[TobyBradshaw]

Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Sat Jun 22, 2013 11:12 am

Looking for some guidance on diagnostics before meeting with my mom's team at Moffitt (Tampa). The short version so far (some of it secondhand, and lacking detail):

IgM paraprotein (M-spike 4.1 g/dL)
Albumin 2.4 g/dL
Creatinine peaked at 3mg/dL
Hemoglobin 7.6 g/dL

So, evidence for an IgM monoclonal gammopathy of some sort, with severe anemia and renal impairment. Serum calcium has peaked as high as 20 mg/dL, without any of the serious symptoms expected from such a high value, though my mom was hospitalized and treated with IV fluids as a precaution. Maybe the paraprotein binds calcium?

Two bone marrow biopsies (one from each hip) have come back negative for excessive plasma cells (thus there are no cytogenetic data), and a skeletal survey likewise came back negative for lytic bone disease.

This past week a PET scan revealed at least 3 extramedullary masses, one in a lymph node near the lung, and two adjacent to the stomach. No biopsy of these masses has been done.

A few specific questions:

1. Can multiple myeloma be diagnosed definitively without a positive result from a bone marrow biopsy?

2. Although Waldenstrom's macroglobulinemia seems possible, how common is extramedullary disease in WM?

3. Are there alternatives to diagnosis of multiple myeloma or WM? Extranodal MALT B-cell lymphoma?

Last edited by TobyBradshaw on Sat Jun 22, 2013 9:36 pm, edited 1 time in total.

[Dr. Peter Voorhees]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by Dr. Peter Voorhees on Sat Jun 22, 2013 4:40 pm

Dear Toby,

IgM myeloma is quite rare (although it exists). When we see an IgM monoclonal protein, a diagnosis of Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma is most likely. Another type of indolent B cell non-Hodgkin lymphoma (such as a MALT lymphoma) would be another possibility, as you mentioned. With that degree of anemia, one would expect that the marrow would be involved, regardless of what process it is (myeloma vs. lymphoma). Was there no lymphoma seen in the marrow? Alternatively, Waldenstrom macroglobulinemia can be associated with cold agglutinin disease, in which red cells are destroyed as a result of the M protein binding to the red cells. If the kidney issue is long-standing, that can also contribute to the anemia.

The total serum calcium can be artificially high if the IgM M protein binds calcium. She can get an ionized calcium when you go to Moffitt to help make this distinction.

The kidney function in Waldenstrom can sometimes be affected by glomerulonephritis. Make sure a thorough investigation as to the cause of the kidney problems is sought (although it may just be a function of high calcium levels, which can adversely affect kidney function).

If nothing was found in the marrow, a biopsy of one of these other masses may be needed to make a diagnosis, if safe to do so.

Best of luck and please keep us in the loop!

Pet eV.

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Sat Jun 22, 2013 8:24 pm

Dr. Peter Voorhees wrote:
> With that degree of anemia, one
> would expect that the marrow would be involved, regardless of what process
> it is (myeloma vs. lymphoma). Was there no lymphoma seen in the marrow?

I haven't seen the results from the second biopsy, but I was told that there was no evidence of abnormal cell types/abundance. The first biopsy report was completely normal, attributed to a sampling issue, since most of the other symptoms (at the time) were consistent with the preliminary diagnosis of multiple myeloma.

> Alternatively, Waldenstrom macroglobulinemia can be associated with cold
> agglutinin disease, in which red cells are destroyed as a result of the M
> protein binding to the red cells. If the kidney issue is long-standing,
> that can also contribute to the anemia.

I'll have to look further into the kidney issues, but there is a multi-year history of routine blood work showing normal creatinine and BUN levels. My mom has always been borderline anemic and hypoalbuminemic, but she has worsened considerably very recently.

Feb 2012: Total protein 6.7, albumin 3.2, hemoglobin 11.7
Aug 2012: Total protein 6.7, albumin 3.1, hemoglobin 11.4
Feb 2013: Total protein 9.8, albumin 2.4, hemoglobin 9.1
Apr 2013: Total protein 10.5, albumin 2.4, hemoglobin 9.0
May 2013: Hemoglobin 7.6

So the (presumptive) paraprotein increase is coincident with the decline in Hb and albumin. Thanks for the info on the cold agglutinin mechanism -- that would indeed explain the anemia even if the bone marrow involvement were minimal. Is it reasonable to expect that several multi-cm extramedullary masses could produce enough M protein to cause the anemia by the cold agglutinin mechanism?

