INVESTIGATION OF THE QUALIFICATION OF RADIOLOGICAL TECHNIQUES TO DETECT OSTEOLYTIC LESIONS, FRACTURES, AND OSTEOPOROSIS IN MULTIPLE MYELOMA PATIENTS

Objectives: Multiple myeloma (MM) is characterized by the occurrence of osteolytic lesions. MM treatment usually involves antiresorptive drugs (mainly bisphosphonates). Case Report: A patient with an MM presented osteolytic lesions of the mandible. Extraction of teeth 45 and 46 was performed 5 years after the diagnosis of periodontitis. Four months later, osteonecrosis of the jaw (ONJ) was diagnosed at the extraction site. X-ray showed an extension of osteolytic lesions on the right side, close to the extraction site, without modification of the lesions on the left side. Two months later, a curettage was performed because of a painful bone sequestration. X-ray showed an extension of the osteolytic lesions on the right side. Results: Histological analysis found a vascularized plasmacytoma of the soft tissues around the ONJ. Analysis of the bone showed mixed lesions with osteonecrotic areas and living bone resorbed by active osteoclasts surrounding a plasmacytoma. The surface area of the osteolytic foci has considerably increased only close to the extraction site. Conclusions: Tooth extraction triggered an ONJ associated with bisphosphonate treatment. However, it also seemed to induce a considerable proliferation of plasma cells at the extraction site; we hypothesize that it is due to the increase in bone remodeling related to the surgical trauma.

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Occult Esophageal Squamous Cell Carcinoma Presenting with Multiple Bony Osteolytic Lesions Clinically Mimicking Multiple Myeloma: A Diagnostic Dilemma

Journal of Laboratory Physicians ◽

10.1055/s-0040-1714193 ◽

2020 ◽

Vol 12 (01) ◽

pp. 76-78

Author(s):

Bifica Sofia Lyngdoh ◽

Biswajit Dey ◽

Vandana Raphael ◽

Iadarilang Tiewsoh

Keyword(s):

Multiple Myeloma ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Diagnostic Dilemma ◽

Osteolytic Lesions ◽

Diagnostic Work ◽

Work Up ◽

Diagnostic Work Up

AbstractBone metastasis as an initial presentation of esophageal carcinoma is uncommon. In the absence of typical presentations like dysphagia, these cases may lead to diagnostic dilemmas both for the clinicians and pathologists. Here, we report a case of disseminated metastasis of esophageal squamous cell carcinoma to the bone in a 47-year-old female, who presented with multiple osteolytic lesions and clinically mimicking multiple myeloma. A detailed diagnostic work-up established the diagnosis of esophageal squamous cell carcinoma.

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Functional Comparison between Healthy and Multiple Myeloma Adipose Stromal Cells

Stem Cells International ◽

10.1155/2020/4173578 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Nicolas Espagnolle ◽

Benjamin Hebraud ◽

Jean-Gérard Descamps ◽

Mélanie Gadelorge ◽

Marie-Véronique Joubert ◽

...

Keyword(s):

Multiple Myeloma ◽

Stromal Cells ◽

Cellular Therapy ◽

Plasma Cells ◽

Bone Lesions ◽

Adipose Stromal Cells ◽

Osteolytic Lesions ◽

Healthy Donors ◽

Bone Damage ◽

First Time

Multiple myeloma (MM) is an incurable B cell neoplasia characterized by the accumulation of tumor plasma cells within the bone marrow (BM). As a consequence, bone osteolytic lesions develop in 80% of patients and remain even after complete disease remission. We and others had demonstrated that BM-derived mesenchymal stromal cells (MSCs) are abnormal in MM and thus cannot be used for autologous treatment to repair bone damage. Adipose stromal cells (ASCs) represent an interesting alternative to MSCs for cellular therapy. Thus, in this study, we wondered whether they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic, and functional comparison of ASCs from MM patients and healthy donors (HDs) relying on their autologous MSC counterparts. In contrast to MM MSCs, MM ASCs did not exhibit major abnormalities. However, the changes observed in MM ASCs and the supportive property of ASCs on MM cells question their putative and safety uses at an autologous or allogenic level.

