myeloma smear What is an M spike?

Q. Here’s a question from Twitter: Can you explain to me what the M protein in multiple myeloma is?

A. Multiple myeloma is a malignant, clonal disorder of plasma cells that originates in the bone marrow. It’s a relatively common disorder, accounting for 1% of all malignancies and 10% of all hematologic malignancies in adults. Patients present with painful, lytic lesions of the bones, recurrent and persistent infections, weakness, renal failure, and hypercalcemia. The prognosis is generally not great, but new chemotherapeutic agents seem to hold some promise.

Patients with myeloma have a monoclonal proliferation of plasma cells in the bone marrow, meaning that there are a ton of malignant plasma cells that all originated from the same initial cell. In the bone marrow aspirate above, you can see tons of malignant plasma cells. A few look a lot like plasma cells, with clock-face chromatin and a hof and everything, but others look for all the world like blasts. That’s one thing to remember about myeloma – malignant plasma cells don’t always resemble their nice little benign counterparts.

The malignant plasma cells almost always secrete immunoglobulin, and because they are monoclonal, they all secrete exactly the same form of immunoglobulin. This is very different than what you see in a patient without myeloma, where there are a bazillion different types of plasma cells, all making different types of immunoglobulin molecules.  This huge  mass of all-the-same immunoglobulin secreted by myeloma cells is called a “monoclonal gammopathy;” the normal immunoglobulins are called “polyclonal.”

Monoclonal gammopathy is so characteristic of myeloma that you can use it for both diagnosis of disease and follow-up of patients. You can detect the monoclonal immunoglobulin using serum electrophoresis (which separates the blood proteins into groups based on charge and size).  There’s a predictable pattern of proteins in normal serum: albumin (the most abundant protein in the blood) migrates to a certain predictable point; other proteins migrate to different places (which are given different names – the alpha 1 region, the alpha 2 region and the beta region). Immunoglobulins migrate to a unique place called the gamma region, and because they are all different (in normal patients), they migrate to slightly different places within that region, giving a gentle bell-shaped curve or smear (depending on whether you’re looking at a tracing or the actual bands on the gel). In myeloma, the immunoglobulin is monoclonal, so it all migrates to exactly the same spot on the gel! Which gives you a big spike (if you’re looking at a tracing) or a very distinct, crisp, strong band (if you’re looking at the gel itself). This spike is called an M-spike (you could remember M for either monoclonal or myeloma), and the corresponding monoclonal protein that it represents is called an M protein.

A few other things to note about this M protein:

1. You need to do electrophoresis on urine too, not just serum. Some cases of myeloma secrete only light chains (these are called Bence-Jones proteins), which are so small that they are passed in the urine (so if you only looked at the blood, you’d miss them).

2. While patients with myeloma have an increase in the total amount of immunoglobulin present in the blood (due to the large monoclonal immunoglobulin spike), they also have a decreased amount of normal, polyclonal immunoglobulins. So when you look at an electrophoresis, you’ll see this huge spike in the gamma region, but also a noticeable depression in the amount of the background normal immunoglobulins.

3. A little trivia regarding the kinds of immunoglobulin expressed by myeloma cells. The most common heavy chain expressed in myeloma is IgG (60%); next is IgA (20%). Rare cases express IgD or IgE, and IgM myeloma is virtually nonexistent (most cases of plasma cell lesions that express IgM turn out to be Waldenström macroglobulinemia). Almost one-fifth of all cases of  myeloma secrete only light chains. And somewhere between 1 and 5% of all cases of myeloma secrete no detectable immunoglobulin at all! Which, without the familiar M-spike, would make for a pretty difficult diagnosis.

66 Responses to What is an M-spike?

  1. Lebon Rex says:

    Thank you Kristine. Lebon

  2. suzierose says:

    That you Kristine!

    Clear, concise explanation…

  3. Peter Jhim says:

    Thanks, helped alot.

  4. varam says:

    Sub epithelial deposits along with m spikes are seen in which renal condition…..

  5. jitender says:

    If M spike is only in Serum test but Not in Urine Test, what does it mean?

  6. Kristine says:

    It means that the monoclonal immunoglobulin is in a form that cannot be excreted by the kidney (which is the case for most immunoglobulins!). Light chains, by the way, are easily excreted in the urine (they’re called Bence-Jones proteins) – so if you have a myeloma that just secretes light chains, you’d have a monoclonal immunoglobulin in the urine, but not in the blood. This is one of the main reasons we always order both a serum and a urine electrophoresis.

