Naiara Vega

Vulvar squamous cell carcinoma arising on human papillomavirus‐independent precursors mimicking high‐grade squamous intra‐epithelial lesion: a distinct and highly recurrent subtype of vulvar cancer

AimsEach category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)‐associated and HPV‐independent, arises on a specific intra‐epithelial precursor: high‐grade squamous intra‐epithelial lesions (HSIL) and differentiated vulvar intra‐epithelial neoplasia (dVIN), respectively. However, a subset of HPV‐independent VSCC arises on an intra‐epithelial precursor closely mimicking HSIL. We aimed to explore the clinicopathological features of the HPV‐independent tumours with HSIL‐like lesions and compare them with HPV‐independent VSCC with dVIN and HPV‐associated tumours with HSIL.Methods and resultsWe retrospectively identified 105 cases of surgically treated VSCC with adjacent intra‐epithelial precursors. The cases were classified into three groups based on the HPV status and the adjacent precursor identified: (i) HPV‐associated VSCC with HSIL (n = 26), (ii) HPV‐independent VSCC with dVIN lesions (n = 54) and (iii) HPV‐independent VSCC with HSIL‐like lesions (n = 25). We analysed the histological and clinical features including the recurrence‐free survival and disease‐specific survival in the three groups. Patients with HPV‐independent VSCC with HSIL‐like lesions and with dVIN were older than patients with HPV‐associated VSCC (76 and 77 versus 66 years, respectively, P < 0.001). HPV‐independent VSCC with HSIL‐like lesions recurred more frequently [hazard ratio (HR) = 3.87; P < 0.001] than HPV‐independent VSCC with dVIN (HR = 2.27; P = 0.1) and HPV‐associated VSCC (HR = 1). In the multivariate analysis, HPV‐independent VSCC with HSIL‐like lesions remained significant for recurrence. No differences in disease‐specific survival were observed between the three groups.ConclusionsEven though VSCC with HSIL‐like lesions are not associated with higher mortality, they are more likely to recur and might benefit from more intensive treatment strategies and closer surveillance after treatment.

p53 Immunohistochemical Patterns in HPV-Independent Squamous Cell Carcinomas of the Vulva and the Associated Skin Lesions: A Study of 779 Cases

Human papillomavirus (HPV)-independent vulvar squamous cell carcinomas (VSCC) and its precursors frequently harbour TP53 mutations. Recently, six p53 immunohistochemical (IHC) patterns have been defined, which have shown strong correlation with TP53 mutation status. However, few studies have applied this new six-pattern framework and none of them exhaustively compared p53 IHC positivity and patterns between invasive VSCC and adjacent skin lesion. We performed p53 IHC in a series of 779 HPV-independent VSCC with adjacent skin and evaluated the IHC slides following the newly described classification. Some 74.1% invasive VSCC showed abnormal p53 IHC staining. A skin lesion was identified in 450 cases (57.8%), including 254 intraepithelial precursors and 196 inflammatory/reactive lesions. Two hundred and ten of 450 (47%) VSCC with associated skin lesions showed an abnormal p53 IHC stain, with an identical staining pattern between the VSCC and the adjacent skin lesion in 80% of the cases. A total of 144/450 (32%) VSCC showed wild-type p53 IHC both in the invasive VSCC and adjacent skin lesion. Finally, 96/450 (21%) VSCC showed p53 IHC abnormal staining in the invasive VSCC but a wild-type p53 staining in the skin lesion. Most of the discordant cases (70/96; 73%) showed adjacent inflammatory lesions. In conclusion, the p53 IHC staining and pattern are usually identical in the VSCC and the intraepithelial precursor.