Reply to <scp>A</scp>dams and <scp>K</scp>wee
Authors: Tzu Hua Chen‐Liang, Andrés Jerez, Francisco José Ortuño
Journal: American Journal of Hematology (2015)

To the Editor: The thoughtful letter by Adams and Kwee 1, in response to our article 2, raises important questions regarding whether increased focal FDG uptake in the bone marrow is sufficient evidence to confirm bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL). First, they consider that it is not possible to discriminate other benign or malignant concomitant conditions without histological proof. As Adams et al. reference, scattered islands of regenerating normal marrow after treatment, with or without the use of G-CSF, can be mistakenly interpreted as lymphomatous 3, 4. In addition, cases showing bone remodeling chronic disorders and myeloproliferative neoplasms mimicking lymphomatous BMI have been reported. As our recommendations concern only the baseline setting, the question we have to address is: how often do we face in the real life a clinically relevant concomitant FDG–avid condition in the initial staging of DLBCL? We reviewed 32 DLBCL cases recruited from our center and none of them presented an inflammatory or malignant disease at the time of diagnosis. Nonetheless, we agree on adding a warning in our recommendation about the appropriateness to confirm by means of a bone marrow biopsy (BMB) those cases where a concomitant benign or a malignant FDG-avid condition could be concurrent or suspected while performing the DLBCL staging. Second, they state that in the setting of DLBCL BMI assessment, BMB has been established as an adverse prognostic factor 5, while this is not the case for FDG-PET/CT-based findings. Consequently, this fact is proposed as a surrogate marker for a relevant number of false-positive cases in the latter setting. This is a key point regarding lymphoma staging and we acknowledge it. However, this issue illustrates the controversy about abandoning BMB in certain DLBCL settings: the lack of a gold reference for BMI assessment. In our study, as in others 6, the sensibility is better for FDG-PET/CT, i.e. BMB has a higher rate of false negatives. Therefore: is it appropriate to use as reference a prognostic factor that cannot be measured in every affected patient? Moreover, those studies provide a worse prognosis for BMB-based involvement: are they overestimating a deleterious effect as they are considering only patients with high tumor burden, detectable by BMB? even more: are those studies representative for patients with positive blinded biopsy and a low tumor burden? Notably, all these questions have no clear answer up to date. We have focussed on accuracy not in survival, therefore our recommendations rise from this fact. In our opinion, to correctly define the predictive value of BMI, a gold standard is needed. Given the unreasonable morbidity of combining PET/CT and multiple guided biopsies, it is our belief that the most reasonable reference will come from the imaging field, either by improving or combining techniques. The exact role of both BMB and FDG-PET/CT in this setting will continue to be a matter of debate in the near future. Tzu Hua Chen-Liang, Andrés Jerez, Francisco José Ortuño* Hematology and Medical Oncology Department, H.J.M. Morales Meseguer, Murcia, Spain