In this lecture we review mGODS: Monoclonal Gammopathies of Dermatological Significance1, an umbrella term that captures diseases such as Cutaneous Amyloidoses, Scleromyxedema, Acquired Cutis Laxa, Mixed Cryoglobulinemia, Nodular Amyloidoses, PEOMS syndrome, Necrobiotic Xanthogranuloma, Schnitzler’s Syndrome etc.
Specifically we will:
Provide an overview of plasma cell dyscrasias
Introduce the concept of mGODS
Review techniques to detect and identify monoclonal proteins
Review how to work up paraproteins
Provide an overview of MGUS
Here, we provide a primer for that lecture. We start with a clinical case and some discrete questions so that you can think through them ahead of the lecture. We will go through these as a group on Thursday.
Ms. S is a 82-year-old who presents for follow up for “Pruritus Without Rash”. She has been seen by two of your colleagues before, but this is the first time you are seeing her. The initial “Pruritus Without Rash” work up was notable for a normal CBC with Diff, CMP, TSH and CXR. Given that this initial work up was non-diagnostic, a second round of investigation was performed and was notable for the following: Serum iron WNL; ferritin WNL; skin biopsy not diagnostic, DIF negative; SPEP demonstrated abnormal band in gamma region, identified by IFE as IgG Kappa, and represents by densitometry 10% (730 mg/dL) of total protein.
Case 1 Clinical Questions:
What does this part of the work up mean?
SPEP demonstrated abnormal band in gamma region
Identified by IFE as IgG Kappa
Represents by densitometry 10% (730 mg/dL) of total protein
What are you next steps in management?
While referral to hematology is never the wrong answer, if you wanted to pursue additional work up, what would be your next steps?
Plasma cell dyscrasia (PCD) is a term used to describe a constellation of pathology of plasma cells
Subsets of PCDs range from Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma
To understand PCDs, it is important to have a basic understanding of plasma cell development. In the figure below we outline some of those major developmental steps
Plasma Cell Development
Monoclonal Gammapathies
Monoclonal gammopathies are the most common form of plasma cell dyscrasia2
Monoclonal gammopathies were first described as a clinical entity in 1960 by Jan Gosta Waldenstrom3
Monoclonal Gammopathy of Undetermined Significance (MGUS) was introduced in 1978 by Kyle et al.4
MGUS is a clonal plasma cell or lymphoplasmacytic proliferative disorder which presents without symptoms and is considered a premalignant process
Diagnosis is made by the presence of the following features:
Detection of a low-level M-protein (<3 g/dL)
An M-protein is a serum Monclonal protein
Less than 10% monoclonal plasma cells on bone marrow biopsy
No end organ damage resulting from the monoclonal process
For example the absence of lytic bone lesions, anemia, hypercalcemia, renal insufficiency or hyperviscosity
MGUS is fairly common and occurs in over 3 percent of the general Caucasian population over the age of 50
More specifically, the prevalence is 1% over age 50 & 3% over age 70
Assuming you are starting with just an M-spike, the following steps is a very reasonable work up:
Step 1 – Interrogate the Monoclonal Protein
Step 2 – Assess for End Organ Dysfunction
Step 3 – Decide if the patient needs a BMBx
Step 4 – Decide Follow Up Interval
In the lecture we will go into the details of each of these four steps, but below we list the take home points for Step 1
Take Home Points on Interrogating the Monoclonal Protein
The most common diagnostic tools to work up monocloncal proteins involves the use of serum protein electropheresis (SPEP), free light chain (FLC) assays and immunofixation (IFE)
For the vast majority of patients, SPEP and FLC is probably sufficient for screening for most plasma cell dyscrasias