Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma

Abstract

In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma. Associations between the histopathological factors (depth of tumor, differentiation, blood vessel invasion, lymphatic invasion, and tumor budding) and late lymph metastasis were analyzed. Although the univariate analysis identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as predictive factors for neck recurrence (p < 0.001), the Cox proportional hazards model identified high-grade tumor budding as an independent predictive factor (p < 0.01). The combination of a tumor depth ≥ 3 mm and high-grade tumor budding yielded high diagnostic accuracy. Tumor depth and budding grade were identified as histopathological risk factors for late neck recurrence in clinical N0 early oral tongue carcinoma.

Keywords: Depth of tumor; Early tongue carcinoma; Lymph node metastasis; Squamous cell carcinoma; Tumor budding.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1

Histopathological reviews with HE and Elastica van Gieson (EvG) staining and immunostaining for D2-40. A Blood vessel invasion was analyzed in EvG for staining elastic fibers. B Lymphatic invasion was immunohistochemically analyzed using D2-40 staining recognizing podoplanin on lymphatic endothelia. C Well differentiated squamous cell carcinoma (SCC) was analyzed with HE staining. D Moderately differentiated SCC was analyzed with HE staining

Fig. 2

Tumor depth was measured from the surface of the tumor to the deepest point of the invasive tumor in HE staining using automatic analyzer

Fig. 3

HE staining demonstrating tumor budding in the tumor invasive front. A Tumor budding is enclosed by the square (at 4 × 10 magnification). B Magnified view of the area enclosed in the square in A (at 20 × 10 magnification). The superior cluster consisting of 4 tumor cells was counted as budding (a) and the inferior cluster consisting of 5 tumor cells was not counted as budding (b), as described in the Materials and Methods.

Fig. 4

Tumor budding was classified as low or high grade at 20 × 10 magnification. The black arrows indicate tumor budding. A Low-grade budding (two). B High-grade budding (eleven)

Fig. 5

Kaplan–Meier curves of A overall survival (OS), B local control (LC), and C regional control (RC). The 5-year OS rate was 93% (Stage I/II 91%/100%), the 5-year LC rate 87% (Stage I/II 84%/100%) and the 5-year RC was 80% (Stage I/II 78%/89%). There were no significant differences of OS, LC, and RC between Stage I and Stage II

Fig. 6

Neck recurrence according to histopathological tumor depth

Fig. 7

Kaplan–Meier curves of A differentiation, B blood vessel invasion, C lymphatic invasion, and D budding grade. The log-rank test identified blood vessel invasion, lymphatic invasion, and high-grade tumor budding as histopathological risk factors for neck recurrence.

Fig. 8

Neck recurrence according to a combination of a tumor depth ≥ 3 mm and high-grade tumor budding