[melissaanne]

Contradiction - bone marrow biopsy vs. M-spike?

by melissaanne on Sun Nov 01, 2015 3:53 pm

Hello, All

We have chatted with our oncologist regarding the lab results below and I am still a bit con­fused on what they mean exactly. He doesn't seem to explain it in such a way that is easy to understand. My mom is currently diagnosed with solitary bone plasmacytoma (SBP) and has not been given any diagnosis of MGUS, smoldering multiple myeloma, or multiple myeloma.

We know my mom's M-spike is there, but her oncologist thinks it could be due to the SBP that she had resected recently. She finishes her radiation treatment (25 sessions) next week! He hopes that this will resolve.

M-Spike (serum): 0.3 g/dl (thought to be due to the plasmacytoma itself)
M-Spike (urine): None detected -- does this matter?

A bone survey was done and there were 5% TOTAL plasma cells but no MONOCOLONAL plasma cells. Could someone explain this to me? FISH was also normal with no chromosomal abnormalities.

Bone Survey: No evidence of lytic or blastic lesions; no radiographic evidence of multiple myeloma
Bone Marrow Biopsy: No monoclonal plasma cells, 5% total plasma cells

FISH: Normal

Free light chain (FLC) testing shows an abnormal ratio and there was a notation on the lab report that stated "IgG kappa monocolonal protein". My question is why did the bone marrow biopsy come back with "no monocolonal protein"?

Kappa Light Chain: 2.30 mg/dl
Lambda Light Chain: 0.98 mg/dl
Kappa/Lambda Ratio: 2.30

Any help on this would be fantastic. Thank you!!

[Multibilly]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by Multibilly on Sun Nov 01, 2015 5:00 pm

Hi Melissa,

This is confusing, isn't it?

First off, a diagnosis of solitary bone plasmacytoma (SBP) is sort of its own unique beast. That is, it is not considered to be only MGUS, smoldering multiple myeloma, multiple myeloma.. So, while it is a plasma cell disorder like the other diseases I mentioned, it is uniquely defined as a solitary bone plasmacytoma. Given that the bone marrow plasma percentage is < 10% in this situation, the condition is technically diagnosed as a "SBP plus MGUS".

As far as why no monoclonal cells showed up in the bone marrow biopsy, this is likely due to the combination of there being a low percentage of monoclonal plasma cells to begin with AND the fact that the bone marrow biopsy was likely a "dry tap". The reason it could likely be a dry tap is because the monoclonal plasma cells associated with plasma cell disorders are never spread uniformly throughout one's bone marrow. So, sometimes the bone marrow biopsy procedure can be a hit-or-miss affair and can reveal no monoclonal plasma cells even in those patients with full-blown symptomatic multiple myeloma (which this is not) and large serum M-spikes (an M-spike of 0.3 g/dL is quite small).

This can also explain why the FISH results were normal, although it is not at all a given that one would have any adverse cytogenetics (unfavorable genetic mutations) even if an abundance of monoclonal plasma cells appeared in the bone marrow sample. For example, I have smoldering multiple myeloma with an 11% bone marrow plasma cell percentage and plenty of monoclonal plasma cells, yet my cytogenetics as determined by FISH are all (thankfully) normal.

Lastly, if you haven't read this article,

"Solitary Bone Plasmacytoma – What Every Patient Should Know," The Myeloma Beacon, May 4, 2012

I might suggest doing so. Good luck with all this.

[melissaanne]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by melissaanne on Sun Nov 01, 2015 5:58 pm

Hi Multibilly-

First of all, thank you for your thorough response! I really appreciate you breaking it down for me. I completely understand now that the reason 'no abnormal plasma cells were present' is that it could be due to the fact that there are few plasma cells in her bone marrow and it could've been a 'dry tap'. My question then is: how should we proceed without (potentially) having accurate FISH results?

We were very happy that her FISH showed no abnormalities ... but if this was due to a 'dry tap' or inadequate sample, then are we to believe that the FISH test was possibly flawed? My guess is they'd run another FISH at her next BMB (even though she's been told she won't need one unless blood / urine labs show reason for concern).

She is set to have follow up blood work 30 days post radiation being completed. They will look for that M-spike ... and hopefully it has diminished or at least decreased. I read the article you sent (thank you!) and that is now the 2nd or 3rd time I've read that an M-spike that goes away following radiation in SBP is a good prognostic factor. Fingers crossed on that.

She does, however, have that FLC ratio abnormality. Is that considered very high relatively? I know it is higher than 'normal', but I am also unsure how that stacks up to what you'd typically seen in full-blown multiple myeloma.

