Diagnostic relevance of 2-[18 F]-FDG PET/CT in patients recently diagnosed with monoclonal gammopathy of undetermined significance.

2-[18 F]-FDG PET/CT is a useful diagnostic technique to assess bone and soft tissue disease in multiple myeloma (MM) but is not recommended by the International Myeloma Working Group for the evaluation of monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to evaluate the role of 2-[18 F]-FDG PET/CT in the management of these patients. An observational retrospective study was conducted on 338 patients with MGUS who underwent 2-[18 F]-FDG PET/CT. The mean age was 70.80 ± 11.84 years, and 69.2% of patients had cardiovascular risk factors. Patients were classified according to their progression risk (Mayo Clinic). The mean post-diagnosis follow-up was 8.35 ± 14.46 months. Pathological findings were recorded in 49 patients: 30 with myeloma bone lesions (15 in the initial study and 15 in follow-up) and 19 with other neoplastic (n = 13) or pathologically significant findings (n = 6). Body mass index, monoclonal component rate (MCR) > 1 g/dL and ≥1 risk factors for MM were significant in univariate logistic regression analyses. The MCR emerged as the main predictor of a positive 2-[18 F]-FDG PET/CT in adjusted multivariate regression analysis, with an area under the receiver operating characteristic curve of 0.785 and cutoff for optimal sensitivity/specificity of 1.0 ng/mL (71.4% sensitivity, 71.2% specificity). 2-[18 F]-FDG PET/CT results correctly classify patients with MGUS and could improve the detection of bone lesions over existing techniques, with the additional possibility of detecting neoplastic processes. The best parameter to predict a positive 2-[18 F]-FDG PET/CT was the MCR.

Review of diffusion-weighted imaging and dynamic contrast-enhanced MRI for multiple myeloma and its precursors (monoclonal gammopathy of undetermined significance and smouldering myeloma).

The last decades, increasing research has been conducted on dynamic contrast-enhanced and diffusion-weighted MRI techniques in multiple myeloma and its precursors. Apart from anatomical sequences which are prone to interpretation errors due to anatomical variants, other pathologies and subjective evaluation of signal intensities, dynamic contrast-enhanced and diffusion-weighted MRI provide additional information on microenvironmental changes in bone marrow and are helpful in the diagnosis, staging and follow-up of plasma cell dyscrasias. Diffusion-weighted imaging provides information on diffusion (restriction) of water molecules in bone marrow and in malignant infiltration. Qualitative evaluation by visually assessing images with different diffusion sensitising gradients and quantitative evaluation of the apparent diffusion coefficient are studied extensively. Dynamic contrast-enhanced imaging provides information on bone marrow vascularisation, perfusion, capillary resistance, vascular permeability and interstitial space, which are systematically altered in different disease stages and can be evaluated in a qualitative and a (semi-)quantitative manner. Both diffusion restriction and abnormal dynamic contrast-enhanced MRI parameters are early biomarkers of malignancy or disease progression in focal lesions or in regions with diffuse abnormal signal intensities. The added value for both techniques lies in better detection and/or characterisation of abnormal bone marrow otherwise missed or misdiagnosed on anatomical MRI sequences. Increased detection rates of focal lesions or diffuse bone marrow infiltration upstage patients to higher disease stages, provide earlier access to therapy and slower disease progression and allow closer monitoring of high-risk patients. Despite promising results, variations in imaging protocols, scanner types and post-processing methods are large, thus hampering universal applicability and reproducibility of quantitative imaging parameters. The myeloma response assessment and diagnosis system and the international myeloma working group provide a systematic multicentre approach on imaging and propose which parameters to use in multiple myeloma and its precursors in an attempt to overcome the pitfalls of dynamic contrast-enhanced and diffusion-weighted imaging.Single sentence summary statementDiffusion-weighted imaging and dynamic contrast-enhanced MRI provide important additional information to standard anatomical MRI techniques for diagnosis, staging and follow-up of patients with plasma cell dyscrasias, although some precautions should be taken on standardisation of imaging protocols to improve reproducibility and application in multiple centres.

