Genetic alterations in chronic lymphocytic leukemia and plasma cell neoplasms - a practical guide to WHO HAEM5.

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) provides a revised classification of lymphoid malignancies including chronic lymphocytic leukemia (CLL) and plasma cell myeloma/multiple myeloma (PCM/MM). For both diseases the descriptions of precursor states such as monoclonal B-cell lymphocytosis and monoclonal gammopathy of uncertain significance (MGUS) have been updated including a better risk stratification model. New insights on mutational landscapes and branching evolutionary pattern were embedded as diagnostic and prognostic factors, accompanied by a revised structure for the chapter of plasma cell neoplasms. Thus, the WHO-HAEM5 leads to practical improvements of biological and clinical relevance for pathologists, clinicians, geneticists and scientists in the field of lymphoid malignancies. The present review gives an overview on the landscape of genetic alterations in CLL and plasma cell neoplasms with a focus on their impact on classification and treatment.

Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021).

The emergence of novel drugs has significantly improved outcomes of patients with plasma cell neoplasms (PCN). The Japanese Society of Hematology conducted a prospective observational study in newly diagnosed PCN patients between 2016 and 2021. The analysis focused on 1385 patients diagnosed with symptomatic PCN between 2016 and 2018. The primary endpoint was the 3-year overall survival (OS) rate among patients requiring treatment (n = 1284), which was 70.0% (95%CI 67.4-72.6%). Approximately 94% of these patients received novel drugs as frontline therapy. The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients who received upfront autologous stem cell transplantation (ASCT), versus just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT. The only unfavorable prognostic factor that affected OS in ASCT recipients was an age of 65 or higher. For patients who did not receive ASCT, independent unfavorable prognostic factors included frontline treatment with conventional chemotherapies, international staging system score of 2/3, extramedullary tumors, and Freiberg comorbidity index of 2/3. This study unequivocally demonstrates that use of novel drugs improved OS in Japanese myeloma patients, and underscores the continued importance of upfront ASCT as the standard of care in the era of novel drugs.

Spinal Solitary Plasmacytoma With Minimal Marrow Involvement Presenting With Epidural Spinal Cord Compression.

Solitary plasmacytoma (SPC) is a rare type of plasma cell dyscrasia characterized by the proliferation of neoplastic monoclonal plasma cells. It can involve bone or soft tissue without signs of systemic disease. The solitary bone plasmacytoma typically involves the axial skeleton, most commonly the vertebrae. This article presents a 58-year-old male with a history of Parkinson's disease, hypertension, and cervical spine degenerative joint disease. He arrived at the emergency department with severe thoracic and lumbar back pain, accompanied by numbness and weakness in both legs, which worsened with movement and deep breathing. Magnetic resonance imaging (MRI) findings revealed a sizable mass in the T11 vertebra, leading to thoracic spinal cord compression. Treatment included high-dose dexamethasone, and surgical intervention was undertaken. Subsequent pathology confirmed plasma cell dyscrasia. Radiotherapy and chemotherapy (lenalidomide and dexamethasone) were administered, resulting in no recurrence or new masses after two years. Solitary plasmacytoma is a rare disease with limited clinical trials due to the inability to accrue larger cohorts. Prompt diagnosis and staging of plasmacytomas, involving robust histopathological and radiographic methods, are needed to prevent further complications and possible progression to multiple myeloma. Radiation therapy is the primary treatment, with some studies showing the benefits of lenalidomide and dexamethasone. Further studies are needed to improve treatment options for these patients. This case report adds to the current literature the importance of a multidisciplinary approach to the treatment of SPC.

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells.

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.

Epidural Extramedullary Plasmacytoma Successfully Treated with Surgical Excision and Bortezomib, Cyclophosphamide and Dexamethasone.

Plasma cell neoplasms are common, accounting for more than 1% of all malignancies. Its most common form is multiple myeloma, but others, such as extramedullary plasmacytoma (EMP), exist. Spinal cord compression secondary to these pathologies is not uncommon, however, adjacent bone involvement is usually present. Spinal cord compression caused by isolated epidural EMP is extremely rare, with only one case reported to date. We describe the case of a 75-year-old female patient that presented with paraparesis, due to an isolated epidural EMP associated with light chain amyloidosis. She was treated with surgical decompression and neoadjuvant chemotherapy, and is currently with a 15-month disease-free period.

Pharmacological and therapeutic potentials of cordycepin in hematological malignancies.

