Sisuashvili Lia, Saco Adela, Carreras-Dieguez Núria, Celada Cristina, Marimon Lorena, Montironi Carla, Ordi Jaume, Rakislova Natalia
Barcelona Institute of Global Health (ISGlobal).
Department of Pathology, Hospital Clínic of Barcelona.
Int J Gynecol Pathol. 2025 Mar 1;44(2):120-124. doi: 10.1097/PGP.0000000000001047. Epub 2024 Jul 24.
Vulvar squamous cell carcinoma (VSCC) can be classified according to human papillomavirus (HPV) status as HPV-associated (HPV-A) and HPV-independent (HPV-I). However, a small subset of tumors may show overlapping features and become a serious diagnostic challenge for pathologists. We report an unusual case of VSCC arising in a 21-year-old patient with type 1 diabetes mellitus. The tumor had keratinizing histologic features, was associated with a premalignant lesion with features of a high-grade squamous intraepithelial lesion (HSIL), and showed consistent p53 immunohistochemical (IHC) overexpression, but variable results in the HPV testing and p16 IHC staining. Molecular analysis revealed mutation of TP53 and overexpression of cell cycle-regulating genes (including CCND1) and collagen-coding genes (such as COL6A1). These molecular findings in genes, previously reported as upregulated in HPV-I VSCC, supported an etiological origin independent of HPV for the tumor. In conclusion, molecular analysis may help to correctly classify challenging VSCC, showing puzzling clinical, morphologic, and IHC characteristics.
外阴鳞状细胞癌（VSCC）可根据人乳头瘤病毒（HPV）状态分为HPV相关型（HPV-A）和HPV非依赖型（HPV-I）。然而，一小部分肿瘤可能呈现重叠特征，给病理学家带来严峻的诊断挑战。我们报告了一例罕见的VSCC病例，发生在一名患有1型糖尿病的21岁患者身上。该肿瘤具有角化组织学特征，与具有高级别鳞状上皮内病变（HSIL）特征的癌前病变相关，p53免疫组化（IHC）呈持续过表达，但HPV检测和p16 IHC染色结果不一。分子分析显示TP53突变，细胞周期调控基因（包括CCND1）和胶原蛋白编码基因（如COL6A1）过表达。这些基因中的分子发现，此前报道在HPV-I VSCC中上调，支持该肿瘤的病因起源独立于HPV。总之，分子分析可能有助于正确分类具有挑战性的VSCC，这些VSCC表现出令人困惑的临床、形态学和IHC特征。
