Surufatinib combined with transarterial embolization versus surufatinib monotherapy in patients with liver metastatic neuroendocrine tumors: Study protocol for a prospective, randomized, controlled trial.

BACKGROUND: More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. METHODS: This is a prospective, multicenter, open-label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression-free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator-assessed PFS, liver-specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. DISCUSSION: This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.

68Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study.

INTRODUCTION: Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom 68Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of 68Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration. METHODS AND ANALYSIS: In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo 68Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by 68Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of 68Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300067591.

Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [18F]FDG-PET/CT and bone marrow biopsy findings.

OBJECTIVE: During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [18F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [18F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [18F]FDG-PET/CT. "BM involvement" was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [18F]FDG-PET/CT. The ability of [18F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients' clinical characteristics and survival and prognostic outcomes were respectively analyzed. RESULTS: Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [18F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [18F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [18F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p = 0.011) than PET/BM-positive patients. CONCLUSION: In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [18F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients.

Heterogeneous Uptake of 68 Ga-DOTATATE and 18 F-FDG in Initial Diagnosed Neuroendocrine Tumors Patients : Which Patients Are Suitable for Dual-Tracer PET Imaging?

PURPOSE: This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET. METHODS: Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression. RESULTS: In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P >0.05). CONCLUSION: The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET.

Diagnostic value of dual-time point 68Ga-PSMA PET/CT image for benign and malignant lesions in patients with prostate cancer.

OBJECTIVE: This study aimed to ascertain the diagnostic efficacy of routine 68Ga-PSMA imaging conducted 1 h post-injection, in conjunction with delayed imaging performed 3 h post-injection, for differentiating between benign and malignant lesions in prostate cancer (PCa) patients. METHODS: A retrospective assessment was undertaken on 44 prostate cancer patients who had undergone both routine and delayed 68Ga-PSMA PET/CT scans. Variations in SUVmax and SUVmean values in normal organs, primary prostate cancer sites, metastatic sites, and benign lesions were analyzed. Pathological examination and extended follow-ups were used to confirm all lesions. RESULTS: The study encompassed 44 patients, presenting 35 primary prostate cancer lesions, 44 metastatic lesions, and 30 benign lesions. Delayed imaging (3 h post-injection) demonstrated a decreasing trend in the SUVmax and SUVmean for the liver, blood, and spleen. Conversely, an increasing trend was observed for the parotid, lacrimal, and submandibular glands. For primary lesions, the SUVmax and SUVmean values were 17.63 ± 9.61 and 9.77 ± 5.18 during routine imaging, and 25.09 ± 15.11 and 14.05 ± 8.02 (P < 0.001) during delayed imaging. A comparable increase in SUVmax and SUVmean was seen in the delayed images for metastatic lesions when juxtaposed with routine images. Nevertheless, benign lesions displayed a decrease in SUVmax and SUVmean during delayed imaging when set against routine imaging (SUVmax: 3.56 ± 1.49 vs 2.93 ± 1.47, P = 0.001; SUVmean: 1.99 ± 0.87 vs 1.65 ± 0.87, P = 0.003). CONCLUSION: Imaging using 68Ga-PSMA PET/CT at 3 h post-injection manifested a higher uptake and target-to-background uptake in most malignant prostate cancer lesions, but a diminished uptake in benign lesions. This observation can assist clinicians in distinguishing non-specific PSMA uptake in prostate cancer patients based on PSMA PET/CT image.

Granulomatosis With Polyangiitis of Spinal Dura Presenting With "Bottle Brush Sign" on 18 F-FDG PET/CT.

ABSTRACT: A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18 F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a "bottle brush." Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.

