Department of Pathology.
Institute of Pathology, Lausanne University Hospital, Lausanne University, Lausanne, Switzerland.
Am J Surg Pathol. 2022 Aug 1;46(8):1071-1077. doi: 10.1097/PAS.0000000000001885. Epub 2022 Mar 17.
Most human papillomavirus (HPV)-independent penile squamous cell carcinomas (PSCCs) originate from an intraepithelial precursor called differentiated penile intraepithelial neoplasia, characterized by atypia limited to the basal layer with marked superficial maturation. Previous studies in vulvar cancer, which has a similar dual etiopathogenesis, have shown that about one fifth of HPV-independent precursors are morphologically indistinguishable from high-grade squamous intraepithelial lesions (HSILs), the precursor of HPV-asssociated carcinomas. However, such lesions have not been described in PSCC. From 2000 to 2021, 55 surgical specimens of PSCC were identified. In all cases, thorough morphologic evaluation, HPV DNA detection, and p16, p53, and Ki-67 immunohistochemical (IHC) staining was performed. HPV-independent status was assigned based on both negative results for p16 IHC and HPV DNA. Thirty-six of the 55 PSCC (65%) were HPV-independent. An intraepithelial precursor was identified in 26/36 cases (72%). Five of them (19%) had basaloid features, morphologically indistinguishable from HPV-associated HSIL. The median age of the 5 patients was 74 years (range: 67 to 83 y). All 5 cases were p16 and DNA HPV-negative. Immunohistochemically, 3 cases showed an abnormal p53 pattern, and 2 showed wild-type p53 staining. The associated invasive carcinoma was basaloid in 4 cases and the usual (keratinizing) type in 1. In conclusion, a small proportion of HPV-independent PSCC may arise on adjacent intraepithelial lesions morphologically identical to HPV-associated HSIL. This unusual histologic pattern has not been previously characterized in detail in PSCC. p16 IHC is a valuable tool to identify these lesions and differentiate them from HPV-associated HSIL.
大多数人乳头瘤病毒（HPV）无关的阴茎鳞状细胞癌（PSCC）起源于一种上皮内前体，称为分化的阴茎上皮内肿瘤，其特征为局限于基底细胞层的异型性，伴有明显的表面成熟。在具有类似双重病因的外阴癌的研究中，已经表明，大约五分之一的 HPV 无关前体在形态上与 HPV 相关癌的前体——高级别鳞状上皮内病变（HSIL）无法区分。然而，在 PSCC 中尚未描述这种病变。2000 年至 2021 年，共确定了 55 例 PSCC 的手术标本。所有病例均进行了彻底的形态学评估、HPV DNA 检测以及 p16、p53 和 Ki-67 免疫组化（IHC）染色。HPV 无关状态基于 p16 IHC 和 HPV DNA 均为阴性来确定。55 例 PSCC 中有 36 例（65%）为 HPV 无关型。在 26/36 例（72%）中发现了上皮内前体。其中 5 例（19%）具有基底样特征，与 HPV 相关的 HSIL 在形态上无法区分。这 5 名患者的中位年龄为 74 岁（范围：67 岁至 83 岁）。所有 5 例均为 p16 和 DNA HPV 阴性。免疫组化显示，3 例显示异常的 p53 模式，2 例显示野生型 p53 染色。伴发的浸润性癌在 4 例中为基底样型，在 1 例中为通常的（角化型）。总之，一小部分 HPV 无关的 PSCC 可能起源于形态上与 HPV 相关的 HSIL 相同的相邻上皮内病变。这种不寻常的组织学模式在之前的 PSCC 中尚未详细描述。p16 IHC 是识别这些病变并将其与 HPV 相关 HSIL 区分开来的有用工具。
