We briefly describe a case of mismatch between in vivo histopathological characterization of PNET and imaging assessment by 68Ga-DOTA-PEPTIDE PETCT and 18F-FDG PETCT. This report exemplifies how functional imaging can guide the management of NET, meanwhile highlight the importance of histopathological analysis in the treatment decision.
Peptides linked to DOTA and marked with 68 Ga, exemplified as DOTA0-Tyr3 octreotate (DOTATATE), DOTATOC, and DOTA0-1NaI3 octreotide (DOTANOC), bind specifically to somatostatin receptors (SSTR) in the cell surface membrane. Based on many previous studies, these modalities of PETCT are superior to many other image methods like computed tomography, MR, and single-photon emission computed tomography in the diagnosis of NET (Buchmann et al. 2007; Gabriel et al. 2007; Kabasakal et al. 2012).
The incorporation of 68Ga-labeled somatostatin analogs in PET imaging promoted a better diagnostic approach to NET, demonstrating high accuracy (0.98 in ROC analysis) combined with lower exam duration and radiation dose, in addition to better image resolution (Velikyan 2013). Early-stage lesions also benefit from this approach, as some of them are difficult to detect with conventional imaging, mostly because of their small size. However, as most of them are well-differentiated tumors, they present with higher expression of SSTR-2 and binding between the radiopeptide and the receptor (Fani et al. 2011).
Kayani et al. exemplified the importance of using functional imaging with combined 68Ga-DOTA-PEPTIDE and 18F-FDG PETCT in the assessment of neuroendocrine tumors. Based on a sample of 38 consecutive patients with the diagnosis of primary or recurrent NET, the combination of the two methods presented a sensitivity of 92%, compared to 82% with 68Ga-DOTAPEPTIDE and 66% with 18F-FDG PETCT alone. Additionally, there was greater uptake of 68Ga-DOTA-PEPTIDE than 18F-FDG in low-grade NET (median SUV 29 vs 2.9, p < .001) and higher uptake of 18F-FDG over 68Ga-DOTAPEPTIDE in high-grade NET (median SUV 11.7 vs 4.4, p = .03). As a result, a significant correlation was achieved with predominant uptake of 68Ga-DOTAPEPTIDE or 18F-FDG and tumor grade on histology (p < .0001), with the combination demonstrating the potential for a better comprehensive assessment in intermediate and high-grade tumors (Evangelista et al. 2020).
Historically, false-positive results in PET imaging (especially 18F-FDG) were correlated with overexpression of GLUT1 in the malignant cell. This receptor has been correlated with the cellular accumulation of 18F-FDG in different tissues, but this mechanism is not yet fully understood (Avril 2004; Chung et al. 2004). However, the patient presented with negative expression of GLUT1 in the neoplasm cells by immunohistochemistry, remaining debatable the explanation about the mismatch between the 18F-FDG PETCT high uptake and the low-grade histopathologic analysis.
Several studies have suggested that patients with incidentally discovered, < 1cm in size and low-grade tumors may be safely followed without surgery in some cases, depending on the site of the tumor (Lee et al. 2012; Strosberg et al. 2011). However, based on the possibility of high-grade tumors after functional imaging, we decided that surgery was the first treatment option, and a complete histopathology analysis was possible. Early stage by the AJCC 8th edition (pT1pNxpM0), localized grade 2 and well-differentiated histopathological characterization supported the decision for active surveillance after surgery.