Hyperproteinemia and anemia (hgb=10.6) brought me to the attention of hem/onc, After the usual battery of blood tests (SPEP, etc), I was subjected to a legal form of torture known as bone marrow aspiration and biopsy. The anemia type is still undetermined after significant testing.
The results of BMB were as follows:
- Hypercelluar marrow for age (70%) with trilineage hematopoesis
- 3% plasma cells by aspirate counts with mild kappa excess
- Adequate iron storage (2+/0-4+)
- Abnormal cytogenetics with loss of y chromosome consistent with advanced age (75)
- Normal FISH with no gains, deletions or translocations
The plasma cell % was determined by flow cytometrics on aspirate but there was no percentage offered from the core sample of bone marrow. I thought the best estimation of plasma cell percentage was derived from an average of aspirate and solid marrow counts. Is the aspirate percentage sufficiently accurate for clinical diagnosis?
Since I have anemia of unknown etiology, is the diagnosis of MGUS excluded even with the low plasma cell count of 3%.
Forums
Re: Plasma cell percent - how accurate for diagnosis?
Hello Alex,
Have you asked why you did not get a result from the core? Every facility is different, but at my facility, we get the FISH report but we do not get the pathology report unless we ask for it. It helped me a lot because I just can't absorb it all when I'm at the doctor's office.
Just as an example, they found only 2% plasma cells in the aspirate and 5-10% in the core for me. It is possible to have a low number and yet have disease, but generally it is because there are other issues going on such as CRAB and higher m-spike. It is certainly possible to miss an area that might have a concentration of plasma cells in a BMB.
Do you know what your m-spike is? (If you had more than one measurement, that would be helpful). And can I assume they've tested you for gastrointestinal blood loss?
What other health history? Have you had any other cancer or treatment thereof?
The thing that piques my interest first is the hypercellularity. Did they not give you an explanation for that? The first thing that comes up on a general google search is myleoproliferative disorders. My understanding is that our cellularity decreases with age. I am 51 years old and my cellularity is 40%.
I will leave you to the more well informed group that is the Myeloma Beacon, but I just wanted to share what thoughts I had. I suppose I have more questions than answers and that doesn't help you, but I would not be satisfied with having no answer for your anemia.
All the best.
Have you asked why you did not get a result from the core? Every facility is different, but at my facility, we get the FISH report but we do not get the pathology report unless we ask for it. It helped me a lot because I just can't absorb it all when I'm at the doctor's office.
Just as an example, they found only 2% plasma cells in the aspirate and 5-10% in the core for me. It is possible to have a low number and yet have disease, but generally it is because there are other issues going on such as CRAB and higher m-spike. It is certainly possible to miss an area that might have a concentration of plasma cells in a BMB.
Do you know what your m-spike is? (If you had more than one measurement, that would be helpful). And can I assume they've tested you for gastrointestinal blood loss?
What other health history? Have you had any other cancer or treatment thereof?
The thing that piques my interest first is the hypercellularity. Did they not give you an explanation for that? The first thing that comes up on a general google search is myleoproliferative disorders. My understanding is that our cellularity decreases with age. I am 51 years old and my cellularity is 40%.
I will leave you to the more well informed group that is the Myeloma Beacon, but I just wanted to share what thoughts I had. I suppose I have more questions than answers and that doesn't help you, but I would not be satisfied with having no answer for your anemia.
All the best.
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Toni - Name: Toni
- Who do you know with myeloma?: self - MGUS
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 51
Re: Plasma cell percent - how accurate for diagnosis?
Toni - Thanks for your reply,
The hypercellularity seems to be of little concern since the blasts in the bone marrow are minimal.
My paraprotein is IgG, is elevated, and has gone from 2525 to 2275 over the last two months.The kappa light chains are mildly elevated. No M-spike was detected on SPEP.
I did talk directly with the hemo-pathologist who will locate the numerical quantity of plasma cells from the core biopsy. The report had stated that there was a low % of plasma cells in the core so I assumed it was close to the aspirate count of 3%.
