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Der Radiologe Jan 2022Multiple myeloma (MM) is one of the most common hematological neoplasms and accounts for approximately 1% of human cancers. (Review)
Review
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.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Pathologists; Plasmacytoma; Prognosis
PubMed: 34661686
DOI: 10.1007/s00117-021-00926-z -
American Society of Clinical Oncology... Apr 2022Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple...
Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple myeloma therapeutics has significantly changed over the last 2 decades, with disease remissions lasting much longer. The advent of modern-day induction regimens, usage of high-dose melphalan followed by autologous stem cell transplantation, and well-tolerated maintenance regimens has resulted in deeper and durable responses, with less frequent disease recurrences, and patients are living much longer. Moreover, the conventional testing for response assessments in multiple myeloma was developed at least 60 years earlier, and there was a clear need for more sensitive diagnostics to test measurable residual disease at deeper levels. Next-generation sequencing and next-generation flow cytometry are highly sensitive techniques that were refined over the last decade and have a sensitivity of 10 to 10 (1 cell per 100,000/1 million). More recently, immunotherapy strategies-including the cellular therapies-have allowed us to expand our ability to achieve and maintain measurable residual disease negativity even in the refractory setting. These advances have brought us much closer to a cure for multiple myeloma; clearly, it has become more realistically achievable, challenging the dogma of multiple myeloma as an incurable disease.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Transplantation, Autologous
PubMed: 35623025
DOI: 10.1200/EDBK_349603 -
Clinical Lymphoma, Myeloma & Leukemia Nov 2022Plasma cell neoplasms are exceptionally rare in the pediatric population; the demographic characteristics and the clinical outcomes of plasma cell neoplasms in this...
INTRODUCTION
Plasma cell neoplasms are exceptionally rare in the pediatric population; the demographic characteristics and the clinical outcomes of plasma cell neoplasms in this population are currently poorly understood. The aim of this study was to provide a comprehensive analysis of pediatric plasma cell neoplasms, based on the United-States Surveillance, Epidemiology, and End Results (SEER) program registries.
MATERIALS AND METHODS
All pediatric patients (aged less than 20 years) diagnosed with a malignant plasma cell neoplasm were retrieved from the SEER Program database (18 registries), collecting patient records between 2000 and 2018. The plasma cell neoplasm type, sex, age at diagnosis, year of diagnosis, race and origin, primary disease site, follow-up duration, and vital status at the last known contact were retrieved and analyzed.
RESULTS
The age-adjusted incidence rate of plasma cell neoplasms for 1,000,000 person-years was 0.06 for the pediatric population (compared with 90.6 for the adult population). The types of pediatric plasma cell neoplasms predominantly consisted of plasmacytomas, with 11 solitary extraosseous plasmacytoma (42.3%) and 7 solitary bone plasmacytoma (26.9%), while plasma cell myelomas represented only a minority of the neoplasms (8 patients; 30.8%). Most plasmacytomas were localized in the head and neck region. Hispanic patients represented 50% of the pediatric plasma cell neoplasm cases (but only 11.1% of adult cases, P < .01). Female-to-Male ratio was 1.36. Five-year overall survival rates were 88.2% (95% confidence interval [95% CI]: 74.2%-100%) for pediatric plasmacytoma and 36.5% (95% CI: 12.4%-100%) for pediatric plasma cell myeloma (P = .013).
CONCLUSION
This first population-based study of pediatric plasma cell neoplasms underlines the rarity of this entity and demonstrates its unique characteristics, including the significant predominance of plasmacytomas, of female patients, and of patients from hispanic origin, and the poor clinical outcomes of pediatric plasma cell myeloma patients.
Topics: Adult; Humans; Child; Male; Female; United States; Plasmacytoma; Multiple Myeloma; Neoplasms, Plasma Cell; Bone Neoplasms; Registries
PubMed: 35941071
DOI: 10.1016/j.clml.2022.07.003 -
Blood Advances Mar 2023Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells...
Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells (PCs) and the microenvironment has not yet been analyzed in MM. For this purpose, we performed bone marrow aspirates and imaging-guided biopsies of corresponding lesions in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. PCs were isolated and subjected to whole-exome sequencing (WES). Non-PCs were studied with next-generation flow (NGF) and T-cell receptor sequencing (TCRseq) to analyze the connection between malignant and nonmalignant cells in the bone marrow and in lesions. Although we observed a strong overlap from WES, NGF, and TCRseq in patients with intramedullary disease, WES revealed significant spatial heterogeneity in patients with extramedullary disease. NGF showed significant immunosuppression in RRMM compared with NDMM as indicated by fewer myeloid dendritic cells, unswitched memory B cells, Th9 cells, and CD8 effector memory T cells but more natural killer and regulatory T cells. Additionally, fewer T-cell receptor (TCR) sequences were detected in RRMM compared with NDMM and healthy individuals. After induction therapy, TCR repertoire richness increased to levels of healthy individuals, and NGF showed more regulatory T cells and myeloid-derived suppressor cells, regardless of depth of response. Clinical significance of imaging-guided biopsies of lesions was demonstrated by detection of monoclonal PCs in patients without measurable residual disease (MRD) in aspirates from the iliac crest as well as identification of secondary primary malignancies in MRD- patients. Furthermore, site-specific clones with different drug susceptibilities and genetically defined high-risk features were detected by our workflow.
Topics: Humans; Multiple Myeloma; Bone Marrow; Plasma Cells; Neoplasms, Plasma Cell; Tumor Microenvironment
PubMed: 35868022
DOI: 10.1182/bloodadvances.2022007457 -
Hematology/oncology Clinics of North... Apr 2024Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic... (Review)
Review
Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic drivers underlying this clinical behavior and to target its biology therapeutically. Advances have already been made, with a focus on consensus guidance and the application of novel immunotherapeutic approaches. Cases of HRMM are likely to have impaired prognosis even with novel strategies. However, if disease eradication and minimal disease states are achieved, then cure may be possible.
Topics: Humans; Multiple Myeloma; Prognosis
PubMed: 38195306
DOI: 10.1016/j.hoc.2023.12.008 -
Journal of Oral Pathology & Medicine :... Jul 2021Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a...
BACKGROUND
Plasma cell neoplasms are characterized by the proliferation of a single clone of plasma cells with production of a monoclonal immunoglobulin. They can manifest as a single lesion (plasmacytoma) or as multiple lesions (multiple myeloma).
METHODS
Paraffin-embedded tissue blocks of patients microscopically diagnosed with plasma cell neoplasms in the jaws were retrieved from five pathology files. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed and follow-up status were retrieved from the pathology reports.
RESULTS
Fifty-two cases were retrieved (mean age: 59.4 years) without sex predilection. The mandible was the most affected site (67.3%), usually associated with pain and/or paresthesia (53.8%). Lesions in other bones besides the jaws were reported for 24 patients (46.2%). Radiographically, tumours usually presented as poorly defined osteolytic lesions with unilocular or multilocular images, while microscopy revealed diffuse proliferation of neoplastic plasma cells with nuclear displacement and abundant eosinophilic cytoplasm. Two cases were classified as anaplastic, and amyloid deposits were found in two other cases. Immunohistochemistry was positive for plasma cell markers and negative for CD20 and CD3, and monoclonality for kappa light chain predominated. The overall survival rate after 5 years of follow-up was 26.6%.
CONCLUSION
Plasma cell neoplasms are aggressive tumours with a poor prognosis and involvement of the jaws may be the first complaint of the patient. Thus, oral pathologists, head and neck surgeons and dentists should be aware of their clinical, radiographic and microscopic manifestations.
Topics: Humans; Immunohistochemistry; Jaw; Middle Aged; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
PubMed: 34089204
DOI: 10.1111/jop.13213 -
Cancer Medicine Nov 2023Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic...
BACKGROUND
Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry.
METHODS
Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms.
RESULTS
We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all p <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma.
CONCLUSION
Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.
