Cervical Lymph Node Metastases in Head and Neck Squamous Cell Carcinoma: Patterns, Extranodal Extension, and Diagnostic Performance of Imaging

Background: Lymph node metastases are frequently seen in patients with head and neck squamous cell carcinoma and they are ascribed the role as the most important prognostic factor. However, challenges persist in accurately diagnosing nodal involvement, potentially leading to over- or undertreatment for the patient. In this regard, it is crucial to understand the patterns of cancer metastases to the neck, how histopathological extranodal extension is assessed, and the diagnostic value of imaging.

Aim: To investigate current knowledge and challenges, and improve the diagnosis of lymph node metastases in head and neck squamous cell carcinoma patients 

Methods: The thesis covers three areas within the field of lymph node metastases

1. Patterns and distribution of lymph node metastases a. Retrospective study of 928 surgically treated oropharyngeal squamous cell cancer patients in collaboration with the Mayo Clinic, USA.
2. Extranodal extension a. Systematic review of available literature on the histopathological definition of extranodal extension. b. Inter- and intraobserver study among Danish pathologists evaluating extranodal extension with and without a standardized definition.
3. Imaging a. Meta-analysis of the diagnostic value of conventional imaging modalities in the diagnosis of extranodal extension of lymph node metastases: computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and positron emission tomography/ computed tomography (PET/CT). b. Prospective head-to-head study of the diagnostic value of PET/MRI for detecting lymph node metastases compared to CT, MRI, and PET/CT. 

Results: Nodal metastases are common but rarely seen bilaterally in the neck. Nodal recurrences are rare (5.4%) and occur at a median of 1.0 years. Recurrences are most often seen at the ipsi- and contralateral level II. The definition of histopathological extranodal extension is vague with 44 unique definitions found in the literature. Consequently, the interobserver agreement among pathologists on the diagnosis of extranodal extension demonstrates a moderate level of consistency; however, this can be slightly improved through the adoption of a standardized definition. Currently used imaging modalities have comparable diagnostic efficacy in detecting extranodal extension, with sensitivities ranging between 75% and 80% and specificities between 77% and 83%. The diagnostic performance of PET/MRI for diagnosis of lymph node metastases is similar to that of conventional imaging modalities.

Conclusion: The diagnosis of lymph node metastases and extranodal extension may improve by standardization of the histopathological diagnosis. Imaging techniques are useful in the diagnostics of lymph node metastases, but their performance is moderate. PET/MRI has a commensurate level of accuracy when compared to conventional modalities.