Correlate with cytogenetics

[Enkidu]

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So I spent a day in hemepath yesterday and it was really interesting. It was different than I had expected - so much counting.

One thing that puzzled me, though, was that I would see final pathology reports in the patient's chart that would say "correlation with cytogenetics is recommended". My understanding is that the report was asking the clinician to order cytogenetics. The hematopathologist ordered about a dozens immunos, but apparently couldn't or didn't want to order cytogenetic studies without the clinicians approval. Is this the general practice?

Also - seriously? Counting those bone marrows is ridiculous. How long does it take an attending to do that? It took The med 4 who was rotating 2-3 hours per case, just to count.

 

[pathstudent]

So I spent a day in hemepath yesterday and it was really interesting. It was different than I had expected - so much counting.

One thing that puzzled me, though, was that I would see final pathology reports in the patient's chart that would say "correlation with cytogenetics is recommended". My understanding is that the report was asking the clinician to order cytogenetics. The hematopathologist ordered about a dozens immunos, but apparently couldn't or didn't want to order cytogenetic studies without the clinicians approval. Is this the general practice?

Also - seriously? Counting those bone marrows is ridiculous. How long does it take an attending to do that? It took The med 4 who was rotating 2-3 hours per case, just to count.

Cytogenetics are ordered pretty much on every single bone marrow but take about 7 days before they are ready and only rarely would you wait for them to come back before signing out the case. Most of the time they don't add anything to the diagnosis and most of the time there is really nothing to correlate.

I don't tell the clinician to correlate with cytogenetics as I add the cytogenetics in an addendum and then correlate it myself i.e. "the complex karyotype with the presence of t(9;22) supports a diagnosis of blast transformation of the CML". But most often I just say "Cytogenetics are normal 46,XX".

 

[Enkidu]

Cytogenetics are ordered pretty much on every single bone marrow but take about 7 days before they are ready and only rarely would you wait for them to come back before signing out the case. Most of the time they don't add anything to the diagnosis and most of the time there is really nothing to correlate.

I don't tell the clinician to correlate with cytogenetics as I add the cytogenetics in an addendum and then correlate it myself i.e. "the complex karyotype with the presence of t(9;22) supports a diagnosis of blast transformation of the CML". But most often I just say "Cytogenetics are normal 46,XX".

Oh, I see. The pathologist orders cytogenetics, but doesn't need them to sign out the case. Would clinicians be able to correlate the pathology report with cytogenetic studies on their own? That seems like something that pathology should definitely give some guidance on, unlike what it seemed in the reports that I read yesterday. Especially if the cytogenetic studies are going to suggest something different from what the case was initially signed out as.

What are the cases in which the cytogenetic studies affect the diagnosis? Isn't it embarrassing to have to change your mind based on cytogenetics after you've already signed out the case?

 

[Entgegen]

Also - seriously? Counting those bone marrows is ridiculous. How long does it take an attending to do that? It took The med 4 who was rotating 2-3 hours per case, just to count.

You were with slow or inexperienced residents. They may also have to diff out every different cell within each lineage, which would slow things down too. It usually takes me and most other residents at my program anywhere from 5 to 30 minutes to diff a marrow, depending on how complex (or poor quality) the aspirate is. Then again, we only diff erythroid precursors as such, regardless of maturity (I.e. we don't separate out proerythroblasts from basophilics from polychromatophilic, etc). Similar with the myeloid lineage, we only have 3 categories that we diff...blasts, promyelocytes, and MMBS (myelo, meta, bands, segs). That helps speed things up a bit.

 

[Enkidu]

You were with slow or inexperienced residents. They may also have to diff out every different cell within each lineage, which would slow things down too. It usually takes me and most other residents at my program anywhere from 5 to 30 minutes to diff a marrow, depending on how complex (or poor quality) the aspirate is. Then again, we only diff erythroid precursors as such, regardless of maturity (I.e. we don't separate out proerythroblasts from basophilics from polychromatophilic, etc). Similar with the myeloid lineage, we only have 3 categories that we diff...blasts, promyelocytes, and MMBS (myelo, meta, bands, segs). That helps speed things up a bit.

It seemed like we were lumping bands and segs, but separating out myelocytes and metamyelocytes. The purpose of the exercise wasn't all that clear to me - at the end of our count everything was normal anyway. If our attending hadn't called us over to look at some cool cases, I would have been hugely disappointed in hemepath.

