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JCI Insight 2021 Mar 8;6(5). Epub 2021 Mar 8.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.

Mutations in EPAS1, encoding hypoxia-inducible factor-2α (HIF-2α), were previously identified in a syndrome of multiple paragangliomas, somatostatinoma, and polycythemia. HIF-2α, when dimerized with HIF-1β, acts as an angiogenic transcription factor. Patients referred to the NIH for new, recurrent, and/or metastatic paraganglioma or pheochromocytoma were confirmed for EPAS1 gain-of-function mutation; imaging was evaluated for vascular malformations. Read More

Histol Histopathol 2020 Dec 11:18288. Epub 2020 Dec 11.

School of Medicine, Griffith University, Gold Coast, QLD, Australia.

The nomenclature and classification of pancreatic neuroendocrine neoplasms has evolved in the last 15 years based on the advances in knowledge of the genomics, clinical behaviour and response to therapies. The current 2019 World Health Organization classification of pancreatic neuroendocrine neoplasms categorises them into three groups; pancreatic neuroendocrine tumours (PanNETs)(grade 1 grade 2, grade 3), pancreatic neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) based on the mitotic rate, Ki-67 index, morphological differentiation and/or co-existing tissue subtype. PanNETs are also classified into non-functional NET, insulinoma, gastrinoma, VIPoma, glucagonoma, somatostatinoma, ACTH-producing NET and serotonin producing NET based on hormone production and clinical manifestations. Read More

Endocr Relat Cancer 2021 Feb;28(2):97-109

Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Mosaic or somatic EPAS1 mutations are associated with a range of phenotypes including pheochromocytoma and/or paraganglioma (PPGL), polycythemia and somatostatinoma. The pathogenic potential of germline EPAS1 variants however is not well understood. We report a number of germline EPAS1 variants occurring in patients with PPGL, including a novel variant c. Read More

Int J Endocrinol 2020 6;2020:1030518. Epub 2020 Nov 6.

Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China.

Background: Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. Read More

In Vivo 2020 Nov-Dec;34(6):3573-3582

First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.

Background/aim: Somatostatinomas (SSomas) constitute a rare neuroendocrine tumor. The purpose of this study was to evaluate the current published literature about pancreatic SSomas and report epidemiologic and clinicopathologic data for this entity.

Patients And Methods: A combined automated and manual systematic database search of the literature was performed using electronic search engines (Medline PubMed, Scopus, Ovid and Cochrane Library), until February 2020. Read More

J Bone Miner Res 2021 Feb 22;36(2):315-321. Epub 2020 Nov 22.

Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Fibroblast growth factor 23 (FGF23) is a key phosphate- and vitamin D-regulating hormone. FGF23 circulates as an intact 251 amino acid protein or N- and C-terminal degradation products. Hormone activity resides in the intact molecule, but it has been suggested that high levels of the C-terminal protein can interfere with intact FGF23 (iFGF23) activity. Read More

Exp Ther Med 2020 Oct 3;20(4):3383-3388. Epub 2020 Jul 3.

Department of Gynecology, Emergency University Hospital, 050098 Bucharest, Romania.

Somatostatinoma is a tumour mainly originating from pancreas or duodenum; overall with an incidence of 1/40 million persons. We introduce a narrative review of literature of somatostatinoma including the relationship with neurofibromatosis type 1. Clinical presentation includes: Diabetes mellitus, cholelithiasis, steatorrhea, abdominal pain, and obstructive jaundice while papillary tumour may cause acute pancreatitis. Read More

Diagnostics (Basel) 2020 Aug 21;10(9). Epub 2020 Aug 21.

Oncology Department, Titu Maiorescu University of Medicine, 040051 Bucharest, Romania.

Somatostatinomas are rare neuroendocrine tumors (NET) that arise in the gastrointestinal (GI) tract. Because of their insidious growth, they are usually asymptomatic until late stages, presenting as malignant disease. We report the case of a 50-year-old woman who presented with epigastric abdominal pain, diarrhea and significant weight loss in the last two years. Read More

AJR Am J Roentgenol 2020 10 13;215(4):885-895. Epub 2020 Jul 13.

Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Houston, TX 77030.

Multiple endocrine neoplasia (MEN) syndromes are autosomal-dominant genetic disorders that predispose two or more organs of the endocrine system to tumor development. Although the diagnosis relies on clinical and serologic findings, imaging provides critical information for surgical management with the ultimate goal of complete tumor resection. This article reviews abdominal neoplasms associated with the various subtypes of MEN syndromes, with a focus on clinical presentation and characteristic imaging features. Read More

Neurol Genet 2020 Jun 1;6(3):e414. Epub 2020 Apr 1.

National Institutes of Health (J.S.R., A.J.C., H.W., Z.Z.), National Cancer Institute Neuro-Oncology Branch; National Institutes of Health (D.P.A., J.D.H.), National Institute of Neurological Disorders and Stroke, Surgical Neurology Branch; National Institutes of Health (Y.P., A.J., K.P.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Medical Neuroendocrinology; Georgetown Hospital (M.A.N.), Internal Medicine and Pediatrics, Washington DC; National Institutes of Health (J.P.M., D.R.D.), National Institute of Neurological Disorders and Stroke, Mouse Imaging Facility, Bethesda, MD; George Washington University (J.G.S.), Radiology, Washington DC; National Library of Medicine (J.G.S.), MedPix®; National Institutes of Health (M.M.M.), Center for Cancer Research, National Cancer Institute, Laboratory of Pathology; and National Institutes of Health (R.H.K., B.A.K.), National Heart Lung and Blood Institute, Translational Vascular Medicine Branch, Bethesda, MD.

Objective: To investigate the effect of somatic, postzygotic, gain-of-function mutation of Endothelial Per-Arnt-Sim (PAS) domain protein 1 () encoding hypoxia-inducible factor-2α (HIF-2α) on posterior fossa development and spinal dysraphism in gain-of-function syndrome, which consists of multiple paragangliomas, somatostatinoma, and polycythemia.

Methods: Patients referred to our institution for evaluation of new, recurrent, and/or metastatic paragangliomas/pheochromocytoma were confirmed for gain-of-function syndrome by identification of the gain-of-function mutation in resected tumors and/or circulating leukocytes. The posterior fossa, its contents, and the spine were evaluated retrospectively on available MRI and CT images of the head and neck performed for tumor staging and restaging. Read More

Biochem Biophys Res Commun 2020 05 13;525(4):1032-1037. Epub 2020 Mar 13.

Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori Mizuhoku, Nagoya, 467-8603, Japan. Electronic address:

Pancreatic neuroendocrine tumors (pNETs) occur due to the abnormal growth of pancreatic islet cells and predominantly develop in the duodenal-pancreatic region. Somatostatinoma is one of the pNETs associated with tumors of pancreatic δ cells, which produce and secrete somatostatin. Limited information is currently available on the pathogenic mechanisms of somatostatinoma. Read More

Acta Oncol 2020 Jun 8;59(6):644-651. Epub 2020 Feb 8.

Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium.

Peptide receptor radionuclide therapy (PRRT) is a validated treatment for somatostatin receptor overexpressing neuroendocrine tumors (NETs). The NETTER-1 trial demonstrated a pronounced positive effect on progression-free-survival compared to high dose somatostatin analogs (SSAs), with a strong tendency toward overall survival benefit. Our aim was to investigate the influence of pretreatment with everolimus and/or sunitinib on subacute hematotoxicity of PRRT. Read More

Ann Pathol 2020 Apr 5;40(2):120-133. Epub 2020 Feb 5.

Département de biologie et pathologie médicales, institut Gustave-Roussy, 114, rue Edouard-Vaillant, 94805 Villejuif cedex, France. Electronic address:

About 5% of gastroenteropancreatic and thoracic neuroendocrine neoplasms (NENs) arise in the context of an inherited tumour syndrome. The two most frequent syndromes are: multiple endocrine neoplasia type 1 (MEN1), associated with a large spectrum of endocrine and non endocrine tumours, including duodenopancreatic, thymic and bronchial NENs, and the von Hippel-Lindau syndrome VHL, associated with pancreatic NENs. Two inherited syndromes have a low incidence of NENs: neurofibromatosis type 1 (NF1), associated with duodenal somatostatinomas, and tuberous sclerosis (TSC), associated with pancreatic NENs. Read More

Clin Gastroenterol Hepatol 2021 Mar 15;19(3):e24-e25. Epub 2020 Jan 15.

