Joint Task Force
Abbreviations
Acknowledgements
Introduction
The Three Grades
Key Points & Tips
Examples
Self-Test
Imaging-derived Extranodal Extension (iENE)
in Head and Neck Cancer
This guide from the AOSNHNR-ASHNR-ESHNR Joint Task Force offers radiologists a clear framework for identifying and reporting imaging-derived extranodal extension (iENE) in head and neck cancer, supporting consistent interpretation and better patient care.
Abbreviations
- AJCC: American Joint Committee on Cancer, from the American College of Surgeons
- AOSNHNR: Asian-Oceanian Society of Neuroradiology and Head and Neck Radiology
- ASHNR: American Society of Head and Neck Radiology
- EBV: Epstein-Barr Virus, the causative agent of endemic NPC
- ENE: Extranodal Extension (previously called extracapsular spread, ECS)
- ESHNR: European Society of Head and Neck Radiology
- HNCIG: Head and Neck Cancer International Group
- HNSCC: Head and Neck Squamous Cell Carcinoma
- HPV: Human Papilloma Virus
- HPV+OPSCC: OPSCC with evidence of HPV infection, either via direct viral DNA assay or via p16 protein as a proxy
- iENE: imaging-derived ENE (previously called radiologic ENE or rENE; switched to iENE because the prefix ‘r’ denotes recurrent disease)
- OPSCC: Oropharyngeal Squamous Cell Carcinoma
- NPC: Nasopharyngeal Squamous Cell Carcinoma
- pENE: pathologic ENE
- SCM: Sternocleidomastoid Muscle
- UICC: Union for International Cancer Control
Acknowledgements
Members of the Joint International Task Force on iENE
- Barton F. Branstetter IV, MD, FACR, FSIIM
University of Pittsburgh, USA - Pim de Graaf, MD, PhD
Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands - Ann D. King, MB ChB, FRCP, FRCR, FHKCR, FHKAM, MD
Chinese University of Hong Kong, China - Jeong Hyun Lee, MD
University of Ulsan, South Korea - Roberto Maroldi, MD
University of Brescia, Italy - Eugene Yu, MD
University of Toronto, Canada
The members of the task force wish to thank the following individuals for their assistance in assembling cases and evaluating the clarity and content of this Guide.
- Dr. Qi-yong Hemis AI, PhD, MMed, BMed
Department of Diagnostic Radiology, The University of Hong Kong - Dr. Ho Sang Leung, MBBS (HK), FHKCR
Department of Imaging and Interventional Radiology, Prince of Wales Hospital - Dr. Kwok Yan LI, MBChB (CUHK), FRCR
Department of Radiology, Princess Margaret Hospital
Introduction
Pathologic extranodal extension of metastatic tumor has been shown to be a risk factor for multiple types of cancers in the head and neck. For several years, the radiology community has attempted to determine whether imaging modalities could detect pENE without the need for surgical excision of the affected lymph nodes. More recent studies have shown, however, that iENE represents an independent risk factor for disease-free and overall survival of patients with HNSCC from various primary sites, including NPC and OPSCC. Thus, in the 9th version of the AJCC Staging Manuals, iENE appears as an independent risk factor for clinically upclassifying the lymph nodes in some types of HNSCC, without regard to the pENE status of those nodes.
The goal of this Guide is to provide educational materials for radiologists regarding the diagnosis of iENE, to ensure consistent application of standards and thresholds for positivity. Previous literature has demonstrated weak inter-rater consistency when diagnosing iENE, but these measures are improved with educational and self-assessment tools. This Guide was created by a collaborative task force comprising members of the ASHNR, ESHNR, and AOSNHNR with research and clinical experience regarding iENE. The six members of the committee are radiologists practicing in six different countries, with two members representing each of the sponsoring organizations. This Guide is based on, and aligns with, the classification scheme advocated by the HNCIG.
