[CautiouslyOptimistic]

Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Wed Oct 05, 2016 6:15 pm

I was wondering if anyone could help me make sense of my bone marrow biopsy and phenotyping tests. I asked my doctor, who is a hematologist specializing in multiple myeloma, but all he told me was don't worry about them.

Bone Marrow Biopsy

Diagnosis:

• Slightly hypercellular marrow (70%) w/ trilineage hematopoiesis
• Megakaryocitic hyperplasia
• Plasma cell dyscrasia (1% plasma cells by immunihistochemistry, monoclonal lambda by FCM)

PB smear: Diff (100 cells)

Seg neutrophils 54%
Lymphocytes 34%
Monocytes 10%
Eos 2%

Number & Morphologies of Erythrocytes and Leukocytes: normal or within normal limits
Number & Morphology of Platelets: normal or within normal limits

Aspirate: Diff (500 cells)

Myeloblast 1.0 (0.1 - 1.7) Pro 1.0 (0.1 - 1.1)
Promyelo 3.2 (1.9 - 4.7) Baso 3.2 (0.4 - 2.4)
Myelo 17.0 (8.5 - 16.9) Poly 21.2 (13.1 - 30.1)
Meta 9.0 (7.1 - 24.7) Ortho 7.2 (0.3 - 3.7)
Band 11.2 (9.4 - 15.4) Megs 0.6 (0.1 - 0.4)
Seg 13.4 (3.8 - 11.0) Mono 0.6 (0.0 - 0.6)
Eos 11.4 (1.1 - 5.2) Plasma 0.0 (0.0 - 3.5)
Baso 0.0 (0.0 - 0.2) Lympho 0.0 (8.6 - 23.8)
Other 0.0 Lymphoblasts 0.0

M:E ratio 2.0
Specimen quality: adequate
M:E maturation: normal
Megakaryocytic Morphology: increased w/ occasional small hypolobate forms

Special Stains
Storage Iron: adequate
Sideroblastic Iron: adequate
Ring Sideroblasts: absent

Core Biopsy: Bone Trebeculae: normal

Cellularity: 70%
Trilineage Hematopoiesis
Megakaryocyte: increased, occasional small hypolobate forms and loose clustering

Special Stains/Immunohistochemical Stains
Reticulin Stain: no increase in fibrosis
CD138: Positive in 1% of nucleated cells

Particle Clot: similar to core biopsy

FCM: Specimen: bone marrow aspirate

Interpretation: Abnormal plasma cells CD38++,CD19-, CD20+, CD45-, CD56-, expressing cytoplasmic lambda light chains, normal plasma cells not detected. phenotypically normal myeloid cells w/o evidence of T-cell lymphoproliferative disorder or acute leukemia.

CBC:

WBC: 6.84 K/MCL
RBC: 5.61 M/MCL
HGB: 16.6 G/DL
HCT: 48.4%
MCV: 86.3 FL
MCH: 29.6 PG
MCHC: 34.3 G/DL
RDW: 12.3%
PLT: 307 K/MCL

Differential:

Granulocyte # (%): 3.99 k/uL (58.4)
Eos # (%): 0.24 k/uL (3.5)
Baso # (%): 0.07 k/uL (1.0)
Mono # (%): 0.73 k/uL (10.7)
Lympho # (%): 1.78 k/uL (26.0)
IG # (%): 0.12 k/uL H (1.4H)
Nucleated RBC # (%): < 10 (0.0) normal value: not detected

Gross Description: Specimen taken from right posterior iliac crest.

Now the Phenotyping test.

Your Markers: total 22, CD2(80%), CD3(73%), CD4(42%), CD5(75%), CD7(71%), CD8(26%), CD16(9%), CD56(7%), CD10(4%), CD19(15%), CD20(16%), Kappa(5%), Lambda(5%), Cyto K(See Note), Cyto L(See Note), CD34(<1%), CD11b(4%), CD13(2%), CD33(4%), CD64(2%), CD38(see Note), CD45(see Note)

