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Management of advanced high grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): comprehensive review of the current literature

A Mohamed

A Mohamed Division of Hematology and Medical Oncology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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M Trybula

M Trybula Division of Hematology and Medical Oncology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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S L Asa

S L Asa Department of Medicine, UH Seidman Cancer Center Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA

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T R Halfdanarson

T R Halfdanarson Division of Medical Oncology, Department of Oncology, Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA

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M B Sonbol

M B Sonbol Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Phoenix, Arizona, USA

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The classification and management of neuroendocrine neoplasms (NENs) arising in the tubular gastrointestinal (GI) tract and pancreas have significantly evolved over the last decades. In the latest WHO classification published in 2022, NENs are separated regardless of their primary origin into two main groups: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The substantial changes in the grading system changed the definition of grade 3 to include high-grade well-differentiated NETs (G3-NETs), and poorly differentiated NECs (-NECs). Although these two subgroups are considered high grades with Ki-67 >20%, they have different genomic profiles, prognosis, and clinical behavior, which critically influence their treatment strategies. The available clinical trial data to guide therapy of these high-grade subgroups are extremely limited, which impacts their management. In this review, we will summarize the current advances in the multidisciplinary approach for the management of high-grade gastroenteropancreatic NENs (GEP-NENs) including G3-NETs and NECs.

Article Type:: Review Article

DOI:: https://doi.org/10.1530/ERC-24-0025

Volume/Issue:: Volume 31: Issue 10

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From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal

S L Asa

S L Asa Department of Pathology and Endocrine Oncology Site Group, Princess Margaret Cancer Centre, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

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O Casar-Borota

O Casar-Borota Department of Pathology, Uppsala University Hospital, Uppsala, Sweden

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P Chanson

P Chanson Service of Endocrinology and Reproductive Diseases, Bicêtre Hospital, Paris, France

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E Delgrange

E Delgrange Department of Medicine, University of Louvain, Mont-sur-Meuse, Belgium

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P Earls

P Earls Department of Anatomical Pathology, St Vincent’s Hospital, Sydney, Australia

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S Ezzat

S Ezzat Department of Medicine and Endocrine Oncology Site Group, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada

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A Grossman

A Grossman Department of Endocrinology, University of Oxford, Oxford, UK

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H Ikeda

H Ikeda Research Institute for Pituitary Disease, Southern Tohoku General Hospital, Fukushima, Japan

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N Inoshita

N Inoshita Department of Pathology, Toranomon Hospital, Tokyo, Japan

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N Karavitaki

N Karavitaki Department of Endocrinology, Queen Elizabeth Hospital, University of Birmingham, Birmingham, UK

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M Korbonits

M Korbonits Division of Endocrinology, Queen Mary Hospital, Barts and the London School of Medicine, London, UK

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E R Laws Jr

E R Laws Jr Department of Neurosurgery, Harvard Medical School, Brigham & Women’s Hospital, Boston, Massachusetts, USA

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M B Lopes

M B Lopes Departments of Pathology and Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA

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N Maartens

N Maartens Department of Neurosurgery, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia

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I E McCutcheon

I E McCutcheon Department of Neurosurgery, UT MD Anderson Cancer Center, Houston, Texas, USA

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O Mete

O Mete Department of Pathology and Endocrine Oncology Site Group, Princess Margaret Cancer Centre, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

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H Nishioka

H Nishioka Department of Neurosurgery, Toranomon Hospital, Tokyo, Japan

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G Raverot

G Raverot Department of Endocrinology, Groupement Hospitalier EST, Hospices Civils de Lyon, University of Lyon, Lyon, France

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F Roncaroli

F Roncaroli Department of Neuropathology, Imperial College, London, UK

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W Saeger

W Saeger Institute of Neuropathology of the University of Hamburg, Hamburg, Germany

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L V Syro

L V Syro Department of Neurosurgery, Hospital Pablo Tobon Uribe, Medellin, Colombia

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A Vasiljevic

A Vasiljevic Department of Pathology, Groupement Hospitalier EST, Hospices Civils de Lyon, University of Lyon, Lyon, France

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C Villa

C Villa Department of Pathology, Hôpital Foch, Suresnes, France

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A Wierinckx

A Wierinckx INSERM U1052, Cancer Research Center of Lyon, University of Lyon, Lyon, France

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J Trouillas

J Trouillas Faculty of Medicine Lyon-Est, University of Lyon, Lyon, France

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and the attendees of 14th Meeting of the International Pituitary Pathology Club, Annecy, France, November 2016

and the attendees of 14th Meeting of the International Pituitary Pathology Club, Annecy, France, November 2016
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The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.