Bread slicing pathology

So I've been reviewing my pathology report from 3 years ago, and it says the pathologist received 15 H&E stained slides. They then say the sections examined reveal tumor present less than 1 mm from the right apical urethral margin of resection. It concludes that I had negative margins, no seminal vesicle or lymph node involvement, pT2c.

Now, 3 years later, I had recurrence, am undergoing SRT, and am wondering how the PC cells got out. In reading about how pathology reports are done, I note there are two ways, one is called "bread loafing" and the other is CCPDMA, or "complete circumferential peripheral and deep margin assessment". From what I read, CCPDMA isn't usually done for prostates, it's used for skin cancers, for prostates they use bread loafing.

The way I understand it, bread loafing is just what it implies, the prostate is sliced like slices of bread and the pathologist examines each slide. If this is the case, it appears to me that what is being examined is just a small sample of the prostate. In my case, just 30 slices, if you consider each slide to have two sides of the "bread slice." That may be fine for Gleason scoring and staging, but I wonder about margins. If they find tumor less than 1 mm from the margin on one of these, it seems to me quite possible that it was a false negative margin, they just didn't see a positive margin in the part of the prostate that wasn't on one of the surfaces of the bread slice. That would explain my recurrence.

Do I understand this pathology technique correctly, or have I missed the boat?

Clocknut, yes, I should have mentioned inking. But I don't think that changes my point about the likelihood of false negative margin. So the entire prostate is inked before it's sliced. The pathologist looks at the surface of each slice (the bread, not the crust) and determines if they see cancer cells up to the ink. But they don't look at the crust, do they? Can they tell just by looking at the inked crust whether it's cancer or not? If what I'm thinking is correct, the inking just facilitates their looking at the bread face (to continue the analogy) but does nothing to tell whether a positive margin happened at one of the bread crust points.

That's what my husband's RO told us. The pathology report is just based on examining samples but not the whole prostate. He told us that's the reason why patients with clean pathology reports have BCR later.

I know nothing about prostate slicing, but I have done some tissue prep for histology, the sections are very, very thin (up to several micrometers) when put on a slide to be examined under the microscope. Potentially, you could make thousands of slides from one prostate. Only the pathologist knows how he does this, how he selects what to look at, perhaps you can inquire at your hospital.

This is how it's done...

www.youtube.com/watch?v=dwQ_j3hvhAI

Tony

Whoa!! Thanks for that Tony. It is the first time I have seen the process. I am somewhat surprised the slicing is done manually ----- it is hardly what one would call high tech. Although the tech states that the gland is sliced into approximately 4mm ( a little over 1/8") pieces it is obvious that some are somewhat thicker than that. I would have to agree with Reachout, that given the thickness of the slices, a focal positive margin within a slice could well be overlooked.
Bill

reachout,

I agree completely with you that the post-op is not a complete review of the entire prostate.  There are billions of cells in the gland and they can't slice it 1 cell layer thick for review.  But what we do have is about 30 years of post-op pathologies being done this way.  So, if the method used to examine a prostate was that inaccurate, then they would not see the trending of recurrnce in a particular Gleason score.  It would probably be all over the place with each score.  We know that based on final pathology that people with OC G7 (3+4) seem to have a certain recurrence rate and that has remained steady over the years.  So, they would have to assume that the method used to examine the prostate post-op is somewhat accurate. 

Being a 4+3=7 you were in a higher risk group for recurrence based on what has been seen in people who had your Gleason score previously post-op. 

Reachout,
I wish you the best with your SRT!!Hopefully, the radiation will act like lightning hitting a tree and the grass surrounding it will be killed--Kill the beast!!
Bill

reachout,
I am referring to post prostatectomy pathology. The outside surgical margins are pretty thoroughly examined. There's room for error but not much. The tumor inside the gland that was removed is far less important than the outside margins for staging. Conversely, the tumor inside the gland is needed for Gleason scoring. The glandular structure and how deformed it is is vital to Gleason scoring. Once the tumor has left the prostate there is little if any glandular structure when it grows in lymph nodes or on bones so you can't really determine Gleason grade after the tumor has moved along and manifested itself to distant locations.

Tony

Tony, thanks for the link but it was pretty gross.

