Somatostatin receptor imaging with [68Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma.

PURPOSE: To explore the feasibility of [68Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with non-keratinizing nasopharyngeal carcinoma (NPC) and to evaluate whether [68Ga]Ga-DOTATATE PET/CT could be used for non-invasive determination of somatostatin receptor 2 (SSTR2) expression in NPC. METHODS: This prospective study included patients with NPC who underwent [68Ga]Ga-DOTATATE PET/CT between February and May 2021. The [68Ga]Ga-DOTATATE and [18F]FDG uptakes in primary and metastatic NPC lesions were calculated and compared, and the [68Ga]Ga-DOTATATE uptake between SSTR2 score groups was analysed. RESULTS: A total of 36 participants (25 patients, initial staging; 11 patients, recurrence detection) were included; 33 patients also underwent [18F]FDG PET/CT for staging/restaging as a part of their routine diagnostic workup. [68Ga]Ga-DOTATATE PET/CT showed an intense tracer uptake in primary and metastatic NPC lesions. The radiotracer uptake was higher with [68Ga]Ga-DOTATATE than with [18F]FDG PET in primary NPC lesions (SUVmax: 12.03 vs. 10.07, P = 0.048; tumour-to-brain ratio: 36.16 vs. 0.86, P < 0.001) and regional lymph node metastases (median SUVmax: 9.11 vs. 6.12, P < 0.001) and comparable in bone and visceral metastases. Importantly, most NPC lesions showed intense SSTR2 expression (85.7%), which was strongly correlated with the [68Ga]Ga-DOTATATE uptake. The SUVmax of SSTR2-negative lesions was significantly lower than that of SSTR2-positive lesions (SUVmax: 4.95 vs. 12.61, P = 0.013). CONCLUSION: [68Ga]Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic NPC, with favourable image contrast and comparable diagnostic efficacy when compared to [18F]FDG PET/CT. An intense SSTR2 expression was observed in most NPCs, and this expression was significantly correlated with the [68Ga]Ga-DOTATATE uptake.

Coexistence of ovarian serous papillary cystadenofibroma and type A insulin resistance syndrome in a 14-year-old girl: A case report.

BACKGROUND: Type A insulin resistance syndrome is a rare disorder caused by mutations in the gene encoding the insulin receptor. Its coexistence with ovarian serous papillary cystadenofibroma is even rarer. CASE SUMMARY: A 14-year-old girl developed type A insulin resistance syndrome and showed high fasting insulin, glucose, and hemoglobin A1c (HbA1c) levels. The girl suffered from ovarian serous papillary cystadenofibroma. The laboratory results were as follows: fasting insulin was 2624.90 pmol/L and HbA1c was 8.5%. A heterozygous missense mutation on exon 20 of the insulin receptor gene (c.3601C>T, Arg1201Trp) was observed. The histopathological diagnosis was a cystic lesion that extended to the upper right uterus, indicating a right ovarian serous papillary cystadefibroma accompanied by focal interstitial hyperplasia. The patient was treated with metformin for over 6 mo. Additionally, laparoscopic resection (bilateral) of the ovarian lesion and laparoscopic intestinal adhesiolysis were performed under general anesthesia. Diet therapy combined with exercise was then initiated. The patient had an uneventful recovery. The patient also showed improved blood glucose control, with reduced levels of fasting insulin (857.84 pmol/L) and HbA1c (7.0%). CONCLUSION: Insulin resistance may play a significant role in the induction of tumors. It is important to investigate further the association between insulin resistance and tumors and the underlying mechanism.

Prognostic Value of Programmed Cell Death-Ligand 1 Expression in Tumor-Infiltrating Lymphocytes and Viral Load in Peripheral Blood Mononuclear Cells for Epstein-Barr Virus-Positive Nasopharyngeal Carcinoma.