Topics: Humans; Aged; Cohort Studies; Prospective Studies; Multiple Myeloma; Biological Specimen Banks; Cholesterol, HDL; Cholesterol, LDL; Apolipoproteins B; Risk Factors; Triglycerides; Apolipoproteins A
PubMed: 37908181
DOI: 10.1002/cam4.6649 -
Clinics in Laboratory Medicine Sep 2023Flow cytometry plays a critical role in the diagnosis, prognostication, therapy response evaluation, and clinical management of plasma cell neoplasms. The review... (Review)
Review
Flow cytometry plays a critical role in the diagnosis, prognostication, therapy response evaluation, and clinical management of plasma cell neoplasms. The review summarizes how flow cytometry is used in the initial evaluation to distinguish primary and secondary clonal plasma cell populations from each other and from reactive plasma cells. We further illustrate the kinds of prognostic information the assessment can provide at diagnosis and disease follow-up of primary plasma cell neoplasms. Technical requirements for MRD assays and their use in therapy efficacy assessment and clinical decision-making in multi-myeloma are discussed.
Topics: Humans; Multiple Myeloma; Flow Cytometry; Neoplasms, Plasma Cell; Clinical Decision-Making
PubMed: 37481317
DOI: 10.1016/j.cll.2023.05.003 -
Cells Sep 2023G protein-coupled estrogen receptor 1 (GPER1) activation is emerging as a promising therapeutic strategy against several cancer types. While GPER targeting has been...
G protein-coupled estrogen receptor 1 (GPER1) activation is emerging as a promising therapeutic strategy against several cancer types. While GPER targeting has been widely studied in the context of solid tumors, its effect on hematological malignancies remains to be fully understood. Here, we show that GPER1 mRNA is down-regulated in plasma cells from overt multiple myeloma (MM) and plasma cell leukemia patients as compared to normal donors or pre-malignant conditions (monoclonal gammopathy of undetermined significance and smoldering MM); moreover, lower GPER1 expression associates with worse overall survival of MM patients. Using the clinically applicable GPER1-selective agonist G-1, we demonstrate that the pharmacological activation of GPER1 triggered in vitro anti-MM activity through apoptosis induction, also overcoming the protective effects exerted by bone marrow stromal cells. Noteworthy, G-1 treatment reduced in vivo MM growth in two distinct xenograft models, even bearing bortezomib-resistant MM cells. Mechanistically, G-1 upregulated the miR-29b oncosuppressive network, blunting an established miR-29b-Sp1 feedback loop operative in MM cells. Overall, this study highlights the druggability of GPER1 in MM, providing the first preclinical framework for further development of GPER1 agonists to treat this malignancy.
Topics: Humans; Multiple Myeloma; Hematologic Neoplasms; Smoldering Multiple Myeloma; Plasma Cells; MicroRNAs
PubMed: 37759449
DOI: 10.3390/cells12182226 -
Journal of Veterinary Diagnostic... Jul 2022A 5-y-old spayed female Golden Retriever dog was referred because of severe normocytic normochromic nonregenerative anemia and thrombocytopenia. Serum analysis revealed...
A 5-y-old spayed female Golden Retriever dog was referred because of severe normocytic normochromic nonregenerative anemia and thrombocytopenia. Serum analysis revealed hyperproteinemia and monoclonal or oligoclonal gammopathy. Fine-needle aspiration of the spleen revealed a highly erythrophagocytic population of neoplastic round cells, morphologically suggestive of plasma cells. After euthanasia, histologic assessment of the spleen and liver revealed an erythrophagocytic round cell tumor. Immunohistochemical analysis of the tumor population was positive for MUM1p and negative for CD3, CD20, and Iba-1, confirming the plasma cell origin of the tumor. Erythrophagocytic multiple myeloma is a very rare neoplastic condition in dogs.
Topics: Animals; Dog Diseases; Dogs; Female; Liver; Multiple Myeloma; Spleen
PubMed: 35603564
DOI: 10.1177/10406387221092299