TMeB score may improve risk stratification of high‐risk cutaneous squamous cell carcinoma and guide management of patients: A pilot study

Abstract

Risk factors of poor prognosis in cutaneous squamous cell carcinoma (CSCC) include large tumour diameter, large-calibre perineural invasion, deep tumour invasion, and poorly differentiated histology.1 However, other risk factors likely play a role in tumour aggressiveness.2 Low peritumoural inflammation3 and desmoplasia4 (features of the tumour microenvironment [TMe]) and tumour budding5, 6 (TB) have been associated with poor prognosis in CSCC in a few studies. The present study examines whether these three attributes (considered collectively based on a risk score) improve CSCC risk stratification.

The study was approved by the University Hospital of Salamanca's Ethics Board and complied with STROBE recommendations. In total, 124 high-risk CSCCs (HR-CSCCs), defined as T3/T4-AJCC8, treated with clear-margin surgical excision were included. Cases with microscopical residual disease, bone involvement, or lost in follow-up were excluded. Low peritumoural inflammation, the presence of desmoplasia,4 and the presence of tumour budding (TB)5, 6 were utilized to derive the tumoural microenvironment and budding (TMeB) risk score: 1, no risk factors present; 2, one or two risk factors present; and 3, all three risk factors present. Peritumoural inflammation was defined as brisk/intense (peritumoural continuous), non-brisk/moderate (peritumoural discontinuous), scarce (dotted inflammatory cells), and absent, and it was dichotomized to distinguish low peritumoural inflammation (absent, scarce) from high (brisk, non-brisk). Desmoplasia was present when at least one-third of the tumour showed desmoplastic stroma.4 Tumour budding was defined by isolated tumour cells, or ≥4 groups of ≥5 tumour cells along the invasion front5, 6 (best observed at magnification >100×; Figure 1). Disease-free and event-free survival were assessed using R (v.3.4.1) packages survival (v.2.41-3), survminer (v.0.4.2) and cmprsk (v.2.2_7). Primary endpoints were local recurrence (LR), nodal metastasis (NM), and disease-specific death (DSD). Deaths from non-CSCC causes were considered competing risks.