Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism-The UK Perspective.

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic ß-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose. Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management.

18 F-FDG PET/CT Uptake in Acute Pontine Infarct Mimicking Intracranial Metastasis.

ABSTRACT: Infarcts are generally nonviable and are not avid on an 18 F-FDG PET/CT. Here, we discuss a 53-year-old man who presented with chest pain and raised d -dimer. CT pulmonary angiogram was performed to exclude pulmonary embolism, which identified incidental lung nodules. 18 F-FDG PET/CT was performed for the assessment of lung nodules, which showed incidental focal FDG uptake in the pons. This was concluded as an acute infarct on subsequent MR scan. This highlights the importance of not interpreting all focal FDG uptakes as malignant. In rare circumstances, false-positive benign causes should be considered, such as in this rare case of an acute pontine infarct.

Case report: contradictory genetics and imaging in focal congenital hyperinsulinism reinforces the need for pancreatic biopsy.

BACKGROUND: Congenital Hyperinsulinism (CHI) is an important cause of severe hypoglycaemia in infancy due to excessive, dysregulated insulin secretion. In focal CHI, a localised lesion within the pancreas hypersecretes insulin and, importantly, hypoglycaemia resolution is possible through limited surgical resection of the lesion. Diagnosis of focal CHI is based on a crucial combination of compatible genetics and specialised imaging. Specifically, a focal lesion arises due to a paternal mutation in one of the ATP-sensitive potassium channel genes, KCNJ11 or ABCC8, in combination with post-zygotic loss of maternal heterozygosity within the affected pancreatic tissue. 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)/computed tomography (CT) imaging is used to detect and localise the lesion prior to surgery. However, its accuracy is imperfect and needs recognition in individual case management. CASE PRESENTATION: We report the case of an infant with hypoglycaemia due to CHI and a paternally inherited KCNJ11 mutation, c.286G > A (p.Ala96Thr), leading to a high probability of focal CHI. However,18F-DOPA PET/CT scanning demonstrated diffuse uptake and failed to conclusively identify a focal lesion. Due to unresponsiveness to medical therapy and ongoing significant hypoglycaemia, surgery was undertaken and a small 4.9 × 1.7 mm focal lesion was discovered at the pancreatic neck. This is the second case where this particular KCNJ11 mutation has been incorrectly associated with diffuse 18F-DOPA uptake, in contrast to the correct diagnosis of focal CHI confirmed by pancreatic biopsy. CONCLUSIONS: Identifying discrepancies between genetic and imaging investigations is crucial as this may negatively impact upon the diagnosis and surgical treatment of focal CHI. This case highlights the need for pancreatic biopsy when a strong suspicion of focal CHI is present even if 18F-DOPA imaging fails to demonstrate a discrete lesion.

First case on fluorodeoxyglucose positron emission tomography/computerized tomography of a distant skip metastases to parotid node from esophageal adenocarcinoma.

We are presenting the first case of a gastro-oesophageal junction adenocarcinoma with metastasis only to the intraparotid lymph node simulating Warthin's tumor. A 66-year-old man underwent an esophagogastroduodenoscopy that found circumferential ulcerated esophageal tumor beginning 40 cm from incisors resulting in stricture and two discrete erosions in the proximal third of esophagus. Biopsies from the stricture have demonstrated a poorly differentiated gastric adenocarcinoma. Computerized tomography (CT) confirmed the site of primary without evidence of distant metastasis. Positron emission tomography/CT showed high uptake in the known carcinoma in distal esophagus involving the gastro-oesophageal junction extending into the cardia of the stomach, the maximum standardized uptake value (SUVmax) 7.4. Furthermore, there was a focus of high-grade tracer activity, SUVmax 6.2, in the left intraparotid nodule which was initially thought to represent Warthin's tumor rather than metastasis; there was no evidence to suggest metastases elsewhere. Fine needle aspiration and biopsy from the enlarged intraparotid lymph node revealed that the histology was consistent with a poorly differentiated adenocarcinoma, metastasis from upper gastrointestinal tract.

Clinical Diversity in Focal Congenital Hyperinsulinism in Infancy Correlates With Histological Heterogeneity of Islet Cell Lesions.

Background: Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established. Aims: We aimed to correlate the diversity in clinical profiles of patients with islet cell organization in CHI-F pancreatic tissue. Methods: Clinical datasets were obtained from 25 patients with CHI-F due to ABCC8/KCNJ11 mutations. 18F-DOPA PET-CT was used to localize focal lesions prior to surgery. Immunohistochemistry was used to support protein expression studies. Results: In 28% (n = 7) of patient tissues focal lesions were amorphous and projected into adjoining normal pancreatic tissue without clear delineation from normal tissue. In these cases, severe hypoglycaemia was detected within, on average, 2.8 ± 0.8 (range 1-7) days following birth. By contrast, in 72% (n = 18) of tissues focal lesions were encapsulated within a defined matrix capsule. In this group, the onset of severe hypoglycaemia was generally delayed; on average 46.6 ± 14.3 (range 1-180) days following birth. For patients with encapsulated lesions and later-onset hypoglycaemia, we found that surgical procedures were curative and less complex. Conclusion: CHI-F is associated with heterogeneity in the organization of focal lesions, which correlates well with clinical presentation and surgical outcomes.