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A New Insight into the Formation of Osteolytic Lesions in Multiple Myeloma

New England Journal of Medicine ◽

10.1056/nejmp038176 ◽

2003 ◽

Vol 349 (26) ◽

pp. 2479-2480 ◽

Cited By ~ 21

Author(s):

Donald A. Glass ◽

Millan S. Patel ◽

Gerard Karsenty

Keyword(s):

Multiple Myeloma ◽

Osteolytic Lesions ◽

Insight Into

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Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone.

Journal of Clinical Oncology ◽

10.1200/jco.1983.1.4.255 ◽

1983 ◽

Vol 1 (4) ◽

pp. 255-262 ◽

Cited By ~ 261

Author(s):

M A Knowling ◽

A R Harwood ◽

D E Bergsagel

Keyword(s):

Multiple Myeloma ◽

Lymph Nodes ◽

Plasma Cell ◽

Progression Free Survival ◽

Regional Lymph Nodes ◽

Osteolytic Lesions ◽

Radiation Fields ◽

Bony Lesion ◽

Tumors Of Bone ◽

Extramedullary Plasmacytomas

Patients with solitary osseous plasmacytomas (SOP) differ from those with extramedullary plasmacytomas (EMP) in that they are younger and the proportion of males is smaller. The median survival of the two groups is similar: 86.4 mo for SOP, and 100.8 mo for EMP. Progression-free survival, however, is much better for EMP. Only five EMP patients have progressed following initial radiation therapy: one developed a single bony lesion, two progressed to multiple myeloma, and two developed multiple EMP. Thus, 71% of EMP patients are progression free at 10 yr, and most deaths do not result from plasma cell neoplasia. In contrast, 13 SOP patients have progressed to develop additional osteolytic lesions, so that only 16% of SOP patients are progression free at 10 yr; death resulted from progression to multiple myeloma in most of these patients. In EMP patients the occurrence of involved lymph nodes at the time of diagnosis in seven, and initial relapse in regional nodes in three, suggest that consideration should be given to including regional lymph nodes in the radiation fields used to treat these patients.

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Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw

BioMed Research International ◽

10.1155/2020/9879876 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Alessandro Allegra ◽

Manuela Mania ◽

Angela D’Ascola ◽

Giacomo Oteri ◽

Enrico Nastro Siniscalchi ◽

...

Keyword(s):

Multiple Myeloma ◽

Metabolic Pathways ◽

Noncoding Rna ◽

Protective Action ◽

Noncoding Rnas ◽

Osteonecrosis Of The Jaw ◽

Base Pairs ◽

Osteolytic Lesions ◽

Ctrl Group ◽

Rna Molecules

Bisphosphonates (BPs) are inhibitors of osteoclast-mediated bone resorption used for the treatment of multiple myeloma (MM) patients with osteolytic lesions. Bisphosphonate-induced osteonecrosis of the jaw (BONJ) is an infrequent drug-caused adverse event of these agents. Long noncoding RNAs (lncRNAs) are a set of more than 200 base pairs, noncoding RNA molecules, which are critical posttranscriptional regulators of gene expression. Our study was aimed at evaluating 17 lncRNAs, whose targets were previously validated as key elements in MM, bone metabolism, and angiogenesis in MM subjects without BONJ (MM group), in MM subjects with BONJ (BONJ group), and a group of healthy controls (CTRL group). Our results demonstrated a different lncRNA profile in BONJ patients compared to MM patients and controls. Two lncRNAs (DANCR and MALAT1) were both downregulated compared to controls and MM, twelve (HOTAIR, MEG3, TP73-AS1, HOTTIP, HIF1A-AS2, MANTIS, CTD-2201E18, CTD1-2003C8, R-471B22, RP1-43E13, RP11-553L6.5, and RP1-286D6) were overexpressed in MM with BONJ, and one (H19) was upregulated compared with only MM. Two lncRNAs (JHDMD1 and MTMR9LP) had higher expression, but these differences were not statistically significant. The examined lncRNAs target several genes and metabolic pathways. An altered lncRNA signature could contribute to the onset of BONJ or have a protective action. Targeting these lncRNAs could offer a possibility for the prevention or therapy of BONJ.

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Zoledronic Acid Inhibits Protein Prenylation in Plasmacytoma Tumors In Vivo and Enhances Survival in the INA-6 SCID Mouse Model.

