International Consensus Recommendations of Diagnostic Criteria and Terminologies for Extranodal Extension in Head and Neck Squamous Cell Carcinoma: An HN CLEAR Initiative (Update 1)

Ruta Gupta; Timothy Fielder; Munita Bal; Simion I Chiosea; Jane E Dahlstrom; Aanchal Kakkar; Katalin Kiss; Jan Laco; Neha Mittal; Sunil Pasricha; Spinder Samra; Nina Zidar; Martin Bullock; Rebecca Chernock; William Faquin; Shao Hui Huang; Jean Yang; Sun Och Yoon

doi:10.1007/s12105-025-01753-7

International Consensus Recommendations of Diagnostic Criteria and Terminologies for Extranodal Extension in Head and Neck Squamous Cell Carcinoma: An HN CLEAR Initiative (Update 1)

Head Neck Pathol. 2025 Feb 7;19(1):20. doi: 10.1007/s12105-025-01753-7.

Authors

Ruta Gupta^{1

2

3

4

5}, Timothy Fielder⁶, Munita Bal⁷, Simion I Chiosea⁸, Jane E Dahlstrom^{9

10}, Aanchal Kakkar¹¹, Katalin Kiss¹², Jan Laco^{13

14}, Neha Mittal⁷, Sunil Pasricha¹⁵, Spinder Samra¹⁶, Nina Zidar¹⁷, Martin Bullock¹⁸, Rebecca Chernock¹⁹, William Faquin²⁰, Shao Hui Huang²¹, Jean Yang²², Sun Och Yoon²³

Affiliations

¹ Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, Sydney, NSW, Australia. ruta.gupta@health.nsw.gov.au.
² Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. ruta.gupta@health.nsw.gov.au.
³ NHMRC Center of Research Excellence for Applied Innovations in Oral Cancer, Sydney, NSW, Australia. ruta.gupta@health.nsw.gov.au.
⁴ Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital| NSW Health Pathology, Building 12, Missenden Road, Camperdown, NSW, 2050, Australia. ruta.gupta@health.nsw.gov.au.
⁵ University of Sydney, Central Clinical School, Royal Prince Alfred Hospital, Building 12, Missenden Road, Camperdown, NSW, 2050, Australia. ruta.gupta@health.nsw.gov.au.
⁶ Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, NSW Health Pathology, Sydney, NSW, Australia.
⁷ Department of Pathology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
⁸ Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁹ ACT Pathology, Canberra Health Services, Canberra, Australia.
¹⁰ School of Medicine and Psychology, ANU College of Science and Medicine, Canberra, Australia.
¹¹ Department of Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India.
¹² Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹³ The Fingerland Department of Pathology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
¹⁴ The Fingerland Department of Pathology, Charles University Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
¹⁵ Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
¹⁶ Department of Pathology, NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia.
¹⁷ Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
¹⁸ Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁹ Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
²⁰ Department of Anatomic and Molecular Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
²¹ Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada.
²² Department of Mathematics and Statistics, University of Sydney, Sydney, Australia.
²³ Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.

Abstract

Purpose: Extranodal extension (ENE) increases the risk of recurrence and death in head and neck squamous cell carcinoma (HNSCC) patients and is an indication for treatment escalation. Histopathology forms the mainstay of diagnosing ENE. There is substantial variation in the diagnosis of ENE and related terminology. Harmonising the diagnostic criteria for ENE was identified as a priority by the Head and Neck Consensus Language for Ease of Reproducibility (HN CLEAR) Steering Committee and its global stakeholders.

Methods: An international working group including 16 head and neck pathologists from eight countries across five continents evaluated whole slide images of haematoxylin and eosin-stained sections depicting potential diagnostic problems through nine virtual meetings to develop consensus guidelines.

Results: ENE should be diagnosed only when viable carcinoma extends through the primary lymph node (LN) capsule and directly interacts with the extranodal host environment with or without desmoplastic stromal response. Identifying the original LN capsule and reconstruction of its contour can assist in the detection and assessment of ENE. The term matting is recommended for confluence of two or more nodes due to histologically identifiable tumour extending from one LN to another. Matting constitutes major form of ENE. On the other hand, the terms fusion/adhesion/confluence/conglomeration and other synonyms of adhesion should be limited to confluence due to fibrosis or inflammation without histologically identifiable tumour between involved lymph nodes. Tumour extension along narrow needle tracks or spillage of cyst contents following an FNA do not constitute ENE.

Conclusions: The consensus recommendations encompassing the definition of ENE, macroscopic and histologic examination of lymph nodes (LN) and practical guidelines for handling challenging cases are provided.

Keywords: Diagnosis; Extranodal extension (ENE); Head and neck; Histology; Lymph node; Macroscopy; Matting; Soft tissue deposit; Squamous cell carcinoma.

Publication types

Letter

MeSH terms

Consensus
Extranodal Extension* / diagnosis
Extranodal Extension* / pathology
Head and Neck Neoplasms* / diagnosis
Head and Neck Neoplasms* / pathology
Humans
Squamous Cell Carcinoma of Head and Neck* / diagnosis
Squamous Cell Carcinoma of Head and Neck* / pathology
Terminology as Topic*