Still no response to my original questions regarding aspirate counts being sufficient for diagnosis and whether my anemia excludes a MGUS diagnosis.
The hypercellularity seems to be of little concern since the blasts in the bone marrow are minimal.
My paraprotein is IgG, is elevated, and has gone from 2525 to 2275 over the last two months.The kappa light chains are mildly elevated. No M-spike was detected on SPEP.
I did talk directly with the hemo-pathologist who will locate the numerical quantity of plasma cells from the core biopsy. The report had stated that there was a low % of plasma cells in the core so I assumed it was close to the aspirate count of 3%.
Still no response to my original questions regarding aspirate counts being sufficient for diagnosis and whether my anemia excludes a MGUS diagnosis.
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Alex M - Name: Alex M
- Who do you know with myeloma?: No one
Re: Plasma cell percent - how accurate for diagnosis?
Hi Alex,
It doesn't look like you meet the criteria for either MGUS, smoldering myeloma, or multiple myeloma.
For an MGUS diagnosis, you have to meet all three of the following criteria:
1. M-spike < 3.0 g/dL AND
2. Clonal (abnormal) plasma cells < 10% based on a bone marrow biopsy AND
3. NO myeloma-related organ or tissue impairment (i.e., no "CRAB" criteria)
where the "CRAB" criteria are (quoting Multibilly):
[C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of normal
[R] Renal insufficiency S. Creatinine > 2 mg/dl
[A] Anemia Hemoglobin < 10 g/dl or 2 g < normal
[B] Lytic bone lesions or osteoporosis
Now, you don't have an M-spike. What you described as your "paraprotein" level is, I believe, just your IgG level. It's elevated, but that could be for a variety of reasons. Your SPEP indicates, as you said, that you do not have an M-spike. So apparently the elevated IgG levels are for some reason other than have monoclonal proteins.
Your plasma cell percentage is less than 10 percent, so you meet that criteria for having an MGUS.
It's not clear from what you've written whether you have the C, R, or B symptoms of multiple myeloma. Whether your hemoglobin number meets the A (anemia) criteria depends on whether you are male or female (it determines the reference range that is relevant) and the reference ranges used.
I've found two reference ranges:
Mayo Clinic: Men, 13.5 - 17.5; Women: 12.0 - 15.5 g/dL
MedlinePlus: Men, 13.8 - 17.2; Women: 12.1 - 15.1 g/dL
To meet the "A" criteria for a multiple myeloma diagnosis, your hemoglobin number has to be either less than 10, or less than the relevant reference range. So, if you're male, your either slightly above, or slightly below, the hemoglobin cutoff. If you're female, you're well above the cutoff.
The key things, however, are that you have no M-spike and a very low plasma cell percentage -- arguably a completely normal plasma cell percentage. Those make me wonder why a plasma cell disorder such as MGUS or myeloma is being considered as the source of your low hemoglobin level.
I hope this is helpful. You can find an overview of the criteria for MGUS, smoldering myeloma, and multiple myeloma at Wikipedia here:
http://en.wikipedia.org/wiki/Multiple_myeloma#Diagnostic_criteria
A more detailed description also can be found here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T2/
I hope you're able to figure out the source of your anemia. If you have any more questions, let us know.
It doesn't look like you meet the criteria for either MGUS, smoldering myeloma, or multiple myeloma.
For an MGUS diagnosis, you have to meet all three of the following criteria:
1. M-spike < 3.0 g/dL AND
2. Clonal (abnormal) plasma cells < 10% based on a bone marrow biopsy AND
3. NO myeloma-related organ or tissue impairment (i.e., no "CRAB" criteria)
where the "CRAB" criteria are (quoting Multibilly):
[C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of normal
[R] Renal insufficiency S. Creatinine > 2 mg/dl
[A] Anemia Hemoglobin < 10 g/dl or 2 g < normal
[B] Lytic bone lesions or osteoporosis
Now, you don't have an M-spike. What you described as your "paraprotein" level is, I believe, just your IgG level. It's elevated, but that could be for a variety of reasons. Your SPEP indicates, as you said, that you do not have an M-spike. So apparently the elevated IgG levels are for some reason other than have monoclonal proteins.