 

[yaah]

Cytogenetics can define the diagnosis is hemepath, so you have to correlate. You basically have to put a comment like that in for acute leukemias or MDS or MPD, because cytogenetic results can alter the diagnosis. It doesn't really "change" it except it rare cases where you thought it wasn't enough for AML but a defining AML translocation comes back which makes it AML regardless of blast %. That is rare. Usually it modifies it somewhat. Case is signed out as AML but comes back with a specific translocation and then it becomes "AML with t(9;21)" or something. A clonal abnormality can also signify MDS in cases where you weren't sure whether it is or not initially.

Our marrows come with aspirates and the clinicians leave it up to us whether to order flow, cytogenetics/FISH, both, or neither. Works well that way. We also keep track of our cases so that when the cytogenetic results get issued (we don't have our own cytogenetic lab) we get the report so we can issue an addendum.

Counting marrows should not take 2-3 hours. Some cases you have to count several times if they are unusual or borderline, but typically one 500 cell count is fine and that can be done in less than 15 minutes. I have never timed mine but suspect it is 5-10 minutes.

 

[2121115]

So I spent a day in hemepath yesterday and it was really interesting. It was different than I had expected - so much counting.

One thing that puzzled me, though, was that I would see final pathology reports in the patient's chart that would say "correlation with cytogenetics is recommended". My understanding is that the report was asking the clinician to order cytogenetics. The hematopathologist ordered about a dozens immunos, but apparently couldn't or didn't want to order cytogenetic studies without the clinicians approval. Is this the general practice?

Also - seriously? Counting those bone marrows is ridiculous. How long does it take an attending to do that? It took The med 4 who was rotating 2-3 hours per case, just to count.

Wait. You have attendings counting a bone marrow diff? You must be at an incredibly low volume program. I've never seen or heard of an attending counting marrow diffs. Geez, how would you get anything done? That is tech-level work.

 

[Enkidu]

Wait. You have attendings counting a bone marrow diff? You must be at an incredibly low volume program. I've never seen or heard of an attending counting marrow diffs. Geez, how would you get anything done? That is tech-level work.

No, the attending didn't count. I just assumed that he would have in private practice where there are no residents. Is there a tech that can count in the community?

 

[yaah]

No, the attending didn't count. I just assumed that he would have in private practice where there are no residents. Is there a tech that can count in the community?

Probably, depends on what the pathologists want and what the best use of tech time is. We all count our own diffs. Techs don't do any. I think it's more efficient and appropriate at our place for the pathologist to do it. But it depends on your institution.

 

[thebouque]

No, the attending didn't count. I just assumed that he would have in private practice where there are no residents. Is there a tech that can count in the community?

I live in Canada, but here counting is the job of techs. Residents learn how to count to trouble shoot if a tech is having a problem. But once they're done with the learning, residents and attendings never count diffs.

 

[Path or bust]

I live in Canada, but here counting is the job of techs. Residents learn how to count to trouble shoot if a tech is having a problem. But once they're done with the learning, residents and attendings never count diffs.

I'm in private practice and I count my own marrows. I also gross my own specimens.

 

[Alteran]

Also - seriously? Counting those bone marrows is ridiculous. How long does it take an attending to do that? It took The med 4 who was rotating 2-3 hours per case, just to count.

It takes me about 5 minutes to do a 500 cell diff on a very well stained aspirate...longer if it's of poorer quality. We also don't separate out the erythroid lineage (only the granulocytes), so that speeds things up a bit. MDS marrows are challenging...but honestly, if the dysplasia is so bad that you can't tell what the cells are, get a blast count and take your best guess at the other cell lines.

The attendings count all their own marrows at all the private practice places I know of. They could have techs count, but I'm told the techs mess them up frequently so the attendings would rather just do it right the first time themselves.

 

[Thrombus]

I spent extraordinary time counting as a resident and learning to eyeball things now so I quickly know if something is out of sorts. I would recommend counting a couple thousand on each marrow you see after you eyeball it. Getting an M:E ratio is also very important and learning to eyeball this is also crucial to formulating what you think is going on in each patient.

Unless it is a complex t cell lymphoproliferative case or leukemia of undetermined lineage, AND there was no flow done, I have a very hard time believing that your pathologist was doing anything other than running up the patients bill with a dozen IHC on a marrow. That is shameful behavior IMO.