Reachout,

Both of the following studies found that a close surgical margin ≤1 mm doubles the risk of recurrence:

Short (≤1 mm) positive surgical margin and risk of biochemical recurrence after radical prostatectomy.

A close surgical margin after radical prostatectomy is an independent predictor of recurrence.

- Allen

Reachout;
You are absolutely correct. My surgeon told me during my preop consultation that there is a small recognized "underdiagnosis" or "false negative" call of clear capsular invasion or clear margin on the final surgical pathology due to "bread loafing." Now, I must confess to all that I cheated. In my town, one of the best pathologists is a personal friend. He came in on the day of my surgery and processed my prostate himself, submitting the entire capsular surface for examination, ie., CCPDMA. But, this is above and beyond the usual standard of care.
Now, here is the major point I want to raise. The pathology department always keeps all of the wax cassettes containing each slab of the gland, and can always go back and make additional slices and slides from a particular slab of tissue. Your pathologist may have had one slide prepared from one slab showing tumor extending to less than 1 mm from a margin. If they had asked at that time for more slices to be made from that cassette, and if the slides revealed that, say 1 mm away, the tumor DID extend to the margin, would your treatment have been different? Perhaps you would have been offered AXT. Would this have made a difference in your clinical outcome? I don't know, but I'm sure others can comment on this.
If there is obvious tumor extending to or through the capsule, this is usually detected by they pathology physician assistant who usually cuts up the gland and submit the slabs for sectioning. However, if the tumor extends close to, or if there is microscopic invasion, this may not be appreciated at the time of sectioning.
Again, here is my point. Who is responsible to read the pathology report in detail; not just the "IMPRESSION" but the body of the report? If it is clinically important to know if there is microscopic capsular invasion or positive margins, who should followup on the pathology report? Should the pathologist ask for more slides to be made? Should the surgeon closely read the report to see if more slides should be evaluated? If your case was presented at a hospital tumor board, perhaps a savvy medical oncologist or radiation oncologist would have raised this issue. Should we, as patients, obtain and critically review all of our own pathology reports? It should not be our responsibility, however, as patients, sometimes we are our own best advocates, if we know what to look for and what to ask. I'm afraid I may have opened a can of worms, but this is an issue I have been concerned about since my own surgery. But, we need to educate ourselves, spread the word, and become proactive in our own care. Let the comments begin.

Peaty: thanks, what your doctor and pathologist said and did are consistent with what I was thinking. Also, i'ts more than just the slicing, but the slides. My pathology report says they evaluated 15 slides. At first I thought this meant 15 slices but in reality it's 15 extremely thin sections from the bread slices, which reduces even more the amount sampled.

You're lucky you had an expert pathologist helping out with CCPDMA. From what I've read it's uncommon to use that for prostates. I think I had an excellent surgeon but the pathology was just so-so. I don't know the pathologist but they did have a confusing statement on the report that not even my surgeon knew what it meant. The report says I had extracapsular extension but did not have extraprostatic extension. My surgeon said he didn't know what that meant but it didn't matter, my PSA would tell the story from then on. Well, the story is that my PSA went up and now I'm in SRT. I asked my radiation oncologist and he thought it was a typo in the pathology report.

EnglishAlf: good link. From that link it says "When you submit the entire gland, people think you’re evaluating every aspect of the prostate, but you’re not. (You will, however, see more of the surface area than if the specimen is not submitted in its entirety.) When you slice the prostate for routine, non-whole-mount sections, each slice ranges from 2 to 3.5 millimeters in thickness, but from each of those slices, the histology lab takes slices that are only about 5 microns thick to make slides. [A human hair is 100 microns thick.] So there’s actually a relatively large surface area that you don’t see. If you were to look at the entire prostate, that would mean looking at hundreds of slides, and that’s not done."

So, again, we're dealing with extremely small samples.

I don't want to give the wrong impression. I'm sure that in the vast majority of cases, the pathologist gets it right, in spite of the challenges of examining large specimens and having to make calls at the cellular level. My original question was about borderline cases like mine, where a mistake might be made. In a sense my surgeon was right, even if a mistake was made, it probably would not have changed my therapy. Well, maybe I would have had adjuvant instead of salvage radiation, who knows. Anyway, too late now.