1.LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115. EB, MHZG: these authors contribute equally. email@example.com; firstname.lastname@example.org; email@example.com
Plasma Cell Neoplasms are a family of disorders characterized by clonal proliferation of a plasma cell. These include: Multiple Myeloma (MM) and its precursor states MGUS and SMM, solitary osseous or non-osseous plasmacytoma, POEMS syndrome, heavy chain disease, and systemic AL amyloidosis. The hallmark characteristics of plasma cell neoplasms are: (1) histopathologic confirmation of excess clonal plasma cells; and (2) excessive production and secretion of an intact monoclonal protein (M spike) or free light chains (FLC; not in association with heavy chains) in the serum and/or urines. Plasma cell neoplasms can be premalignant (e.g. MGUS) or malignant (e.g. MM).
Transformation of normal plasma cells into myeloma cells thought to result from one of two primary genetic events: either (1) hyperdiploidy or (2) aberrant class switch recombination (CSR). Secondary cytogenetic abnormalities result in progression of MGUS to SMM, MM, and plasma cell leukemia (Ho et al, 2017).
Similar to MM in that cell of origin is plasma cell; expresses antigens associated with myelomonocytes (CD33), megakaryocytes (GpIIb/IIIa), erythroid cells (glycophorin) (Nikhil Sangle, 2011).
Deletions, insertions or point mutations in the constant 1 (CH1) domain of the IgH are acquired during the process of somatic hypermutation. These mutations typically result in: (1) inability to bind and reach a stable quaternary structure with IgL chain; (2) inability to bind to the chaperone heat shock protein 78 (HSP 78), which mediates proteasomal degradation of free IgH (Goossens et al., 1998). As a result, free IgH can be detected in both serum and urine. Pathogenesis is unknown. Autoimmune disease is present in ~25% of patients and typically precedes by many years the onset of gamma HCD (Wahner-Roedler et al., 2003).
Etiology unknown. Major feature of POEMS syndrome is the chronic overproduction of pro-inflammatory cytokines (e.g. VEGF; IL6). Thought to be a paraneoplastic syndrome caused by an underlying plasma cell disorder (Zou et al 2015).
Matthew Ho Zhi Guang ; Giada Bianchi ; Elijah Buon
Plasma Cell Neoplasms: an overview
Atlas Genet Cytogenet Oncol Haematol. 2017-11-01
Online version: http://atlasgeneticsoncology.org/haematological/1793/plasma-cell-neoplasms-an-overview