The Clinical Utility of FDG PET-CT in Evaluation of Bone Marrow Involvement by Diffuse Large B Cell Lymphoma

In lymphoma, bone marrow (BM) involvement is a sign of extensive disease and BM biopsy is a standard method in the evaluation of BM infiltration by disease. Because of patchy BM involvement pattern by lymphoma, the reported rates of unilateral involvement in bilateral biopsies range from 10% to 50%. However BM biopsy is an invasive and painful procedure. The value of unilateral versus bilateral BM biopsy remains controversial. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is a noninvasive imaging technique and currently it shows potential to detect BM involvement by lymphoma. Aims. We assess the abilities of FDG PET-CT to ascertain the presence of BM involvement in diffuse large B cell lymphoma (DLBCL) patients and to define the possibility that bilateral BM biopsies could be replaced by unilateral biopsy for DLBCL staging workup. Methods. We retrospectively reviewed medical records of histologically proven DLBCL patients from 2004 through 2010 at the Asan Medical Center and Hallym University Medical Center. All patients were examined by FDG PET-CT and bilateral BM biopsy at both posterior iliac crests for initial staging workup. Evaluation of PET studies was performed by board-certified nuclear medicine physicians of each institution. Quantitative analysis of FDG uptake was not performed. Data were expressed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for FDG PET-CT in evaluation of BM involvement by DLBCL, using BM biopsy as the reference standard. Two sets (right & left biopsy site) of pathologic and imaging data were analyzed separately. Results. Study population comprised 478 patients (median age 57, range 17–85 years; 269 male) with newly diagnosed DLBCL. Ann Arbor stage I, II, III and IV patients were 96, 120, 40 and 222, respectively. Overall, BM involvement by DLBCL that confirmed by bilateral BM biopsy occurred in 63 patients (13.2%, 15, 12, and 36 at right, left and both side biopsy, respectively). From the data of right side biopsy and FDG PET-CT images, comparison of the former and the later results revealed concordant positive findings in 22 cases (4.6%) and concordant negative findings in another 418 cases (87.4%). In 29 patients (6.1%) in whom FDG PET-CT returned findings of normal marrow, iliac crest BM biopsy revealed lymphomatous infiltration. On the other hand, in 9 patients (1.9%) in whom bilateral iliac crest BM biopsy had failed to reveal any abnormality, FDG PET-CT showed increased uptake. The calculated values for FDG PET-CT in evaluation of right BM infiltration were 43.1% (22/51) of sensitivity, 97.9% (418/427) of specificity, 71% (22/31) of PPV and 93.5% (418/447) of NPV. The values oriented from left BM biopsy and FDG PET-CT images were similar (sensitivity 41.7% (20/48), specificity 97.9% (421/430), PPV 69% (20/29), NPV 93.7% (421/449)). Conclusions. This study has the largest DLBCL cases among ever reported articles, and demonstrates not excellent sensitivity of FDG PET-CT against the results of BM biopsy for the detection of BM involvement in DLBCL patients. BM biopsy could not be completely replaced with FDG PET-CT. But it has relatively good PPV, FDG PET-CT will be a useful tool for image-guided biopsy for DLBCL staging. And in daily practice, clinicians could consider the possibility to do efficient unilateral BM biopsy for DLBCL patients who have increased posterior iliac crest FDG uptake, instead of bilateral biopsy.

Kim:Novartis: Research Funding.