Comparison of Lugano Criteria Versus RECIL and PERCIST as Prognostic Factors in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: This study aimed to compare the criteria of the Lugano, RECIL, and PERCIST for prognosis in patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: We retrospectively evaluated 335 patients with diffuse large B-cell lymphoma. All patients underwent baseline 18 F-FDG PET/CT. Among them, 252 and 213 patients underwent interim PET/CT (I-PET/CT) and end-of-treatment PET/CT (EoT-PET/CT), respectively. Scans were interpreted by 2 nuclear medicine physicians using Lugano, RECIL, and PERCIST. RECIL and PERCIST were compared with Lugano for predicting progression-free survival (PFS) and overall survival (OS). RESULTS: All 3 response criteria could be used to predict PFS and OS. In I-PET/CT, the concordance index of Lugano in predicting PFS and OS was higher than that of RECIL (both P = 0.043) or PERCIST ( P = 0.008 and P = 0.034, respectively). In EoT-PET/CT, the concordance index of Lugano for predicting PFS and OS was similar to RECIL and not significantly different from PERCIST ( P = 0.597 and P = 0.231, respectively). CONCLUSIONS: For I-PET/CT, using the Lugano criteria is more accurate than RECIL or PERCIST in predicting PFS and OS. However, for EoT-PET/CT, the PERCIST criteria are minimally better.

Intracranial Phosphaturic Mesenchymal Tumor Detected by 68 Ga-DOTATATE PET/CT.

ABSTRACT: A 68 Ga-DOTATATE PET/CT scan was conducted to locate the causative tumor responsible for suspected tumor-induced osteomalacia in a 56-year-old woman. The PET/CT images showed a focus in the right occipital region. Subsequent MRI showed an extra-axial nodule in the right occipital region, mimicking a meningioma. Although rare, an intracranial phosphaturic mesenchymal tumor was still suspected because of the typical clinical settings. Finally, phosphaturic mesenchymal tumor was confirmed by the postoperative pathology.

Appropriate timing to perform an interim 18F-FDG PET/CT in patients with nasal-type extranodal natural killer/T cell lymphoma.

Interim 18F-FDG PET/CT (I-PET) has a role in response evaluation and treatment guidance in patients with nasal-type extranodal natural killer/T cell lymphoma (ENKTL). However, there was no agreement on the timing of I-PET performed, after chemotherapy or after chemoradiotherapy. We aimed to find the appropriate timing for I-PET by assessing the prognostic value of I-PET in response evaluation in ENKTL patients. Two hundred and twenty-seven ENKTL patients who had undergone I-PET were retrospectively included. All patients were grouped based on their therapeutic strategy received, chemotherapy or chemoradiotherapy. The Deauville 5-point score (DS) was used to interpret the I-PET images. The hazard ratio (HR) and C-index were used to measure the discriminatory and prognostic capacities of I-PET performed at different times. One hundred and six patients underwent the I-PET after chemotherapy (chemotherapy group), while I-PET was performed after chemoradiotherapy in 121 patients (chemoradiotherapy group). Eighty-seven patients were classified as metabolic remission (DS score of 1-3), while the other 140 were classified as non-metabolic remission (DS score of 4-5) according to the Deauville criteria. There were no significant survival differences between patients in metabolic remission and in non-metabolic remission in either progression-free survival (PFS, p = 0.406) or overall survival (OS, p = 0.350). In the chemotherapy group, patients in metabolic remission had significantly superior PFS than patients in non-metabolic remission (p = 0.012). For OS, a discriminative trend was also found on the survival curve between patients in metabolic remission and in non-metabolic remission (p = 0.082). In the chemoradiotherapy group, there was no significant difference in PFS (P = 0.185) or OS (P = 0.627) between patients in metabolic remission and in non-metabolic remission. I-PET after chemotherapy yields higher discriminative power and has the ability for prognostic prediction in nasal-type ENKTL patients. I-PET after radiochemotherapy has no prognostic value. Thus, the appropriate timing for I-PET is after chemotherapy but before radiotherapy for response evaluation in nasal-type ENKTL patients.

The image quality, amyloid-ß detectability, and acquisition time of clinical florbetapir positron emission tomography in Alzheimer's disease and healthy adults.