Your plasma cell percentage is less than 10 percent, so you meet that criteria for having an MGUS.
It's not clear from what you've written whether you have the C, R, or B symptoms of multiple myeloma. Whether your hemoglobin number meets the A (anemia) criteria depends on whether you are male or female (it determines the reference range that is relevant) and the reference ranges used.
I've found two reference ranges:
Mayo Clinic: Men, 13.5 - 17.5; Women: 12.0 - 15.5 g/dL
MedlinePlus: Men, 13.8 - 17.2; Women: 12.1 - 15.1 g/dL
To meet the "A" criteria for a multiple myeloma diagnosis, your hemoglobin number has to be either less than 10, or less than the relevant reference range. So, if you're male, your either slightly above, or slightly below, the hemoglobin cutoff. If you're female, you're well above the cutoff.
The key things, however, are that you have no M-spike and a very low plasma cell percentage -- arguably a completely normal plasma cell percentage. Those make me wonder why a plasma cell disorder such as MGUS or myeloma is being considered as the source of your low hemoglobin level.
I hope this is helpful. You can find an overview of the criteria for MGUS, smoldering myeloma, and multiple myeloma at Wikipedia here:
http://en.wikipedia.org/wiki/Multiple_myeloma#Diagnostic_criteria
A more detailed description also can be found here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T2/
I hope you're able to figure out the source of your anemia. If you have any more questions, let us know.
-
JimNY
Re: Plasma cell percent - how accurate for diagnosis?
Thanks Jim
I am well aware of all the requisites for MGUS and am familiar with the content of the links you have provided. A strict interpretation of the requisites would exclude the dx for me due to the presence of the anemia of unknown etiology. I have none of the other CRAB symptoms or findings.
As you realize, everything is not black or white in medicine and many disease presentations don't follow the strict textbook rules. I believe in my case that the heme/path and heme/onc believe my overall myeloma profile is closer to MGUS than to smoldering or frank myeloma. I'm sure I'm not the only patient that has presented with mixed findings that don't neatly fit into a pre-determined classification.
At any rate, I still don't have a definitive answer to my two original questions.
Jim, thanks again for taking the time to respond.
Cheers
Alex
I am well aware of all the requisites for MGUS and am familiar with the content of the links you have provided. A strict interpretation of the requisites would exclude the dx for me due to the presence of the anemia of unknown etiology. I have none of the other CRAB symptoms or findings.
As you realize, everything is not black or white in medicine and many disease presentations don't follow the strict textbook rules. I believe in my case that the heme/path and heme/onc believe my overall myeloma profile is closer to MGUS than to smoldering or frank myeloma. I'm sure I'm not the only patient that has presented with mixed findings that don't neatly fit into a pre-determined classification.
At any rate, I still don't have a definitive answer to my two original questions.
Jim, thanks again for taking the time to respond.
Cheers
Alex
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Alex M - Name: Alex M
- Who do you know with myeloma?: No one
Re: Plasma cell percent - how accurate for diagnosis?
Hi Alex,
Jim is right about his comment that the statement below isn't quite right.
"My paraprotein is IgG, is elevated, and has gone from 2525 to 2275 over the last two months"
This is simply your quantified IgG level, and several things could cause it it be elevated. By itself, it doesn't indicate that you have paraproteins present.
It sounds like you've already done a lot of homework here and there probably is a clear indication somewhere that you are in fact dealing with some sort of monoclonal gammopathy. But to be clear:
How do you know that your paraprotein is IgG-type? DId you have an immunoxifaxation (IFE) that showed the presence of any monoclonal protein (paraprotein) and indicated its type?
Did you have a 24 hour urine protein electrophroresis (UPEP) that showed the presence of any monoclonal protein?
What actually were your serum kappa and lambda free light chain values?