BACKGROUND: Epstein-Barr virus (EBV) infection has a role in the development and progression of nasopharyngeal carcinoma (NPC); however, it is unclear whether EBV load correlates with tumor prognosis or the need for immunotherapy. This study evaluated whether the EBV DNA concentration in peripheral blood mononuclear cells (PBMC) or programmed cell death-ligand1 (PD-L1) expression in tumor-infiltrating lymphocytes (TIL) could predict the clinical outcomes of patients with NPC. METHODS: Clinicopathological parameters of 198 patients with NPC were analyzed retrospectively from June 2012 to May 2018. Patients' EBV loads were determined by droplet digital PCR. TIL PD-L1 was analyzed by immunohistochemistry. RESULTS: A log value of 1.98 log IU/mL for PBMC EBV DNA and a percentage of PD-L1 expression of 15% in TILs marked distinguishing cutoffs in NPC prognosis. The 5-year progression-free survival (PFS) rates in patients with high vs low log (PBMC EBV DNA) were 68.2% and 93.1%, respectively (P = 0.002). The 5-year PFS rates in patients with high vs low TIL PD-L1 expression were 66.3% and 33.7%, respectively (P = 0.03). The 5-year PFS rates of the high-risk group (high log [PBMC EBV DNA] and low TIL PD-L1), low-risk group (low log [PBMC EBV DNA] and high TIL PD-L1), and those in between (intermediate group) were 0%, 91.9%, and 71.4%, respectively (P < 0.001). CONCLUSION: Concentrations of PBMC EBV DNA and TIL PD-L1 expression can be used as prognostic markers in NPC. The combination of both an increased EBV DNA concentration and suppressed TIL PD-L1 expression is associated with metastasis or relapse.

Usefulness of [18F]fluorodeoxyglucose PET/CT for evaluating the PD-L1 status in nasopharyngeal carcinoma.

PURPOSE: To explore the relationship between [18F]fluorodeoxyglucose (18F-FDG uptake) and PD-L1 expression and determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in tumour cells (TCs) and tumour-infiltrating immune cells (TIICs) in patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively evaluated the records of 84 eligible patients who received an initial histopathological diagnosis of NPC between December 2016 and March 2019. All tissue specimens and PET/CT images were collected prior to treatment. High PD-L1 expression in TCs and TIICs was defined as ≥ 50% of stained cells. RESULTS: There was a significant difference in 18F-FDG uptake according to the PD-L1 status in TCs and TIICs. Univariate analysis showed that PD-L1 expression in TCs was associated with tumour maximum standardized uptake value (SUVmax) (P < 0.001), primary tumour total lesion glycolysis (TLG; P < 0.001), and T stage (P = 0.044), but not with plasma Epstein-Barr virus (EBV) load (P = 0.816), whereas PD-L1 expression in TIICs was related to SUVmax (P = 0.011), TLG (P = 0.001), T stage (P = 0.028), and plasma EBV load (P = 0.003). In multivariate logistic regression, PD-L1 expression in TCs was positively associated with SUVmax (P = 0.003) and TLG (P = 0.001), and in TIICs, negatively associated with SUVmax (P = 0.038) and plasma EBV load (P = 0.025). CONCLUSIONS: 18F-FDG uptake in NPC lesions was positively correlated with PD-L1 expression in TCs and negatively correlated with PD-L1 expression in TIICs. Thus, 18F-FDG PET/CT may be useful for evaluating the PD-L1 status in patients with NPC.

Concordance of PD-L1 Status Between Image-Guided Percutaneous Biopsies and Matched Surgical Specimen in Non-Small Cell Lung Cancer.

OBJECTIVE: Programmed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS) between biopsies and matched surgical specimens remains controversial. This study aims to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens. METHOD: We evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies retrospectively. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen's kappa (κ) coefficient. RESULTS: Immunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 84.1% (116/138), and the κ value was 0.73 (95% CI: 0.63-0.83, P < 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy [88.6% (62/70, κ value: 0.81) vs 79.4% (54/68, κ value: 0.66)]. CONCLUSION: PD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, the routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy.

Mismatch repair status and high expression of PD-L1 in nasopharyngeal carcinoma.