Division of Gastroenterology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health System, New Hyde Park, New York.

JAMA Ophthalmol 2020 02;138(2):148-155

Neuro-Oncology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland.

Importance: Patients with the EPAS1 gain-of-function mutation syndrome (or Pacak-Zhuang syndrome) present with multiple paragangliomas or pheochromocytomas, duodenal somatostatinoma, polycythemia, headaches, and sometimes diminished visual acuity at an early age. The characteristic phenotype and known genetic cause of the syndrome provide an opportunity to study the role of hypoxia-inducible factor 2α (HIF-2α) in oxygen sensing, development in regions of physiologic hypoxia, and other pathological processes.

Objectives: To describe the ocular lesions in EPAS1 gain-of-function mutation syndrome and to establish whether early-onset diminished visual acuity is developmental or associated with long-term physiologic sequelae of the syndrome. Read More

Pediatr Blood Cancer 2020 04 25;67(4):e28096. Epub 2019 Dec 25.

Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.

We report an index case of a male patient who presented with all clinical manifestations of Pacak-Zhuang syndrome, including early-age polycythemia, multiple pheochromocytomas/paragangliomas, duodenal somatostatinoma, and ocular findings. Sequencing analysis detected an EPAS1 mutation in all tumors tested, but not in the germline. Read More

Arkh Patol 2019 ;81(5):11-21

M.F.Vladimirsky Moscow Regional Research Clinical Institute, Moscow, Russia.

An important role in the differentiation of tissues in different organs is played by transforming factors (TFs); pancreatic and duodenal homebox 1 (PDX-1) is one of the earliest factors for pancreatic cells. Many malignant tumors, including neuroendocrine tumors (NETs), are similar in structure, and therefore the actual problem of oncomorphology is to search for narrow-specific markers and TFs.

Aim: to comparatively analyze and assess the value of the expression of the TF PDX-1 in NETs and non-NETs of different localization and histogenetic origin. Read More

Endocrinol Diabetes Metab 2019 Oct 27;2(4):e00083. Epub 2019 Jun 27.

Division of Endocrinology and Diabetes, Department of Internal Medicine University Hospital of Zurich Zurich Switzerland.

Introduction: Somatostatin-secreting neuroendocrine tumours may present with diabetes, cholelithiasis and steatorrhoea. In addition, hypoglycaemia has been associated with somatostatinomas. However, the mechanism of hypoglycaemia in patients with somatostatinomas has not been well characterized. Read More

Case Rep Gastrointest Med 2019 9;2019:9506405. Epub 2019 May 9.

Division of Gastroenterology, Providence-Providence Park Hospital and Medical Center, Michigan State University/College of Human Medicine, Southfield, Michigan, USA.

Somatostatinoma is a rare neuroendocrine tumor with an incidence rate of 1 in 40 million people. It presents mostly as asymptomatic tumor diagnosed incidentally on imaging or surgery when evaluating or treating possible causes of abdominal pain. It also can present with vague symptoms, or as a clinical triad of glucose intolerance, steatorrhea, and achlorhydria. Read More

Int J Mol Sci 2019 Jun 10;20(11). Epub 2019 Jun 10.

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

A syndrome of multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia due to somatic mosaic gain-of-function mutation of , encoding HIF-2α, was previously described. HIF-2α has been implicated in endochondral and intramembranous ossification. Abnormal bone growth of the skull base may lead to Chiari malformation type I. Read More

Cancers (Basel) 2019 May 14;11(5). Epub 2019 May 14.

Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

We previously identified a novel syndrome in patients characterized by paraganglioma, somatostatinoma, and polycythemia. In these patients, polycythemia occurs long before any tumor develops, and tumor removal only partially corrects polycythemia, with recurrence occurring shortly after surgery. Genetic mosaicism of gain-of-function mutations of the gene (encoding HIF2α) located in the oxygen degradation domain (ODD), typically p. Read More

Curr Radiopharm 2019 ;12(2):135-155

Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, United Kingdom.

Introduction: Pancreatic Neuroendocrine Tumours (p-NETs) are an important disease entity and comprise of peptide-secreting tumours often with a functional syndrome. Accounting for a small percentage of all pancreatic tumours, they have a good overall survival rate when diagnosed early, with surgery being curative. The role of nuclear medicine in the diagnosis and treatment of these tumours is evident. Read More

Cancer 2019 04 15;125(8):1258-1266. Epub 2019 Jan 15.

Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Background: Somatic mutations in hypoxia-inducible factor 2α (HIF2A) are associated with polycythemia-paraganglioma syndrome. Specifically, the classic presentation of female patients with recurrent paragangliomas (PGLs), polycythemia (at birth or in early childhood), and duodenal somatostatinomas has been described. Studies have demonstrated that somatic HIF2A mutations occur as postzygotic events and some to be associated with somatic mosaicism affecting hematopoietic and other tissue precursors. Read More

BMJ Case Rep 2019 Jan 10;12(1). Epub 2019 Jan 10.

Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Science Center School of Medicine, Lubbock, Texas, USA.

Somatostatinomas are rare neuroendocrine tumours, mostly located in the pancreas or duodenum, with an estimated incidence of 1 in 40 million. Duodenal somatostatinomas (DSs) are usually found in association with neurofibromatosis type 1 (NF1), tuberous sclerosis and Von Hippel-Lindau syndrome. Gastrointestinal stromal tumours (GIST) have also been described in NF1, but the association with somatostatinoma is very uncommon. Read More

Neuro Endocrinol Lett 2018 Sep;39(3):149-155

Clinical Department of Endocrinology, Jagiellonian University in Krakow, Poland.

Neurofibromatosis type 1 (NF1, von Recklinghausen disease) is inherited in autosomal dominant way genetic disorder, with an incidence at birth 1:3000. It is one of the most common congenital disorders. It is characterized by café-au-lait spots, neurofibromas, and less common MPTST and gliomas of the optic nerve. Read More

Eur J Endocrinol 2018 10 1;179(4):219-228. Epub 2018 Oct 1.

‘Lendület’ Hereditary Endocrine Tumours Research Group, Hungarian Academy of Sciences – Semmelweis University, Budapest, Hungary

Objective: Pancreatic neuroendocrine neoplasms (PanNENs) are rare tumors arising from the endocrine pancreas; however, their prognosis differs significantly upon their proliferative state, which is characterized by histopathological grading. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to identify miRNAs with altered expression upon proliferation which can be used as prognostic biomarkers in PanNENs. Read More

Adv Anat Pathol 2019 Jan;26(1):13-30

Departments of Pathology, Massachusetts General Hospital, Boston, MA.

This review focuses on discussing the main modifications of the recently published 2017 WHO Classification of Neoplasms of the Neuroendocrine Pancreas (panNEN). Recent updates separate pancreatic neuroendocrine tumors into 2 broad categories: well-differentiated pancreatic neuroendocrine tumors (panNET) and poorly differentiated pancreatic neuroendocrine carcinoma (panNEC), and incorporates a new subcategory of "well-differentiated high-grade NET (G3)" to the well-differentiated NET category. This new classification algorithm aims to improve the prediction of clinical outcomes and survival and help clinicians select better therapeutic strategies for patient care and management. Read More

Gland Surg 2018 Feb;7(1):20-27

Department of Medical Sciences, Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden.

Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Read More

Pancreas 2018 Apr;47(4):e19-e20

Department of Gastrointestinal Surgery and Liver Transplantation AIIMS New Delhi, India Department of Pathology AIIMS New Delhi, India Department of Radiodiagnosis AIIMS New Delhi, India Department of Gastrointestinal Surgery and Liver Transplantation AIIMS New Delhi, India.