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Andrew Sanchez M.D.

17 تغريدة 39 قراءة Aug 18, 2022

💥 Monoclonal Gammopathies of Clinical Significance! 💥
Everyone knows MGUS.
Monoclonal proteins are simply blameless protein markers until clonal B-cells progress to Myeloma, Waldenstrom's, or another disorder, right?
...It turns out, not quite!
Let's explore!

First, some review. Where does monoclonal protein come from?
- Clonal B-cells 👉 Monoclonal protein secretion
- Such protein is also called "M-protein" or "Paraprotein"
Ref: @cullen_lilley

Secreted M-protein can be one of several protein types related to the immunoglobulin (Ig) structure:
🟢Heavy & Light chain (ie intact Ig)
🟢Light chain (eg AL amyloidosis)
🟢Heavy chain (eg Heavy chain disease)

🔬M-protein is traditionally detected by SPEP & Serum Immunofixation, but light chains may be missed by these modalities given low concentration & molecular weight
🔬Therefore, a full gammopathy work-up requires measurement of serum/urine free light chains
Ref: @cullen_lilley

🐴 When M-protein is blameless, patients w/ M-protein (<3 g/dL) are labeled as having MGUS
🦓 However, patients w/ M-protein + unexplained symptoms may actually harbor disease!
🦓 In these patients, disease may be due to M-protein, the B-cell clone itself, or another mechanism

The spectrum of diseases that encompasses patients w/ M-protein + related symptoms was defined as "Monoclonal
Gammopathies of CLINICAL Significance" (MGCS).
The clinical manifestations of these diseases can be widespread & profound! See below!

The DDx of MGCS was elegantly described in a review published by @ADispenzieri, where the diseases are grouped by the center-of-gravity of their presentations.
In other words, there are:
- Neurologic-centered diseases
- Cutaneous-centered diseases
- Renal-centered diseases

Renal-centered diseases are complex and well-described in a recent @NEJM review on "Monoclonal Gammopathies of Renal Significance."
For more on those diseases (organized by pattern of Ig deposits on histopathology), check out their review:
nejm.org

nejm.org/doi/10.1056/NE…

Monoclonal Gammopathy of Renal Significance | NEJM

Review Article from The New England Journal of Medicine — Monoclonal Gammopathy of Renal Significanc...

Now, let's run through some abbreviated illness scripts from the other buckets!

Neurologic-centered diseases that additionally have systemic features:
🟣 POEMS
🟣 AL amyloidosis
🟣 Cryoglobulinemia

Neurologic-centered diseases w/o systemic features:
🟣 CANOMAD
🟣 DADS-M
🟣 Sporadic, late-onset nemaline myopathy

Cutaneous-centered diseases:
🟤 Scleromyxedema
🟤 Necrobiotic xanthogranuloma
🟤 Schnitzler syndrome
🟤 TEMPI

One more cutaneous-centered disease:
🟤 Systemic capillary leak syndrome

🏁 That's it for my overview of MGCS!
🏁 Note: I am not a hematologist! This was a markedly simplified approach summarized via @ADispenzieri's review article & my sporadic reading (see references below)