Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

Abstract

Tumor breaching the capsule of a lymph node is termed extranodal extension (ENE). It reflects aggressiveness of a tumor, creates anatomic challenges for disease clearance, and increases the risk of distant metastasis. Extranodal extension can be assessed on a pathology specimen, by radiology studies, and by clinical examination. Presence of ENE in a pathology specimen has long been considered a high-risk feature of disease progression and would ordinarily benefit from the addition of chemotherapy to adjuvant radiotherapy. Although the eighth edition of the Union for International Cancer Control/American Joint Committee on Cancer stage classification dichotomizes pathologic ENE according to its presence or absence, emerging evidence suggests that the extent of a pathologic ENE may provide additional value for risk stratification to guide adjuvant therapy. Recent data suggest that the prognostic importance of pathologic ENE is also applicable for HPV-associated head and neck squamous cell carcinoma. In addition, compelling data demonstrate that indisputable radiologic ENE is a powerful risk stratification tool to identify patients at high risk for treatment failure, especially distant metastasis, applicable for both HPV-positive and HPV-negative head and neck squamous cell carcinoma. However, the definition and taxonomy of radiologic ENE requires standardization. The goal of this review is to clarify the contemporary understanding of the prognostic implications of ENE in head and neck squamous cell carcinoma, present the nuances of what is presently known and unknown, and elucidate how to classify ENE pathologically and radiologically with an understanding of the strengths and weaknesses of each approach. Finally, with the development of several risk stratification methods, the relative role of ENE and other prognostic schema will be explored.

Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort

“…Lower neck LN referred to any involved LN with a border extending into or beyond level IV or VB per consensus definition [3]. rENE grade was also recorded based on published literature [5,8,12,15] (Fig. 1): G1-rENE: Tumour invading individual/separate lymph node(s) capsule(s) but confined to perinodal fat, characterized by clearly discernible loss of the sharp definition between the nodal capsule and its surrounding fat, or irregular nodal borders in individual LNs.…”

Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy

“…Many previous reports have compared concordance between rENE and pENE ( 17 – 22 ). It has the potential to refine the cN classification and facilitate treatment selection in both viral-related and viral-unrelated HNSCC ( 24 – 27 ). Diagnosis of rENE based on our criteria has shown it to be a good prognostic factor for survival and predictor of response to treatment.…”

Differential expression of podoplanin in metastatic lymph node is associated with extranodal extension in oropharyngeal cancer

“…Meanwhile, in both ENE subdivisions, podoplanin expression and mean score were significantly higher in the perinodal stroma than in the intranodal area, this seems to be the result of reproducing our main data in which podoplanin was significantly expressed in perinodal stroma in the entire ENE-positive group. Even if major ENE showed worse prognosis than microscopic ENE in several studies of non-OPSCC ENE, the universal consensus was not achieved, and especially in HPV-related OPSCC, the value of ENE subdivision is more ambiguous 20 . Therefore, verification of the relationship between podoplanin expression which reflects tumor aggressiveness, and ENE subcategories could be contributed to establish the clinical implication of ENE progression.…”