Department of Pathology, Barcelona Institute of Global Health (ISGlobal), Hospital Clínic-University of Barcelona.
Public Research Consortium of Epidemiology and Public Health (CIBER).
Am J Surg Pathol. 2020 Nov;44(11):1506-1514. doi: 10.1097/PAS.0000000000001540.
Two etiopathogenic types of vulvar squamous cell carcinoma (VSCC) have been described: human papillomavirus (HPV)-associated and HPV-independent. Precursor lesions, frequently identified in the adjacent skin, are also distinct in the 2 types of VSCC: high-grade squamous intraepithelial lesions (HSILs) in HPV-associated VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) or vulvar acanthosis with altered differentiation in HPV-independent VSCC. Although HPV-independent precursors mimicking HSIL have been described in the vulva, their frequency and morphologic spectrum have not been completely characterized. We explored, in a large series of HPV-independent VSSC, the frequency and the histologic features of precursors mimicking HSIL. We included 779 DNA HPV-negative/p16-negative VSCC with at least 1 cm of adjacent skin. We evaluated the histologic and immunohistochemical (p16 and p53) characteristics of the intraepithelial lesions, focusing on precursors mimicking HPV-associated vulvar HSIL. A total of 254 tumors (33%) had adjacent premalignant lesions. Of them, 186 (73%) had dVIN, 22 (9%) had vulvar acanthosis with altered differentiation, and 46 (18%) had lesions that mimicked HSIL. The mean age of the patients with these HSIL-like lesions was 72±15 years. Twenty-six of these HSIL-like lesions had basaloid morphology, 13 warty, and 7 mixed basaloid/warty features. All the HSIL-like precursors were DNA HPV-negative/p16-negative; 74% of them showed p53 abnormal staining and 35% of them had areas of conventional dVIN. In conclusion, about one fifth of the HPV-independent precursors mimic HSIL, showing either basaloid or warty features. Older age and the presence of areas of typical HPV-independent intraepithelial lesions, together with p16 negativity, should raise suspicion of an HPV-independent etiology.
两种外阴鳞状细胞癌 (VSCC) 的发病机制已被描述：人乳头瘤病毒 (HPV) 相关和 HPV 不相关。前体病变，常在外阴相邻皮肤中发现，在外阴鳞状细胞癌的 2 种类型中也有明显的区别：HPV 相关的 VSCC 中的高级别鳞状上皮内病变 (HSIL) 和 HPV 不相关的 VSCC 中的分化型外阴上皮内瘤变 (dVIN) 或外阴棘皮病伴分化改变。虽然在外阴已经描述了类似于 HSIL 的 HPV 不相关前体，但它们的频率和形态谱尚未完全确定。我们在一系列大型 HPV 不相关的 VSCC 中探索了类似于 HSIL 的前体的频率和组织学特征。我们纳入了 779 例至少有 1 厘米相邻皮肤的 DNA HPV 阴性/p16 阴性 VSCC。我们评估了上皮内病变的组织学和免疫组织化学 (p16 和 p53) 特征，重点是类似于 HPV 相关的外阴 HSIL 的前体。共有 254 例肿瘤 (33%) 有相邻的癌前病变。其中，186 例 (73%) 为 dVIN，22 例 (9%) 为外阴棘皮病伴分化改变，46 例 (18%) 为类似于 HSIL 的病变。这些类似 HSIL 病变患者的平均年龄为 72±15 岁。这些类似 HSIL 的病变中有 26 例为基底细胞样形态，13 例为疣状，7 例为基底细胞样/疣状混合形态。所有类似 HSIL 的前体均为 DNA HPV 阴性/p16 阴性；74%的病例存在 p53 异常染色，35%的病例存在典型的 HPV 不相关上皮内病变。总之，大约五分之一的 HPV 不相关的前体类似于 HSIL，表现为基底细胞样或疣状特征。年龄较大，存在典型的 HPV 不相关上皮内病变，以及 p16 阴性，应怀疑为 HPV 不相关的病因。
