Table 2.

Consensus recommendations for the evaluation of MGRS-associated disorders

Modality	Recommendations	Refs
Kidney biopsy	Recommended in the following patients: • Those with monoclonal gammopathy and unexplained kidney disease • Those with known risk factors for chronic kidney disease but an atypical clinical course • Patients with kidney disease and monoclonal gammopathy aged <50 years	NA
Protease immunofluorescence on kidney biopsy	Recommended in the following scenarios: • When glomeruli are lacking in frozen tissue samples • In patients with suspected LCPT and other forms of crystalline nephropathies, such as CSH and crystalglobulin-induced nephropathy • In patients with a monoclonal gammopathy in whom kidney biopsy samples show C3 glomerulonephritis or unclassified proliferative glomerulonephritis in the context of negative findings by immunofluorescence on frozen tissue samples (including in patients with features of cryoglobulinaemic glomerulonephritis on light or electron microscopy) • In patients with fibrillary glomerulonephritis who have apparent light-chain restriction detected by immunofluorescence on frozen tissue	NA
Renal amyloid typing by liquid chromatography and mass spectrometry	Recommended in the following situations: • When frozen tissue for immunofluorescence is not available • Negative immunofluorescence staining for κ and λ light chains, with negative immunoperoxidase staining for SAA and LECT2 • Equal staining for κ and λ light chains by immunofluorescence • Bright staining for IgG and/or IgA by immunofluorescence • Equivocal Congo red staining • To enable distinction between AHL amyloidosis and congophilic fibrillary glomerulonephritis	108
Flow cytometry or other immunotyping	• Neoplastic plasma cells frequently show aberrant loss of CD45 and CD19, as well as aberrant expression of CD56 and CD117; therefore, these markers (in addition to κ and λ light chains and CD38) are useful in identifying small plasma cell clones • Including CD5 and CD20 in the immunophenotyping of B cells can frequently separate small clones from polytypic cells • The most sensitive assay available at a given institution should be used. Although there is no established gold standard, many laboratories have the capability to determine minimal residual disease in MGRS at a sensitivity of 10−4 to 10−6 monoclonal cells. The sensitivity of flow cytometry immunophenotyping depends on the total number of collected cells, the number of antibodies used to find an aberrant phenotype, the phenotype of the abnormal clone and sample quality	118
Immunohistochemistry	• Immunohistochemistry of bone marrow biopsy samples has a low sensitivity for detecting κ-expressing and λ-expressing plasma cells and could be useful only if there is a major plasma cell clone and a lack of polyclonal plasma cells • Immunohistochemistry might be useful in the evaluation of atypical lymphoid infiltrates, particularly if flow cytometry is not available or infiltrates are very focal • If an abnormal clone is detected, the light-chain isotype should be compared with that present in renal lesions and additional information should be obtained	NA
Mutational analysis	The MYD88 L265P mutation is found in over 90% of patients with lymphoplasmacytic lymphoma or Waldenström macroglobulinaemia but in only 40–60% of individuals with IgM MGUS	119–121
FISH	Cyclin D1 FISH with immunostaining for CD10, BCL2 and BCL6 to subclassify diffuse large cell lymphoma, and prognostic FISH panels for MM and CLL, can also be useful	119–121

AHL, immunoglobulin A heavy-and-light chain; CLL, chronic lymphocytic leukaemia; CSH, crystal-storing histiocytosis; FISH, fluorescence in situ hybridization; LCPT, light-chain proximal tubulopathy; LECT2, leukocyte cell-derived chemotaxin 2; MGRS, monoclonal gammopathy of renal significance; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; NA, not applicable; SAA, serum amyloid A protein.