Comparison of different histomorphological grading systems in vulvar squamous cell carcinoma.

Background: Histopathological biomarkers of carcinomas and their prognostic relevance, such as Broder's grading system (based on the total number of undifferentiated cells) or Bryne's grading system (rating morphological features at the tumor invasive front), have been repeatedly and successfully put to test. Since most studies focus on head and neck cancers or oral carcinomas, for squamous cell carcinoma of the vulva, no standardized and agreed on pathological tumor grading system, yielding prognostic significance, could be determined so far.

Material and methods: To determine prognostic associations of different grading systems with regard to groin lymph node metastasis, 73 cases of vulvar carcinomas (VC) were re-examined within our study and Broder's and Bryne's grading system individually performed. To sub-classify between HPV-associated or HPV-independent VC, immunohistochemical p16 stainings were performed. Statistical relationships were evaluated using Spearman correlation and logistic regression analysis, validation was achieved by employment of the likelihood ratio test (LRT) and assessment of ROC curves/AUC values.

Results: Within our cohort, Broder's grade I (40≈55%) and Bryne's grade II (48≈66%) were the most frequently assigned histological gradings. We determined a positive correlation of Bryne's grading with the extent of lymph node involvement in HPV-associated tumors and demonstrated the feasibility of Bryne's grading to predict the presence of carcinoma cells within groin lymph nodes (LRT p = 0.0066; AUC value≈0.91) in this cohort. On the other hand, our data suggest that especially HPV-independent tumors may not sufficiently be characterized by current standardly performed grading approaches.

Conclusion: Since only Bryne's grading system correlated positively with lymph node involvement in HPV-associated squamous cell carcinoma of the vulva, we propose to include it by name next to the distinct tumor entity on the histopathological report, allowing not only the interpretation of its prognostic relevance but also future research attempts.