Instituto de Patología e Investigación, Asunción, Paraguay.
Am J Surg Pathol. 2010 Mar;34(3):385-92. doi: 10.1097/PAS.0b013e3181cdad23.
From the pathogenic point of view, penile cancers may be grouped in human papillomavirus-related and unrelated tumors, each one of them with distinctive morphologic features. The former are predominantly composed of small, undifferentiated basaloid cells, with more or less prominent koilocytic changes, and the latter of keratinizing differentiated squamous cells. The same cellular types are observed in precancerous lesions. On the basis of these observations, we constructed a novel nomenclature for penile precancerous lesions and classified them as penile intraepithelial neoplasia (PeIN) of differentiated, warty, basaloid, and warty-basaloid types. The aim of this study was to test the usefulness of immunohistochemical p16 overexpression, considered as a surrogate for high-risk human papillomavirus infection, using this classification system. We pathologically evaluated 141 patients with PeIN, associated (123 cases) and unassociated (18 cases) with invasive cancer. Distribution of PeIN types was: differentiated, 72%; basaloid, 9%; warty-basaloid, 7%; warty, 4%; and mixed, 7%. There was a striking similarity in the morphology of in situ and invasive squamous cell carcinomas. Differentiated PeIN was commonly associated with usual, verrucous, papillary, and other low-grade keratinizing variants of squamous cell carcinoma whereas in basaloid and warty carcinomas the presence of in situ lesions with similar morphology was habitual. We evaluated p16 overexpression using a 4-tiered (0, 1, 2, and 3) pattern-based system. To properly distinguish differentiated PeIN from in situ lesions with warty and/or basaloid features only pattern 3, which requires full-thickness staining in all epithelial cells, was considered positive. Using this approach, there was a significant association of the negative patterns and differentiated PeIN and of the positive pattern and warty, basaloid, and warty-basaloid PeIN (P<0.0001). Basaloid variant had the strongest association. The sensitivity rate of p16 positivity for discriminating types of PeIN was of 82%, with a specificity of 100% and an accuracy of 95%. Lichen sclerosus was identified in 42 cases and their epithelial component was p16 negative in all cases. Although more studies are necessary to confirm these observations, p16 overexpression seems to be a useful tool for discriminating differentiated from warty, basaloid, and warty-basaloid PeIN.
从发病机制的角度来看，阴茎癌可分为 HPV 相关肿瘤和非 HPV 相关肿瘤，每种肿瘤都有独特的形态特征。前者主要由小而未分化的基底样细胞组成，伴有不同程度的空泡状细胞改变，后者由角化分化的鳞状细胞组成。在癌前病变中也观察到相同的细胞类型。基于这些观察，我们为阴茎癌前病变构建了一种新的命名法，并将其分为分化型、疣状型、基底样型和疣状-基底样型的阴茎上皮内瘤变（PeIN）。本研究的目的是使用这种分类系统来测试免疫组织化学 p16 过表达（被认为是高危型 HPV 感染的替代物）的有用性。我们对 141 例伴有（123 例）和不伴有（18 例）浸润性癌的 PeIN 患者进行了病理评估。PeIN 类型的分布为：分化型，72%；基底样型，9%；疣状-基底样型，7%；疣状型，4%；混合性，7%。原位和浸润性鳞状细胞癌的形态非常相似。分化型 PeIN 通常与常见的、疣状的、乳头状的和其他低级别角化的鳞状细胞癌相关，而在基底样和疣状癌中，存在形态相似的原位病变是常见的。我们使用 4 级（0、1、2 和 3）基于模式的系统评估 p16 过表达。为了正确区分分化型 PeIN 与具有疣状和/或基底样特征的原位病变，只有全层上皮细胞染色的模式 3 被认为是阳性。使用这种方法，阴性模式与分化型 PeIN 以及阳性模式与疣状、基底样和疣状-基底样 PeIN 之间存在显著关联（P<0.0001）。基底样变体的相关性最强。p16 阳性对区分 PeIN 类型的敏感性为 82%，特异性为 100%，准确性为 95%。在 42 例中发现了硬化性苔藓，其上皮成分在所有病例中均为 p16 阴性。尽管还需要更多的研究来证实这些观察结果，但 p16 过表达似乎是区分分化型与疣状、基底样和疣状-基底样 PeIN 的有用工具。
