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Blood Reviews Mar 2024Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC... (Review)
Review
Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification. Other molecular methods are increasingly being utilised to provide a genome-wide view at high resolution (e.g. single nucleotide polymorphism (SNP) microarray analysis) and these can detect abnormalities in most cases. Despite their wide application at diagnostic assessment, both FISH and SNP-array have relatively low sensitivity, limiting their use for identification of prognostically significant low-level sub-clones or for disease monitoring. Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.
Topics: Humans; Multiple Myeloma; Chromosome Aberrations; Translocation, Genetic; In Situ Hybridization, Fluorescence; Gene Rearrangement
PubMed: 38212176
DOI: 10.1016/j.blre.2024.101168 -
International Journal of Clinical and... 2015Plasma cell neoplasm (PCM) is a medullary and extra medullary proliferation of clonal plasma cells that occurs due to accidental translocation of proto-oncogenes into...
UNLABELLED
Plasma cell neoplasm (PCM) is a medullary and extra medullary proliferation of clonal plasma cells that occurs due to accidental translocation of proto-oncogenes into immunoglobulin (Ig) gene loci. While the majority of plasma cell neoplasms are monoclonal, up to 2% of the PCMs [1] considered being biclonal based on electrophoretic analysis, characterized by secretion of paraprotein with two distinct heavy chains or light chains are possible and present unique diagnostic challenges.
METHODS
Traditionally protein electrophoresis has been used to diagnose, characterize, and monitor progression of plasma cell neoplasm. To characterize neoplastic plasma cells, in our institution, other ancillary studies, including in situ hybridization, flow cytometric analyses of plasma cell surface markers and cytoplasmic immunoglobulins with DNA ploidy, are also utilized routinely.
RESULTS
We present two cases of plasma cell myeloma in which the neoplastic plasma cells shows production of cytoplasmic kappa and lambda light chain, with secretion of free lambda light chain only. Co-expression of kappa and lambda light chain by the same neoplastic plasma cells is a rare but reported phenomenon.
CONCLUSIONS
Our study indicates that serum electrophoresis alone could mischaracterize biphenotypic myeloma as monotypic plasma cell myelomas in the absence of additional testing methods.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Electrophoresis, Capillary; Fatal Outcome; Female; Flow Cytometry; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunohistochemistry; Immunophenotyping; In Situ Hybridization; Male; Middle Aged; Multiple Myeloma; Phenotype; Predictive Value of Tests; RNA, Messenger; Treatment Outcome
PubMed: 26339430
DOI: No ID Found -
Pathology Feb 2022Plasma cell neoplasms are notorious for having diverse morphological presentations, and less frequently, unusual immunophenotypical profiles. This unexpected... (Review)
Review
Plasma cell neoplasms are notorious for having diverse morphological presentations, and less frequently, unusual immunophenotypical profiles. This unexpected immunomorphological variability could lead to erroneous impressions upon initial assessment, potentially delaying the generation of a final accurate diagnosis. In this review, we present a concise, yet comprehensive summary of both morphological and immunophenotypical variants of plasma cell neoplasms from the archives of MD Anderson Hematopathology Department, with emphasis on possible diagnostic pitfalls precluding a timely and accurate assessment.
Topics: Diagnosis, Differential; Humans; Immunophenotyping; Multiple Myeloma; Neoplasms, Plasma Cell; Plasma Cells; Plasmacytoma
PubMed: 34887091
DOI: 10.1016/j.pathol.2021.09.011 -
Annual Review of Medicine 1991Plasma cell myeloma results from malignant transformation in an early hemopoietic precursor cell. The disease progresses from an asymptomatic stable phase through a... (Review)
Review
Plasma cell myeloma results from malignant transformation in an early hemopoietic precursor cell. The disease progresses from an asymptomatic stable phase through a symptomatic phase to a terminal acute phase marked by aggressive cell growth and marrow failure. The activation of a series of oncogenes may govern the initiation and stepwise progression of these neoplasms. Chemotherapy causes the tumor to regress in about 50% of patients and improves survival, but it does not alter the course of the disease. Interferon maintenance therapy prolongs remission durations and appears to alter the course of the disease.
