Extranodal extension (ENE)
Extranodal extension means cancer in a lymph node has burst through the node's capsule into the surrounding fat; in head and neck cancer it is the single finding after surgery that most often turns radiotherapy into chemoradiotherapy, and in HPV-negative disease it moves the stage up.
Overview
What is measured: growth of nodal metastasis through the lymph node capsule into perinodal tissue. How: the pathologist's examination of the neck dissection specimen, graded in AJCC 8th edition as major (more than 2 mm beyond the capsule or soft-tissue deposit) or minor (2 mm or less), with pathological N stage for HPV-negative head and neck and cutaneous squamous cell carcinomas upstaged to pN2a or pN3b by its presence; radiological extranodal extension on CT or MRI (irregular capsule, infiltration of fat, matted nodes) is moderately accurate and is not used to stage HPV-positive disease. What a positive result changes: in the pooled analysis of EORTC 22931 and RTOG 9501, extranodal extension and positive margins were the two findings for which adding cisplatin to postoperative radiotherapy (60 to 66 Gy) improved survival, so either mandates chemoradiotherapy in head and neck squamous cell carcinoma; in HPV-positive oropharyngeal cancer its prognostic weight is smaller and the ECOG 3311 and PATHOS trials test whether chemotherapy can be omitted after transoral surgery; in melanoma, breast (extracapsular extension) and penile and vulvar carcinoma it raises the risk of regional relapse and drives adjuvant nodal radiotherapy. Where it matters: oral cavity, oral tongue and buccal cancers, HPV-negative and HPV-positive head and neck cancer, salivary duct and mucoepidermoid carcinoma.
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