BackgroundOral (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.MethodsDepth 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.ResultsTumor 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).ConclusionAnalyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.

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Despite early diagnosis and treatment, almost 20% of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95% confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95% CI 0.95-2.25). In addition, mortality from early OTSCC was also predicted by DOI (HR 2.44, 95% CI 1.34-4.47) and by WPOI (HR 2.34, 95% CI 1.26-4.32). We suggest that clinically early-stage oral tongue carcinomas 4 mm or deeper, or with a growth pattern of small cell islands or satellites, should be considered as high-risk tumors which require multimodality treatment.

We conclude that TSR is a simple histopathological feature that is useful for prognostication of early-stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE-stained slides.