Hematological malignancies(HMs) are highly heterogeneous diseases with globally rising incidence. Despite major improvements in the management of HMs, conventional therapies have limited efficacy, and relapses with high mortality rates are still frequent. Cordycepin, a nucleoside analog extracted from Cordyceps species, represents a wide range of therapeutic effects, including anti-inflammatory, anti-tumor, and anti-metastatic activities. Cordycepin induces apoptosis in different subtypes of HMs by triggering adenosine receptors, death receptors, and several vital signaling pathways such as MAPK, ERK, PI3K, AKT, and GSK-3ß/ß-catenin. This review article summarizes the impact of utilizing cordycepin on HMs, and highlights its potential as a promising avenue for future cancer research based on evidence from in vitro and in vivo studies, as well as clinical trials.

Soft Tissue Mass Extramedullary Plasmacytoma Following Radiation Therapy for Solitary Bone Plasmacytoma.

Soft tissue involvement in extramedullary plasmacytoma (EMP) is an exceptionally rare occurrence within the spectrum of plasma cell neoplasms. This case report presents the unique scenario of a patient who developed a soft tissue mass EMP subsequent to receiving radiation therapy for a solitary bone plasmacytoma at a distinct anatomical site. The primary objective of this report is to elucidate the clinical characteristics, diagnostic complexities, and management considerations associated with this uncommon presentation. Through a comprehensive review of existing literature, we aim to provide valuable insights and expertise to healthcare providers involved in the assessment and treatment of similar cases.

A Case of Recurrent Multiple Myeloma as Testicular Plasmacytoma Without Systemic Disease.

Plasma cell neoplasms include various conditions ranging from indolent conditions such as monoclonal gammopathy of undetermined significance (MGUS) to more aggressive forms such as multiple myeloma (MM). The World Health Organization classifies plasmacytomas into two types: solitary osseous plasmacytoma (SOP) and extramedullary plasmacytoma (EMP). Most primary EMPs occur in the upper gastrointestinal tract, head and neck, upper respiratory system, central nervous system, lungs, liver, spleen, and kidneys. However, the occurrence of EMP involving the testis site is quite rare. Given the rarity of testicular plasmacytoma, there is no consensus on the standard of treatment for this diagnosis. Most EMP is radiosensitive, with few localized types responding to surgical intervention. Tumor recurrence and disseminated infiltration are treated with adjuvant chemotherapy after radiation or surgery. Our patient has a unique presentation of an individual who developed recurrent myeloma of the testis 12 years after his initial diagnosis of myeloma.

POEMS syndrome: origination from clonal plasma cells or B cells?

OBJECTIVES: POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome. METHODS: A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered. RESULTS: After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal. DISCUSSION: POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome. CONCLUSION: We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies.

Plasma cell neoplasms and related entities-evolution in diagnosis and classification.

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.

Renal Riddles Unveiled: Decoding Homogeneous Kidney Enlargement in Multiple Myeloma.

Renal plasmacytoma is a rare extramedullary manifestation of plasma cell neoplasms (PCN). We present the case of a 62-year-old male with a history of relapsed refractory multiple myeloma (MM) who developed secondary renal plasmacytoma after an eight-year remission period. Radiological findings on plain CT raised concern for the most common renal malignancy, i.e. renal cell carcinoma (RCC), while further imagining evaluation with MRI suggested renal lymphoma, highlighting the diagnostic challenge of renal plasmacytoma on imagining. A renal mass biopsy confirmed a kappa-restricted plasma cell tumor, emphasizing the need for accurate differentiation between renal plasmacytoma and other renal malignancies to guide appropriate treatment strategies. Increased awareness of such cases can lead to timely recognition and tailored management for this rare entity.

Lenalidomide-induced autoimmune enteropathy complicating treatment of multiple myeloma with concurrent systemic mastocytosis.

Lenalidomide is an IMiD drug which has been associated with a variety of potential immune related complications. We describe the case of a patient with newly diagnosed multiple myeloma along with a history of systemic mastocytosis who developed evidence of an autoimmune enteropathy shortly after initiating lenalidomide based therapy.

Monoclonal Gammopathies in a Fracture Liaison Service.

