Diagnostic Accuracy of Immunoglobulin Heavy Chain Rearrangement, FDG-PET/CT and Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Diffuse Large B Cell Lymphoma
Authors: Jung Seung-Yeon , Jung Sung-Hoon , Ahn Seo-Yeon , Lee Je-Jung , Kim Hyeoung-Joon , Lee Jun Hyung , Shin Myung Geun , Yoo Su Woong , Yang Deok-Hwan 
Published: October 2019

Abstract
Bone marrow involvement (BMI) has important clinical implication in diffuse large B cell lymphoma (DLBCL) as a component of staging and International Prognostic Index (IPI). However, there are some limitations of BMI assessment using iliac bony trephination, such as low sensitivity to patchy or focal lymphomatous involvement, inter-observers variability, inappropriately obtained specimens in terms of technical problem. This study investigated that whether the combined evaluation with 18F-FDG PET/CT and molecular analysis of monoclonal Immunoglobulin heavy chain (IgH) rearrangement could increase the diagnostic accuracy of BMI at the time of diagnosis in DLBCL.
Methods
This observational study conducted in 100 patients with newly diagnosed DLBCL from January 2017 to May 2018 from single institution. The specimens for IgH rearrangement polymerase chain reaction (PCR) to detect the clonality were obtained by fine-needle aspiration and unilateral trephination biopsy. In addition, 18F-FDG PET/CT assessment was performed at the time of diagnosis and classified into two patterns (focal vs diffuse) based on the type of bony FDG uptakes. The section specimens were reviewed by hematopathologists according to the World Health Organization (WHO) classification.
Results
53 patients were diagnosed with advanced stage and 9 patients (9%) were confirmed morphologic BMI (mBMI) by section biopsy. IgH monoclonality (IgH BMI) was detected in 17 patients (17%) and bony involvement on PET/CT assessment (PET BMI) was observed in 16 patients (16%), respectively. All nine patients with mBMI were linked together with either IgH BMI or PET BMI. Of 17 patients with IgH BMI, 6 patients (35.2%) were concordant with mBMI. Overall diagnostic accuracy of IgH BMI for detection of mBMI was 86%, and it`s sensitivity and specificity was 66.7% and 87.9% with 96.4% of negative predictve value (NPV), respectively. In addition, among the patients with PET BMI, 11 patients were sub-classified into focal type (68.8%, 11/16) with median 7.9 of SUVmax compared to diffuse type with median 5.6 of SUVmax. 5 patients (31.3%, 5/16) were concordant with mBMI. Two of these five concordant cases were focal type. PET/CT assessment showed 85% of diagnostic accuracy with 55.6% of sensitivity, 87.9% of specificity and 95.2% of NPV, respectively. However, the combination of IgH rearrangement with PET/CT assessment resulted in 100% of sensitivity and 79.1% of specificity with 100% of NPV, respectively. Total 28 patients had positive results either IgH rearrangement or PET BMI. 11 patients showed only PET BMI, and another 12 showed only IgH BMI.
Conclusion
Each PET/CT assessment and PCR-technique for IgH rearrangement was associated with low sensitivity and high NPV for detecting mBMI. However, combined evaluation with IgH monoclonality and initial PET/CT could give more information to predict bone marrow involvement of DLBCL

Disclosures
No relevant conflicts of interest to declare.