Analysis: FCM of bone marrow aspirate: 7% of CD45+ leukocytes are lymphcytes, 3% are monocytes, and 90% are myeloid cells. 73% of lymphocytes are T-cells, 9% are NK cells, and 16% are B-cells. T-cells appear phenotypically normal, CD4:CD8 ratio 1.6. 25% of CD19+ B-cells express CD10, variable CD20, but lack surface light chains and are consistent w/ hematogones. Mature B-cells have normal intensity CD20, polytypic, w/ K:L ratio 1.0. Abnormal plasma cells expressing bright CD38, monotypic cytoplasmic lambda light chains, CD19-, CD20+, CD45-, CD56-. Myeloid cells demonstrate phenotypically normal expression patterns for markers evaluated. 1% CD34 positive myeloblasts. Specimen viability: 93%

I know this a lot of info. I was initially evaluated for a myeloproliferative neoplasm (poly­cythemia vera). I am a 40 year old male and I have had a lot of excruciating bone pain, intermittently abnormal CBC and CMP tests for over 5 years now.

Like I said originally, I was referred to this doc because my RBC, HCT, and HGB kept going to high. My doc discounted both of these tests, saying they were normal and not to worry about them, but when I read through the reports after I asked for copies, I became a little worried about the plasma cell dyscrasia diagnosis of malignancy. My grandfather died of multiple myeloma, so the reports kinda hit a nerve.

I found this site while doing research and it has answered a lot of questions, but I still have a ton more. Right now I am wondering if any of this stands out or should have prompted my doc to say more than, "don't worry about them. The results are normal for someone your age."

[Multibilly]

Re: Deciphering bone marrow biopsy & phenotyping results

by Multibilly on Wed Oct 05, 2016 8:58 pm

I would tend to trust the opinion of a hematologist that specializes in multiple myeloma.

Also, note that plasma cell dyscrasias such as multiple myeloma tend to lower one's RBC, HCT and HGB levels, not raise them like PV does.

But what is curious to me is that your biopsy detected monoclonal lambda light chains and I don't believe that goes along with a PV diagnosis (but I'm not a doc and not 100% positive about this).

Given that bone marrow biopsies can hit different densities of disease in your bone marrow and can sometimes under-represent the true extent of one's plasma cell dyscrasia, it would seem prudent to me to follow up with a serum protein electrophoresis, serum immunofixation, quantified immunoglobulin and serum free light chain assay to better evaluate the extent of your plasma cell dyscrasia. While a lot of folks are walking around with undetected plasma cell dyscrasias such as MGUS and will go through life none the worse for it, it's not "normal" and ought to be correctly diagnosed IMHO.

Note that it's also not unheard of to be diagnosed with both a myeloproliferative neoplasm and a plasma cell dyscrasia:

Badelita, J., et al., "The simultaneous occurrence of multiple myeloma and JAK2 positive myeloproliferative neoplasms - Report on two cases," Journal of Medicine and Life, Jan-Mar 2015 (full text of article)

Malhotra, J., et al, "Coexistence of Myeloproliferative Neoplasm and Plasma-Cell Dyscrasia," Clinical Lymphoma, Myeloma, and Leukemia, Feb 2014 (abstract)

[CautiouslyOptimistic]

Re: Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Thu Oct 06, 2016 12:01 pm

Hi Multibilly.

Thanks for your reply. I have been through the ringer as far as tests go for polycythemia vera (PV). Been through 5 docs, two have been hematologists. I know this is not a PV forum, but the gene mutations that 99% of those with PV have (JAK2), I have tested negative for. I've been tested 3 different times for all known secondary causes as well. All negative.

I should mention my last 4 months of labs (CBCs and CMPs) have shown elevated serum calcium in the range of 11 to 11.5 mg/dL. My current doc did order a serum IFE test. The results stated IgD and IgE not detected. G, A, and M were not listed on the test. I asked my doc about that, and the SPEP and FLC assay after finding this site and reading through some posts, and so far he has just ignored my questions.

Of course, he has also "asked" me on several occasions if I was on anabolic steroids, though it was more of an accusation than a question. I understand he had to ask because 5 years ago I was put on testosterone replacement shots because my levels were "lower than a 90 year old man" I think is how the doc at the time explained it. However, those didn't last long, as my hematocrit and RBC count kept skyrocketing. My last CBC actually showed a decrease in RBC, hematocrit, and hemoglobin levels. Which is weird because they have never gone down on their own since I was diagnosed with PV in 2011. They always go up, from one draw to the next. Right now my doc is not even sure I have PV anymore.

