**1. Introduction**

Multiple myeloma (MM) is a neoplastic plasma cell disorder, characterized by the uncontrolled, clonal proliferation of plasma cells in the bone marrow. It is the second most common hematologic malignancy after non-Hodgkin lymphoma and accounts for approximately 1% of neoplastic diseases [1]. MM is almost always preceded by a premalignant precursor condition (monoclonal gammopathy of undetermined significance, MGUS), which then develops into asymptomatic or smoldering myeloma (SMM) and, finally, into symptomatic disease [2,3]. SMM represents a highly heterogeneous entity with a progression risk to MM of 10% per year during the first five years after diagnosis [4]. Different risk stratification models for progression of SMM to MM have been developed, the most popular being the Mayo Clinic model, which utilizes M-protein, bone marrow plasma cell infiltration and the ratio of serum free light chain, and the Spanish model, which uses flow-cytometry to define the proportion of aberrant plasma cells in the marrow and the presence of immunoparesis [5,6]. The identification of those SMM patients who have a high risk of progression to active, symptomatic disease is of utmost clinical importance, since these patients would benefit from early treatment commencement [7,8]. In this context, in 2014, the definition of MM was revised by the International Myeloma Working group (IMWG), including the subset of SMM patients with an 80% two-year risk of progression to symptomatic MM, based on findings from bone marrow biopsy, serum free light chain and magnetic resonance imaging (MRI) [9].

**Citation:** Sachpekidis, C.; Türk, M.; Dimitrakopoulou-Strauss, A. Quantitative, Dynamic 18F-FDG PET/CT in Monitoring of Smoldering Myeloma: A Case Report. *Diagnostics* **2021**, *11*, 649. https://doi.org/ 10.3390/diagnostics11040649

Academic Editors: Lioe-Fee de Geus-Oei and F.H.P. van Velden

Received: 2 March 2021 Accepted: 2 April 2021 Published: 3 April 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

The role of positron emission tomography/computed tomography (PET/CT) with the radiotracer 18F-fluorodeoxyglucose (18F-FDG) in multiple myeloma (MM) has been markedly upgraded in recent years. A steadily increasing amount of literature has highlighted the value of the imaging modality in diagnosis, prognosis and treatment response evaluation of the disease [10–15]. Proof of the established role of PET/CT in MM management, is its inclusion in the latest updated criteria for the diagnosis of the disease by IMWG. In particular, the detection of one or more osteolytic lesions on CT or PET/CT fulfills the criteria of bone disease and, therefore, of symptomatic MM requiring treatment [10]. Although still limited, the first results of the application of 18F-FDG PET/CT in asymptomatic SMM have been promising, reflecting the potential role of the modality in predicting the risk of progression to symptomatic disease [16,17].

On the other hand, in myeloma—more than in other malignancies—issues on the evaluation of 18F-FDG PET/CT exist. This is mainly attributed to the different patterns of bone marrow involvement in the disease, which results in poor inter-observer reproducibility in scan interpretation [18]. In an attempt to standardize the interpretation of 18F-FDG PET/CT scans in MM, several efforts have been undertaken, making use of visual [18,19] as well as semi-quantitative and quantitative approaches [20–24]. However, none of these methods have been ye<sup>t</sup> extensively applied in clinical practice.

We herein report on a patient with an initial diagnosis of SMM who was monitored throughout the physical history of the disease by means of quantitative, dynamic 18F-FDG PET/CT.