[Radiological diagnosis of multiple myeloma : Role of imaging and the current S3 guideline]. / Radiologische Diagnostik des multiplen Myeloms : Rolle der Bildgebungsverfahren und aktuelle S3-Leitlinie.

CLINICAL ISSUE: Multiple myeloma is a clonal B­lymphocyte neoplasm of terminally differentiated plasma cells and accounts for approximately 10% of all hematologic malignancies. Reduction of bone mass, seen on computed tomography (CT) as focal osteolysis, or general osteopenia is mainly caused by tumor-induced resorption of bone. STANDARD RADIOLOGICAL METHODS: Imaging methods are used in multiple myeloma to record the extent of various dimensions of the disease manifestations (damage to bone substance, bone marrow infiltration, extramedullary involvement) and the disease course. The aim of this review article is to summarize and outline the recommendations of the S3 guideline "Diagnostics, therapy and follow-up care for patients with monoclonal gammopathy of unclear significance (MGUS) or multiple myeloma" in terms of radiographic imaging. APPRAISAL AND PRACTICAL RECOMMENDATIONS: The use of the conventional X­ray skeletal status (Paris scheme) is obsolete. When a patient with symptomatic multiple myeloma is initially diagnosed, a whole-body CT should be performed to determine the extent of skeletal damage. The S3 guideline also regards CT as the first imaging modality in relapse and progression.

The "Undetermined Significance" of 18F-FDG PET/CT or PET/MRI in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS).

Monoclonal gammopathy of undetermined significance (MGUS) is a highly prevalent condition with the possible risk of progression to multiple myeloma (MM) or a lymphoproliferative neoplasm in a small percentage of patients. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI) are imaging methods increasingly used in patients with MM. The aim of this communication is to underline that, taking into account current evidence-based data, compared to MM the role of 18F-FDG PET/CT or PET/MRI in MGUS is still undetermined and more studies should be performed before suggesting 18F-FDG PET/CT or PET/MRI for evaluation of MM progression in patients with MGUS.

Diagnostic relevance of 18F-FDG PET/CT in newly diagnosed patients with monoclonal gammopathy of undetermined significance (MGUS): Single-center experience.

Monoclonal gammopathy of undetermined significance (MGUS) is a known precursor of more serious cancers, such as multiple myeloma (MM), Waldenström macroglobulinemia (MW) and other lymphoproliferative disorders. Using 18F-FDG PET/CT, we aimed to evaluate its benefit in early detection of various accompanying disorders and illnesses in MGUS patients. We prospectively analyzed the diagnostic relevance of 18F-FDG PET/CT in 390 newly diagnosed MGUS patients. On 18F-FDG PET/CT scans, the presence of focal or diffuse areas of detectable increased tracer uptake was recorded in 37 (9.5%) MGUS patients. The most frequent pathology was lymphadenopathy (3.8%), followed by thyroid diseases (2.1%), rheumatic diseases (1.8%), and other solid malignancies (1.5%). These results have major implications for confirmed associations of MGUS with numerous malignant and non-malignant disorders. We believe that 18F-FDG PET/CT imaging in newly diagnosed MGUS patients may be useful in early detection of other serious pathologies, not only in predicting progression of MGUS to active MM, and should be strongly recommended if available.

Gamma-heavy chain monoclonal gammopathy with undetermined significance (MGUS).

