Plasma cell neoplasms and related entities—evolution in diagnosis and classification

Abstract

Plasma cell neoplasms including multiple myeloma (MM) and related terminally differentiated B-cell neoplasms are characterized by secretion of monoclonal immunoglobulin and stepwise development from a preneoplastic clonal B and/or plasma cell proliferation called monoclonal gammopathy of undetermined significance (MGUS). Diagnosis of these disorders requires integration of clinical, laboratory, and morphological features. While their classification mostly remains unchanged compared to the revised 2016 WHO classification and the 2014 International Myeloma Working Group consensus, some changes in criteria and terminology were proposed in the 2022 International Consensus Classification (ICC) of mature lymphoid neoplasms. MGUS of IgM type is now divided into IgM MGUS of plasma cell type, precursor to the rare IgM MM and characterized by MM-type cytogenetics, lack of clonal B-cells and absence of MYD88 mutation, and IgM MGUS, NOS including the remaining cases. Primary cold agglutinin disease is recognized as a new entity. MM is now formally subdivided into cytogenetic groups, recognizing the importance of genetics for clinical features and prognosis. MM with recurrent genetic abnormalities includes MM with CCND family translocations, MM with MAF family translocations, MM with NSD2 translocation, and MM with hyperdiploidy, with the remaining cases classified as MM, NOS. For diagnosis of localized plasma cell tumors, solitary plasmacytoma of bone, and primary extraosseous plasmacytoma, the importance of excluding minimal bone marrow infiltration by flow cytometry is emphasized. Primary systemic amyloidosis is renamed immunoglobulin light chain amyloidosis (AL), and a localized AL amyloidosis is recognized as a distinct entity. This review summarizes the updates on plasma cell neoplasms and related entities proposed in the 2022 ICC. Key points • Lymphoplasmacytic lymphoma can be diagnosed with lymphoplasmacytic aggregates in trephine biopsies < 10% of cellularity and evidence of clonal B-cells and plasma cells. • IgM MGUS is subdivided into a plasma cell type and a not otherwise specified (NOS) type. • Primary cold agglutinin disease is recognized as a new entity. • The term “multiple myeloma” replaces the term “plasma cell myeloma” used in the 2016 WHO classification. • Multiple myeloma is subdivided into 4 mutually exclusive cytogenetic groups and MM NOS. • Minimal bone marrow infiltration detected by flow cytometry is of major prognostic importance for solitary plasmacytoma of bone and to a lesser extent for primary extraosseous plasmacytoma. • Localized IG light chain amyloidosis is recognized as a separate entity, distinct from systemic immunoglobulin light chain (AL) amyloidosis.

Systemic AL amyloidosis: current approach and future direction

“…Localized AL amyloidosis is not treated by systemic therapy since the long-term prognosis is favorable, and not complicated with systemic AL amyloidosis and is generally managed by local resection [ 18 ]. While a monoclonal gammopathy of unknown significance (MGUS) may develop to systemic amyloidosis or multiple myeloma with an average rate of transformation of 1% per year [ 19 , 20 ], finding of AL amyloidosis in bone marrow is not an indication for systemic treatment in the absence of the organ involvement. This approach is also true in smoldering multiple myeloma with a higher risk of transformation to multiple myeloma of 10% per year [ 20 ].…”

“…While a monoclonal gammopathy of unknown significance (MGUS) may develop to systemic amyloidosis or multiple myeloma with an average rate of transformation of 1% per year [ 19 , 20 ], finding of AL amyloidosis in bone marrow is not an indication for systemic treatment in the absence of the organ involvement. This approach is also true in smoldering multiple myeloma with a higher risk of transformation to multiple myeloma of 10% per year [ 20 ]. In terms of making decision regarding systemic treatment in AL amyloidosis, the provider needs to account the patient’s overall performance status, level of organ dysfunction, and whether the patient is a candidate for HCT [ 21 ].…”

Diagnostic and prognostic molecular pathology of lymphoid malignancies

“…Due to the prognostic impact of genetic alterations, the ICC has formally divided MM into cytogenetic subgroups [ 12 ]. Mutational profiling currently is not of diagnostic relevance outside of clinical studies, but an absence of MYD88 mutations helps to exclude LPL [ 27 ].…”

Renal Riddles Unveiled: Decoding Homogeneous Kidney Enlargement in Multiple Myeloma

“…Multiple myeloma (MM) was once considered a distinct disease but is now recognized as part of a spectrum of plasma cell neoplasms (PCN) [ 1 , 2 ]. PCN involves uncontrolled proliferation of mature B-cells and plasma cells, leading to various symptoms [ 1 ].…”

“…PCN involves uncontrolled proliferation of mature B-cells and plasma cells, leading to various symptoms [ 1 ]. According to the 2022 International Consensus Classification (ICC), PCN includes MM, plasmacytoma, abnormal immunoglobulin deposition diseases, and non-immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) [ 2 ]. Extramedullary plasmacytoma (EMP) can coexist with MM or occur independently [ 3 ].…”