Whole Body Magnetic Resonance Imaging with Diffusion Weighted Imaging Is a Valuable Alternative to Contrast-Enhanced Computed Tomography for the Initial Staging in Hodgkin’s and Non-Hodgkin’s Lymphoma
Authors: Balbo-Musetto Annalisa , Bruna Riccardo , Gueli Angela , Saviolo Chiara , Petracchini Massimo , Gottardi Daniela , De Crescenzo Alberto , Cirillo Stefano , Tarella Corrado 
Published: October 2019

Abstract
Background. The assessment of nodal and extranodal involvement in Hodgkin’s (HL) and non-Hodgkin’s (NHL) lymphoma is mostly performed by Computed Tomography with i.v. iodinated contrast agent (CE-CT) and 18F-FDG Positron Emission Tomography (PET), along with bone marrow (BM) biopsy. Both CE-CT and 18F-FDG-PET require the delivery of considerable dose of ionizing radiation, that may be of concern given the increased risk of secondary malignancies in long surviving patients. Whole body Magnetic Resonance Imaging (Wb-MRI) is a novel and promising radiation-free technique and the development of Diffusion Weighted Imaging (DWI) has enhanced its diagnostic potential. At our Institution, Wb-MRI-DWI has been used as additional diagnostic tool in a series of lymphoma patients at disease onset. The diagnostic accuracy of the procedure is here reported.
Patients and Methods. From February 2010 to October 2013, 41 patients underwent the Wb-MRI-DWI procedure, which was added to the standard procedures in order to further investigate possible bone, liver and kidney involvement. Median age of the patients was 49 yrs. (20-76), histological subtypes included 10 Diffuse Large B-Cell (DLB-CL), 13 Follicular (FL), 3 Mantle-cell (MCL), 1 Burkitt’s (BL) Lymphoma and 14 HL. All patients received the diagnostic procedures required for staging definition, including CE-CT, BM biopsy, and 18F-FDG-PET co-registered with low dose unenhanced CT. Nodal and extra-nodal sites were considered pathologic according to standard parameters employed for imaging technique evaluation. For the present analysis, the Gold Standard (GS) assessment was defined based on: i. the information obtained primarily by 18F-FDG PET-CT and secondary by CE-CT findings; ii. the BM histological examination; iii. the modifications before and after therapy for those lesions with discordant definition at diagnosis; iv. for few lesions, with uncertain definition at diagnosis a biopsy procedure was performed and histological data were considered true positive.
Results. According to GS, among 1,025 nodal regions analyzed in 41 patients, 217 were judged positive for involvement by lymphoma. CE-CT had 22 false negative and 10 false positive errors, whereas Wb-MRI-DWI erroneously considered involved 6 nodes and failed in recognizing 17 localizations, mostly for misdiagnosed nodes in the mediastinum. There were no errors in nodal assessment by 18F-FDG PET-CT. A total of 458 extranodal sites were evaluated and 37 were considered positive. Compared to GS, 18F-FDG PET-CT had four false negative errors, i.e. no detection of BM (three cases) and spleen (one case) involvement; in addition, 18FDG PET-CT had two false positive results, due to presumed tonsil and BM involvement that were not confirmed on histological examination. CE-CT had 17 false negative errors mainly due to misdiagnosis of BM involvement in 13 out of 14 BM positive cases. Other false negative errors with CE-CT were lack of disease detection in the spleen (1 case), oropharyx (2 cases) and vulva (1 case). Wb-MRI-DWI was unable to detect the gastric involvement in one patient, while no false positive were recorded. The comparative analysis indicates that: i.18F-FDG PET-CT alone overstaged two patients (4.9%) (wrong involvement in BM and tonsil), two patients were understaged due to the failure in recognizing BM involvement; ii. CE-CT alone understaged 12 patients (29%), mainly due to low sensibility in detecting BM involvement; no patient was overstaged by CE-CT; iii. Wb-MRI-DWI alone, in spite of the 24 errors, mainly in nodal misdiagnosis, did not fail the final per-patient staging assessment. Wb-MRI-DWI proved to be the most reliable imaging technique for BM evaluation, with no misjudgment recorded, while 18F-FDG PET-TC was unable to correctly assess BM involvement in four patients and CE-CT in 13.
Conclusion. The data indicate that Wb-MRI-DWI is a sensitive and specific imaging technique for malignant lymphoma evaluation. Compared to CE-CT, it detects additional disease that modify clinical stage in a significant percentage of patients, altering their management and outcome. Wb-MRI-DWI is also extremely effective in detecting BM involvement. Thanks to the lack of any radiation exposure and intravenous contrast agent injection, the results here reported further support the use of Wb-MRI-DWI in place of CE-CT for the staging and possibly the follow up monitoring of malignant lymphoma.

Disclosures
No relevant conflicts of interest to declare.