Monoclonal gammopathies are a spectrum of disorders characterized by the overproduction of plasma B-cells and immunoglobulin. Monoclonal gammopathy of uncertain significance (MGUS), a pre-malignant form of multiple myeloma, is defined by relatively low bone marrow concentration of clonal plasma cells and asymptomatic clinical presentation. New evidence, however, points to an association of MGUS with osteoporosis, microarchitectural bone deficiency, and fractures, and it has been suggested that it be renamed "Monoclonal Gammopathy of Skeletal Significance." The prevalence of MGUS in the general geriatric population is estimated to be 3-8%, while the prevalence in geriatric vertebral fracture patients is 15%, and the prevalence in all fracture patients within the Rhode Island Fracture Liaison Service is 10%. Therefore, MGUS and other monoclonal gammopathies should be suspected in all patients diagnosed with osteoporosis or an osteoporotic fracture, and patients diagnosed with monoclonal gammopathies should be evaluated for osteoporosis and fracture risk and treated appropriately.

Cutaneous Involvement in Diseases with Plasma Cell Differentiation: Diagnostic Approach.

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient's work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed.

[Multiple myeloma from the pathologist's perspective]. / Multiples Myelom aus Sicht der Pathologie.

BACKGROUND: Multiple myeloma (MM) is one of the most common hematological neoplasms and accounts for approximately 1% of human cancers. OBJECTIVES: Description of current diagnostics and classification of MM and related plasma cell neoplasms from the pathology viewpoint. MATERIALS AND METHODS: Current knowledge regarding pathology and genetics of MM is summarized and tissue-based diagnostics following international consensus classifications and the current S3 guideline are described. RESULTS: MM and related neoplasms are composed of malignant plasma cells that secrete a monoclonal immunoglobulin, which is an important parameter of disease activity. MM shows a multistage development. Almost all cases are preceded by a clinically inapparent precursor lesion, monoclonal gammopathy of undetermined significance (MGUS), which can progress to smoldering myeloma with a higher tumor burden, but absence of organ damage. Systemic MM needs to be discerned from the localized forms, solitary osseous and primary extramedullary plasmacytoma. MM is genetically very heterogeneous and can be broadly subdivided into two cytogenetic groups, cases with primary IGH translocations and cases with hyperdiploidy. Intratumoral genetic heterogeneity is frequently pronounced and correlates with the size of focal lesions in imaging. CONCLUSIONS: Diagnosis of plasma cell neoplasms is done according to the criteria of the International Myeloma Working Group (IWMG) and requires interdisciplinary evaluation of clinical, serological, pathological and radiological features. In addition to clinical parameters, molecular markers, especially cytogenetic aberrations, are of great prognostic relevance.

Sellar plasmacytoma with massive bleeding during surgery.

Plasmacytoma in the sellar region is an extremely rare occurrence. Sellar plasmacytoma is often difficult to differentiate from pituitary tumors both clinically and radiologically. The occurrence of cranial nerve palsy, the preservation of pituitary hormone function, the presence of sellar floor destruction, and better contrast enhancement are regarded as the differentiating factors between sellar plasmacytoma and pituitary tumors. We recommend adding the massive bleeding properties of sellar plasmacytoma as another characteristic which differentiates it from a pituitary tumor.

Tumor Microenvironment of Lymphomas and Plasma Cell Neoplasms: Broad Overview and Impact on Evaluation for Immune Based Therapies.

Lymphomas and plasma cell neoplasms are a heterogenous group of malignancies derived from lymphocytes. They are a significant cause of patient morbidity and mortality. Advances in morphologic, immunophenotypic and molecular techniques have led to better understanding of the pathogenesis and diagnosis of these neoplasms. Advances in treatment, particularly immune-based therapies, increasingly allow for targeted therapies of these diseases. Mechanistic studies using animal models and clinical trials have revealed the importance of the tumor microenvironment on disease pathogenesis, progression, and response to therapy in these malignancies. Simultaneous progress in diagnostic techniques has made it feasible to generate high-resolution, high-throughput data from the tumor microenvironment with spatial context. As the armamentarium of targeted therapies and diagnostic techniques grows, there is potential to harness these advances to better stratify patients for targeted therapies, including immune-based therapies, in hematologic malignancies.

Blood-based risk stratification for pre-malignant and symptomatic plasma cell neoplasms to improve patient management.