Gamma-heavy chain disease (γ-HCD) is a rare B-cell tumor producing truncated IgG lacking the light chain. The clinical features of γ-HCD are heterogeneous, similar to lymphoplasmacytic lymphoma, and most patients have generalized and progressive disease. In some γ-HCD patients, autoimmune diseases are associated. Thus, γ-HCD as a restricted or indolent disease is exceptional. A 66-year-old male was referred to our hospital because of subungual hemorrhage at the bilateral halluces. Physical and laboratory examination results were nonspecific, and the hemorrhage was revealed to be traumatic. However, serum electrophoresis demonstrated a small M-peak, which was monoclonal IgG-Fc without the corresponding light chain on immunofixation and immunoelectrophoresis. Bone marrow aspirate demonstrated a small number of lymphoplasmacytic cells that were positive for CD19, CD38, CD138, and cyIgG, but negative for cyκ- and -λ light chains on flow cytometry. A diagnosis of γ-HCD was made. Chest and abdominal CT demonstrated neither hepatosplenomegaly, lymphadenopathy, nor bone lytic lesions. The serum concentrations of IgG and M-peak configuration have remained relatively unchanged for nearly 3 years. Therefore, this γ-HCD may correspond to a rare form of monoclonal gammopathy with undetermined significance.

Value of low-dose whole-body CT in the management of patients with multiple myeloma and precursor states.

OBJECTIVE: To determine the value of low-dose whole-body CT (WBCT) in the management of patients with multiple myeloma (MM) and precursor states. MATERIALS AND METHODS: The study group comprised 116 patients (mean age: 68 ± 11 years, 48% women) who underwent WBCT for the work-up or surveillance of MM or MM precursor disease. WBCTs were reviewed for the presence of MM-related bone disease and incidental findings requiring therapy. The medical records, results from bone marrow aspirations and biopsies and follow-up imaging studies were reviewed to assess the influence of WBCT on patient management. RESULTS: Whole-body CT led to a change in management in 32 patients (28%). Of those, 17 patients with MM precursor disease were found to have MM-related bone disease, 13 patients had progression of MM, requiring a change in treatment, in one patient hepatocellular carcinoma was diagnosed, requiring a change in therapy, and one patient had a rib lesion requiring intervention. In 65 patients (56%), WBCT was performed for surveillance of MM precursor disease or stable treated MM, and did not detect new lesions, thereby providing reassurance to the hematologist on disease status and management. In 15 patients (13%) WBCT was performed as a new baseline before a change or new therapy. In 4 patients (3%), WBCT was performed for a change in symptoms, but did not detect lesions that would lead to a change in management. CONCLUSION: Whole-body CT provides important information for disease monitoring and detection of incidental findings, thereby improving the management of patients with MM.

Disrupted radial and tibial microarchitecture in patients with monoclonal gammopathy of undetermined significance.

Patients with monoclonal gammopathy of undetermined significance (MGUS) had abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness at both the radius and tibia by high-resolution peripheral quantitative CT compared to matched controls. This is the first report demonstrating that patients with MGUS have microarchitectural deficits at multiple skeletal sites. INTRODUCTION: Fracture risk is elevated in patients with monoclonal gammopathy of undetermined significance (MGUS). However, the pathogenesis of bone disease in these patients is poorly understood. Prior work using high-resolution peripheral CT (HRpQCT) demonstrated abnormal microarchitecture at the radius, with predominantly cortical abnormalities. We hypothesized that patients with MGUS have abnormal microarchitecture at both radius and tibia compared to controls, reflecting global skeletal effects of the disease. METHODS: This case-control study enrolled 36 subjects; patients with MGUS (n = 12) were matched 1:2 by age, sex, and race to controls (n = 24). Areal BMD (aBMD) was measured by DXA, vBMD, and microarchitecture by HRpQCT, and whole bone stiffness by finite element analysis. Serum was drawn for markers of bone metabolism and inflammation. RESULTS: By DXA, MGUS patients had lower aBMD at the lumbar spine, femoral neck, and 1/3 radius. Markers of bone metabolism and inflammation did not differ. By HRpQCT at the radius, MGUS patients had lower total, trabecular and cortical density, lower trabecular number, and greater trabecular separation and heterogeneity. At the tibia, MGUS patients had lower total and trabecular density, lower trabecular number, greater separation and heterogeneity, and lower whole bone stiffness. CONCLUSIONS: Patients with MGUS had lower vBMD, cortical, and trabecular abnormalities at the radius compared to matched controls. At the tibia, trabecular abnormalities predominated. These results suggest that in addition to previously described cortical deficits, deterioration of trabecular bone may contribute to a generalized skeletal fragility in patients with MGUS.

