[TomNYC]

MGUS Diagnosis?

by TomNYC on Thu Sep 05, 2013 11:33 am

I am new to the forum and understand it is not a replacement for medical advice, but in short, here is my story: About a month ago I was experiencing some strange sensations in my left arm and ended up seeing a Neurologist, who gave me an EMG which came back with mild neuropathy in lower extremities (and mild carpal tunnel), but also ran a series of blood/urine tests, including ESR, ANA, LYME, CBC CDIFF, Chem 10, TSH, RPR, B12/6, Celiac, LFTS, Hep Panel, SPEP/UPEP, h6a1c. All tests came back within normal range except my UPEP, which read "Urine Protein Electrophoresis reveals a slight restriction that may indicate the presence of a monoclonal immunoglobulin. Suggest urine immunofixation if clinically indicated." I also got an MRI of the brain and cervical spine, head fine, cervical spine had some small bulges and spurs, but they said nothing out of the ordinary.
Based on the UPEP findings, I then went to a hematologist who repeated spep/upep, (Spep normal again, UPEP had same fractions message "slight restriction" as the first one), immunofixation serum (no monoclonal proteins detected), Immunofixation Urine (no monoclonal proteins detected). IGG and IGA Serum were normal, but IGM was slightly low (44 on a range of 48-271). Free Kappa Serum was normal (9.8). CBC and all other tests appeared normal, although total urine protein was a little bit high. I also got bone density test which appeared normal, and skeletal survey demonstrated diffuse osteopenia but no lytic or blastic lesions, paraspinous soft tissues unremarkable, degenerative changes of cervical spine noted. lungs clear and costophrenic angles sharp. I should also mention that I am 49 and I believe I have only one kidney.
The hemotologist told me yesterday that I have MGUS. I do not understand this DX because subsequent urine and serum immunofixation reveals no monoclonal protein. Does this sound right? How can a MGUS dx be made when there is no evidence of an M-Protein? He felt that the upep restriction in and of itself was enough to dx MGUS.
Finally, I should also mention that I extremely panicked and have no idea what to do. I called an old GP friend of mine and he suggested that I get a 24 hr urine test because he felt there may be some renal impairment of some kind (although CBC blood work was fine for renal). He was suspect of the MGUS dx. I live in NYC and am in the process of setting up an appointment with one of the Myeloma specialists here in town.
Any advice or thoughts gratefully appreciated.
Thanks very much.
Tom

[Dr. Ken Shain]

Re: MGUS Diagnosis?

by Dr. Ken Shain on Sat Sep 07, 2013 9:47 am

The most critical thing is to get to myeloma center of excellence as you stated. MGUS - or monoclonal gammopathy of the undetermined significance - is defined by the presence of a small clonal population of plasma cells in you bone marrow (<10%) and the presence of a quantifiable monoclonal paraprotein (e.g. s M-spike <3gm) and the absence of end organ damage (typically CRAB-I: hyperCalcemia, Renal (kidney) failure, Anemia, Boney lytic lesions, and serious Infections). It does not sound as though you have had a bone marrow biopsy to date.

Neuropathy, although not classically part of the CRAB criteria, is not an uncommon presentation of monoclonal gammopathies. As part of the work up for neuropathies neurologists will frequently order a serological work-up for MGUS or multiple myeloma as ~10% of cryptic neuropathies may be associated with MGUS. As "MGUS with neurological significance" does occur- most frequently associated with IgM, but IgG, igA, IgD, IgE, and light chain (kappa or lambda) can also occur. These are associated with the production or destruction of myelin and specific antibodies (anti-MAG anti- SGPG, Anti GM1, anti-GB1).

The big questions in MGUS with associated neuropathies are: 1) are they truly associated events or parallel events? 2) At what point do you consider therapeutic intervention (risk/benefit of symptoms vs side effects)? The major concerns have to revolve around the degree of neuropathy and the long term risk of progression to myeloma or other B cell malignancies (Waldenstrom Marcoglobulinemia, CLL, ...). Rate of transformation is ~1% per year.

In your case - It is also important to note that neuropathy can be associated with transient reactive elevations in paraproteins that may disappear-not likely related to MGUS and therefore another issue. However, continued monitoring and work-up will be important - with a myeloma expert and neurologist as you have planned.

Best of luck

[TomNYC]

Re: MGUS Diagnosis?

by TomNYC on Sat Sep 07, 2013 2:29 pm

Dear Doctor, thank you for your thoughtful response. Between my initial post and your response, (and while waiting for an available appointment at the myeloma center for excellence), I was able to identify a very competent Hemotologist who has been helpful, and is encouraged by the negative urine immunofixation, however it should be noted that both UPEP tests I've taken were administered from a single urine sample and not a 24 hour collection. The new Hemotologist has ordered the 24 collection (and more blood work), so perhaps that will yield more information. She was, in general, encouraging of what she sees so far, and this has at least been helpful for my spirit during this extremely confusing time.
As far as the neuropathy goes, it really doesn't bother me at the present time, in fact I didn't even know I had it. Perhaps that will change over time and decisions regarding treatment will need to be addressed, but for now I'm all set.
Thanks again.
Tom

[Dr. Ken Shain]

Re: MGUS Diagnosis?

by Dr. Ken Shain on Sun Sep 08, 2013 9:08 am

Good to hear. And you are correct. Spot urine tests do not provide the appropriate amount of information for a case such as yours.