 

[Enkidu]

I spent extraordinary time counting as a resident and learning to eyeball things now so I quickly know if something is out of sorts. I would recommend counting a couple thousand on each marrow you see after you eyeball it. Getting an M:E ratio is also very important and learning to eyeball this is also crucial to formulating what you think is going on in each patient.

Unless it is a complex t cell lymphoproliferative case or leukemia of undetermined lineage, AND there was no flow done, I have a very hard time believing that your pathologist was doing anything other than running up the patients bill with a dozen IHC on a marrow. That is shameful behavior IMO.

Well - that marrow had a metastatic adenocarcinoma in it as well as a leukemia. I'm not sure if he ordered exactly 12 either - so lets not judge our guy too much.

 

[Giemsa]

I count my own BM diffs. Low volume site in Canada.

 

[2121115]

Interesting answers. I'm in a busy private practice, and techs count all diffs. They are very good, and I've never had an issue. At my residency/fellowship programs, techs also did all the diffs, so I've never even heard of attendings counting diffs.

 

[Entgegen]

Interesting answers. I'm in a busy private practice, and techs count all diffs. They are very good, and I've never had an issue. At my residency/fellowship programs, techs also did all the diffs, so I've never even heard of attendings counting diffs.

So you've never done a diff yourself?

 

[2121115]

So you've never done a diff yourself?

We had a rotation in residency where we learned to count diffs, basics of peripheral smears, etc. After that, no never in residency or fellowship.

 

[thebouque]

I'm in private practice and I count my own marrows. I also gross my own specimens.

Ok.

 

[Kilgoretrout 65]

It seemed like we were lumping bands and segs, but separating out myelocytes and metamyelocytes. The purpose of the exercise wasn't all that clear to me - at the end of our count everything was normal anyway. If our attending hadn't called us over to look at some cool cases, I would have been hugely disappointed in hemepath.

The reason you count is that doing the process of counting you notice things (dysplasia, unclassifiable cells, bugs) that help you formulate a diagnosis. As said above, alot of hemepath diagnoses require correlation with cytogenetics which come back days later, CML, MDS etc. That being said, I will recount the resident or tech diff if I suspect that it is wrong or to confirm their plasma cell or blast %. I will signout a marrow with no count and my "gestalt" depending on the circumstance such as a marrow for staging etc. Without the constant stream of interruptions I am guessing it takes about ten minutes to count a marrow.

As far as ordering a test on a patient, wouldn't you want that ordered by the clinician for resulting and billing purposes?

As far as being embarrassed when my diagnose is "wrong" when the cytogenetics come back, luckily it does not happen often and adds some interest to the streams of "rule out MDS" marrows we look at.

As far as "correlate with cytogenetics" some feel that is over used and should be limited to the morphologically difficult cases.

 

[Enkidu]

As far as ordering a test on a patient, wouldn't you want that ordered by the clinician for resulting and billing purposes?

I'm not sure I understand. Could you elaborate on this a little?

As far as "correlate with cytogenetics" some feel that is over used and should be limited to the morphologically difficult cases.

You mean cytogenetic studies are overused in general? Do cytogenetics have any independent therapeutic or prognostic value beyond the line diagnosis?

 

[TMZ2007]

We say "correlate with cytogenetics/molecular results" on the heme cases at our program, but we just mean that the clinician should check the results of the report which we have already ordered when it arrives in their mailbox, not that the clinician needs to order the appropriate ancillary testing. This is statement is probably superfluous because we also addend the salient points of the ancillary report into the final path report anyway.

When I first started hemepath, I counted marrows. After 10 or so laborious full counts, I noticed my counts were coming up within a few % of the tech count and I quit counting them. To my knowledge, the attendings never count. I might count my own if the blast % is near a diagnostic cutoff or something meaningful like that. I guess in the 5-10 minutes I look at aspirates for the gestalt impression I could also count 500 cells as well.

For those who get tech counts: do you just get one count from one tech? I have no idea if what we do at my program is standard, but we seem to get an average of 4 diffs from at least 2 techs.

 

[pathstudent]

I'm not sure I understand. Could you elaborate on this a little?



You mean cytogenetic studies are overused in general? Do cytogenetics have any independent therapeutic or prognostic value beyond the line diagnosis?

In many cases cytogenetics is ordered when it is not needed (staging marrow for lymphomas), and FISH has obviated it in many other instances, but in my experience it adds important information 25-50% of the time in cases of "bonafide MDS"/AML/MPN that alters therapy (when to go for SCT) which is intimately tied to prognosis. So I would not say it overused in those myeloid diseases.