We were concerned that her oncologist just wasn't 'calling a spade a spade' and that maybe her results showed more of a multiple myeloma diagnosis than he was leading on. But really, upon researching, it doesn't look like that's her case (at least as of yet). We are praying she's in the small percentile that don't progress.

So, in your opinion, would you have a FISH test redone? You'd think the lab report would state that they didn't have any (or enough) plasma cells to test for abnormalities (and FISH). I would think they'd let us know that, because this can completely alter her course of treatment in the long run I would think.

I have always been confused on high risk vs. low risk. I know the FISH results play into that, but is that the only factor?

Thank you for all your information! This site has been such a wealth of knowledge and I am so thankful!!

[Multibilly]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by Multibilly on Sun Nov 01, 2015 8:01 pm

So, an M-spike of 0.3g/dL coupled with those just slightly-off free light chains and a bone marrow plasma cell (BMPC) of 5% would make her case purely MGUS if not for the presence of the single plasmactyoma. So, that is why the diagnosis was "SBP PLUS MGUS". Her kappa FLC is just elevated a tiny amount, which is throwing off her FLC ratio. Be clear that most people on this forum would love to have a low M-spike and FLC values like your mom's.

Building off what you said, the doctor will probably NOT order another bone marrow biopsy (BMB) unless the M-spike or FLCs changed significantly over a period of a few tests, or the patient was starting to clearly develop one of the CRAB criteria. I'm pretty sure this is also what my doctor would recommend as a course of action under the circumstances. After all, BMBs are not without risk to the patient and they are quite expensive, so doctors are usually pretty conservative when it comes to ordering them.

Additionally, even if the doc did order another BMB and it was discovered that there were some adverse cytogentics, there really isn't anything that he/she would do with that information until such time that that the patient developed one of the CRAB criteria or an MDE and required treatment. Adverse cytogenetics as revealed by FISH simply are not actionable by themselves from a treatment standpoint. Their presence merely helps guide treatment and assists in determining prognosis.

See this article on the latest diagnostic criteria:

SV Rajkumar, "New Criteria For The Diagnosis Of Multiple Myeloma And Related Disorders," The Myeloma Beacon, Oct 26, 2014

Regarding risk, I am assuming that you are probably most worried about risk-of-progression as opposed to the risk stratification associated with treatment for symptomatic multiple myeloma (this is where cytogenetics play a really important role) and prognosis. Most of us MGUS and smoldering patients worry primarily about the risk of progression to symptomatic multiple myeloma ... at least that is what I think about the most come testing time.

There is a discussion on absolute risk-of-progression for MGUS patients as determined by the Mayo in this article:

N Korde et al, "Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies," Blood, May 2011 (full text of article)

It states:

The Mayo Clinic risk stratification model for MGUS identifies 3 major risk factors for progression: non-IgG isotype, serum M-protein concentration > 1.5 g/dL, and a skewed FLC-ratio (normal reference: 0.26-1.65). At 20 years of follow-up, absolute risk of progression for MGUS patients with 0, 1, 2, and 3 risk factors is 5%, 21%, 37%, and 58%, respectively

Make sense?

Last edited by Multibilly on Sun Nov 01, 2015 9:14 pm, edited 1 time in total.

[Tigerboy74]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by Tigerboy74 on Mon Nov 02, 2015 12:55 pm

I have similar results.

Let me ask you what you would call this though.

Low M-Spike under 1.0 g/dL.

Light chains high.

Solitary plasmacytoma from 2007 has not returned, but 2 other found due to PET scan.

Nothing in bone marrow, MRI or full skeletal.

What would you call this?

Best. Fight on my friends!

[melissaanne]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by melissaanne on Mon Nov 02, 2015 3:27 pm

Multibilly-

Again, thank you for all this information!!

I completely understand what you're saying about this being SBP plus MGUS. I do realize that many would love to have the numbers my Mother has- and we are so very grateful!

I would like to clarify: the statistics you wrote out on risk of progression. You stated:

The Mayo Clinic risk stratification model for MGUS identifies 3 major risk factors for progression: non-IgG isotype, serum M-protein concentration > 1.5 g/dL, and a skewed FLC-ratio (normal reference: 0.26-1.65). At 20 years of follow-up, absolute risk of progression for MGUS patients with 0, 1, 2, and 3 risk factors is 5%, 21%, 37%, and 58%, respectively,

My question is, do these statistics apply to my Mother's case since she is not "just MGUS" but actually SBP plus MGUS? Would you think this would increase her risk of progression or even be considered a myeloma-defining event?

I really appreciated the link to the diagnostic criteria. That helps. I am often confused because CRAB indicates that bone involvement is a myeloma defining event and she does have that ... but again, it's just in the one location and so far, has only been diagnosed as SBP. So I wonder if she truly has criteria to meet the B in CRAB. She is also anemic, but that only started post-surgery.