Perhaps the most important overarching philosophy, as emphasized by the AJCC and UICC, is that indeterminate or equivocal findings should be regarded as “negative” for iENE. Although radiologists may choose to report equivocal findings for radiotherapy planning, only definitive, unequivocal radiologic findings should be used during staging to assign the N category. The reasoning behind this decision is that patients who are improperly upstaged may be denied potentially curative surgery or unnecessarily subjected to the morbidity of chemoradiation.
The Three Grades
For example, if a patient has equivocal evidence of muscle invasion (Grade 3), definitive evidence of coalescent nodes (Grade 2), and definitive evidence of perinodal fat invasion (Grade 1), then the correct diagnosis is Grade 2 iENE. In this example, the evidence pointing to Grade 3 is not utilized because it is equivocal. The definitive Grade 1 iENE is overshadowed by the definitive Grade 2 iENE.
Grades of iENE may be used differently for staging of different types of HNSCC. For example, all Grades might be considered high-risk for HPV+OPSCC, while only Grade 3 in cervical nodes (not retropharyngeal nodes) is considered high-risk for NPC. It is incumbent upon radiologists to report not only the presence or absence of iENE, but also the Grade, to ensure proper staging of the patient but also for future research endeavors that will improve our understanding of the impact of different Grades of iENE on patient prognosis.
Absence of definitive iENE may referred to as Grade 0, or “negative for iENE.”
Key Points and Tips for Grading iENE
- Grade 1 (invasion of perinodal fat)
- Grade 2 (coalescent nodes)
- Grade 3 (invasion of surrounding organs)
Irregular or indistinct capsule alone is not sufficient; these must be accompanied by projections/spikes into the perinodal fat to be considered Grade 1.
Be wary when assessing treated nodes, potentially infected nodes, or nodes that have recently undergone tissue sampling. Expected findings in such nodes may mimic iENE.
- Three imaging criteria must be met: 1) loss of fat planes between the nodes; 2) loss of convexity of at least one node at the point of contact; 3) loss of acute angle between nodes on at least one edge of contact (i.e. merging of at least one boundary)
- Care is needed to ensure that a single node with solid and necrotic components is not mistaken for multiple conglomerate nodes.
- Lobulated margins may be found in either single nodes or coalescent nodes, so multiple slices and multiple planes of imaging are usually required to distinguish between the two.
- Muscle involvement can refer to any muscle, but the sternocleidomastoid muscle is most frequently involved. Loss of the fat plane between node and muscle is not sufficient. Equivocal enhancement of the muscle is not sufficient.
- Arterial involvement requires encasement (at least 270° of the circumference) of major arteries (common carotid artery, internal carotid artery, external carotid artery origin, vertebral artery). Smaller arteries are not included in the assessment.
- Compression or displacement of the internal jugular vein is insufficient. Tumor thrombus must be seen within the vein, or the vein must be completely obliterated without flow. Thus, unenhanced CT or MRI cannot definitively assess this feature. Smaller veins are not included.
- Direct nerve invasion is difficult to detect radiologically unless there is radiologic or clinical evidence of nerve palsy (such as muscle denervation).
- Skin involvement requires loss of the subcutaneous fat with thickening, ulceration, or an exophytic mass.
- Involvement of major glands requires definitive invasion through the capsule of the gland into the parenchyma. Displacement or distortion of the gland is insufficient.
- The merger of nodal metastases with an adjacent primary tumor (most frequently oral cavity or hypopharynx/larynx) is considered Grade 3 iENE (with the exception of retropharyngeal nodes in NPC).
- Tumor adjacent to a muscle may induce edema (T2 signal change) without true invasion. Compare the T2 signal and the post-contrast signal within the muscle to that of the nearby tumor to avoid overcalling invasion.
Examples
Round 1
Initial Examples of iENE Grades
Round 2
“Probable iENE” Should Be Considered Grade 0
Round 3
Complex Cases and Borderline Cases
Self Test
Accurate assessment of imaging extranodal extension (iENE) is critical for staging head and neck cancers and ensuring appropriate treatment decisions. Standardized grading helps radiologists apply consistent criteria, improving diagnosis and patient outcomes.
Take this self-test to assess your understanding of iENE classification and its impact on staging.
Self-Test is under development and is planned for Fall 2025