Putting aside the anemia issue, I don't quite see how a diagnosis of MGUS can be made from just the lab results you've posted here. Again, you probably are already on top of all this.
Jim is right about his comment that the statement below isn't quite right.
"My paraprotein is IgG, is elevated, and has gone from 2525 to 2275 over the last two months"
This is simply your quantified IgG level, and several things could cause it it be elevated. By itself, it doesn't indicate that you have paraproteins present.
It sounds like you've already done a lot of homework here and there probably is a clear indication somewhere that you are in fact dealing with some sort of monoclonal gammopathy. But to be clear:
How do you know that your paraprotein is IgG-type? DId you have an immunoxifaxation (IFE) that showed the presence of any monoclonal protein (paraprotein) and indicated its type?
Did you have a 24 hour urine protein electrophroresis (UPEP) that showed the presence of any monoclonal protein?
What actually were your serum kappa and lambda free light chain values?
Putting aside the anemia issue, I don't quite see how a diagnosis of MGUS can be made from just the lab results you've posted here. Again, you probably are already on top of all this.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Plasma cell percent - how accurate for diagnosis?
"Since I have anemia of unknown etiology, is the diagnosis of MGUS excluded even with the low plasma cell count of 3%."
Since the source of the anemia has not been identified yet, it still could be an anemia from something other than a monoclonal gammopathy, so your anemia does not exclude MGUS. I think Multibilly tried to answer this question with regard to your hemoglobin levels being right on the edge of qualifying for SMM or multiple myeloma diagnosis.
I believe what Multibilly is trying to address is exactly what I was wondering too: how can you be diagnosed with MGUS, SMM or multiple myeloma if there is no evidence of cloning? So it must be you have Bence Jones proteins (monoclonal free light chains of immunoglobulins) in the urine? If this is the case, then MGUS, SMM or multiple myeloma can be identified.
So as you are aware, you can have a very high level of immunoglobulin, as you do, but it does not mean that high level is due to a cloning within that immunoglobulin.
I hope you find the answers you seek. Often times it takes a lot of reading and searching for each of our individual situations to figure it out.
All the best.
Since the source of the anemia has not been identified yet, it still could be an anemia from something other than a monoclonal gammopathy, so your anemia does not exclude MGUS. I think Multibilly tried to answer this question with regard to your hemoglobin levels being right on the edge of qualifying for SMM or multiple myeloma diagnosis.
I believe what Multibilly is trying to address is exactly what I was wondering too: how can you be diagnosed with MGUS, SMM or multiple myeloma if there is no evidence of cloning? So it must be you have Bence Jones proteins (monoclonal free light chains of immunoglobulins) in the urine? If this is the case, then MGUS, SMM or multiple myeloma can be identified.
So as you are aware, you can have a very high level of immunoglobulin, as you do, but it does not mean that high level is due to a cloning within that immunoglobulin.
I hope you find the answers you seek. Often times it takes a lot of reading and searching for each of our individual situations to figure it out.
All the best.
-
Toni - Name: Toni
- Who do you know with myeloma?: self - MGUS
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 51
Re: Plasma cell percent - how accurate for diagnosis?
Your second question was with regard to aspirate counts. MGUS, SMM and multiple myeloma are not diagnosed by a singular line of testing. They are diagnosed only in the context of multiple diagnostic tools. Those three tools are exactly what Jim outlined: Bone marrow biopsy; level of monoclonal gammopathy (m-spike or Bence Jones); and systemic presentation of CRAB.
While you can have "hot spots" in bone marrow which will have a higher concentration of plasma cells, generally the BMB is a pretty accurate representation of the greater level of involvement. So for people like you and me, a 3% plasma finding is at the worst, a confirmation of MGUS.
While you can have "hot spots" in bone marrow which will have a higher concentration of plasma cells, generally the BMB is a pretty accurate representation of the greater level of involvement. So for people like you and me, a 3% plasma finding is at the worst, a confirmation of MGUS.
