The ability of FDG-PET to image lymphomas depends on the tumor's characteristic of high glucose uptake. However, the mechanisms by which this excess glucose uptake occurs, though currently under investigation, are still not completely understood. While this increased glucose uptake could act as a compensatory mechanism for highly anabolic cells to obtain building blocks for growth and proliferation, an alternative possibility is that high glucose uptake is a fundamental property of malignant cells. In the former case, one would expect that FDG avidity would depend on tumor grade, while in the latter case, the avidity may be independent of grade. Several groups have investigated different subtypes of lymphoma in an attempt to define which of these may be reliably imaged by FDG-PET.

Varying results have been reported regarding the utility of FDG-PET in imaging indolent tumors. Leskinen-Kallio and colleagues, in an early study examining FDG uptake in NHL, found poor uptake in indolent tumors.13 In contrast, Newman et al. described comparable FDG uptake by both low- and intermediate-grade tumors.14

To evaluate this issue more decisively, investigators have studied the utility of FDG-PET in specific histo-logic subtypes of lymphoma. Elstrom and colleagues systematically evaluated specific World Health Organization (WHO) subtypes for their detectability by FDG-PET.15 While 93% of lymphoma patients overall had tumor detectable by PET, those tumors that were not reliably detected fell within specific WHO subtypes, including marginal zone lymphoma (MZL), peripheral T-cell lymphoma (PTCL), and cutaneous B-cell lymphoma (CBCL). One limitation of this study was poor representation of some histologic subtypes, such as small lymphocytic lymphoma (SLL). Jerusalem et al. investigated FDG-PET in indolent lymphomas and found that it has poor sensitivity in imaging SLL.16 Follicular lymphoma (FL), in contrast, including grade 1 tumors, was nearly uniformly detected in both of the above studies. These results suggest that tumor grade is not the most important predictor of FDG avidity, but rather that this avidity is based on other, as yet poorly defined, biological characteristics of the tumor.

Hoffmann and colleagues have further explored the situations in which FDG-PET imaging is useful in lymphoma. In one study they showed that, while 5 of 6 nodal MZLs were detected by FDG-PET, none of 14 extranodal MZL evaluated showed FDG avidity.17 In another study, an evaluation of eight cases of duodenal FL, a rare manifestation of this tumor, showed that none of these lymphomas could be imaged by FDG-PET.18 Of note, the one FL not detected by FDG-PET in the study by Elstrom et al. was an intestinal tumor. This raises the possibility that, even within broad WHO subtypes, subtle biological differences may define different imaging characteristics.

In summary, FDG-PET reliably detects most lymphomas. In the case of the most common aggressive NHL and HL, FDG-PET imaging represents an accurate assessment of disease activity. In these cases, FDG-PET can likely be used in follow-up of patients even without a baseline scan to document utility. However, in some tumors, particularly SLL, extran-odal MZL, and intestinal FL, FDG avidity should be documented prior to therapy if the clinician plans to use this imaging modality for follow-up. Further studies of these issues will further clarify the general-izability of these findings.

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