18F-FDG PET/CT of extramedullary disease in newly diagnosed multiple myeloma: imaging findings and its correlation with clinical indicators and outcome

Objectives: Extramedullary disease (EMD) is a type of multiple myeloma(MM) refers to extra bone marrow clonal plasma cell infiltration. Clinically it can be described as bone-related EMD (bEMD) that is a tumor mass adjacent to bone and extending to soft tissue, and strict EMD (sEMD) that is soft tissue or visceral tumor that is not connected to the bone or clonal plasma cell diffuse infiltration of organs without any obvious focal lesion. EMD often indicates a poor outcome and resistance to treatment. The purpose of this article is to describe the PET / CT imaging characteristics of EMD in newly diagnosed multiple myeloma and correlate them with clinical indicators and outcome. Materials and methods: Ninety consecutive newly diagnosed MM patients undergoing PET/CT imaging in our hospital from October 2011 to April 2019, including 50 males and 40 females, with an average age of 60.6 ± 9.9 years, were enrolled in this retrospective study. The PET / CT images were reviewed according to the IMPeTUs visual evaluation criteria. All patients underwent blood routine, biochemical, and immunofixation electrophoresis tests, of which 74 patients completed β2 microglobulin assay, 84 patients completed bone marrow morphology and flow cytology, and 61 patients completed bone marrow fluorescence in situ hybridization. The median follow-up was 20 (3 to 90) months, and the end of follow-up was June 30, 2019. Statistical analysis was performed to determine if SUVmax and Deauvill scores differed between bEMD and sEMD, as well as laboratory results between patients with and without EMD, using independent sample t-test or chi-square test. Kaplan-Meier method was used to draw a survival curve to analyze the overall survival (OS) and progression-free survival (PFS) between patients without EMD, with bEDM, and with sEMD. Differences between groups were compared by Log-rank test. All statistical analyses were performed using SPSS 24.0 software. P <0.05 was considered statistically significant.

Results: In this group of 90 patients with newly diagnosed myeloma, a total of 80 EMD were detected in 41 (45.6%) patients, of which 63 were bEMD. and most lesions were located in spine (26), followed by ribs (19), pelvis (7), Skull (4), scapula (3), long limbs (2), sternum and mandible (1 each). 17 are sEMD, among which 4 were located in lymph nodes, 4 in kidney, 3 in muscle space, 2 in pancreas, 1 each in orbit, nasal cavity, chest and breast. The SUVmax of bEMD lesions was lower than sEMD (5.67 ± 5.85 and 12.24 ± 12.41, t = -2.12, p = 0.048), but there was no statistical difference in Deauville scores of bEMD and sEMD lesions (X² = 2.01, p = 0.367). Hemoglobin, creatinine, serum calcium, lactate dehydrogenase, β2 microglobulin, immunoglobulin type, DS, ISS and RISS clinical stage composition ratio, and the occurrence rate of high-risk cytogenetic phenotypes showed no statistical difference between the two groups with or without EMD. The proportion of bone marrow plasma cells and the proportion of CD38/CD138 positive cells in patients with EMD were lower than those without EMD (t=2.41, p=0.018 and t=2.22, p=0.029). By the end of the follow-up, a total of 26.7% (24/90) patients had died. The mortality rate of patients without EMD, with bEMD and with sEMD was 16.3% (8/49), 36.4% (12/33) and 50.0% (4/8), respectively. Kaplan-Meier survival analysis showed that patients without EMD had better OS than those with bEMD or sEMD (X²=3.923, p=0.048, X²=5.553, p=0.018). There was no statistical difference in OS between patients with bEMD and patients with sEMD (X²=0.213, p=0.645). There were no significant differences in PFS between patients without EMD, with bEMD, and with sEMD (X²=2.099, p=0.350).

Conclusions: When myeloma patients developed EMD, most of them were bEMD involving axial skeleton, sEMD was relatively rare. PET/CT detection of EMD indicates poor prognosis, but it is not related to the type of EMD.