Background: Florbetapir positron emission tomography (AV45 PET) is a widely employed modality for detecting cerebral amyloid-ß (Aß) deposition. However, in clinical settings, patients with cognitive impairment are frequently unable to sustain adequate stillness during the scanning procedure. Therefore, we aimed to investigate the effects of a short acquisition time on the image quality and Aß detectability of AV45 PET. Methods: In this cross-sectional study, 29 patients with Alzheimer's disease (AD) and 13 healthy participants underwent 15-minute AV45 PET/magnetic resonance imaging scanning. The PET data were subsequently reconstructed into 15-, 10-, 8-, 6-, 4-, 2-, and 1-minute duration groups (G15, G10, G8, G6, G4, G2, and G1). Subjective PET image quality was scored based on a 5-point Likert scale (poor-excellent: 1-5), and objective image quality was evaluated by the signal-to-noise ratio (SNR) of the 1 cm3 region of interest (ROI) inside the cerebellum. Aß detectability was assessed by the calculation of regional standardized uptake value ratio (SUVR) values in all groups. The Kruskal-Wallis rank sum test and paired t-test were performed to compare the subjective scores, SNR, and SUVR values. The visual inspection was also performed by 2 nuclear physicians to give a binary diagnosis to each case. Results: The subjective scores were decreased in the groups with shortened scanning time relative to the G15 group (4.67±0.48, all P<0.05). Notably, a good image quality score was also given to the G10 group (4.40±0.63), and sufficient image quality could be achieved with the G8 (3.86±0.68) and G6 (3.14±0.52) groups. The SNR values were decreased by 10.33%, 17.74%, and 23.26% in the G10, G8, and G6 group, respectively (all P<0.05). Compared with the G15 group (1.48±0.16), the composite SUVR values were increased in the G10 (1.50±0.16), G8 (1.50±0.17), and G6 groups (1.51±0.18, all P<0.05). By visual inspection, the diagnoses of each case in the G10, G8, and G6 group were identical with those in the G15 group. Conclusions: The acquisition time of AV45 PET is required to reach at least 6 minutes to achieve acceptable image quality and maintained Aß detectability.

Physiological Uptake Characteristics of Breast on 68Ga-FAPI-04 PET/CT.

PURPOSE: Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological 68Ga-FAPI-04 uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological 68Ga-FAPI-04 uptake in normal breast. PROCEDURES: A total of 143 consecutive women with 68Ga-FAPI-04 PET/CT data were reviewed retrospectively. SUVmax, density and thickness of breast, as well as SUVmax of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs. RESULTS: Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast. There was no difference in 68Ga-FAPI-04 uptake between bilateral breasts (right: median, 1.14[IQR, 0.85-1.54] vs. left: median, 1.09[IQR, 0.86-1.54]; P = 0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median SUV, 3.91 [IQR, 2.85-4.35]) than those with expected moderate (early follicular, early luteal and late luteal phases; median SUV, 1.57 [IQR, 1.39-2.08]; P < 0.001) or low level (menopause and post-operation; median SUV, 0.98 [IQR, 0.83-1.21]; P < 0.001). Menstrual status was an independent predictors of breast SUV (r2 = 0.689, P < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status (P = 0.913).

68Ga-PSMA PET/CT versus 18F-FDG PET/CT for detecting lesions in a case of fumarate hydratase-deficient renal cell carcinoma.

Gallium-68 (68Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and fluorine-18-fluorodeoxyglucose(18F-FDG) PET/CT were performed for staging in a 51-year-old man with renal cell carcinoma. Compared with 18F-FDG PET/CT, no obvious tracer uptake in right renal mass and less metastatic lesions were found on 68Ga-PSMA PET/CT. Postoperative pathology demonstrated the diagnosis of fumarate hydratase-deficient renal cell carcinoma (FHRCC).

Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma Recurrence at Penile Glans Masquerading Urinary Contamination on 18 F-FDG PET/CT.