Standard risk stratification (sRisk) guides clinical management in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM). Nonetheless, clinical results are considerably heterogeneous among patients with similar risk status. Blood and bone marrow samples from 276 MGUS, 56 SMM and 242 MM in regular clinical practice were analyzed at diagnosis by flow cytometry. Higher levels of aberrant circulating plasma cells (cPC) (> 0.0035% of leukocytes), combined with albumin, beta2-microglobuline and lactate-dehydrogenase levels, offered minimally-invasive risk stratification (RcPC) with results comparable to sRisk. RcPC and sRisk 10-year progression-free-survival (10y-PFS) rates were: 93.8% vs. 95.1% for low-risk, 78.4% vs. 81.7% for intermediate-risk and 50.0% vs. 47.8% for high-risk MGUS; 58.3% vs. 57.8% low-risk, 44.4% vs. 45.8% intermediate-risk and 8.9% vs. 15.0% high-risk SMM; and 44.4% vs. 44.4% low-risk, 36.1% vs. 36.8% intermediate-risk, and 13.3% vs. 16.2% high-risk MM. Circulating-PC > 0.0035% vs. cPC<0.0035% was an independent prognostic factor for PFS (HR=4.389, P=1.2×10-15, Harrell C-statistic =0.7705±0.0190) and over-all survival (OS, HR=4.286, 2.3×10-9, Harrell C-statistic =0.8225±0.0197) that complemented sRisk in patients with low-sRisk (10y-PFS rates 48.1% vs. 87.3%, P=1.2×10-8) and intermediate-sRisk (10y-PFS rates 28.9% vs. 74.1%, P=8.6×10-12). Patients with high cPCs values are associated with higher proliferation and lower apoptosis rates of PC. Circulating-PC > 0.0035% identified MGUS, SMM and MM patients at higher risk of progression or death and predicted a cohort of patients that after relapse from stringent complete response showed shorter OS. These patients could benefit from early consolidation therapy, tandem ASCT or intensive maintenance.

Increased complexity of t(11;14) rearrangements in plasma cell neoplasms compared with mantle cell lymphoma.

Plasma cell neoplasms (PCN) and mantle cell lymphoma (MCL) can both harbor t(11;14)(q13;q32) (CCND1/IGH), usually resulting in cyclin D1 overexpression. In some cases, particularly at low levels of disease, it can be morphologically challenging to distinguish between these entities in the bone marrow (BM) since PCN with t(11;14) are often CD20-positive with lymphoplasmacytic cytology, while MCL can rarely have plasmacytic differentiation. We compared the difference in CCND1/IGH by fluorescence in situ hybridization (FISH) in PCN and MCL to evaluate for possible differentiating characteristics. We identified 326 cases of MCL with t(11;14) and 279 cases of PCN with t(11;14) from either formalin-fixed, paraffin-embedded tissue or fresh BM specimens. The "typical," balanced CCND1/IGH FISH signal pattern was defined as three total CCND1 signals, three total IGH signals, and two total fusion signals. Any deviation from the "typical" pattern was defined as an "atypical" pattern, which was further stratified into "gain of fusion" vs "complex" patterns. There was a significantly higher proportion of cases that showed an atypical FISH pattern in PCN compared with MCL (53% vs 27%, P < .0001). There was also a significantly higher proportion of cases that showed a complex FISH pattern in PCN compared with MCL (47% vs 17%, P < .0001). We confirmed these findings using mate-pair sequencing of 25 PCN and MCL samples. PCN more often have a complex CCND1/IGH FISH pattern compared with MCL, suggesting possible differences in the genomic mechanisms underlying these rearrangements in plasma cells compared with B cells.

Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma.

BACKGROUND: Monocyte/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment. METHODS: We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS (n = 23), SMM (n = 14) and MM (n = 99) patients vs. healthy donors (HD; n = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers. RESULTS: Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM (p ≤ 0.02), in association with lower blood counts of recently-produced CD62L+ cMo in SMM (p = 0.004) and of all subsets of (CD62L+, CD62L- and FcεRI+) cMo in MM (p ≤ 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS (p ≤ 0.03), SMM (p ≤ 0.03) and MM (p ≤ 0.002), while normal (MGUS and SMM) or decreased (MM; p = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1ß were observed in MGUS (p = 0.007) and SMM (p = 0.01), higher concentrations of serum IL8 were found in SMM (p = 0.01) and MM (p = 0.002), and higher serum IL6 (p = 0.002), RANKL (p = 0.01) and bone alkaline phosphatase (BALP) levels (p = 0.01) with decreased counts of FcεRI+ cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1ß and/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly (p = 0.01) decreased blood counts of immunomodulatory FcεRI+ cMo-, typical of MM presenting with bone lesions. CONCLUSIONS: These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of FcεRI+ cMo in normal bone homeostasis.