PET-CT Invisible Diffuse Large B-Cell Lymphoma Features a Silent B-Cell Receptor Signaling

Background:¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) has been widely used in lymphoma patients for diagnosis, staging, assessment of response and surveillance. And the standardized uptake value (SUV), a commonly used indicator in PET-CT scan, can quantitatively reflect the glucose uptake and glycolysis of the tumor. Diffuse large B-cell lymphoma (DLBCL), one of the most common subtypes of aggressive lymphomas, is supposed to exhibit high standardized uptake value (SUV) in ¹⁸F-FDG PET-CT due to high rate of glucose (¹⁸F-FDG) uptake and high level of glycolysis. Nevertheless, PET-CT "invisible" DLBCL cases have also been described, which featuring a relatively low ¹⁸F-FDG uptake denoted by low SUV. Herein, we analyzed this subgroup of under-estimated disease.

Methods: Nineteen cases each with PET-CT "invisible" (PET-CTi) and PET-CT "visible" (PET-CTv) de novo DLBCL were submitted for an immunohistochemical detection for the expression level of B-cell receptor (BCR) signaling-related molecules. Nine xenografts derived from BCR-dependent and BCR-independent DLBCL cell lines were further submitted for a small animal ¹⁸F-FDG PET-CT scanning and the following immunohistochemical detection for BCR signaling-related molecules.

Results: The immunohistochemical expression level of pSYK (pY525/526), a key effector molecule for BCR signaling, was significantly lower in PET-CTi DLBCL tumor tissues compared with that in PET-CTv DLBCL cases (P <0.01). With regard to in vivo PET-CT experiment, the xenografts derived from BCR-independent DLBCL cell lines exhibited remarkable lower SUV level than those derived from BCR-dependent cell lines (P < 0.01). And BCR-independent DLBCL xenografts featured relatively lower expression level of pSYK compared with those BCR-dependent ones (P <0.01).

Conclusions:¹⁸F-FDG PET-CT negative DLBCL features a silent BCR signaling and ¹⁸F-FDG PET-CT may be of use in evaluating BCR signaling status.