Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer

Abstract

Background: Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.

Methods: Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.

Results: Tumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17-3.55; HR, 2.55; 95% CI, 1.25-5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59-12.51).

Conclusion: Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.

Keywords: cancer-associated fibroblast; depth of invasion; disease-specific mortality; histologic risk score; oral tongue squamous cell carcinoma; prognosis; tumor budding; worst pattern of invasion.

Figure 1

Histological appearance of tumor budding at the invasive front of early oral tongue squamous cell carcinoma (SCC); tumor budding shown by arrows as an isolated single cancer cell or a cluster composed of <5 cancer cells. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 2

Histologic risk assessment model, (A) worst pattern of invasion type 4 associated with weak lymphocytic host response (type 3); (B) worst pattern of invasion type 5 (tumor satellite); and (C) perineural invasion (small nerve). Cancer associated fibroblasts, (D) poor; (E) medium; and (F) rich. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 3

Kaplan–Meier curves describing the cumulative mortality of patients during the follow-up period from oral tongue squamous cell carcinoma (A1–D1) and from other causes of death (A2–D2). The markers were tumor budding (high = ≥5 buds; low = <5 buds; A1, A2); tumor depth (high = ≥4 mm; low = <4 mm; B1, B2); histologic risk score (low = <3; high = ≥3; C1, C2); and cancer-associated fibroblast (CAF) score (high = high CAF density; low = medium and low CAF density; D1, D2). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

Figure 4

Kaplan–Meier curves for cumulative mortality of patients from oral tongue squamous cell carcinoma (SCC; A1), and from other causes (A2) in relation to the worst pattern of invasion (WPOI). The patients with high WPOI (<15 cells in an invasive island, single cells, or satellite tumor cells) were associated with a higher mortality compared to those with a low WPOI score (pushing borders, finger-like, and cohesive invasion). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]