 

[cmz]

I spent extraordinary time counting as a resident and learning to eyeball things now so I quickly know if something is out of sorts. I would recommend counting a couple thousand on each marrow you see after you eyeball it. Getting an M:E ratio is also very important and learning to eyeball this is also crucial to formulating what you think is going on in each patient.

Unless it is a complex t cell lymphoproliferative case or leukemia of undetermined lineage, AND there was no flow done, I have a very hard time believing that your pathologist was doing anything other than running up the patients bill with a dozen IHC on a marrow. That is shameful behavior IMO.

If you've ever looked at the 'snazzy' Genoptix BMs and looked at their panels, it is amazing to see the amount of glut that is present. Iron stains on aspirate, core, clot section. PAS on core and clot. Tons of immunos, etc -- though, I bet you can probably come up with a 'valid' excuse to order each and every immuno. Not that I am trying to single Genoptix out or anything...

Speaking from experience, most attendings will re-diff the borderline cases (e.g. RAEB-2 vs evolving AML vs AML). Residents (and even experienced techs) will often miss-judge what they call 'blasts'. I've seen quite a few cases where residents misinterpret 'small blasts' as lymphocytes. Same deal with plasma cell neoplasms... say a resident focuses on one field only and probably doesn't look at the entire set of aspirate smears/touch imprints. These are things I would catch at sign-out and obviously ask said resident to please re-diff now that they know what to look out for. Other than that, yeah... given a cursory glance at any aspirate, you should be able to ball-park the M:E.

The bit about cytogenetics. We just follow-up with the results at our institution and issue addenums a couple of weeks later -- unless the results are crucial, and we may hold a case for sign-out until we get results back.

 

[KCShaw]

Residents and techs can be unreliable. Some are great, some not so much. Of the hemepaths I worked with, all did some sort of diff -- if they had pretty good faith in whoever (if anyone) had already done it then they might only do a truncated count to look for inconsistencies, but generally they were of the cautious variety and did their own. They also tended to do oodles of immunos. Of the pathologists who also-did-heme the approach was quite different, but the diagnostic lines were relatively vanilla too. Get what you pay for, so to speak.

 

[Enkidu]

In many cases cytogenetics is ordered when it is not needed (staging marrow for lymphomas), and FISH has obviated it in many other instances, but in my experience it adds important information 25-50% of the time in cases of "bonafide MDS"/AML/MPN that alters therapy (when to go for SCT) which is intimately tied to prognosis. So I would not say it overused in those myeloid diseases.

When is cytogenetics ordered and when is FISH ordered?

 

[cmz]

When is cytogenetics ordered and when is FISH ordered?

This is a loaded question to try and answer and it mainly depends on the case at hand that you're reviewing. I'll just give a couple examples...

We routinely order conventional cytogenetics at my institution on every BM and tissue specimen (that is submitted for lymphoma workup). Different labs may have different FISH protocols (e.g. MDS FISH panels, AML FISH panels, Multiple Myeloma FISH panels, etc). We let clinicians request those when applicable and we may request specific FISH probes be run depending on what we see on morphology. Do you suspect an APML? Ask for 15;17.

Say you're looking at a bone marrow trying to evaluate for MDS and conventional cytogenetics is normal -- would adding FISH probes to look for 5q, 7q, +8, or del20q (probe sets that usually are part of a MDS FISH panel) add anything? The answer depends on how good your sample is and how many metaphase cells your lab was able to score. Maybe there are better articles out there, but take a look at http://ajcp.ascpjournals.org/content/135/6/915.full

Of course, I didn't mention other entities such as double hit lymphomas, etc.

 

[Enkidu]

We routinely order conventional cytogenetics at my institution on every BM and tissue specimen (that is submitted for lymphoma workup). Different labs may have different FISH protocols (e.g. MDS FISH panels, AML FISH panels, Multiple Myeloma FISH panels, etc). We let clinicians request those when applicable and we may request specific FISH probes be run depending on what we see on morphology. Do you suspect an APML? Ask for 15;17.

The article was really interesting. Am I right in understanding that cytogenetics should always be ordered to at least screen the karyotype? If the sample is inadequate (<20 metaphase cells) or there's an abnormality, then FISH can be used to clarify specific findings.

