Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
Am J Surg Pathol. 2011 Apr;35(4):474-83. doi: 10.1097/PAS.0b013e31820f709e.
Lymphoepithelioma-like carcinoma (LELC) in the urinary tract is a rare malignancy, named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. Investigation of immunohistochemical and molecular characteristics of bladder LELC is limited. The pathogenesis and biological behavior of these tumors are controversial.
We examined clinicopathologic features of the urinary tract LELC, including light microscopy; immunohistochemistry for cytokeratin 7 (CK7), CK20, 34βE12, p53, p63, α-methylacyl-CoA racemase, thyroid transcription factor-1, Epstein-Barr virus latent membrane protein-1, and CD30; in situ hybridization for human papillomavirus; and UroVysion fluorescence in situ hybridization (FISH).
We identified tumors from 34 patients, the largest series to date, (male:female, 2.8:1), ranging from 54 to 84 years of age (mean, 70 years). Urothelial carcinoma in situ was identified in 50% of patients. 34βE12 (75%), CK7 (57%), and p63 (53%) were frequently positive in tumor cells, whereas thyroid transcription factor-1 and CD30 were consistently negative. Expression of p53 was noted in a subset of tumors (61%), whereas CK20 staining was negative with weak positivity in a single case. UroVysion FISH showed frequent chromosomal abnormalities similar to those of urothelial carcinoma. In tumors with concurrent urothelial, squamous, sarcomatoid, and glandular components, identical FISH abnormalities were noted in both areas. In situ hybridization for human papillomavirus and immunostaining for Epstein-Barr virus were negative in all studied lesions. Five patients with pure or predominant LELC tumors treated with transurethral resection and followed by chemotherapy were alive without evidence of disease at 2 to 5 years. In contrast, 2 patients treated in this manner with <50% LELC morphology had death from disease or distant metastasis.
Urinary tract LELC is a rare histologic variant of urothelial carcinoma. The frequent presence of UroVysion FISH abnormalities, urothelial carcinoma in situ, and p53 positivity by immunohistochemistry in cases of urinary tract LELC suggests a similar pathogenesis to high-grade invasive urothelial carcinoma. In contrast to typical urothelial carcinoma, CK20 is frequently negative in LELC. Our findings support the hypothesis that pure or predominant LELC may be treated with transurethral resection and chemotherapy. However, a large-scale study with long-term follow-up is needed to better understand the biological behavior of urinary bladder LELC.
尿路淋巴上皮样癌（LELC）是一种罕见的恶性肿瘤，因其类似于鼻咽未分化癌或淋巴上皮样癌而得名。对膀胱 LELC 的免疫组织化学和分子特征的研究有限。这些肿瘤的发病机制和生物学行为存在争议。
我们检查了尿路 LELC 的临床病理特征，包括光镜检查；细胞角蛋白 7（CK7）、CK20、34βE12、p53、p63、α-甲基酰基辅酶 A 消旋酶、甲状腺转录因子-1、EB 病毒潜伏膜蛋白-1 和 CD30 的免疫组织化学；人乳头瘤病毒原位杂交；以及 UroVysion 荧光原位杂交（FISH）。
我们鉴定了来自 34 名患者的肿瘤，这是迄今为止最大的系列，（男：女，2.8:1），年龄从 54 岁到 84 岁（平均 70 岁）。50%的患者存在尿路上皮原位癌。34βE12（75%）、CK7（57%）和 p63（53%）在肿瘤细胞中经常呈阳性，而甲状腺转录因子-1和 CD30 始终呈阴性。部分肿瘤中存在 p53 表达（61%），而 CK20 染色为阴性，仅在单个病例中呈弱阳性。UroVysion FISH 显示出与尿路上皮癌相似的常见染色体异常。在具有同时存在的尿路上皮、鳞状、肉瘤样和腺性成分的肿瘤中，在两个区域均观察到相同的 FISH 异常。在所有研究的病变中，人乳头瘤病毒原位杂交和 EBV 免疫染色均为阴性。5 名接受经尿道切除术和化疗治疗的纯或主要 LELC 肿瘤患者在 2 至 5 年内无疾病证据存活。相比之下，2 名接受这种治疗方法且 LELC 形态<50%的患者死于疾病或远处转移。
尿路 LELC 是尿路上皮癌的一种罕见组织学变异型。尿路 LELC 中 UroVysion FISH 异常、尿路上皮原位癌和 p53 免疫组化阳性的频繁出现表明其发病机制与高级别浸润性尿路上皮癌相似。与典型的尿路上皮癌不同，CK20 在 LELC 中经常为阴性。我们的研究结果支持这样的假设，即纯或主要的 LELC 可能通过经尿道切除术和化疗来治疗。然而，需要进行大规模的长期随访研究，以更好地了解膀胱 LELC 的生物学行为。
