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

Abstract

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 5 0.560; P 5 0.0101). SUVmax did not correlate with the number of total follicles (P 5 0.8947) but correlated significantly with the number of secondary follicles (r 5 0.535; P 5 0.0152). In addition, a strong positive correlation between SUVmax and the follicular reactivity index was demonstrated (r 5 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.

Reactive Tonsillar Enlargement Showing Strong 18F-Fdg Uptake During the Follow-Up of Follicular Lymphoma

“…Moreover, it has been showed that the grade of follicular hyperplasia is significantly higher in false-positive lymph nodes than those true-negative lymph nodes. This can be explained by the finding that, besides the inflammatory component above mentioned, dendritic follicular cells consistently express GLUT protein [20,21]. Similar to our case, several studies have reported FDG-PET/CT false-positives in patients with previous history of lymphoma.…”

Differentiation of benign from malignant cervical lymph nodes in patients with head and neck cancer using PET/CT imaging

“…Indeed, many prior studies have used either visual assessment or arbitrary pre-set SUV value cutoffs for differentiation/detection of malignant metastasis. [17]. They found that a SUV-max cutoff of 3.5 has 75% sensitivity and 94% specificity for metastasis in enlarged cervical lymph nodes [17].…”

“…[17]. They found that a SUV-max cutoff of 3.5 has 75% sensitivity and 94% specificity for metastasis in enlarged cervical lymph nodes [17].…”

“…Moreover, inter-reviewer variability in diameter measurement may affect size-based stratification of lymph nodes. Unlike prior studies that have adopted preset SUV-max and diameter cutoff values for differentiation of malignant from benign cervical nodes [7,14,17], we used ROC analysis to determine the test characteristics of different cutoff values for differentiation of malignant cervical lymph nodes.…”

“…The SUV-max values of the suspicious lymph nodes were automatically calculated after free-hand volume-of-interest segmentation. The SUV-max values were calculated using the attenuation-corrected images, adjusting for the amount of injected FDG, the body weight of each patient, and the cross-calibration factors between the PET and the dose calibrator [17]. The long-and short-axis diameters of all lymph nodes were determined on axial images by each reviewer.…”