PURPOSE: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment. PATIENTS AND METHODS: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining. RESULTS: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I-III accounted for 35 (49.3%) cases, while stage IVa-IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein-Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001). CONCLUSION: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted.

Non-ossifying fibroma with a pathologic fracture in a 12-year-old girl with tricho-rhino-phalangeal syndrome: a case report.

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture. CASE PRESENTATION: A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared. CONCLUSIONS: In conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.

A rare case of pregnancy complicated by mesenteric mass: what does chylous ascites tell us?

Mesenteric fibromatosis is a rare benign nonmetastatic neoplasm that appears as a sporadic lesion or occurs in patients with familial polyposis, while chylous ascites associated with aggressive mesenteric fibromatosis during pregnancy has never been reported thus far. Here we present the case of a 28-year old pregnant woman, in whom an aggressive mesenteric fibromatosis with chylous ascites was detected, involving the jejunum, superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and pancreas. One year after a successful surgical excision, the patient had no signs of recurrence. The authors report the case for its rarity and emphasize on combining clinicopathological, radiological and immunohistochemistry analysis for management of the disease.

[Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in ectopic and eutopic endometrium].

OBJECTIVE: To study the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ectopic and eutopic endometrium in patients with endometriosis. METHODS: The expressions of MMP-9 and TIMP-1 in ectopic and eutopic endometrium were detected by immunohistochemistry streptavidin-biotin peroxidase (SP) method in 45 patients with endometriosis (study group) and in 32 patients with uterine fibroid (control group). RESULTS: In the ectopic and eutopic endometrium of group and in the control group endometrium, the expression of MMP-9 was respectively 0.381, 0.336 and 0.276; the expression of TIMP-1 was respectively 0.239, 0.253, 0.267. As a result, the ratio of MMP-9/TIMP-1 in ectopic and eutopic endometrium of study group and in the control group endometrium was respectively 1.594, 1.293, 1.034. The difference of MMP-9, MMP-9/TIMP-1 in ectopic and eutopic and the control group endometrium was markedly significant (P < 0.01 or P < 0.05). The difference of the expression of TIMP-1 between ectopic and the control group endometrium was also markedly significant (P < 0.01). Higher expression of MMP-9 and lower expression of TIMP-1 in ectopic endometrium and higher expression of MMP-9 in eutopic endometrium occurred in the whole menses period, in which higher expression of MMP-9 in ectopic endometrium than in eutopic endometrium only took place in proliferative phase. CONCLUSION: The change of expression of MMP-9 and TIMP-1 in ectopic endometrium may be related to the pathogenesis of endometriosis.

[Expression of PTEN protein and its correlation with p27kip1 and cyclin D1 expression in primary breast cancer].

OBJECTIVE: To study the expression of phosphatase and tensin homology deleted on chromosometen ten (PTEN) protein, a tumor suppressor gene in breast cancer and its correlation with p27(kip1) and cyclin D1 expression. METHODS: PTEN protein expression, p27(kip1) and cyclin D1 protein expression were detected by immunohistochemical method in paraffin sections from 61 women with primary breast cancer. PTEN protein expression was compared with clinico-pathologic parameters as related to p27(kip1) and cyclin D1. RESULTS: PTEN, being shown in the cytoplasm, was negative in 6.6% (4/61), reduced in 41.0% (25/61) and positive in 52.5% (32/61) samples. PTEN expression level was correlated with axillary lymph node status, loss of estrogen receptor stain, recurrence and metastasis. On univariate analysis, the disease-free survival rate of patients with higher PTEN expression (> 50% cells stained) was better than those with lower expression (P = 0.0101). However, there was no correlation between p27(kip1), cyclin D1 expression or PTEN expression. CONCLUSION: PTEN, its lower expression being correlated with poor outcome of breast cancer patients, plays a prominent role in breast cancer. p27(kip1) or cyclin D1 may not be the primary downstream genes of PTEN in breast cancer.