Histomorphology and utility of CK17, p53 dual stain with CK 13 in the diagnosis of differentiated vulvar intraepithelial neoplasia

Abstract

Differentiated vulvar intraepithelial neoplasia (dVIN) is a known precursor for HPV-independent vulvar squamous cell carcinoma (VSCC). Diagnosis of dVIN can be challenging, and immunohistochemistry (IHC) may be a useful aid in this setting. A mutated pattern of p53 staining is associated with dVIN. This retrospective study evaluated the histological features and immunohistochemical utility of p53/Cytokeratin 17 (CK17) dual staining and cytokeratin 13 (CK13) staining in dVINs. At our institution, the diagnosis of dVIN is primarily based on morphology, and p53 stain is not routinely performed, especially in cases with concurrent invasive carcinoma or in recurrences. Thirty-two cases of dVIN identified from the pathology archives included 21 cases with p53 mutations and 11 cases without p53 mutations. Fourteen cases were biopsies. The staining patterns of CK17 and CK13 were compared in p53-mutated and non-mutated dVINs. p53/CK17 dual stain was used, which helped assess aberrant CK17 staining patterns adjacent to the mutated p53 patterns. Of the p53-mutated dVINs, 18/21(85.7 %) cases showed full-thickness CK17 staining. Of the remaining 11 cases with p53 wild-type staining, 5 cases showed full-thickness CK17 staining (45 %). Of the p53-mutated dVIN cases, 8/21 (38.09 %) showed full-thickness CK13 staining. Only 2/21 (9.5 %) showed loss of CK13 staining, as seen in oral dysplasia. Amongst dVINs with wild-type p53 staining, 50 % showed full-thickness CK13 staining. None of the lichen sclerosus cases showed full-thickness staining for CK13. The utility of CK13 staining in dVIN has been studied in only one previous study. A Panel consisting of p53, CK13, and CK17 antibodies may aid in increasing the accuracy of dVIN diagnosis, especially when a full-thickness staining pattern of CK13 and CK17 is noted. Further investigation of dVINs with full-thickness CK13 staining in a larger cohort is needed to confirm the results.