I have asked for my other immunoglobulins to be tested, but he tells me that it wouldn't do any good because my total protein values are (relatively) normal. They typically hang out between 7.8 - 8.5 g/dL, but have been up in the high 8s.

I understand I won't get any kind of "diagnosis" here nor am I looking for one. I was just hoping to get other people's perspective on some of the values from my tests. I'm a research scientist, so for me the devil is in the details. For instance, my bone marrow biopsy values under PB smear do not match the values given on my CBC, and if I have plasma cells in my bone marrow that are abnormal, then why do they not show up in the aspirate differential, and likewise I have no lymphocytes detected in the aspirate when the normal range is 8.6-23.8? So confusing.

I do appreciate your response, and any others as well. Especially if anyone knows how to convince a doc to run tests which seem to be pretty standard for this condition. Even if it is just to rule the condition out.

[CautiouslyOptimistic]

Re: Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Thu Oct 06, 2016 12:07 pm

I should also mention the bone marrow biopsy and the leukocyte / lymphocyte pheno­typing tests were done about 20 days after a phlebotomy to treat the PV. My CBC right before that phlebotomy was:

Test Value Range
WBC 10.32 k/uL 3.20 - 10.60 k/uL
RBC 5.97 M/uL 4.69 - 6.07 M/uL
HGB 18.3 g/dL 14.6 - 17.8 g/dL H
HCT 51.4 % 40.8 - 51.9 %
MCV 86.2 fL 77.8 - 94.0 fL
MCH 30.7 pg 26.5 - 32.6 pg
MCHC 35.7 g/dL 32.7 - 36.9 g/dL
RDW 13.0 % 10.8 - 14.1 %
Platelet 296 k/uL 177 - 406 k/uL
MPV 8.4 fL 5.9 - 9.8 fL
Granulocyte % 67.5 % 44.0 - 76.0 %
Monocyte % 6.1 % 4.0 - 8.9 %
Eosinophil % 4.1 % 0.0 - 6.0 %
Basophil % 1.6 % 0.0 - 1.7 %
Granulocyte # 7.0 k/uL 1.3 - 7.0 k/uL
Monocyte # 0.6 k/uL 0.2 - 0.7 k/uL
Eosinophil # 0.4 k/uL 0.0 - 0.4 k/uL
Basophil # 0.2 k/uL 0.0 - 0.1 k/uL H
Lymphocyte % 20.8 % 14.7 - 42.6 %
Lymphocyte # 2.2 k/uL 0.8 - 3.1 k/uL

Another thing I forgot to mention, my LDH levels have always been elevated. Usually ranges around 250-260 with normal range of 100-250 U/L. The thing to note is the swing in WBC and differentials. There either right up on the high limits or down on the lower limits. Only a few times have I had elevated WBC counts, they were in the 13 to 15 k/uL if I remember correctly. All of these values are absent an illness or infection of any type.

[Multibilly]

Re: Deciphering bone marrow biopsy & phenotyping results

by Multibilly on Thu Oct 06, 2016 12:33 pm

If you haven't done so already, I might suggest seeing a different hematologist who is tied to a large cross-functional specialist team, such as they have at the Mayo Clinic or Dana Farber.

[CautiouslyOptimistic]

Re: Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Thu Oct 06, 2016 9:53 pm

Yeah, I was kicking around the idea of a new hematologist. If I went that route, it would be the sixth doc in as many years. I've never "quit" a doc before. Always been referred on to the next one because apparently I'm " a unique and very complicated case". Thing is I don't want to be unique! I'd rather be a straight forward case.

I read though those papers you posted. They were quite interesting. I've come across a few others that talk about a myeloproliferative neoplasm and a plasma cell disorders occurring in the same individual. Most of them describe myelofibrosis and one of plasma cell disorders. This is the first reports I've seen that mention polycythemia vera and a plasma cell disorder. Might be useful to take that into my doc the next appointment.

The Mayo Clinic might be an option at some point. I'm at a university hospital now and was told if anyone could figure me out, they could. To go anywhere is a long way for me, though, because I live in a very unpopulated area of the country. Six hour drive to my current doc and closest Mayo Clinic I think is twice that distance.

[CautiouslyOptimistic]

Re: Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Wed May 17, 2017 12:55 pm

Just wanted to post an update for my situation in case there was anybody interested. I know I haven't been on in awhile. I've been busy trying to get all this sorted out.