My other concern is she hasn't had a full body PET/CT. She did have a CT when she was admitted into emergency, but that was from the neck to pelvis looking for any masses (as they thought, at first, it was metastatic cancer). So, a full body PET/CT seems like it would be helpful. She did have a full bone survey which came up clear with no other lesions. I do understand, though, that her bone would have to be >30% involved before a bone survey might pick up the lesion. That's is concerning to me!

Thank you in advance for your help!

Tigerboy74 - Your case sounds similar to my Mom's! Where was your solitary bone plasma­cytoma located and how did you find it, if you don't mind me asking? Also, did you do radiation to treat? Any chemo? When were your others found on the PET scan?

Thanks!

[Multibilly]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by Multibilly on Mon Nov 02, 2015 4:03 pm

Hi Melissa,

I have no idea how to answer the risk-of-progression question with respect to somebody who has had a solitary bone plasmacytoma that has been treated. Maybe somebody else can address this question. But then you have to ask yourself what would you really do differently if the risk of progression increased in 20 years from something like 20% to 30% because of the SBP history?

I'm not a doc, but getting a full-body PET/CT or whole body MRI (WBMRI) doesn't seem like an unreasonable ask. If the doc doesn't agree to one right away, it also seems like a very reasonable ask for the next time she is scheduled to get imaged (which I'm guessing might be in a year or so, unless her markers really go south before then).

If you have access to a WBMRI, I would probably personally go with that simply because of how much radiation she has already been exposed to. But if an WBMRI is not an option (they aren't widely available yet), then a PET/CT would be a really good second choice.

BTW, this is a great posting which discusses the pros and cons of various imaging modalities:

Dr. P Kapoor, "To PET or not to PET" (forum posting, July 24, 2014)

[melissaanne]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by melissaanne on Mon Nov 02, 2015 4:06 pm

Multibilly-

Thank you!

I just wasn't sure if the plasmacytoma would be enough of a CRAB indicator to push her from MGUS to something more.

I know this disease is super confusing with various different presentations. No two cases of this disease are the same.

I will certainly push for an WBMRI or PET/CT at her next imaging appointment. I agree, not too much to ask!

Thank you!

[JimNY]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by JimNY on Mon Nov 02, 2015 4:30 pm

Hi Melissa,

I just want to add a little to the excellent advice Multibilly has given you already.

Your mother appears to have a solitary bone plasmacytoma. While Multibilly is correct that, given her M-spike, you can think of her disease as a bone plasmacytoma with MGUS, tech­nically it's just a solitary bone plasmacytoma. People with a solitary bone plasmacytoma often have an M-spike (see the Beacon article that Multibilly mentioned). But the diagnosis is still just solitary bone plasmacytoma.

The fact that your mother has no monoclonal plasma cells in her bone marrow biopsy fits perfectly with the solitary bone plasmacytoma diagnosis. It's actually one of the requirements for the diagnosis. One of the criteria for an SBP diagnosis is that there not be any monoclonal plasma cells on a bone marrow biopsy.

There is a second category of SBP in the latest myeloma diagnostic criteria called "solitary bone plasmacytoma with minimal marrow involvement". It is for those cases where someone has just one plasmacytoma and no CRAB symptoms or other "myeloma-defining events", but there are some monoclonal plasma cells in the bone marrow ... just not too much. The bone marrow clonal plasma cell percentage has to be less than 10%.

For cases of a true solitary bone plasmacytoma, such as your mother appears to have, the risk of progression to multiple myeloma within 3 years is about 10%.

The risk of progression is higher for cases of SBP "with minimal marrow involvement" – about 60% if the solitary plasmacytoma is in the bone, and 20% if the plasmacytoma is outside the bone (extramedullary). And, no, I did not reverse those percentages – the risk of progression is actually lower in cases where the solitary plasmacytoma is extramedullary.

So it's good news that there doesn't appear to be any clonal plasma cells in her bone marrow biopsy sample.

A couple of other quick thoughts that may be helpful:

• FISH results don't really make sense if you don't have myeloma cells to perform the FISH testing on. The test is designed to show the chromosomal abnormalities present in myeloma cells, not healthy plasma cells
• M-spikes take a while to decline after treatment because immunoglobulin, whether monoclonal or polyclonal, has a half life in the body of several weeks. Free light chains, on the other hand, have very short half lives, which is why they are a kind of "early warning system"

[Multibilly]

Re: Contradiction - bone marrow biopsy vs. M-spike?

by Multibilly on Mon Nov 02, 2015 8:17 pm

Jim,

Nice follow up. You correctly pointed out that there is a very distinct difference between a diagnosis of a SBP and a SBP+MGUS ... which I failed to do.