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

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Abstract

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 18fluorine-fluorodeoxyglucose (18F-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 123Iodine-serum amyloid P component (123I-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 123I-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.

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Abbreviations

18F-FDG:

18Fluorine-fluorodeoxyglucose

99mTc-MIBI:

99metaTechnetium-methoxyisobutyl isonitrile

123I-SAP:

123Iodine-serum amyloid P component

ASCT:

Autologous stem cell transplantation

BPs:

Bisphosphonates

CR:

Complete response

CRAB:

Increased calcium, renal failure, anemia, and bone lesions

CRSS:

Conventional radiographic skeletal survey

CT:

Computed tomography

DW-MRI:

Diffusion-weighted magnetic resonance imaging

EMD:

Extra-medullary disease

EMP:

Extra-medullary plasmacytoma

GEP:

Gene expression profiling

IMWG:

International myeloma working group

ISS:

International staging system

MDCT:

Multidetector computed tomography

MGUS:

Monoclonal gammopathy of undetermined significance

MM:

Multiple myeloma

MRI:

Magnetic resonance imaging

MTV:

Metabolic tumor volume

ONJ:

Osteonecrosis of the jaw

OS:

Overall survival

PET:

Positron-emission tomography

PFS:

Progression-free survival

ROTI:

Related organ or tissue impairment

SBP:

Solitary bone plasmacytoma

SCT:

Stem cell transplantation

SMM:

Smoldering multiple myeloma

SP:

Solitary plasmacytoma

SUV:

Standardized uptake value

TTP:

Time-to-progression

VGPR:

Very good partial response

WB:

Whole body

WBDW:

Whole-body diffusion weighted

WBMRI:

Whole-body magnetic resonance imaging

WBPR:

Whole-body planar radiographs

WM:

Waldenström’s macroglobulinemia

β2m:

Serum beta-2 microglobulin

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Acknowledgments

This study was supported by the Italian Association for Cancer Research (AIRC), Milan, and the Italian Ministry of University and Scientific and Technological Research, Rome.

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The authors report no potential conflict of interest relevant to this article.

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Authors and Affiliations

  1. Guido Baccelli Unit, Department of Internal Medicine and Clinical Oncology, Policlinico, University of Bari Medical School, Piazza G. Cesare, n. 11, 70124, Bari, Italy

    Franco Dammacco, Angelo Vacca & Vito Racanelli

  2. Nuclear Medicine Unit, Department of Interdisciplinary Medicine, University of Bari Medical School, Bari, Italy

    Giuseppe Rubini & Cristina Ferrari

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  1. Franco Dammacco
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  2. Giuseppe Rubini
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Correspondence to Franco Dammacco.

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Dammacco, F., Rubini, G., Ferrari, C. et al. 18F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders. Clin Exp Med 15, 1–18 (2015). https://doi.org/10.1007/s10238-014-0308-3

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