mGODS - Monoclonal Gammopathies Of Dermatological Significance

• 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.

Pre-Lecture Questions

CASE 1

• 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.

Additional Pre-Lecture Questions

Plasma Cell Dyscrasias

Overview

• 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

Detection and Identification of Monoclonal Proteins

Overview

• 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
  • 94% sensitivity for all plasma cell dyscrasias⁵
    
  • SPEP + FLC + IFE
    • 97% sensitivity
      • The disease where IFE may provide the most additive sensitivity is LCDD and POEMS
        
  • SPEP + FLC + IFE + UIFE
    • 98.6% sensitive (thus adding urine adds about 1.6% sensitivity)
      
  • SPEP
    • Allows for quantification of the M-protein (i.e. serum concentration)
      
    • Does not identify class of Ig or light chain component
      
    • About 79% sensitive for detecting all comers
      
  • IFE
    • More sensitive than SPEP in detection M proteins
      
    • Does not allow for serum concentration of M-protein
      
    • Thus always done in conjunction with SPEP
      
    • Is usually reflexed when M-protein detected; however, not always done, so if don’t order it and all you
      
    • About 87% sensitive for detecting all comers

References