> The total serum calcium can be artificially high if the IgM M protein binds
> calcium. She can get an ionized calcium when you go to Moffitt to help
> make this distinction.

I have been expecting that to be done. It may even have been done -- I can check when I see her next week. I've been wondering where all the calcium is coming from since there's no evidence of bone involvement.

> The kidney function in Waldenstrom can sometimes be affected by
> glomerulonephritis. Make sure a thorough investigation as to the cause of
> the kidney problems is sought (although it may just be a function of high
> calcium levels, which can adversely affect kidney function).

Thanks -- I'll see what I can find out. I haven't seen any data on my mom's serum viscosity, but could hyperviscosity also produce the kidney damage?

> If nothing was found in the marrow, a biopsy of one of these other masses
> may be needed to make a diagnosis, if safe to do so.

Yes, I'm assuming that Moffitt will want to biopsy one or more of the masses, both for histology and cytogenetics, since we have yet to see an abnormal B-cell or plasma cell. My mom wasn't too clear on whether the masses were in lymph nodes near the lungs and stomach, or actually in/on the organs themselves. But perhaps I can get some more complete info on that when I visit her next week. I'm pretty sure that I can get my hands on the PET scans and radiologist's report.

> Best of luck and please keep us in the loop!

Thanks. Will do. Your expert contributions to this forum are greatly appreciated.

Toby

[Dr. Peter Voorhees]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by Dr. Peter Voorhees on Sun Jun 23, 2013 4:36 am

Kidney damage by hyperviscosity would be unusual, especially in the absence of other symptoms of hyperviscosity (lethargy, headaches, vision changes, ringing in the ears and/or hearing loss, lightheadedness, shortness of breath). Glomerulonephritis, amyloidosis, cryoglobulinemia or direct infiltration of the kidneys with Waldenstroms/lymphoplasmacytic lymphoma have all been shown to adversely affect kidney function in patients with Waldenstrom's. Given the low albumin for some time, is there any history of excessive protein in the urine?

The IgM level is quite high given the burden of disease you describe, but this can vary substantially from one patient to the next. As such, not impossible.

Keep us posted and good luck!

Pete V.

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Sun Jun 23, 2013 12:31 pm

Dr. Peter Voorhees wrote:
> Given the low albumin for some time, is there any history
> of excessive protein in the urine?

As far as I know there hasn't been routine urinalysis, but I'll check with my mom's primary care physician. He has always attributed her hypoalbuminemia/hypoproteinemia to malnourishment. My mom is about 62" and ca. 90 pounds, and has been very thin her entire adult life. She's 77 now.

I should get the radiologist's report on the PET scan next week, and I'll report back.

Thanks again.

Toby

[pdenardis]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by pdenardis on Thu Jun 27, 2013 8:16 am

Toby,

Please understand, I am not a doctor, but, rather a fellow lymphoma patient - one who has WM. From my readings of journal articles about WM, I have seen that it can happen that one has high IgM with little or no bone marrow involvment...sometimes this is classified as WM, and sometimes as MGUS (Monoclonal Gammopathy of Undetermined Significance). And, I have seen where folks with IgM circulating in their blood stream, and low bone marrow involvment also experiencing extramedullary tumors (I was one of them). What's the prevalence of such tumors in WM patients? From an "unofficial" polling of WM folks, it appears to be about 1 to 2% of WM patients have this manifestation. (I do believe there are journal articles that also back this up, but I can't locate them right now).

If you indeed are diagnosed with WM, and need some assistance or additional information, please don't hesitate to contact me or the IWMF (International Waldenstroms Macroglobulinemia Foundation) - we'd be glad to assist!

Pete DeNardis
IWMF Trustee and Discussion List Manager

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Thu Jun 27, 2013 2:34 pm

pdenardis wrote:
> If you indeed are diagnosed with WM, and need some assistance or additional
> information, please don't hesitate to contact me or the IWMF (International
> Waldenstroms Macroglobulinemia Foundation) - we'd be glad to assist!
>
> Pete DeNardis
> IWMF Trustee and Discussion List Manager

Thanks, Pete. Much appreciated.