Topics: Cell Transformation, Neoplastic; Chromosome Aberrations; Chromosome Disorders; Humans; Multiple Myeloma
PubMed: 2035963
DOI: 10.1146/annurev.me.42.020191.001123 -
Seminars in Diagnostic Pathology Aug 2003This article emphasizes both the morphologic and phenotypic features of the bone marrow in plasma cell myeloma. It details the morphologic features of both trephine... (Review)
Review
This article emphasizes both the morphologic and phenotypic features of the bone marrow in plasma cell myeloma. It details the morphologic features of both trephine biopsies and marrow aspirations. It emphasizes the salient phenotypic features of marrow myeloma cells, in contrast with normal plasma cells. The myeloma cell phenotype is discussed from the perspective of both tissue section immunohistochemistry (IHC) and flow cytometry (FACS analysis). The specific criteria for myeloma diagnosis are discussed and illustrated in Figures 1-12. Finally, the emphasis is on the key morphologic and phenotypic diagnostic criteria of each of the plasma cell neoplasms.
Topics: Biomarkers, Tumor; Bone Marrow; Flow Cytometry; Humans; Immunohistochemistry; Multiple Myeloma; Phenotype; Plasma Cells
PubMed: 14552432
DOI: 10.1016/s0740-2570(03)00027-3 -
Hematology. American Society of... 2008
Topics: Antineoplastic Agents; Combined Modality Therapy; History, 20th Century; Humans; Melphalan; Multiple Myeloma; Neoplasms, Plasma Cell; Stem Cell Transplantation; Transplantation, Autologous
PubMed: 19074099
DOI: 10.1182/asheducation-2008.1.297 -
American Journal of Clinical Pathology Jan 2024Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We...
OBJECTIVES
Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting.
METHODS
The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed.
RESULTS
Fluorescence-activated cell sorting-FISH increased the detection rate of abnormalities in comparison with cIg-FISH, with abnormal results documented in 54% vs 50% of cases, respectively (P < .001). It improved the detection of IGH::CCND1 (P < .001), IGH::MAF (P < .001), IGH::MAFB (P < .001), other IGH rearrangements (P < .001), and gains/amplifications of 1q (P < .001), whereas the detection rates of IGH::FGFR3 fusions (P = .3), loss of 17p (P = .3), and other abnormalities, including hyperdiploidy (P = .5), were similar. Insufficient PC yield for FISH analysis was decreased between cIg-FISH and FACS-FISH (22% and 3% respectively, P < .001). Flow cytometry allowed establishment of ploidy status in 91% of cases. In addition, FACS-FISH decreased analysis times, workload efforts, and operating costs.
CONCLUSIONS
Fluorescence-activated cell sorting-FISH is an efficient PC purification strategy that affords significant improvement in diagnostic yield and decreases workflow requirements in comparison with cIg-FISH.
Topics: Humans; Plasma Cells; In Situ Hybridization, Fluorescence; Multiple Myeloma; Neoplasms, Plasma Cell; Antibodies; Chromosome Aberrations
PubMed: 37658775
DOI: 10.1093/ajcp/aqad108 -
Haematologica Oct 2022
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasms, Plasma Cell; Thalidomide
PubMed: 35734925
DOI: 10.3324/haematol.2022.280660 -
Blood Feb 2023
Topics: Humans; Multiple Myeloma; Neoplasms, Plasma Cell; Immunomodulating Agents
PubMed: 36757732
DOI: 10.1182/blood.2022018461 -
Clinics in Laboratory Medicine Dec 2017Plasma cell dyscrasia (PCD) is a heterogeneous disease that has seen a tremendous change in outcomes due to improved therapies. Over the past few decades,... (Review)
Review
Plasma cell dyscrasia (PCD) is a heterogeneous disease that has seen a tremendous change in outcomes due to improved therapies. Over the past few decades, multiparametric flow cytometry has played an important role in the detection and monitoring of PCDs. Flow cytometry is a high-sensitivity assay for early detection of minimal residual disease (MRD) that correlates well with progression-free survival and overall survival. Before flow cytometry can be effectively implemented in the clinical setting, sample preparation, panel configuration, analysis, and gating strategies must be optimized to ensure accurate results. Current consensus methods and reporting guidelines for MRD testing are discussed.
Topics: Flow Cytometry; Humans; Multiple Myeloma; Neoplasm, Residual; Paraproteinemias
PubMed: 29128071
DOI: 10.1016/j.cll.2017.08.001