But I don't understand why clinicians would order studies like FISH. If it provides needed diagnostic information then wouldn't it be part of the pathology workup? If the pathologist doesn't need that information to sign the case out, then why does the clinician want to spend money getting information that doesn't help anybody? Or - if there is some prognostic or therapeutic significance to the FISH studies, why wouldn't they be part of the initial pathology report anyway? I thought that was how it worked, like how all NSCLCs get tested for EGFR and ALK mutations or whatever.

 

[pathstudent]

We routinely order conventional cytogenetics at my institution on every BM and tissue specimen (that is submitted for lymphoma workup).

.

What would be the point of ordering cytogenetics up front on a staging marrow for hodgkins. Or any lymphoma staging for that matter?

 

[cmz]

What would be the point of ordering cytogenetics up front on a staging marrow for hodgkins. Or any lymphoma staging for that matter?

There really is no point. I should rephrase my statement and say that the case comes as is... and the conventional cytogenetics is already ordered by the clinician. Now, do ALL cases have cytogenetics? Nope. I will say that for tissue specimens that are submitted for lymphoma work-up, we do order cytogenetics ourselves. Not all institutions do that, but ours does.

 

[yaah]

There have been studies about the utility of FISH in MDS cases. Most cases with a true abnormality will be picked up by karyotype. The only FISH studies we routinely order are myeloma FISH (because it has prognostic abilities) and occasionally BCR/ABLm t(11;14) and PML/RARA up front. The other times we order FISH are usually where we don't have karyotype abilities such as off paraffin blocks.

I think it is helpful for clinicians to send specimens for possible flow and cytogenetics on every case because unexpected findings occur. But that doesn't mean they need to be run.

 

[2121115]

But I don't understand why clinicians would order studies like FISH. If it provides needed diagnostic information then wouldn't it be part of the pathology workup? If the pathologist doesn't need that information to sign the case out, then why does the clinician want to spend money getting information that doesn't help anybody? Or - if there is some prognostic or therapeutic significance to the FISH studies, why wouldn't they be part of the initial pathology report anyway? I thought that was how it worked, like how all NSCLCs get tested for EGFR and ALK mutations or whatever.

The answer is that it is not that simple. If FISH studies are needed for the diagnosis, patholgiosts order it. But for the prognostic side of things, as pathologists we do not have access to all of the information the clinician does (i.e. are they even going to treat at all? what treatment regimen will they pick and will the test matter for it, etc).

 

[Enkidu]

The answer is that it is not that simple. If FISH studies are needed for the diagnosis, patholgiosts order it. But for the prognostic side of things, as pathologists we do not have access to all of the information the clinician does (i.e. are they even going to treat at all? what treatment regimen will they pick and will the test matter for it, etc).

Interesting - but sometimes the prognostic and therapeutic markers *are* part of the pathology workup, right? Is that just an example of reflex testing only for certain diagnoses, like NSCLC for EGFR, or HER2/NEU for whatever breast cancer, while other diagnoses don't have that type of reflex testing? Our neuropathologist ordered 1p/19q for every oligodendroglioma, which I guess is some sort of marker for chemotherapy sensitivity.

 

[2121115]

Interesting - but sometimes the prognostic and therapeutic markers *are* part of the pathology workup, right? Is that just an example of reflex testing only for certain diagnoses, like NSCLC for EGFR, or HER2/NEU for whatever breast cancer, while other diagnoses don't have that type of reflex testing? Our neuropathologist ordered 1p/19q for every oligodendroglioma, which I guess is some sort of marker for chemotherapy sensitivity.

Those kinds of things are set up by interdisciplinary meetings with oncologists and pathologists ahead of time, so I would not say they are part of the "work up" per se. For instance, at our institution it has been worked out ahead of time that we should order KIT mutation analysis on every GIST, so whenever I get a GIST I order it, but I don't need it to diagnose a GIST. And it has been worked out to do ER, PR, HER2, and Ki67 on every invasive breast carcinoma. And so on.

Other testing is more patient specific, and depends on clinical situations that we are not privy to, so the clinicians order those.

 

[Enkidu]

Other testing is more patient specific, and depends on clinical situations that we are not privy to, so the clinicians order those.

When a clinician orders a molecular test, does a pathologist have to sign it out with an interpretation, or is the result just reported to the clinician without any interpretation?

 

[2121115]

When a clinician orders a molecular test, does a pathologist have to sign it out with an interpretation, or is the result just reported to the clinician without any interpretation?

You should have seen this kind of thing on your pathology rotations. It is different for different specimens and different hospitals.