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  • Immune deposits are considered monotypic if they display light chain restriction.

  • Heavy chain restriction without light chain restriction is not considered monotypic as several polyclonal diseases can have heavy chain isotype restriction.

  • C3 glomerulonephritis and thrombotic microangiopathy do not have immunoglobulin deposits but can be due to monoclonal gammopathy.

  • Immunofluorescence (IF) on paraffin tissue after protease digestion should be performed on all cases of C3 glomerulonephritis with monoclonal gammopathy to look for masked immunoglobulin deposits.

  • All amyloidosis cases should undergo tissue typing prior to initiation of chemotherapy.




General Considerations


Plasma cell dyscrasias are diseases or conditions secondary to clonal proliferation of plasma cells. These conditions are typically characterized by the overproduction of a monoclonal protein causing a monoclonal gammopathy. Plasma cell dyscrasias are categorized by their clonal burden and end organ damage. Classically, the categories are monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and symptomatic multiple myeloma (MM). Patients with MGUS have less than 10% bone marrow clonal plasma cells and less than 3 g/dL of monoclonal (M) protein in the serum. By definition, no end organ damage can be present as a result of the plasma cell dyscrasia. SMM is characterized by more than 10% bone marrow clonal plasma cells or more than 3 g/dL of M-protein also without end organ damage. MM is defined by the presence of end organ damage in someone who meets the criteria for SMM. End organ damage has been represented by the mnemonic CRAB (hyperCalcemia, Renal impairment, Anemia, and Bone lesions). Recently, three additional diagnostic criteria were added to the definition of MM. They are an involved to uninvolved free light chain (FLC) ratio more than 100 with the involved FLC having a level of more than 10 mg/dL, bone marrow plasma cells more than 60% and more than 1 focal boney lesion on MRI. However, it has been increasingly appreciated that the kidney can be injured without meeting the criteria for MM. Since treatment is currently only recommended for patients with MM, a conflict is created by these patients. To resolve the conflict, the term monoclonal gammopathy of renal significance (MGRS) was created. MGRS encompasses all B-cell/plasma cell proliferative disorders that do not meet criteria for MM or malignant lymphoma but are associated with a kidney disease. These clones usually have lower proliferative rates and behave more like MGUS than MM. However, they produce a nephrotoxic M-protein which differentiates them from MGUS. Kidney diseases associated with plasma cell dyscrasias are the focus of this discussion. It is important to note that these diseases are not exclusive to plasma cell clones. Kidney diseases can arise from any clone producing a nephrotoxic M-protein.



Kyle  RA  et al: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives ...

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