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Abstract：
BACKGROUND: We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit.
METHODS: A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases.
CONCLUSIONS: This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.
METHODS: A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases.
CONCLUSIONS: This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.
摘要：
背景：我们遇到了一种宫颈淋巴上皮癌（LEC），其结构主要是固体，具有缺陷性错配修复（dMMR）和SWI/SNF（SWItch/蔗糖非发酵）染色质重塑复合物亚基的表达缺失。这是第一例LEC伴dMMR和SWI/SNF复合物亚基丢失的病例报道。
方法：一位34岁女性患者出现月经不调和异常阴道出血。磁共振成像显示子宫颈后部有外生性肿块。活检标本证实鳞状细胞癌，2018年国际妇产科联合会（FIGO）子宫宫颈癌分期为IB2。在随后的锥化标本中，肿瘤出现外生性。微观上,肿瘤细胞形成了主要的固体结构。观察到大量淋巴细胞浸润。病理诊断：人乳头瘤病毒（HPV）相关性鳞状细胞癌，LEC型，pT1b2。免疫组织化学，高程序性死亡配体1（PD-L1）表达，dMMR,和开关/蔗糖不可发酵家族相关的损失，矩阵关联，染色质亚家族成员4（SMARCA4）/BRG1，SWI/SNF复合物亚基的肌动蛋白依赖性调节因子，被观察到。患者接受了根治性子宫切除术，一年零五个月后无疾病存活。我们对另外5例LEC病例的分析显示，与高危HPV和PD-L1表达升高有一致的关联。除了目前的情况,另一名患者表现为dMMR。SWI/SNF复合物被保留,除了在本情况下。所有病例预后良好。
结论：这个独特的LEC伴dMMR的病例提示了一个具有潜在免疫治疗意义的独特临床实体。对其他5例LEC病例的分析显示，LEC是免疫热的，免疫检查点抑制剂可能是有效的。两个dMMR病例显示MLH1和PMS2表达缺失，和肿瘤PD-L1显著高表达。在这些情况下,dMMR可能与LEC的形态特征有关。
方法：一位34岁女性患者出现月经不调和异常阴道出血。磁共振成像显示子宫颈后部有外生性肿块。活检标本证实鳞状细胞癌，2018年国际妇产科联合会（FIGO）子宫宫颈癌分期为IB2。在随后的锥化标本中，肿瘤出现外生性。微观上,肿瘤细胞形成了主要的固体结构。观察到大量淋巴细胞浸润。病理诊断：人乳头瘤病毒（HPV）相关性鳞状细胞癌，LEC型，pT1b2。免疫组织化学，高程序性死亡配体1（PD-L1）表达，dMMR,和开关/蔗糖不可发酵家族相关的损失，矩阵关联，染色质亚家族成员4（SMARCA4）/BRG1，SWI/SNF复合物亚基的肌动蛋白依赖性调节因子，被观察到。患者接受了根治性子宫切除术，一年零五个月后无疾病存活。我们对另外5例LEC病例的分析显示，与高危HPV和PD-L1表达升高有一致的关联。除了目前的情况,另一名患者表现为dMMR。SWI/SNF复合物被保留,除了在本情况下。所有病例预后良好。
结论：这个独特的LEC伴dMMR的病例提示了一个具有潜在免疫治疗意义的独特临床实体。对其他5例LEC病例的分析显示，LEC是免疫热的，免疫检查点抑制剂可能是有效的。两个dMMR病例显示MLH1和PMS2表达缺失，和肿瘤PD-L1显著高表达。在这些情况下,dMMR可能与LEC的形态特征有关。