Blood ◽

10.1182/blood.v104.11.3360.3360 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3360-3360

Author(s):

Andreas Guenther ◽

Sharon Gordon ◽

Frank Bakker ◽

Renate Burger ◽

Jonathan R. Green ◽

...

Keyword(s):

Multiple Myeloma ◽

Zoledronic Acid ◽

Cell Lines ◽

Scid Mouse ◽

Tumour Burden ◽

Protein Prenylation ◽

Osteolytic Lesions ◽

Osteolytic Bone Disease ◽

Anti Tumour Effect

Abstract Bisphosphonates such as zoledronic acid (ZOL) are effective at preventing osteolytic bone disease in patients with multiple myeloma. ZOL inhibits bone resorption by inhibiting FPP synthase and preventing the prenylation of small GTPases in osteoclasts. In vitro studies have demonstrated previously that ZOL can also directly affect the growth and viability of myeloma cells by inhibiting protein prenylation and therefore could, potentially, have a direct anti-tumour effect in vivo in addition to effects on osteoclasts. To examine this further, the effect of ZOL on six myeloma cell lines, including the IL-6 dependent INA-6 line, was investigated. ZOL caused cell cycle arrest and concentration-dependent growth inhibition in all six cell lines, with varying sensitivity (IC50= 30–285 μM). The potential anti-tumour effect of ZOL on INA-6 cells in vivo was studied in a SCID mouse xenograft model, in which mice injected intraperitoneally with INA-6 cells develop plasmacytomas but do not develop significant osteolytic lesions. In several experiments involving more than 50 mice, ZOL was administered subcutaneously (sc) or intravenously (iv). ZOL, at a dose of 8 μg or 2 μg three times per week for two weeks after inoculation of INA-6 cells, significantly reduced tumour burden and increased survival of the mice (p= 0.002). The effect of ZOL on protein prenylation in plasmacytomas dissected from the mice was measured by western blotting to specifically detect the unprenylated form of the small GTPase Rap1A. Unprenylated Rap1A was virtually absent from tumour samples of untreated animals, while a single iv injection of 8 μg ZOL induced a marked accumulation of unprenylated Rap1A in the tumours after 24–72 hours. These studies are the first to demonstrate that ZOL can inhibit protein prenylation in plasmacytomas in vivo. Together with the decreased tumour burden and increased survival, the data suggest that ZOL may have direct anti-tumour effects in this animal model. Thus, nitrogen-containing bisphosphonates such as ZOL may have therapeutic potential in multiple myeloma beyond the prevention of osteolytic lesions.

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Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

Cancers ◽

10.3390/cancers13215258 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5258

Author(s):

Sara Reis Moura ◽

Hugo Abreu ◽

Carla Cunha ◽

Cláudia Ribeiro-Machado ◽

Carla Oliveira ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Disease ◽

Area Under The Curve ◽

Genetic Alterations ◽

Disease Stage ◽

Bone Lesions ◽

Healthy Controls ◽

Osteolytic Lesions ◽

Circulating Micrornas ◽

Myeloma Bone Disease

Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miRNAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel of miRNAs associated with MM onset and progression, or with bone remodeling, was analyzed in the plasma of 82 subjects (47 MM patients; 35 healthy controls). Results show that miR-16-5p, miR-20a-5p, and miR-21-5p are differently expressed between MM patients and healthy controls. Receiver operating characteristic analyses indicate that their combined expression has potential as a molecular marker (Area Under the Curve, AUC of 0.8249). Furthermore, significant correlations were found between the analyzed miRNAs and disease stage, treatment, β2 microglobulin, serum albumin and creatinine levels, but not with calcium levels or genetic alterations. In this cohort, 65.96% of MM patients had bone lesions, the majority of which were in the vertebrae. Additionally, miR-29c-3p was decreased in patients with osteolytic lesions compared with patients without bone disease. Interestingly, circulating levels of miR-29b-3p correlated with cervical and thoracic vertebral lesions, while miR-195-5p correlated with thoracic lesions. Our findings suggest circulating miRNAs can be promising biomarkers for MM diagnosis and that their levels correlate with myeloma bone disease and osteolytic lesions.

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