The Association Between Venous Invasion and Distant Metastasis in Head and Neck Squamous Cell Carcinoma

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Abstract
In surgically treated cases of head and neck squamous cell carcinoma (HNSCC), even pathological N0 (pN0) cases according to the Tumor, Node, and Metastasis (TNM) Classification, distant metastases can occur relatively early postoperatively. Therefore, we hypothesized that hematogenous distant metastasis may be related to the degree of venous invasion. Lymphatic invasion is considered to be a poor prognostic factor in HNSCC, but knowledge about venous invasion is scarce. We therefore investigated the association between venous invasion and distant metastasis, an important poor prognostic factor, in cases of HNSCC from our institution. Between April 2020 and December 2023 (four years and nine months), there were 89 cases in which a postoperative pathological evaluation of microvascular invasion was conducted after HNSCC surgery at our institution. Of these, 73 were retrospectively reviewed, after excluding six cases with positive margins and 10 cases with extranodal extension of metastatic lymph nodes. The observation period ranged from 13 to 54 months (mean: 32.5 months). The correlations between the presence/absence of venous or lymphatic invasion at the primary site and distant metastasis were investigated. Among the 73 cases, venous invasion was found at 31 primary sites, and lymphatic invasion was observed in 38 cases. Distant metastases were found in 10 cases. All cases showed both venous out lymphatic invasion, and none of the cases where these were negative showed distant metastasis. There were significantly more distant metastases in both the venous invasion-positive group (p=0.001) and the lymphatic invasion-positive group (p=0.004). The absence of distant metastasis in cases that were negative for venous invasion and venous invasion being present in all cases with distant metastasis indicated that venous invasion by the primary tumor is an important factor in distant metastasis. Venous invasion was also found to increase in frequency as the T and N stages progressed.

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