# Evaluation of Tumor Budding and Poorly Defined Clusters as Histological Biomarkers in Squamous Cell Carcinomas of the Vulva

## TL;DR

This study explores how specific tissue patterns in vulvar cancer, like tumor budding, can predict patient outcomes and survival rates.

## Contribution

The study identifies tumor budding and poorly defined clusters as novel histological biomarkers with prognostic value in vulvar squamous cell carcinomas.

## Key findings

- Peritumoral tumor budding is linked to a lower risk of metastasis and better survival.
- Absence of intratumoral tumor budding correlates with reduced local recurrence.
- Patients without peritumoral budding show significantly improved overall survival.

## Abstract

Although histological features such as intratumoral/peritumoral tumor budding and poorly defined clusters have been previously studied in a variety of solid tumors, very little is yet known about their prognostic relevance in squamous cell carcinomas of the vulva. Therefore, we evaluated the prognostic relevance of the above-mentioned morphological biomarkers in vulvar cancer and indeed determined a superior rate of survival as well as a lower metastasis rate in patients without the formation of tumor buds. We are thus contributing to the establishment of a future research focus on new pathological biomarkers with the ultimate goal of improving the diagnostic and prognostic accuracy in patients with vulvar neoplasia.

Background/Objectives: Several histopathological risk factors have been examined in vulvar cancer (VC) so far. However, the prognostic relevance of morphological biomarkers such as tumor budding (TB) and poorly defined clusters (PDCs) remains to be determined. Material and Methods: We histologically analyzed the formation of peritumoral and intratumoral TB and PDCs in a cohort of 157 patients with VC. We assessed their association with clinico-pathological features and evaluated their prognostic impact in terms of the risk of local recurrence and occurrence of metastasis (Fisher’s exact test) as well as overall survival (Log-rank test). Results: We determined a distinct prognostic relevance of peritumoral TB with regard to occurrence of metastasis (Fisher’s exact test; p = 0.0415) as well as a significant reduced risk of local recurrence in the group with absent intratumoral TB (Fisher’s exact test; p = 0.0004). Furthermore, we showed that patients without peritumoral budding formation had a significant superior prognosis in terms of overall survival (p = 0.0366, x2 = 4.370). Conclusions: This study shows that several new histomorphological biomarkers may serve useful in predicting the clinical course of patients with VC, identifying patients at a lower risk of developing metastases/local recurrence as well as improved overall survival.