Predictors of Local Invasion in Infiltrative Basal Cell Carcinoma: Tumour Budding Outperforms the WHO Subtyping

Abstract

Tumour budding (TB) correlates with increased local invasion in various neoplasms. Certain basal cell carcinomas (BCCs) exhibit local aggressiveness. Detecting adverse prognostic factors in partial biopsies could aid in identifying cases with heightened local risk. The absolute number of TB (≤ 3 tumour cells) in excision specimens of 271 infiltrative BCCs (0: absent; 1: 1-2 foci; 2: ≥ 3 foci; 3: ≥ 10 foci), the histopathological subtype and depth of infiltration, perineural invasion, and other histological features were evaluated. A significant correlation was found between TB and both depth of infiltration (rho 0.445, p < 0.001) and perineural invasion (p = 0.009). In the multivariate analysis of depth and perineural invasion (multiple regression, stepwise), TB was identified as a significant covariate together with diameter, inflammation, and perineural invasion for the former, and depth for the latter. Conversely, no correlation existed between the WHO histological subtypes (infiltrating, sclerosing, and micronodular), and depth of infiltration or perineural invasion. This study demonstrates the value of TB as a biomarker for local invasiveness in BCC. In routine practice, a count of ≥ 3 TB foci in lesions incompletely excised or with narrow tumour-free surgical margins would be a straightforward and reproducible method to guide BCC treatment.

Fig. 1

Tumor budding (TB) quantification. Quantification of TB was performed after examining all sections, with the criterion that only groups of 3 or fewer tumour cells were considered for scoring. (A) Score 0 corresponds to cases with a total absence of tumour budding, as seen in this example of infiltrating BCC with a micronodular growth pattern. (B) Cases with score 1 presented only 1 or 2 tumour buds (red circle), sometimes with an equivocal appearance, making it challenging to distinguish them from reactive endothelial cells or fibroblasts. (C) Score 2 was assigned when the total number of tumour buds ranged between 3 and 10. This field contains many groups of more than 3 cells and 2 clear tumour buds (red circles) close to an area of perineural invasion. (D) Score 3 was assigned when the total number of tumour buds (red circles) exceeded 10.