Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [¹⁸F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [¹⁸F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUV_max). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUV_max cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion: In this large single-centre series of vulvar cancer patients, [¹⁸F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUV_max.

This article provides an overview of the use of ¹⁸F-FDG PET/CT in various clinical scenarios of head–neck squamous cell carcinoma, ranging from initial staging to treatment-response assessment, and post-therapy follow-up, with a focus on the current evidence, debated issues, and innovative applications. Methodological aspects and the most frequent pitfalls in head–neck imaging interpretation are described. In the initial work-up, ¹⁸F-FDG PET/CT is recommended in patients with metastatic cervical lymphadenectomy and occult primary tumor; moreover, it is a well-established imaging tool for detecting cervical nodal involvement, distant metastases, and synchronous primary tumors. Various ¹⁸F-FDG pre-treatment parameters show prognostic value in terms of disease progression and overall survival. In this scenario, an emerging role is played by radiomics and machine learning. For radiation-treatment planning, ¹⁸F-FDG PET/CT provides an accurate delineation of target volumes and treatment adaptation. Due to its high negative predictive value, ¹⁸F-FDG PET/CT, performed at least 12 weeks after the completion of chemoradiotherapy, can prevent unnecessary neck dissections. In addition to radiomics and machine learning, emerging applications include PET/MRI, which combines the high soft-tissue contrast of MRI with the metabolic information of PET, and the use of PET radiopharmaceuticals other than ¹⁸F-FDG, which can answer specific clinical needs.

Currently, there is a discrepancy among the available guidelines on the usefulness of nuclear medicine techniques in medullary thyroid cancer (MTC) diagnosis and treatment. Aim of this review is to provide an update on diagnostic and therapeutic nuclear medicine techniques in this setting. Evidence-based data clearly demonstrates the usefulness of PET/CT with different radiopharmaceuticals in recurrent MTC (in particular when serum calcitonin is higher than 150 pg/mL or calcitonin doubling time is shortened) and ¹⁸F-FDOPA should be the preferred PET radiopharmaceutical. If ¹⁸F-FDOPA PET/CT is negative or unavailable, ¹⁸F-FDG PET/CT or ⁶⁸Ga-DOTA-peptides PET/CT could be performed for MTC restaging. There is currently insufficient evidence to recommend PET/CT with several radiopharmaceuticals for MTC staging. Clinical experience on PET/MRI with different radiopharmaceuticals in MTC is still limited. Several investigational nuclear medicine therapeutic options are currently under evaluation in metastatic MTC. More data are needed to evaluate the efficacy, toxicity, and role of these therapeutic options in the management of MTC patients.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients. Fifteen patients (12 males, 3 females; median age 73 years; range 41–81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site. Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of “personalized medicine.”

Purpose: To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and ¹⁸F-FDG-PET/CT parameters (when available) were also correlated. Methods: Among 551 patients who underwent SSTR-PET/CT with ⁶⁸Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, ¹⁸F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman’s rank correlation test. Results: Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUV_max values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUV_max values corresponding to negative IHC and higher SUV_max values to positive IHC (p = 0.002). Conclusion: This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUV_max values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available.