High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma.

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.

Abdominal adipose tissue in MGUS and multiple myeloma.

OBJECTIVE: To determine abdominal adipose tissue parameters on PET/CT in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) that may serve as predictors of progression of MGUS to MM. We hypothesized that patients with MM had higher abdominal adiposity and higher fat metabolic activity compared to patients with MGUS. MATERIALS AND METHODS: Our retrospective study was IRB approved and HIPAA compliant. The study group comprised 40 patients (mean age 64 ± 13 years) with MGUS and 32 patients (mean age 62 ± 10 years) with recently diagnosed MM (mean time since diagnosis of MM 3.0 ± 3.9 months) who had not undergone MM treatment. All patients underwent whole body FDG-PET/CT. Total abdominal adipose tissue (TAT), abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) cross sectional areas (CSA) (cm(2)) and metabolic activity (SUV) were assessed. Groups were compared using ANOVA. ROC curve analysis was performed to determine cutoff values for abdominal adipose tissue parameters to detect MM. RESULTS: Patients with recently diagnosed MM had higher TAT and SAT CSA (p ≤ 0.03) and higher fat metabolic activity (p < 0.01). VAT metabolic activity showed the highest sensitivity and specificity for identifying patients with MM (area under the curve 0.95 with cutoff value of >0.34, sensitivity 90.6 %, specificity 92.5 %, p < 0.0001). CONCLUSIONS: Patients who were recently diagnosed with MM had higher abdominal fat CSA and higher fat metabolic activity compared to patients with MGUS. These parameters may serve as novel biomarkers of progression of MGUS to MM.

Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.

Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging.

The incidence and importance of bone marrow involvement and/or early bone lesions in multiple myeloma (MM) precursor diseases is largely unknown. This study prospectively compared the sensitivity of several imaging modalities in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and MM. Thirty patients (10 each with MGUS, SMM and MM) were evaluated with skeletal survey, [18F]FDG-PET/CT, [18F]NaF-PET/CT and morphologic dynamic contrast enhanced (DCE)-MRI. An additional 16 SMM patients had skeletal surveys and FDG-PET/CT. Among MGUS patients, DCE-MRI found only one focal marrow abnormality; other evaluations were negative. Among 26 SMM patients, five (19%) were re-classified as MM based on lytic bone lesions on CT and six had unifocal or diffuse marrow abnormality. Among MM, marrow abnormalities were observed on FDG-PET/CT in 8/10 patients and on DCE-MRI in nine evaluable patients. Abnormal NaF uptake was observed only in MM patients with lytic lesions on CT, providing no additional clinical information.

¹8F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders.

Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a higher screening and diagnostic sensitivity and specificity over the skeleton X-ray. In patients with monoclonal gammopathy of undetermined significance and in those with smoldering MM, PET/CT is consistently unable to detect focal and/or diffuse marrow abnormalities. Conversely, based on a systematic review of 18 studies comprising almost 800 MM patients, PET/CT was able to detect MM osteolytic lesions with a sensitivity of approximately 80-90% and a specificity of 80-100%. Importantly, a poor degree of concordance has also been emphasized between PET/CT and whole-body magnetic resonance imaging (WB-MRI) in that when both techniques were applied to the same patients, double-positive results were recorded in approximately 30% of the cases, but in the majority of them, a higher number of lesions were revealed with PET/CT than with MRI. Double-negative results, on the other hand, were found in about 22% of the patients. Because PET/CT is able to identify tumor foci throughout the body, it can be usefully applied to the study of solitary bone plasmacytoma and extra-medullary plasmacytoma: In both conditions, the detection of additional, previously overlooked sites of skeletal involvement would falsify the diagnosis of single-district disease, upstage the tumor, and therefore require a different therapeutic approach. In addition, although PET/CT is poorly sensitive to diffuse bone marrow infiltration, it can anticipate a site of impending fracture throughout the body and can discriminate old from new pathologic fractures. MRI should, however, be preferred when vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. PET/CT is a sensitive and reliable procedure to evaluate the response to chemotherapy and/or radiotherapy, which is shown by a remarkable reduction and sometimes total disappearance of FDG accumulation in the involved bony structures, although these structures remain morphologically abnormal. Conversely, an increased focal uptake of FDG in apparent remission patients often precedes clinically overt relapse. PET/CT should be preferred to other imaging techniques to assess the remission status after autologous stem cell transplantation. In patients with primary and remission-induced non-secretory MM, the use of PET/CT may help to early detect single or multiple districts of focal non-secretory relapse. Osteonecrosis of the jaw, its location, and extent in MM patients receiving bis-phosphonates are better defined by both PET/CT and contrast-enhanced MRI compared with dental panoramic views derived from cone beam CT imaging. Little is known as to the possible role of PET/CT in the assessment of disease extension, tumor load, and response to therapy in patients with Waldenström's macroglobulinemia (WM). In a study conducted on 35 WM patients, comparative PET/CT before and after therapy was able to detect positive findings in 83% of the patients, in contrast with the previous results achieved with conventional imaging that reported visceral involvement in much lower percentages. Similarly scanty are the data on the use of PET/CT in localized and systemic amyloidosis, given the small number of patients studied so far. A retrospective study has shown that, at variance from (123)Iodine-serum amyloid P component ((123)I-SAP) scintigraphy, which was found to be positive in about one-third of the patients with localized amyloidosis, an increased FDG uptake was detected at the amyloid site in virtually all of them. On the contrary, none of the patients with systemic amyloidosis showed an increased FDG uptake in sites of known deposition, whereas (123)I-SAP scintigraphy tested positive in the large majority of them. In another study, however, no such remarkable difference of positive PET/CT scans between localized and systemic amyloidosis was reported. Finally, false-positive and false-negative PET/CT findings can occur in different conditions that should be kept in mind to avoid wrong or omitted diagnoses.

Analysis of thymidine kinase serum levels by novel method DiviTum in multiple myeloma and monoclonal gammopathy of undetermined significance - comparison with imaging methods 99mTc-MIBI scintigraphy and 18F-FDG PET/CT.

AIMS: The study aimed at comparing two methods for evaluating thymidinekinase TK in serum - an older RIA method and novel DiviTum - in patients with MM and MGUS, and also comparing them with biochemical markers and degree of activity evaluated by imaging methods 99mTc-MIBI scintigraphy and 18F-FDG PET/CT. METHODS: Serum thymidinekinase TK levels were evaluated by DiviTum and an RIA method (TK REA kit by Immunotech);The study analyzed correlation of TK activity in serum with biochemical markers reflecting activity of MM: ß2-m, LDH, the ratio of kappa to lambda (κ/λ) free light chains and percentage of bone marrow plasma cells (BMPC). 99mTc-MIBI scintigraphy and 18F-FDG PET/CT were performed at the time of diagnosis. The degree of activity was expressed semiquantitatively. Scans were classified as 0 (normal activity), 1 (diffuse positivity) or 2 (focal positivity). RESULTS: We found a strong positive correlation between TK in serum evaluated by DiviTum and by TK REA.. The DiviTum analytic method extended the detection range and was able to detect higher levels of TK than the RIA method. DiviTum technique found positive correlation with ß2-m (r = 0.497) and LDH (r = 0.502) and moderate positive correlation with BMPC (r = 0.368). Significantly higher TK values measured by TK REA and DiviTum in the group of patients with MM (stages I, II or III) than in those with MGUS. Increased TK levels were observed in MIBI- or PET/CT-positive patients. Analysis of repeated measurements of TK in serum during treatment of MM patients found a correlation between change in TK measured by DiviTum and LDH during treatment. CONCLUSIONS: Analysis revealed a significant correlation between TK in serum and LDH, ß2-m and BMPC. Increased levels of TK in serum were observed in MIBI- or PET/CT-positive patients. Combination of positivity of imaging methods which can localize active tumor lesions and increased levels of TK in serum can have an impact on decision-making and optimization of the therapeutic approach.

[Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ]. / Monoklonální gamapatie nejistého významu a asymptomatický mnohocetný myelom z pohledu roku 2014.

Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in some cases produce toxic monoclonal immunoglobulin which can damage the body's own antibody activity by binding to specific antigens (such as cold agglutinin disease), or their deposits in organs (e.g. kidney damage) or physical properties (e.g. cryoglobulinemia). Therefore, it is recommended that this group of people is regularly checked with the aim to capture not only transformation into symptomatic multiple myeloma or another malignant disease, but also the formation of the above-mentioned complications. Moreover, it is recommended to monitor patients with asymptomatic myeloma and to initiate treatment only after symptoms of multiple myeloma are observed. In 2014, discussion of subdivision of subgroups of patients with asymptomatic myeloma with high ( 80 %) probability of early (within 2 years) transformation in multiple myeloma which would be beneficial for early initiation of treatment is ongoing. According to first proposals, patients with asymptomatic myeloma that meet at least one of the three conditions: more than 60 % of plasma cells in the bone marrow, ratio of free light kappa and lambda chains is greater than 100 or less than 0.01, or multiple focal lesions on whole-body MRI of the skelet. The review contains current opinions on prognostic classification and appropriate intervals and extent of control examinations.

Tc 99m Sestamibi Scanning in Multiple Myeloma--a New look with SPECT-CT.

UNLABELLED: A variety of diagnostic tools including biochemistry, radiological imaging bone marrow studies and recently metabolic imaging with FDG PET are used for assessment of disease extent in myeloma. AIM: To evaluate the role of metabolic imaging with Tc99m Sestamibi (Mibi) SPECT-CT in Multiple myeloma. MATERIALS AND METHODS: Patients in various stages of Myeloma were scanned after 20mCi Tc99m Sestamibi was injected i/v. Whole body planar scans were obtained with a dual head gamma camera and SPECT-CT imaging was done. Images were analyzed for degree and extent of abnormal Mibi uptake, extent of lesions seen on low-dose CT and fusion of these images. RESULTS: 112 Whole body Sestamibi Scans were performed in 84 patients (46 Males; 38 Females). Out of these 24 (28.5%) were recently diagnosed cases (Pre-therapy); 35 (41.7 %) were follow-up cases who had received Chemotherapy in the past (Post-therapy), there were 2 cases (2.3%) of Smouldering Myeloma, 4 cases (4.7%) of Plasmacytoma, 13 cases (15.5%) of MGUS (Monoclonal gammopathy of Unknown Significance) and 3 cases (3.6%) of suspected Myeloma (not biopsy confirmed). Myeloma lesions showed good concentration of Mibi. Additionally, the CT scan component of SP.ECT-CT allowed visualization of osteolytic lesions of myeloma. Mibi uptake becomes positive on scan earlier than radiological changes and in follow-up cases, the presence or absence of Mibi uptake could differentiate active from old burnt-out lesions. Whole body scan could detect additional lesions in Plasmacytoma patients. Patients of MGUS showed poor concentration of Sestamibi. CONCLUSION: Whole body Sestamibi Imaging (WBSI) is very useful for evaluating the extent of disease in multiple myeloma. Being a metabolic imaging modality it is superior to radiological (X-ray or CT) assessment alone, and where FDG PET scan is not available, it is a valuable tool for myeloma assessment at a much lower cost.