ABSTRACT: A 69-year-old man with a history of extranodal NK/T-Cell lymphoma, nasal type (ENKTL-NT) performed an interim 18 F-FDG PET/CT for response evaluation. It showed an intense focal uptake at his penile glans, which was suspected as urinary contamination initially. However, he complained with redness and swelling of his penis during further history inquiry. After careful observation, the diagnosis of ENKTL-NT recurrence at penile glans was highly suspected. It was confirmed by percutaneous biopsy of the penile glans finally.

Primary Hepatocellular Carcinoma Revealed on 68 Ga-DOTATATE in a Patient With Nasopharyngeal Carcinoma.

ABSTRACT: A 56-year-old man underwent a prospective study (ChiCTR2300070081), which is a head-to-head comparison of 18 F-FDG and 68 Ga-DOTATATE PET/MR in EB-positive nonkeratinizing nasopharyngeal carcinoma after chemotherapy. Bilateral cervical abnormal lymph nodes were both detected by 18 F-FDG and 68 Ga-DOTATATE PET/MRI, whereas 2 hepatic lesions only were shown on 68 Ga-DOTATATE, which subsequent pathologically proved to be primary hepatocellular carcinoma.

Quality and consistency of clinical practice guideline recommendations for PET/CT and PET: a systematic appraisal.

OBJECTIVES: To systematically appraise the methodologies used for guidelines for positron emission tomography (PET) imaging and to compare the consistency of these recommendations. METHODS: We searched PubMed, EMBASE, four guideline databases, and Google Scholar to identify evidence-based clinical practice guidelines pertaining to the use of PET, PET/computed tomography (CT), or PET/magnetic resonance in routine practice. We assessed the quality of each guideline using the Appraisal of Guidelines for Research and Evaluation II instrument and compared recommendations regarding indications for 18F-fluorodeoxyglucose (FDG) PET/CT. RESULTS: Thirty-five guidelines for PET imaging, published between 2008 and 2021, were included. These guidelines performed well in the domains of scope and purpose (median 80.6%, inter-quartile range [IQR] 77.8-83.3%) and clarity of presentation (median 75%, IQR 69.4-83.3%), but poorly in applicability (median 27.1%, IQR 22.9-37.5%). Recommendations for 48 indications in 13 cancers were compared. Considerable inconsistencies in the direction of whether to support the use of FDG PET/CT were observed in 10 (20.1%) indications pertaining to 8 cancer types: head and neck cancer (treatment response assessment), colorectal cancer (staging in patients with stages I-III disease), esophageal cancer (staging), breast cancer (restaging and treatment response assessment), cervical cancer (staging in patients with stage < IB2 disease and treatment response assessment), ovarian cancer (restaging), pancreatic cancer (diagnosis), and sarcoma (treatment response assessment). CONCLUSIONS: Current guidelines for PET imaging vary in methodological quality and provided considerably inconsistent recommendations. Efforts are needed to improve adherence to guideline development methodologies, to synthesis high-quality evidence, and to adopt standard terminologies. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42020184965. CLINICAL RELEVANCE STATEMENT: Guidelines for PET imaging provide considerably inconsistent recommendations and vary in methodological quality. It is suggested that clinicians be critical of these recommendations when applying them in practice, that guideline developers adopt more rigorous development methodologies, and that researchers prioritize research gaps identified by current guidelines. KEY POINTS: • PET guidelines vary in methodological quality and provided inconsistent recommendations. Efforts are needed to improve methodologies, synthesize high-quality evidence, and standardize terminologies. • Among six domains of methodological quality assessed by the AGREE II tool, guidelines for PET imaging performed well in scope and purpose (median 80.6%, inter-quartile range 77.8-83.3%) and clarity of presentation (75%, 69.4-83.3%), but poorly in applicability (27.1%, 22.9-37.5%). • Among the 48 recommendations (for 13 cancer types) compared, conflicts in the direction of whether to support FDG PET/CT use were observed in 10 (20.1%), for 8 cancer types (i.e., head and neck, colorectal, esophageal, breast, cervical, ovarian, pancreatic, and sarcoma).

Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase-deficient renal cell carcinoma.

BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. METHODS: In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. RESULTS: Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. CONCLUSIONS: Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Quantifying the contribution of 18F-FDG PET to the diagnostic assessment of pediatric patients with fever of unknown origin: a systematic review and meta-analysis.

BACKGROUND: The value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the diagnostic assessment of pediatric fever of unknown origin is not known, and evidence from adults is not applicable. OBJECTIVE: To quantify the contribution of 18F-FDG PET to pediatric fever of unknown origin, considering its diagnostic limitations. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials up to Feb. 18, 2021. We included studies on patients with pediatric fever of unknown origin presenting sufficient data to calculate the likelihood of achieving definite diagnosis (based on pathology or clinical follow-up) between those with abnormal PET findings versus those with normal PET findings. We assessed the risk of bias using a modified Newcastle-Ottawa quality assessment scale and quantified the value of PET by pooling the likelihood of achieving definite diagnosis using a random-effects model. RESULTS: We included 6 studies and found that pediatric patients with abnormal PET findings were about 17 times more likely to achieve definite diagnoses than those with normal PET findings (odds ratio [OR]: 16.75, 95% confidence interval [CI] 8.0-35, P < 0.00001). Sensitivity analyses using a fixed-effect model (OR 16.91, 95% CI 8.1-35, P < 0.0001) or removing one study at a time (OR 12-20, 95% CI lower bound 3.8-8.6, 95% CI upper bound 33-45, P < 0.0001) did not significantly alter the results. Sample size (interaction P = 0.75), imaging modality (interaction P = 0.29), length of follow-up (interaction P = 0.37), fever of unknown origin subclasses (interaction P = 0.89) and geographical areas (interaction P = 0.74) of studies showed no statistically significant influence on the results. CONCLUSION: 18F-FDG PET is a promising approach in the diagnostic work-up of pediatric fever of unknown origin. Further studies are warranted to support routine use in clinical care.

IgA Nephropathy in a Patient With Metastatic Carcinoma of Unknown Primary: Findings on 18F-FDG PET/MRI.

ABSTRACT: A 35-year-old man with mesenteric metastases of unknown primary was referred for 18F-FDG PET/MRI. The images demonstrated that FDG accumulated in the chest, abdomen, bilateral kidneys, and external genitalia. Renal and testicular metastases were suspected. The primary tumor was still not found. In addition, kidney biopsy findings indicated a diagnosis of IgA nephropathy.

FDG PET/CT Showing a Primary Vaginal NK/T Cell Lymphoma.

ABSTRACT: A 28-year-old woman with vaginal discharge was admitted to the hospital. Colposcopy examination found several ulcers with pus in the vagina. Biopsy demonstrated extranodal natural killer/T-cell lymphoma. PET/CT scan was subsequently performed for staging. It revealed intense FDG uptake in the vagina. No FDG-avid lesion was seen in the rest of the body. A primary vaginal extranodal natural killer/T-cell lymphoma was diagnosed.

Primary Intraosseous Squamous Cell Carcinoma of the Mandible Mimicking Inflammation on FDG PET/CT.

ABSTRACT: Primary intraosseous squamous cell carcinoma (SCC) is an uncommon malignant cancer involving the jaw bones. We herein reported the imaging findings of a primary intraosseous SCC of the mandible in a 47-year-old man. He was diagnosed as cancer of unknown primary in the cervical node. FDG PET/CT revealed a focal hypermetabolic lesion around the tooth root of the right lower molar. MRI showed the lesion had hyperintensity on T2-weighted imaging and significant enhancement on T1-weighted imaging fat saturate images. The final diagnosis of primary intraosseous SCC of mandible was confirmed pathologically.