  7. Eve says:

    I have been taking a small amount of frankincense each day for the last six months, an essential oil. My m-spike went from 1.2 six months ago to .6 last week.

  8. uttam bhatta says:

    that really helped in touching the basics
    thanks a lot!
    b blessed

  9. Lee says:

    Hi,

    I just received a call from my doctor who on a routine blood test found that I have M spikes of 0.08. He has suggested I see an oncologist immediately. I have an appointment on December 1st.

    I’ve been reading all these sites, and I now realize that although having an M spike of any number is abnormal, does it always indicate a cancerous or dangerous disease. Are there any other reasons for having it?

    I have had a torn rotator cuff for a year now, and the second surgeon has decided it should be operated on. As I will be in a sling for a month, I’ve decided to wait until Spring. I was wondering if having an inflammation in ones system for a year, as I have with my torn rotator cuff, could it cause this type of response on my blood test?

    If one has an M spike does it always mean cancer? Please advise. Thank you.

    Lee

  10. Kristine says:

    Hi Lee –
    No – an M spike does NOT always mean cancer. Many people develop something called monoclonal gammopathy of undetermined significance (MGUS) which is a benign condition in which you have a small M spike. This occurs with greater frequency in older patients. Sometimes MGUS develops into myeloma (or another malignant disease) but most of the time it does not. Having a large M spike (over 3) does tend to go along with malignancy – but yours is so low that I doubt it indicates myeloma. It would still be a good idea to have it investigated just to be sure – and then to follow the spike to make sure it doesn’t go up. In answer to your second question, no – having a lot of inflammation would not lead to an M spike. Let me know if you have other questions!

  11. Dr. Rajendra Modi says:

    Hi,
    I have been suffering from Multiple Myeloma for the last two and a half years. my M band was 5gm/dL and after taking chemo(Bartezomib) for six months the M band disappeared completely and it remained like that for around a year. now again this time, when the SPEP was done M band is raising its head, as the reports show 200mg/dL M band. Does it mean that Myeloma is coming back? If yes when should I go for chemo again? and shall I be given the same salt i.e. Bartezomib or some other salt has come into the market? I am a general surgeon living in India.I request you to kindly guide me.
    thanks in anticipation.

  12. Kristine says:

    Hi Dr. Modi –
    I wish I could give you a good answer but your question would be better directed to someone who practices clinical hematology. I know about the pathology part – but the clinical treatment of myeloma, like many hematologic diseases, is constantly changing – and it would be important to get an opinion from someone who practices in the field. Best of luck!

    Kristine

  13. I Apologize if ths gets printed twice not sure first time went,i recently got blood test back shows 0.4 M spike, Iron saturation low 14 and Immoglobin e 136 . I have a follow up with Hem. in 2 weeks but would like to prepare my self scared to death I may have multiple mel. My daughter a nurse said my spike is very low. Wondering if I will need treatment etc.?

  14. Kristine says:

    Hi Linda –
    Your M spike is indeed very low. Usually such a low spike is not of concern for myeloma (in myeloma, the magnitude is usually above 3.0 g/dL). I would try not to worry (easier said than done, I know!) – and see what the hematologist recommends. He/she will likely simply want to follow you with periodic checks to make sure it isn’t creeping up. Many people develop a monoclonal spike as they get older – and when it is so small, it usually is not ominous at all. The iron saturation will need to be investigated too – most likely that is a totally separate issue. You’d want to also get a serum iron and a ferritin level to sort out the different types of anemia that have iron abnormalities (iron-deficiency anemia and anemia of chronic disease are the two main ones). Best of luck! Let us know how it goes :)

  15. Mary Stamm says:

    I donate at Biolife Plasma and they have detected an M spike. (really SMALL) that has always been the same since donating for over 3 years. Now it’s an issue. Anything I should be worried about? The nurse said just a tiny edge up in my curve. ???

  16. Kristine says:

    Hi Mary – I would not worry too much about it. Many people develop a small M spike as they age – and most of the time it doesn’t turn into anything dangerous. You may wish to see a doctor to be evaluated and to get exact numbers for the M spike. Most likely they will just want to follow you periodically to make sure it doesn’t rise precipitously. Best of luck!

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