I finally convinced my primary healthcare provider to order the slew of tests to look for multiple myeloma. She did say she would not be able to interpret them, though, as this was way beyond her level of expertise. I told her that was fine as long as we get them done. I'll find a doc to interpret. I'll keep the test results short:

IgG level was low @ 526 mg/dL (767-1590 mg/dL)
IgA level was low @ 55 mg/dL (61-356 mg/dL)
IgM level was low @ 31 mg/dL (37-286 mg/dL)

B2M was 1.95 mcg/mL (no range specified)

Kappa serum free light chain normal @ 0.6640 mg/dL (0.3300-1.94 mg/dL)
Lambda serum free light chain low @ 0.2960 mg/dL (0.5700-2.63 mg/dL)
Kappa-lambda ratio high @ 2.24 (0.2600-1.65)

SPEP IFE
Alb 4.2 g/dL (3.4-4.7 g/dL) 4.1
A1G 0.3 g/dL (0.1-0.3 g/dL) 0.2
A2G 1.1 g/dL (0.6-1.0 g/dL) H 1.1 H
BetaG 1.3 g/dL (0.7-1.2 g/dL) H 1.5 H
GammaG 0.7 (0.6-1.6 g/dL) 0.65
A/G 1.26 1.18
TP 7.5 g/dL (6.3-7.9 g/dL) 7.6
IMP No apparent M protein No M-protein detected

I found a new oncology doctor after the hematologist I was seeing said there was nothing of interest in these results and I should stop looking for something that is not there. The new doctor took one look at ALL of my lab results going back to my bone marrow biopsy and then started discussing with me the possibility of a true nonsecretory multiple myeloma.

She said all of my immunoglobulins were low, which is called immunoparesis. My light chains were not elevated, which would indicate a light chain myeloma or one of the other light chain diseases, and in fact the ratio is too high, which indicates there is something going on.

She said nonsecretory multiple myeloma is extremely rare is a diagnostic nightmare. She then asked if I had ever had a bone survey done. I told her no, if it's not in my records, then it hasn't been done! She said she was going to consult with a colleague of hers before we order any more tests, so we can get this taken care of.

She did make a diagnosis of MGUS for now based on the bone marrow biopsy and the free light chain tests. She said if a bone survey finds any lesions she will re-diagnose with nonsecretory multiple myeloma. I'm now praying my bone survey comes back clean!

I'll try and update when I have some more info.

[Multibilly]

Re: Deciphering bone marrow biopsy & phenotyping results

by Multibilly on Wed May 17, 2017 6:56 pm

Sorry to hear about this C.O.

If it were me and I had suspected nonsecretory myeloma, I'd be pushing to get a PET/CT or whole body MRI (if whole-body MRI is available in your area) instead of a bone survey to look for any myeloma-related damage. To better understand the tradeoffs of various imaging techniques, see this article:

Kapoor, P, "To PET or not to PET" (July 24, 2014)

Good luck!

[CautiouslyOptimistic]

Re: Deciphering bone marrow biopsy & phenotyping results

by CautiouslyOptimistic on Wed Jun 28, 2017 5:18 pm

Thanks for your kind words, Multibilly!

After meeting with the new oncologist a couple more times, I am just as confused as ever. Her decision has been to "hold off on bone surveys". Right now my PV is really the most pressing issue. Blood production has nearly tripled. I have undergone phlebotomies every 2 weeks (4 in the last 2 months) to bring down my numbers and they still are barely able to keep me where they want.

I asked the oncologist how in the world I could have nonsecretory myeloma if I have PV, wouldn't they sorta offset each other? She said she is stumped with the PV and what, by all indications, appears to be nonsecretory myeloma. Every blood test (2 weeks apart) show indications of active disease from both. Her words, not mine. I don't know. All I know is every 2 weeks they are draining a unit of blood out of me, my iron or ferritin levels are now considered deficient, and 2 weeks later it's like they did nothing, all that blood is back.

Watching my lab values right now is like watching a drama / action movie! Unremarkable, slightly scary, OMG! There's no way you should be upright! Values are all over the place! The only thing that has been somewhat consistent is my albumin levels have steadily decreased from 5.1-5.3 to about 3.7. (though one lab came back with a value of 1.7!).

This for sure must be one heck of a roller coaster I'm riding.