Monoclonal gammopathy of undetermined significance: a new proposal of workup.

OBJECTIVE: Diagnostic criteria for monoclonal gammopathy of undetermined significance (MGUS) require quantification of bone marrow plasma cells (BMPCs) and skeletal survey to discriminate between MGUS and multiple myeloma (MM). By contrast, recent published guidelines suggest that these procedures could be avoided in the presence of serum monoclonal spike (M-spike) of small amount (≤1.5 g/dL). Aim of this study is to better quantify the risk of missing a diagnosis of MM, not performing bone marrow aspirate and skeletal survey in patients with M-spike ≤ 1.5 g/dL asymptomatic for bone pain. METHODS: We reviewed data of 2282 patients consecutively observed from January 1974 to December 2010 in our single hematology department. We considered eligible for this study 1271 patients with grade <2 NCI bone pain, confirmed to have an MGUS or an MM after extensive standardized diagnostic workup including bone marrow biopsy, skeletal bone survey and laboratory tests. RESULTS: The risk of finding a BMPC infiltration ≥10% in patients with an M-spike ≤ 1.5 g/dL was very low (7.3%), although significantly different according to IgH isotype (4.7% for IgG vs. 20.5% for IgA). The risk of finding bone lesions with M-spike ≤ 1.5 g/dL was negligible (2.5%), regardless of IgH isotype. CONCLUSION: In asymptomatic patients with M-spike of small amount (≤1.5 g/dL): (i) BMPC evaluation may be reasonably avoided in patients with IgG M-spike, while should always be part of diagnostic workup in the presence of IgA M-spike and (ii) skeletal survey, less predictive for MM, should not be routinely indicated irrespective of IgH isotype.

Can whole-body low-dose multidetector CT exclude the presence of myeloma bone disease in patients with monoclonal gammopathy of undetermined significance (MGUS)?

RATIONALE AND OBJECTIVES: To determine the benefit of using whole-body low-dose computed tomography (WBLD-CT) in patients with monoclonal gammopathy of undetermined significance (MGUS) for exclusion of multiple myeloma (MM) bone disease. MATERIALS AND METHODS: Seventy-one consecutive patients with confirmed MGUS (as defined by the latest criteria of the International Myeloma Working Group) who underwent WBLD-CT for diagnosis were identified retrospectively by a search of our institution's electronic medical record database (2002-2009). Patients were classified as low-risk or intermediate/high-risk and followed over a ≥2-year period with additional CT imaging and/or laboratory parameters. Presence of osteolysis, medullary, or extramedullary abnormalities compatible with involvement by MM was recorded. A diffuse or focal increase in medullary density to Hounsfield unit (HU) values >20 HU/>0 HU was considered suspicious for bone marrow infiltration if no other causes identifiable. RESULTS: The presence of osteolysis was excluded in all 71 patients with MGUS at initial diagnosis and patients were surveilled for ≥2 years. Lytic changes were observed at follow-up in 1/71 patients that progressed to MM and were detectable via WBLD-CT at an early stage (even before a significant rise in M-protein was recorded). In 3/71 patients with MGUS (4%) suspicious bone marrow attenuation values were measured, disclosing disease progression to smoldering myeloma in another patient and false-positive results in 2/71 patients. Bone marrow attenuation assessment resulted in a specificity and negative predictive value of 97%, respectively. No significant difference with respect to bone marrow attenuation was observed in patients with low-risk MGUS versus intermediate- to high-risk MGUS. One of 71 patients showed serologic disease progression to active MM without bone abnormalities detectable. CONCLUSION: WBLD-CT reliably excludes findings compatible with myeloma in MGUS and thereby complements hematologic laboratory analysis.