Diagnostic Relevance of 18F-FDG PET/CT in Newly Diagnosed Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) : Single- Center Experience

Introduction:

The International Myeloma Working Group (IMWG) consensus aimed to provide recommendations for the optimal use of positron emission tomography-computed tomography (PET/CT) in patients with multiple myeloma (MM) and other plasma cell disorders, including smouldering multiple myeloma (SMM) and solitary plasmocytoma (Cavo M et al., Lancet Oncol. 2017). Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common pre-malignant disorders, in which the probability of progression to MM or other lymphoproliferative disorders is 1% per year (Kyle RA. Blood 2003). MGUS patients have an increased risk of developing hematologic and non-hematologic malignancies (Mailankody S, et al. Blood. 2011; Gregersen H et al., Am J Hematol. 2000). Data for the role of ¹⁸F-FDG PET/CT in diagnostic relevance in newly MGUS patients are still limited. We think, that using ¹⁸F-FDG PET/CT imaging in newly MGUS patients may be useful in early detection of other serious pathologies, not only in predicting progression of MGUS to active MM.

Patients and methods:

We prospectively analyzed the diagnostic relevance of ¹⁸F-FDG PET/CT in 390 newly MGUS patients . All MGUS patients were diagnosed and monitored at the Department of Internal Hematology and Oncology in Brno, Czech Republic from January 2010 to December 2016. The diagnosis of MGUS was made according to updated 2010 International Myeloma Working Group diagnostic criteria (Kyle RA et al., Leukemia 2010). Imaging scans were reviewed by a radiologist and a nuclear medicine physician. The aim of this analysis was to evaluate the benefit of ¹⁸F-FDG PET/CT in early detection of other serious illnesses in newly MGUS patients. This study did not focuse on the MGUS patients re-classified as MM. Patients underwent ¹⁸F-FDG PET/CT within 6 months of MGUS diagnosis. At the time of ¹⁸F-FDG PET/CT imaging the patients showed no specific symptoms indicative of later diagnosed serious illnesses.

Results:

A total of 390 newly diagnosed MGUS patients were evaluated, and by IMWG definition had no lytic lesions on skeletal survey. On ¹⁸F-FDG PET/CT, presence of focal or diffuse areas of detectable increased tracer uptake on at least two consecutive slices was recorded in 36 (9.2%) of MGUS patients. The most frequent pathology was lymphadenopathy (3.8%), followed by thyreopathy (2.1%), rheumatologic diseases (1.8%) and others solid tumors (1.3%). Primary malignancy was confirmed by biopsy in 17 (4.4%) patients. This included 12 (3.1%) patients with lymphoproliferative diseases and 3 (0.8%) patients with colon cancers. In 1 case prostate and thyroid cancer was diagnosed.

On ¹⁸F-FDG PET/CT focal lymph nodes abnormalities were detected in 15 (3.8%) evaluable patients. Twelve (3.1%) patients were reclassified as having lymphoproliferative diseases. Among the remaining 3 patients with lymph nodes abnormalities 1 patient was detected with Sjögren's syndrome, 1 patient with sarcoidosis, and 1 patient with reactive lymphadenopathy ,without detection of malignant cells after biopsy. None of the patients had symptoms typical for lymphoproliferative diseaseas at the time of ¹⁸F-FDG PET/CT imaging. Thyreopathy was the second most common pathology in our study, observed in 8 (2.1%) patients. In 1 patient thyroid carcinoma was diagnosed; among the remaining 7 (1.8%) patients with focal thyreoid abnormalities nontoxic struma was found. All patients' thyroid hormones tested within the normal range at the time of ¹⁸F-FDG PET/CT imaging. Rheumatologic diseases were the third most common pathology, occurring in 7 (1.8%) of all scanned patients. Specifically, there were 4 (1.1%) patients with rheumatoid arthritis, 2 (0.5%) patients with polymyalgia rheumatica and 1 patient with giant-cell temporal arteritis. In 1 patient thymoma and schwannoma of the femoral nerve were identified. For all these patients, all diseases were early-onset without typical symptoms.

Summary:

In conclusion, using newer sensitive imaging tool we detected 36 (9.2%) patients with serious pathologies before the first symptoms. Therefore we believe, that ¹⁸F-FDG PET/CT imaging can be recommended to be done not only in all MGUS patients with suspected SMM or active MM, but also for early identification of other serious pathologies.