Detection of occult cervical micrometastases in patients with head and neck squamous cell cancer

OBJECTIVE: The incidence of occult nodal metastases associated with head and neck squamous cell carcinoma (HNSCC) and the clinical significance of nodal micrometastases by cytokeratin immunohistochemical analysis are examined. STUDY DESIGN: In all, 1012 lymph nodes from 50 patients treated between 1992 and 2001 at the University of Colorado Health Sciences Center (Denver, CO) were evaluated retrospectively for micrometastases. METHODS: Serial sectioning in 5-to 6-microm interval specimens stained either with hematoxylin and eosin (H&E) or immunostaining for cytokeratins using the monoclonal antibody cocktail AE1/AE3 was performed in 21 N0, 11 N1, and 14 N2 patient cases. Cases that showed scattered cells with suspect staining qualities but without morphological features consistent with HNSCC were further evaluated by epithelial membrane antigen (EMA) immunohistochemical analysis. RESULTS: H&E-stained and cytokeratin-stained sections revealed occult nodal micrometastases in 3.8% of N0 and 5% of N1 cases. Overall, 26 micrometastases were identified in N0 and N1 patients, causing 29% of N0 patients and 45% of N1 patients to be upstaged. Cytokeratin immunostaining detected micrometastases in eight cases that were negative on H&E serial sectioning. Serial sectioning by H&E alone identified three additional micrometastases. Negative EMA immunostaining confirmed the absence of malignant cells in lymph node sections that were equivocal on cytokeratin staining. CONCLUSIONS: The use of serial sectioning with H&E and cytokeratin immunohistochemical analysis increases the detection of micrometastases that are often elusive by routine processing in patients with HNSCC. Improved methods of detecting micrometastases may provide a basis for improved planning of postoperative therapy for patients already at risk for tumor recurrence.