The prognostic role of histologic grade, worst pattern of invasion, and tumor budding in early oral tongue squamous cell carcinoma: a comparative study

Abstract

Major pathology guidelines often mandate stating the histologic grade as a component of the pathology report for various types of cancer. However, the prognostic value of histologic grade in head and neck squamous cell carcinoma (HNSCC) is controversial at best, and there is a need for more reliable prognostic histologic factors to better stratify and manage patients with HNSCC. In this study, we compared three relevant histopathologic features (histologic grade, worst pattern of invasion (WPOI), and tumor budding) in a large single-center retrospective cohort of early oral tongue squamous cell carcinoma (OTSCC) with tumor greatest dimension ≤ 4 cm. Only histologic grade predicted distant metastasis free survival (DMFS) on univariate analysis. Tumor budding was associated with nodal metastasis, overall survival (OS), regional recurrence-free survival (RRFS), and DMFS and was a significant predictor for nodal metastasis on the multivariable logistic regression model. WPOI 5 was associated with high frequency of nodal metastasis and shortened OS and was an independent adverse prognostic factor for OS on multivariate analysis using the Cox proportional hazards model. WPOI and tumor budding were prognostically more relevant than histologic grade. Consideration should be given to include WPOI and tumor budding in the pathology reporting of OTSCC.

Keywords: Histologic grade; Oral tongue squamous cell carcinoma; Pattern of invasion; Prognosis; Tumor budding.

Figure 1.. Worst pattern of invasion (POI), Tumor budding, and histologic grade in oral tongue squamous cell carcinoma (OTSCC).

(A) WPOI 1: broad pushing invasion. (B) WPOI 2: finger-like tumor front. (C) WPOI 3: large tumor islands > 15 cells, (D-F) WPOI 4: small tumor islands ≤15 cells. (G) POI 5: satellite nodule(s) at least 1 mm away from the main tumor. A tumor bud (black arrows) is defined as a tumor cluster of <5 tumor cells or single tumor cells. Tumor budding is assessed at 20X objective (field size 0.785 mm²) and is classified as low (0–4 buds, panel D), intermediate (5–9 buds, panel E), and high ((≥10 buds, panel F). By definition, a tumor with WPOI 1–3 lacks tumor buds (i.e. low tumor budding), whereas a tumor with WPOI 4–5 may show any degree of budding. Histologic grade is classified using a combination of keratinization, cytonuclear atypia and infiltration pattern. Well-differentiated OTSCCs (panels A, B, and C) show minimal cytologic atypia and abundant keratinization. Moderately-differentiated tumors (panels D and G) are infiltrative, have notable cytologic atypia, and show a certain degree of differentiation/keratinization. Poorly-differentiated OTSCCs (E and F) frequently lack clear evidence of differentiation/keratinization and demonstrate marked nuclear pleomorphism and a growth pattern of single cells/small tumor clusters.

Figure 2.. Kaplan Meier curves for overall survival (top rows), regional recurrence free survival (RRFS, bottom left) and distant metastasis free survival (DMFS, bottom middle and right).

On univariate survival analysis, high tumor budding was associated with decreased overall survival, RRFS, and DMFS. Pattern of invasion 5 was associated with adverse overall survival. Poorly differentiated carcinoma predicted decreased DMFS but not overall survival.