Solitary Temporal Plasmocytoma: A Case Report

Introduction: Solitary plasmacytoma is a malignant plasma cell tumor that is much rarer than multiple myeloma. The location in the vault of plasmacytoma is extremely rare. We report the case of a plasmacytoma of the cranial vault in a 53-year-old adult. Observation: A 53-year-old man consulted for tinnitus, left hypoacusis and trigeminal neuralgia of the left V2 and V3, which had been evolving for one year and was aggravated one month later by the appearance of a left temporal swelling with decreased visual acuity on the left. The MRI confirmed the existence of a lesional process of the temporal vault, in T1 iso signal, T2 hypersignal and flair, intensely and heterogeneously enhanced after injection of gadolinium. Anatomopathological study revealed a solitary temporal plasmacytoma, which was referred to oncology for further management. Discussion: Plasmacytoma is defined as an isolated malignant plasma cell tumor without clinical, biological, or radiological signs of Myeloma. Craniocerebral localization is rare and constitutes only 0.7% of all solitary plasmacytomas. Conclusion: Cranial plasmacytoma is a rare tumor that should be investigated for associated myeloma. Although the imaging appearance is not very specific, plasmacytoma should be considered in the differential diagnosis of any invasive lytic lesion of the cranial vault.

Are the Derived Indexes of Peripheral Whole Blood Cell Counts (NLR, PLR, LMR/MLR) Clinically Significant Prognostic Biomarkers in Multiple Myeloma? A Systematic Review And Meta-Analysis

BackgroundMultiple myeloma (MM) is an incurable malignant plasma cell tumor. Whole blood cell count (WBCC) derived indexes are widely used as a predictive biomarker for various types of solid and hematological malignant tumors. Our study is to evaluate its effectiveness in MM by meta-analysis.MethodsRelevant literatures were retrieved from PubMed, Embase and Web of Science databases according to PRISMA guideline. All relevant parameters were extracted and combined for statistical analysis.ResultsNineteen studies incorporating 3818 MM patients were eventually included in this meta-analysis. 13 studies evaluated that elevated NLR was significantly associated with poor survival outcomes (OS: HR=2.04, P<0.001; PFS: HR=1.96, P=0.003). Elevated NLR was revealed to correlate with ISS stage (ISS III VS I-II, OR=2.23, P=0.003). A total of 7 studies have shown that elevated LMR predicts a better prognosis in MM patients (OS: HR=0.57, P<0.001; PFS: HR=0.49, P<0.05), and two other studies demonstrated that increased MLR was related to poor OS/PFS (OS: HR=1.58, P<0.05; PFS: HR=1.60, P<0.05). However, in the other 6 studies including 1560 patients, the prognostic value of PLR had not been confirmed (OS: HR=0.89, P>0.05; PFS: HR=0.87, P>0.05).ConclusionsThe indexes NLR and LMR/MLR derived from WBCC were validated to be useful biomarkers to predict the prognosis in MM patients, but the evidence of PLR was insufficient.

Targeted Therapies for Multiple Myeloma

Multiple myeloma continues to be a challenging disorder to treat despite improved therapies and the widespread use of proteasome inhibitors and immunomodulatory drugs. Although patient outcomes have improved, the disease continues to invariably relapse, and in the majority of cases, a cure remains elusive. In the last decade, there has been an explosion of novel drugs targeting cellular proteins essential for malignant plasma cell proliferation and survival. In this review, we focus on novel druggable targets leading to the development of monoclonal antibodies and cellular therapies against surface antigens (CD38, CD47, CD138, BCMA, SLAMF7, GPRC5D, FcRH5), inhibitors of epigenetic regulators such as histone deacetylase (HDAC), and agents targeting anti-apoptotic (BCL-2), ribosomal (eEF1A2) and nuclear export (XPO1) proteins.