68Ga-DOTATATE uptake in pineal gland, a rare physiological variant: case series.

(68)Ga-DOTATATE PET-CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had (68)Ga-DOTATATE PET-CT scans and one underwent (68)Ga-DOTATATE PET-MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of (68)Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.

Incidental Neurofibroma on 18F-Fluorocholine PET/MR.

Neurofibromas are benign peripheral nerve sheath tumors. We described a unique case of recurrent prostate cancer with coexisting neurofibroma diagnosed on F-fluorocholine PET/MRI.

68Ga-DOTATATE PET/MR Imaging of Urinary Bladder Paraganglioma.

Paragangliomas of the urinary bladder are very rare. They are extra-adrenal autonomic nervous system tumors. This report presents a case of a 13-year-old boy with urinary bladder paraganglioma and the role of somatostatin receptor imaging with simultaneous positron emission tomography magnetic resonance (PET/MR). We have also described appearances of iodine-123 metaiodobenzylguanidine ((123)I-MIBG) single photon emission computed tomography (SPECT/CT) in comparison to somatostatin receptor imaging.

Adolescent With 68Ga DOTATATE-Avid Vertebral Hemangioma Mimicking Metastasis in PET Imaging.

68Ga DOTATATE PET/CT is a well-established method in the diagnostic workup of neuroendocrine tumors. We report the case of a 15-year-old adolescent boy with histologically proven appendiceal carcinoid tumor referred for 68Ga DOTATATE PET/CT to identify residual or metastatic disease. PET images showed increased tracer uptake in the body of T4 vertebra. This uptake could be misdiagnosed for bone metastasis, but CT characteristic appearance was in keeping with vertebral hemangioma. Both bone metastasis in carcinoid tumor and bone hemangiomas in adolescents are rare conditions, but the combined metabolic and morphological information on PET/CT can lead to the correct diagnosis.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography in diagnosis of post-transplant lymphoproliferative disorder.

The aim of the present study was to investigate the role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the diagnosis of post-transplant lymphoproliferative disorder (PTLD), a serious complication of solid organ and bone marrow transplant. Between January 2004 and January 2012, 40 patients (22 males; median age 52 ± 17.4 years, range 11-77 years) underwent (18)F-FDG PET/CT scans in our department for diagnostic evaluation of PTLD. Twenty-three (57.5%) patients had negative (18)F-FDG PET/CT and 17 (42.5%) had a positive examination. In five patients PET/CT revealed extranodal disease (adrenal, pleural, spleen, liver, lung, esophagus and bone involvement). On the basis of our results, (18)F-FDG PET/CT had a sensitivity of 88.2% (95% confidence interval [CI] 0.62-0.98), a specificity of 91.3% (CI 0.70-0.98), a positive predictive value of 88.2% (CI 0.62-0.98) and a negative predictive value of 91.3% (CI 0.70-0.98). The diagnostic performance of CT in patient-based analysis was: a sensitivity of 87.5% (CI 0.60-0.97), a specificity of 88.8% (CI 0.64-0.98), a positive predictive value of 87.5% (CI 0.60-0.97) and a negative predictive value of 88.8% (CI 0.64-0.98). PET/CT in five cases revealed more findings than CT, upstaging the disease, and revealed three extranodal findings, not visualized in conventional imaging. (18)F-FDG PET/CT plays a significant role in the setting of PTLD diagnosis, demonstrating its high accuracy in detecting PTLD.

Painful knee prosthesis: can we help with bone SPECT/CT?

OBJECTIVES: The aim of the study was to evaluate the value of single-photon emission computerized tomography/computed tomography (SPECT/CT) in the clinical assessment of painful knee prostheses. MATERIALS AND METHODS: Between 2009 and 2011 we identified 105 patients who had undergone Tc-hydroxydiphosphonate SPECT/CT for painful knee prosthesis. Complete follow-up data were available for 69 patients (50 women and 19 men; mean age, 71 years) with painful knee prostheses (59 total, nine unicompartmental, one patellofemoral) and clinical suspicion of infection or loosening. The imaging test report in conjunction with the clinical data from the patient's notes was used to gauge how useful the test had been in terms of patient management. RESULTS: SPECT/CT confirmed the suspected clinical diagnosis of loosening in nine patients (13%) and of infection in two (2.9%) and identified other causes in 43 patients (62.3%). In 85.5% of patients, SPECT/CT was clinically useful (both positive and negative results), whereas in 14.5% it had no clinical impact on patient management. Revision surgery was performed in 24/69 (34.8%) patients and confirmed the SPECT/CT diagnosis in 21 patients (seven loosening, one infection, two subchondral fractures, two postoperative inflammation and nine patellofemoral osteoarthritis). CONCLUSION: SPECT/CT is a useful tool for the evaluation of painful knee prosthesis in 85.5% of cases and helps in confirming mechanical loosening and in excluding other causes such as infection and patellofemoral osteoarthritis.