-
Toni - Name: Toni
- Who do you know with myeloma?: self - MGUS
- When were you/they diagnosed?: April 2014
- Age at diagnosis: 51
Re: Plasma cell percent - how accurate for diagnosis?
I want to thank all who responded to my query. Your comments were all well reasoned and quite pertinent.
As I pointed out in my opening remarks, I did have all the diagnostic blood and urine tests recommended for a workup of suspected plasma cell dyscrasia, specifically multiple myeloma. The results of these tests, as well as skeletal imaging and bone marrow examination, were all consistent with a diagnosis of MGUS with one caveat, and that was one abnormality in the CRAB evaluation, namely anemia.
After discussion with two hemapathologists, I feel confident that the anemia is not related to the plasma cell dyscrasia and therefore would not exclude the diagnosis of MGUS.
For those interested, I will list some of the pertinent testing results.
SPEP No M-spike observed but there was an abnormal elevation
of the gamma region measuring 2.1 g/dL
IFE Monoclonal IgG kappa and monoclonal IgG lambda identified
Quant IgG 2525 mg/dL
sFLC
Kappa 246 mg/L
Lambda 56 mg/L
Kappa/lambda 4.34
uFLC
Kappa 60
Lambda 5.5
Kappa/lambda 10.8
uIFE Bence Jones protein positive; kappa type
Finally in summary, according to two hemapathologists from prominent institutions, my two original questions have been answered.
Cheers
Alex
As I pointed out in my opening remarks, I did have all the diagnostic blood and urine tests recommended for a workup of suspected plasma cell dyscrasia, specifically multiple myeloma. The results of these tests, as well as skeletal imaging and bone marrow examination, were all consistent with a diagnosis of MGUS with one caveat, and that was one abnormality in the CRAB evaluation, namely anemia.
After discussion with two hemapathologists, I feel confident that the anemia is not related to the plasma cell dyscrasia and therefore would not exclude the diagnosis of MGUS.
For those interested, I will list some of the pertinent testing results.
SPEP No M-spike observed but there was an abnormal elevation
of the gamma region measuring 2.1 g/dL
IFE Monoclonal IgG kappa and monoclonal IgG lambda identified
Quant IgG 2525 mg/dL
sFLC
Kappa 246 mg/L
Lambda 56 mg/L
Kappa/lambda 4.34
uFLC
Kappa 60
Lambda 5.5
Kappa/lambda 10.8
uIFE Bence Jones protein positive; kappa type
Finally in summary, according to two hemapathologists from prominent institutions, my two original questions have been answered.
- My anemia is likely not due to the limited capacity of bone marrow secondary to plasma cell dyscrasia.
- Plasma cell aspirate counts are more accurate than core bone marrow counts due to the homogeneity of aspirate and heterogeneity of the core bone marrow. In my case, both the flow cytometry using bright CD38 markers and the manual microscopic examination yielded identical results of 3%.
Cheers
Alex
-
Alex M - Name: Alex M
- Who do you know with myeloma?: No one
Re: Plasma cell percent - how accurate for diagnosis?
Hello,
I have a friend who was anemic, and it took one full year to diagnose her because she was non-secretory and she was transfusion dependent by the time she saw a myeloma specialist at Dana Farber who figured it out quickly.
Since you have monoclonal proteins on IFE, I would say that it is a good possibility that the cause of your anemia is multiple myeloma and that you would require repeat bone marrows over the next few months to confirm the diagnosis.
I'm not a doctor, but I have seen this before and perhaps my friend will post and provide additional insight.
Best,
J
I have a friend who was anemic, and it took one full year to diagnose her because she was non-secretory and she was transfusion dependent by the time she saw a myeloma specialist at Dana Farber who figured it out quickly.
Since you have monoclonal proteins on IFE, I would say that it is a good possibility that the cause of your anemia is multiple myeloma and that you would require repeat bone marrows over the next few months to confirm the diagnosis.
I'm not a doctor, but I have seen this before and perhaps my friend will post and provide additional insight.
Best,
J
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jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
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