Neuroendocrine neoplasms of head and neck, genitourinary and gynaecological systems, unknown primaries, parathyroid carcinomas and intrathyroid thymic neoplasms - ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up - Special Article

Q: What proportion of neuroendocrine neoplasms have an unidentified primary site?

The primary tumour site remains unidentified in 13%–20% of cases.

Q: How are neuroendocrine neoplasms pathologically classified in the guideline?

Classification relies on differentiation (well vs poorly differentiated), presence or absence of necrosis, and grade assessed by Ki-67 index and/or mitotic count.

Q: Why is immunohistochemistry important for diagnosis?

Immunohistochemistry biomarkers can help identify primary sites and support accurate grading within a comprehensive pathology report.

Sep 21, 2026

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ESMO Clinical Practice Guideline addresses neuroendocrine neoplasms spanning head and neck, genitourinary and gynaecological systems, including cases with unknown primary, parathyroid carcinomas, and intrathyroid thymic neoplasms. It summarizes incidence and epidemiology, highlighting the substantial proportion of primary sites that remain unidentifed and the increasing burden of unknown-primary NENs. The guideline then details diagnosis and pathological classification, emphasizing differentiation, necrosis status, and Ki-67 and mitotic count–based grading, supported by immunohistochemistry to clarify primary origin and improve reporting consistency.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Neuroendocrine neoplasms: incidence and epidemiology

Diagnosis and pathological classification

Pathological classification

Immunohistochemistry and pathology report elements

SPECIAL ARTICLE Neuroendocrine neoplasms of head and neck, genitourinary and gynaecological systems, unknown primaries, parathyroid carcinomas and intrathyroid thymic neoplasms: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up5 J. Hadoux1, A. Lamarca2, 3, 4y, E. Grande5y, D. Deandreis1, 6y, G. Kaltsas7, E. T. Janson8, B. Tombal9, M. Pavel10, J. Thariat11, M. F. van Velthuysen12, P. Herman13, C. Dromain14, E. Baudin1 & A. Berruti15, on behalf of the ESMO Guidelines Committee􀀂 1Département d’Imagerie, Service d’Oncologie Endocrinienne, Gustave Roussy, Villejuif, France; 2Department of Oncology, OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain; 3Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester; 4Division of Cancer Sciences, University of Manchester, Manchester, UK; 5Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain; 6Nuclear Medicine Service, Gustave Roussy, Villejuif, France; 7First Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece; 8Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University, Uppsala, Sweden; 9Institut de Recherche Clinique, Cliniques Universitaires Saint-Luc (UCLouvain Saint-Luc), Woluwe-Saint-Lambert, Belgium; 10Department of Medicine 1, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuernberg, Erlangen, Germany; 11Department of Radiation Oncology, Baclesse Cancer Center, Caen, France; 12Department of Pathology, Erasmus Medical Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands; 13Department of Otorhinolaryngology, Head and Neck Surgery, Hôpital Lariboisière AP-HP, Paris, France; 14Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; 15Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy Available online 1 October 2024 Key words: diagnosis, ESMO guideline, intrathyroid carcinoma, management, parathyroid carcinoma, rare endocrine neoplasms NEUROENDOCRINE NEOPLASMS Incidence and epidemiology Neuroendocrine neoplasms (NENs) encompass welldifferentiated neuroendocrine tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) . The primary tumour site for NENs remains unidentiﬁed in 13%-20% of cases.1 NENs account for w8% of unknown primary (UKP) malignancies and UKP-NENs represent the fourth most common NEN with an increasing incidence of 8.4 per million, representing 10%-15% of NETs and NECs.1,2 Genitourinary and gynaecological (GUGy)-NENs account for 1%-2% of GUGy malignancies, 12% of NECs and 4% of NETs.3 Their estimated incidence in Europe is 0 .5-1 per million.4 GUGy-NENs arise from the bladder, kidney, ureter, ovary, cervix, endometrium, prostate, testis or presacral space5-7 (see Section 1 of the Supplementary Material, *Correspondence to: ESMO Guidelines Committee, ESMO Head Ofﬁce, Via Ginevra 4, CH-6900 Lugano, Switzerland E-mail: [clinicalguidelines@esmo.org](clinicalguidelines@esmo.org) (ESMO Guidelines Committee). 5Note: Approved by the ESMO Guidelines Committee: June 2024. yCo-second authors. 2059-7029/© 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). available at [https://doi.org/10.1016/j.esmoop.2024.1036](https://doi.org/10.1016/j.esmoop.2024.1036)[ ](https://doi.org/10.1016/j.esmoop.2024.1036)[64](64)) . NENs arising from the head and neck (HN) account for <1% of HN malignancies, 2% of NECs and 0 .6% of NETs.4 Their estimated incidence in Europe is 0.1-0.15 per million.4 HN-NENs arise most frequently from the larynx8 followed by the middle ear9 and sinonasal tract10 (see Sect

FAQs

What proportion of neuroendocrine neoplasms have an unidentified primary site?

The primary tumour site remains unidentified in 13%–20% of cases.

How are neuroendocrine neoplasms pathologically classified in the guideline?

Classification relies on differentiation (well vs poorly differentiated), presence or absence of necrosis, and grade assessed by Ki-67 index and/or mitotic count.

Why is immunohistochemistry important for diagnosis?

Immunohistochemistry biomarkers can help identify primary sites and support accurate grading within a comprehensive pathology report.

Sep 21, 2026

Upload by Quinn