Emerging Therapeutic Strategies to Overcome Drug Resistance in Multiple Myeloma

Multiple myeloma is a malignant plasma cell neoplasm that remains incurable and is ultimately fatal when patients acquire multi-drug resistance. Thus, advancing our understanding of the mechanisms behind drug resistance in multi-relapsed patients is critical for developing better strategies to extend their lifespan. Here, we review the understanding of resistance to the three key drug classes approved for multiple myeloma treatment: immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. We consider how the complex, heterogenous biology of multiple myeloma may influence the acquisition of drug resistance and reflect on the gaps in knowledge where additional research is needed to improve our treatment approaches. Fortunately, many agents are currently being evaluated preclinically and in clinical trials that have the potential to overcome or delay drug resistance, including next-generation immunomodulatory drugs and proteasome inhibitors, novel small molecule drugs, chimeric antigen receptor T cells, antibody-drug conjugates, and bispecific antibodies. For each class, we discuss the potential of these strategies to overcome resistance through modifying agents within each class or new classes without cross-resistance to currently available drugs.

Pathway-Directed Therapy in Multiple Myeloma

Multiple Myeloma (MM) is a malignant plasma cell disorder with an unmet medical need, in particular for relapsed and refractory patients. Molecules within deregulated signaling pathways, including the RAS/RAF/MEK/ERK, but also the PI3K/AKT-pathway belong to the most promising evolving therapeutic targets. Rationally derived compounds hold great therapeutic promise to target tumor-specific abnormalities rather than general MM-associated vulnerabilities. This paradigm is probably best depicted by targeting mutated BRAF: while well-tolerated, remarkable responses have been achieved in selected patients by inhibition of BRAFV600E alone or in combination with MEK. Targeting of AKT has also shown promising results in a subset of patients as monotherapy or to resensitize MM-cells to conventional treatment. Approaches to target transcription factors, convergence points of signaling cascades such as p53 or c-MYC, are emerging as yet another exciting strategy for pathway-directed therapy. Informed by our increasing knowledge on the impact of signaling pathways in MM pathophysiology, rationally derived Precision-Medicine trials are ongoing. Their results are likely to once more fundamentally change treatment strategies in MM.

Preliminary Establishment of a Spinal Stability Scoring System for Multiple Myeloma

Background: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, which SINS scoring system may not be fully applicable to MM patients. We designed a stability evaluation system to evaluate the spinal stability of patients with MM spinal involvement in order to guide clinical treatment.Methods: By using Delphi method, information was collected and extracted through a series of questionnaires and improved via feedback and we preliminary establishment of a spinal stability scoring system for multiple myeloma.Results: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The scoring system consisted of the following six components. The MM spinal stability scoring system was created by calculating the scores of the six separate components: Location, Pain, Number of segments, Physiological curvature, Comorbidities and Neurological function. The minimum value was ‘0’, and the maximum value was ‘24’. A score of ‘0-10’ indicated ‘spine stability’, a score of ‘11-17’ indicated ‘potential instability’, and a score of ‘18-24’ indicated ‘spine instability’. Patients with a score of ‘11-24’ need an intervention such as surgery.Conclusions: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM. Trial registration: The conducted study contains a retrospective analysis of medical records of our hospital database. Beijing Chao-yang Hospital Human Research Ethics Committee classifies this as a retrospective audit. The ethics approval and consent was given for the conducted retrospective data analysis.

From light chain deposition to multiple myeloma – Case report and literature review

Monoclonal gammopathies consist of a broad spectrum of diseases, ranging from asymptomatic monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Multiple myeloma is a malignant plasma cell disorder and accounts for 10% of all hematological malignancies and 1% of all malignancies. Differential diagnosis may be challenging, considering the variety of clinical entities with similar behavior. About 15­‑20% of MM only secretes monoclonal light chains, called light chain MM, which is associated with poorer outcome. Two intermediate concepts were recently introduced, monoclonal gammopathy of renal significance (MGRS) and a wider concept of monoclonal gammopathy of clinical significance (MGCS). The former behaves as a clonal proliferative disorder with associated nephrotoxicity, but does not have the hematological criteria for MM, while MGCS expands this concept to other organs. A subtype of MGCS is monoclonal immunoglobulin deposition disease, a multisystemic disorder characterized by light or heavy chain deposition of monoclonal immunoglobulin in various organs and encompasses three clinical entities: Light­‑Chain, Light­‑ and Heavy­‑Chain, and Heavy­‑Chain Deposition Disease (LCDD, LHCDD and HCDD, respectively). We describe an unusual case of LCDD in which MM was subsequently considered although the proposed criteria are not met. We demonstrate the variability of clinical­‑pathological presentation of LCDD, requiring a rapid decision­‑making, particularly in terms of kidney and survival outcomes.

