Search

Introduction Paragangliomas (PGL) are rare neuroendocrine tumours and account for approximately 10% of all chromaffin tumours. They may occur in the retroperitoneum, mediastinum, skull and the urinary bladder. Paragangliomas of the urinary bladder are rare entities accounting for 10% of all paragangliomas and 0.06% of all bladder tumours. Approximately 10% of urinary bladder paragangliomas are malignant. Bladder paragangliomas can be either functional or non-functional. Main symptoms of functional PGLs are due to catecholamine excess with palpitations, paroxysmal hypertension during micturition, sweating and headaches. Functional bladder PGL are diagnosed on biochemical analysis. Non-functional bladder PGLs present with haematuria and are often misdiagnosed as bladder cancer as they may cystoscopically and histologically resemble a urothelial neoplasm. Clinical cases: We present a case series of 4 surgically treated patients with urinary bladder paragangliomas who presented to Cambridge University Hospital over the last 3 years. All patients were female with an age range between 21 and 44 years. All four patients had SDHB deficient tumours, and all four patients were diagnosed with a pathogenic variant in the SDHB gene. Three patients had no family history of SDHx associated neoplasia whereas one had a paternal aunt who died from a metastatic pheochromocytoma. Three patients had presented with palpitations and hypertensive episodes, one of whom experienced symptoms while micturating. Biochemical analysis revealed elevated plasma normetadrenaline levels in all patients. On presentations, one patient had a synchronous paratracheal paraganglioma while two patients had lymph node metastasis. All patients were surgically treated with two patients undergoing fertility preserving cystectomy and bladder substitution, one undergoing partial cystectomy, radical hysterectomy and ureteric implantation and one managed with robot-assisted partial cystectomy. None of the patients have evidence of biochemical or radiological tumour recurrence on follow-up with a mean follow-up time of 23 months (range 12 to 40 months). Conclusion and points for discussion The diagnosis of urinary bladder PGL is challenging. Biochemical assessment to assess catecholamine production and imaging studies like CT, MRI and NM Ga68 DOTATATE PET CT are helpful modalities in diagnosis. Patients presenting with extra adrenal paragangliomas including bladder paragangliomas require genetic testing because of the strong hereditary predisposition, with mutations in the SDHx genes being most common with this clinical phenotype. The surgical approach should be tailored to the individual patient, agreed by a multi-disciplinary team and the risk of malignancy should be weighed against the potential morbidity associated with a curative oncological surgery. As urinary bladder PGLs have malignant potential and are frequently hereditary (as demonstrated in this series), lifelong follow-up is required to screen for synchronous tumours and tumour recurrence. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m.

Summary A 38-year-old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.1304delG) through predictive genetic testing, following a diagnosis of familial hyperparathyroidism. Routine screening for parathyroid and pituitary disease was negative. However, cross-sectional imaging by CT revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed the lesion to be a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1in situ pT2 (23 mm) grade 1, N0 (ER positive; HER2 negative). Following mastectomy, our patient underwent a successful distal pancreatectomy to resect the pNET. Loss of heterozygosity (LOH) at the MEN1 locus was found in both the breast tumour and pNET, thereby in keeping with a 'two-hit' hypothesis of oncogenesis, a suggestive but non-definitive clue for causation. To obtain further support for a causative relationship between MEN1 and breast cancer, we undertook a detailed review of the published literature which overall supports the notion that breast cancer is a MEN1-related malignancy that presents at a younger age and histologically, is typically of ductal subtype. Currently, clinical guidance regarding breast cancer surveillance in MEN1 does not exist and further research is required to establish a clinical and cost-effective surveillance strategy). Learning points We describe a case of pNET and breast cancer diagnosed at a young age of 38 years in a patient who is heterozygous for a pathogenic MEN1 variant. Loss of the wild-type allele was seen in both breast tissue and pNET specimen. Breast cancer may be an under-recognised MEN1-associated malignancy that presents at a younger age than in the general population with a relative risk of 2–3. Further research is required to determine the cost-effectiveness of breast cancer surveillance approach at a younger age in MEN1 patients relative to the general population .

Background [68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called ‘wild-type’ GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST. Aims To investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST. Methods [68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study. Results [68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST. Conclusions Our data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST.

CONTEXT Multiple endocrine neoplasia type 1 (MEN1) is a hereditary condition characterised by the predisposition to hyperplasia/tumours of endocrine glands. MEN1-related disease, moreover, malignancy related to MEN1, is increasingly responsible for death in up to two-thirds of patients. Although patients undergo radiological and biochemical surveillance, current recommendations for radiological monitoring are based on non-prospective data with little consensus or evidence demonstrating improved outcome from this approach. Here, we sought to determine whether cumulative radiation exposure as part of the recommended radiological screening programme posed a distinct risk in a cohort of patients with MEN1. PATIENTS AND STUDY DESIGN A retrospective review of 43 patients with MEN1 attending our institution between 2007 and 2015 was performed. Demographic and clinical information including phenotype was obtained for all patients. We also obtained details regarding all radiological procedures performed as part of MEN1 surveillance or disease localisation. An estimated effective radiation dose (ED) for each individual patient was calculated. RESULTS The mean ED for the total patient cohort was 121 mSv, and the estimated mean lifetime risk of cancer secondary to radiation exposure was 0.49%. Patients with malignant neuroendocrine tumours (NETS) had significantly higher ED levels compared to patients without metastatic disease (P