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Thu Jul 04, 2013 12:07 am

Here are the basics of my mom's PET scan (skull base to mid-thigh):

1. Soft tissue mass medial aspect right lung apex involving posterior medial second rib, 3.3 x 1.3cm, SUV 3.5.

2. Soft tissue posterior to the carina, 1.6 x 0.6cm, SUV 3.2.

3. Pleural thickening lateral eighth rib, SUV 3.8.

No lymphadenopathy, no pleural or pericardial effusion.

4. Soft tissue posterior to left external iliac vessels at S1 level, SUV 3.6.

5. Soft tissue along left pelvic sidewall, 6.7 x 2.1cm, SUV 4.6.

6. Soft tissue right pelvic sidewall abutting bladder, 4.9 x 3.9cm, SUV 5.1.

Summary. Multifocal soft tissue malignancy with minimal bone involvement. Consistent with multiple myeloma but differential should include lymphoma.

From what I have read this would be a very unusual case of multiple myeloma -- monoclonal IgM and no bone or marrow involvement (by 2 biopsies, skeletal survey, and PET scan).

If it is lymphoma it appears to be entirely extranodal.

I suppose that without a biopsy of at least one of the tumors it will be difficult to make a definitive diagnosis. I'm not sure which (if any) of the masses can be accessed without surgery.

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Wed Jul 17, 2013 5:18 pm

An update on my mom's condition:

Last week the radiology/pathology team at Moffitt did a CT-guided biopsy of the left-side mass on the pelvic wall. The results were made available today. The short story is that the biopsy revealed that the tumor is an IgM kappa-restricted monoclonal extramedullary plasmacytoma. So, this appears to be one of those rare cases of IgM multiple myeloma, as well as a rare case of multiple myeloma without significant bone marrow involvement -- just extramedullary disease.

Her M-spike is currently 4.6g/dl, and B-2-microglobulin is 3.5g/dl. Albumin is up to 3.8g/dl.

Her anemia has become less severe (hemoglobin 10.7), and her serum calcium levels have returned to normal (9.6mg/dl), but the kidney problems persist (creatinine 1.2mg/dl).

Because of my mom's recent hypercalcemia, ongoing renal insufficiency, currently mild anemia, and age (77), the team at Moffitt is recommending treatment with cyclophosphamide, bortezomib, and dexamethasone.

[TobyBradshaw]

Re: Mutiple myeloma vs Waldenstrom + extramedullary

by TobyBradshaw on Wed Sep 18, 2013 7:05 pm

An update that may be useful, especially to those with IgM and/or extramedullary disease.

My mom had 1 cycle of cyclophosphamide, dexamethasone, and bortezomib, which she tolerated well. She felt fine (walked her usual 3 miles) the Monday morning of the start of Cycle 2, but the following day she began to have severe diarrhea. She lost her appetite and was nauseated, eating and drinking almost nothing for several days. By Friday we had to take her to the emergency room for hydration and potassium replacement. The diarrhea was finally brought under control. She was in the hospital for 2 days, and upon discharge she was still very weak.

Treatment was suspended. She spent most days in bed, too fatigued to carry out even simple tasks. Her weight dropped to 84 pounds (normally in the low 90s). Some days were better than others, but all were worse than any day before she started treatment. She has had peripheral neuropathy (presumably from the Velcade) and debilitating leg pain (also probably from the Velcade). Overall quality of life is much lower than before treatment began. Lack of food and sleep have taken their toll.

She had a followup PET scan last week. All 6 soft tissue masses had "resolved" -- no elevated SUV anywhere. So, even though the CyBorD treatment was brief, it was very effective (and very taxing). No more anemia, kidney function normal. SPEP is still in process, so we don't yet know how the M-spike was affected by the treatment.

Because of the unexpectedly good response of the disease to treatment, and the unfortunately serious side effects, the decision was made to adopt a "watchful waiting" approach with monthly monitoring, to allow my mom to recover from the chemo and (hopefully) enjoy some disease-free time. She is taking low-dose (2.5mg) oxycodone for the pain, which has been effective. She may try gabapentin to treat the neuropathy. Her appetite is slowly returning, so we are optimistic that her strength will return, as well.