Mentrikoski Mark J, Stelow Edward B, Culp Stephen, Frierson Henry F, Cathro Helen P
Departments of *Pathology †Urology, University of Virginia, Charlottesville, VA.
Am J Surg Pathol. 2014 Oct;38(10):1340-8. doi: 10.1097/PAS.0000000000000124.
Penile squamous cell carcinoma (SCC) is sometimes an aggressive disease that has a variable worldwide incidence, in part due to differing rates of inflammatory and infectious risk factors. In the developed world, penile SCC is a rare malignancy, and most studies therefore originate in less developed countries. The current study was undertaken to examine the morphologic and immunohistochemical features of penile SCC from a region with low disease incidence. Sixty-two complete or partial penectomy specimens from 59 patients were reviewed. Twenty-six patients had metastasis, 3 had recurrent disease, and 7 were dead due to tumor. Most patients were uncircumcised (72%). Twenty-two percent of carcinomas were associated with lichen sclerosis. Perineural invasion was significantly associated with metastasis (P=0.007). Most SCCs (65%) had the usual keratinizing morphology, and these tumors were significantly associated with the differentiated form of intraepithelial lesion (P<0.0001), p53 positivity (P=0.002), cyclin D1 positivity (P=0.007), and EGFR overexpression (P=0.003). Human papilloma virus (HPV)-associated tumors accounted for 27% and were basaloid (8%), warty (10%), mixed (6%), or lymphoepithelioma-like carcinoma (4%) variants. These were significantly associated with p16 expression (P<0.0001) and the undifferentiated form of intraepithelial lesion (P<0.001). Among all SCCs, there was no difference in the immunohistochemical or in situ hybridization profile between primary tumors and metastases. Although penile SCC is rare in the United States, the tumor variants, immunohistochemical profiles, and proportion of HPV-associated tumors are similar to those in less developed countries. Two distinct pathways appear to lead to carcinogenesis; one is related to underlying chronic inflammatory states, involves p53 mutation, cyclin D1 overexpression, and culminates in classic keratinizing SCC. The other pathway involves high-risk HPV infection, demonstrates strong p16 expression, and results in SCC with varied, but distinctive morphologies.
阴茎鳞状细胞癌（SCC）有时是一种侵袭性疾病，其全球发病率各不相同，部分原因是炎症和感染风险因素的发生率不同。在发达国家，阴茎SCC是一种罕见的恶性肿瘤，因此大多数研究都来自欠发达国家。本研究旨在检查疾病发病率较低地区阴茎SCC的形态学和免疫组化特征。对59例患者的62份完整或部分阴茎切除标本进行了回顾。26例患者发生转移，3例有复发性疾病，7例因肿瘤死亡。大多数患者未行包皮环切术（72%）。22%的癌与扁平苔藓硬化症相关。神经周围浸润与转移显著相关（P=0.007）。大多数SCC（65%）具有常见的角化形态，这些肿瘤与上皮内病变的分化形式（P<0.0001）、p53阳性（P=0.002）、细胞周期蛋白D1阳性（P=0.007）和表皮生长因子受体（EGFR）过表达（P=0.003）显著相关。人乳头瘤病毒（HPV）相关肿瘤占27%，包括基底样（8%）、疣状（10%）、混合性（6%）或淋巴上皮瘤样癌（4%）变体。这些与p16表达（P<0.0001）和上皮内病变的未分化形式（P<0.001）显著相关。在所有SCC中，原发性肿瘤和转移灶之间的免疫组化或原位杂交谱没有差异。虽然阴茎SCC在美国很少见，但肿瘤变体、免疫组化谱以及HPV相关肿瘤的比例与欠发达国家相似。似乎有两条不同的致癌途径；一条与潜在的慢性炎症状态有关，涉及p53突变、细胞周期蛋白D1过表达，并最终发展为典型的角化性SCC。另一条途径涉及高危HPV感染，表现为强烈的p16表达，并导致具有不同但独特形态的SCC。
