they presented to the group and we sort of mulled around over the several hours available to us.

Now, we divided our discussion really into two broad themes. The first theme was that of how we standardize the reporting of sarcomas and how we communicate the aspects of sarcomas to clinicians.

This may sound at first like a very banal subject; but I think, as we all realize, if we don't have accurate information on the pathology report, if we don't have accurate diagnoses, if our immunohistochemistry isn't done right, then we are really dealing with faulty information. Then, all the other things that follow--these very elegant molecular profiling--all becomes a house of cards.

I think we wanted to first explore where the issues are in the pathology laboratories, and how we can improve on some of them, so that we can give you the best information to go forward and do some of the very exciting scientific initiatives.

The second area was the issue of developing prognostic and predictive markers in sarcomas.

Slide 2:

Now, the first topic really is how do we get tissue and what do we do with that tissue. We heard some very interesting things yesterday about, for example, MD Anderson. Virtually all the sarcomas seen there are diagnosed on an FNA -- a very, very minimal amount of tissue. That is certainly not my experience, nor the experience of most people in the group. I think most of us felt that, in all fairness to the patients, we are not going to be seeing a lot of incisional biopsies.

Most of us have come to accept and learn to deal with core biopsies; but we felt that if multiple core biopsies were performed, it satisfied the need to obtain tissue expeditiously, it would be adequate to diagnose most sarcomas in patients, and that if you had enough cores, there would be material to save and to archive for further studies. I think this is one thing that we could endorse -- multiple core biopsies, some of which would be preserved in minus 70 degree or even minus 20 degree conditions for future studies.

Slide 3:

Now, the second topic really is how we standardize the reporting of sarcomas. Now, about four years ago, Chris Fletcher, myself, and Dick Kempson from Stanford were tasked with the Association of Directors of Anatomic and Surgical Pathology to come up with a standard template that pathologists would use when they report sarcomas. I quote from our paper, because I think Chris and I were trying to tread a very fine line in telling people what we thought they should do, without mandating it and getting people into a legally vulnerable corner.

We said, the recommendations are intended as suggestions, and adherence to them is completely voluntary. Unfortunately, sometimes people don't take it that way. It is completely voluntary. It reminds me of the story, as I was being driven by an Italian friend from the Venice airport into the city. We were going through red lights and I am saying to him, Andrea, do red lights mean the same thing as they mean in the United States? Andrea looks at me and says, "they are just suggestions." They thought, these are just suggestions.

Another other important point that came out of this report, as we said, it is important to note that parts of these cannot be applied to the growing number of sarcomas that are pre-treated with radiotherapy or chemotherapy. I would just like to make that comment to this group. Because we are a little handicapped. We will do the best we can by you; but there are going to be situations where some of your neoadjuvant therapy or your post-operative therapy may compromise our ability to interpret pathology.

Slide 4:

Now, this is a standard template, and I would say that the group, as I showed it again to this group, endorsed it. It should include typing. It should include grading by whatever grading system you like. It should include a size and greatest diameter. It should say the location, if the pathologist is able to say it.

It should include margins -- positive, negative, or measured, if less than 1.5 centimeters. It should make some reference to necrosis.

Here is a point that I think came up in our discussion. Whereas we say, mention if you do ancillary studies -- there was a strong endorsement that, if you can do ancillary molecular studies for, for example, those translocations which are both specific and now predictive of behavior, they should be done and they should be reported. This would include, for example, translocation in Ewing's sarcoma and in synovial sarcoma.

Slide 5:

Now, having shown you that template, let me tell you that it is not being followed routinely. Raph Pollock shared with us this information from the American College of Surgeon's Commission on Cancer Sarcoma PCE committee. In that report, 31 percent of reports don't have size pre-treatment, 31 percent do not have size by pathology measurements.
You can see, quite a large number do not include grade, and the number that are missing grades is highest with the smallest amount of tissue that the pathologist obtains, not a good situation.

Slide 6:

Reproducibility of histologic grading -- the group shared the following experiences. We know that when patients get referred to large centers, seven to 10 percent of sarcoma diagnoses are in error, and by that I mean a major diagnostic error. In national protocols, it may be as high as 30 percent. In my consult experience, it is about 25 percent. The question comes up, should we be endorsing or recommending second opinions? We did not come to consensus here; but it is something certainly to consider.

Slide 7:

So, what are our final recommendations in dealing with the standard reporting and communication with surgeons regarding sarcomas? First of all, I think multiple core biopsies are adequate. Some should definitely be frozen and stored for special assays. You all must recognize that there will be some limitation based on the small size of the material vis a vis pathology diagnoses.

We feel that pathology reports should be doing and reporting specific predictive molecular markers, such as the translocations which have proven to be of predictive importance.

Because of the issue of disseminating the importance of complete pathology reporting, I think we would like to suggest that there ought to be a central Web-based resource for sarcoma-related information. This could include information relating to diagnosis, treatment, and various testing centers.

Finally, we thought that maybe there should be some encouragement that patients with these rare diseases be referred to specialized centers. I think all of us have been in situations where we have seen patients referred from the outside, with sort of half-done biopsies and half-done procedures, and then it becomes a really complicated issue to treat these patients and salvage these patients.

Finally, the issue, I think, of second opinions. It is certainly one that is real and it is probably best left for further discussion. Jonathan is going to present, I think, his portion and then we will be happy to entertain questions, comments, ideas that perhaps overlapped with ours that came up in your sessions.