Preliminary establishment of a spinal stability scoring system for multiple myeloma

Background: Multiple myeloma is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, which SINS scoring system may not be fully applicable to MM patients. We designed a stability evaluation system to evaluate the spinal stability of patients with MM spinal involvement in order to guide clinical treatment. Methods: By using Delphi method, information was collected and extracted through a series of questionnaires and improved via feedback and we preliminary establishment of a spinal stability scoring system for multiple myeloma. Results: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The scoring system consisted of the following six components.The MM spinal stability scoring system was created by calculating the scores of the six separate components: Location, Pain, Number of segments, Physiological curvature, Comorbidities and Neurological function. The minimum value was ‘0’, and the maximum value was ‘24’. A score of ‘0-10’ indicated ‘spine stability’, a score of ‘11-17’ indicated ‘potential instability’, and a score of ‘18-24’ indicated ‘spine instability’. Patients with a score of ‘11-24’ need an intervention such as surgery. Conclusions: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM. Trial registration: The conducted study contains a retrospective analysis of medical records of our hospital database. Beijing Chao-yang Hospital Human Research Ethics Committee classifies this as a retrospective audit. The ethics approval and consent was given for the conducted retrospective data analysis.

Monoclonal gammopathies of undetermined significance and smoldering myeloma

Monoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder implicated as a precursor of multiple myeloma (MM), while smoldering multiple myeloma (SMM) is a malignant plasma cell disorder without evidence of a myeloma-defining event(s) (MDE). This is a review article of both disorders outlining their current definition and management according to the current standard of care. We focus on the pathogenesis of MM and the role of MGUS and SMM in the development of active MM. MGUS is a benign disorder and, subsequently, is followed by observation. In contrast, for SMM, although the current standard of care is “watch and wait”, this paper will explore the circumstances in which treatment should be considered to prevent MDE.

Preliminary Establishment of a Spinal Stability Scoring System for Multiple Myeloma

Background: Multiple myeloma (MM) is an incurable malignant plasma cell disorder that represents the most common primary malignant bone tumor. It commonly involves bone metastasis in multiple vertebral bodies, which SINS scoring system may not be fully applicable to MM patients. We designed a stability evaluation system to evaluate the spinal stability of patients with MM spinal involvement in order to guide clinical treatment. Methods: By using Delphi method, information was collected and extracted through a series of questionnaires and improved via feedback and we preliminary establishment of a spinal stability scoring system for multiple myeloma. Results: Fifteen clinicians completed a second round of questionnaires and compared their answers with those of the first round of questionnaires to identify significant comments or changes that required group discussions. As a result, no further feedback was used to improve the scoring system. After integrating the information from the expert consultation questionnaire, we established the initial scoring system for MM spine stability and used the scoring system to assess a series of representative clinical cases. The scoring system consisted of the following six components.The MM spinal stability scoring system was created by calculating the scores of the six separate components: Location, Pain, Number of segments, Physiological curvature, Comorbidities and Neurological function. The minimum value was ‘0’, and the maximum value was ‘24’. A score of ‘0-10’ indicated ‘spine stability’, a score of ‘11-17’ indicated ‘potential instability’, and a score of ‘18-24’ indicated ‘spine instability’. Patients with a score of ‘11-24’ need an intervention such as surgery. Conclusions: The initial establishment of the MM spine stability scoring system provides a vital theoretical basis for the evaluation of spine stability in individuals with MM. Trial registration: As this was a retrospective study, it did not require ethical approval; all patients had signed informed consent when they received treatment, and all treatment options were voluntary.