18F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

Unlabelled: PET using (18)F-FDG is acceptable as a preoperative diagnostic tool for head and neck cancer. PET combined with CT provides precise localization of neck lymph nodes. Reactive lymphadenopathy is well known as a principal cause of false-positive findings on PET/CT for nodal staging. We investigated the reactive lymph nodes of oral cancer to elucidate the (18)F-FDG-avid area in these nodes.

Methods: Surgically dissected neck lymph nodes of oral cancer were retrospectively reviewed. Of the patients without pathologic nodal metastasis who underwent preoperative PET/CT, 11 patients with 31 enlarged lymph nodes at 20 levels were enrolled. The maximum standardized uptake value (SUVmax) of each lymph node was recorded. The diameters of the long and short axes were measured by pathologic sectioning, and the sectional surface area was calculated in square millimeters. Besides being stained with hematoxylin and eosin, the sections were immunohistochemically stained by CD79a for B cells, CD3 for T cells, CD68 for macrophages, CD21 for follicular dendritic cells (FDCs), and ubiquitous glucose transporter type 1 (GLUT1). The expression of GLUT1 was compared with staining of lymphoid cells. The numbers of total lymphoid follicles and hyperplastic secondary follicles were counted on CD21 and hematoxylin and eosin sections, respectively. The follicular reactivity index was determined as the ratio of secondary follicles relative to total follicles on the corresponding section. These parameters of reactive lymph nodes were analyzed on a level basis.

Results: GLUT1 was expressed exclusively in lymphoid follicles, whose staining pattern was identical to that of FDCs. The calculated sectional area correlated significantly with the number of total follicles (r = 0.560; P = 0.0101). SUVmax did not correlate with the number of total follicles (P = 0.8947) but correlated significantly with the number of secondary follicles (r = 0.535; P = 0.0152). In addition, a strong positive correlation between SUVmax and the follicular reactivity index was demonstrated (r = 0.829; P < 0.0001).

Conclusion: GLUT1 was expressed on cytoplasmic protrusions of FDCs in lymphoid follicles. The (18)F-FDG accumulation in reactive lymphadenopathy depended on secondary follicles. FDCs in germinal centers of secondary follicles are suggested to be avid for (18)F-FDG and the principal cause of false-positive findings for nodal staging.