[摘要] 宫颈透明细胞癌(CCAC)是一种罕见的宫颈恶性肿瘤,其治疗根据患者临床分期及是否有生育愿望可采取多样的个体化综合治疗。本文就CCAC的病因、临床表现、治疗方案与预后进行综述。
[关键词] 宫颈恶性肿瘤;透明细胞癌;已烯雌酚;罕见恶性肿瘤
[中图分类号] R737.33 [文献标识码] A [文章编号] 1673-7210(2019)04(c)-0035-03
Modern progress of clear cell adenocarcinoma of the cervix
HU Xiaodi WU Yumei
Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100006, China
[Abstract] Cervical clear cell carcinoma (CCAC) is a rare cervical malignancy. The treatment of CCAC is based on the clinical stages of the patients and their desire to have children. This article reviews the etiology, clinical manifestations, treatment and prognosis of CCAC.
[Key words] Cervical cancer; Clear cell adenocarcinoma; Diethylstilbestrol; Rare malignant tumor
宫颈癌是导致女性发病和死亡的第二大恶性肿瘤,仅次于乳腺癌,在妇科恶性肿瘤中居首位[1]。近年来,我国宫颈癌的发病率逐年上升。根据《2018国家癌症报告》[2]显示,宫颈癌在我国女性生殖系统肿瘤中居首位,发病率居城市恶性肿瘤第6位。透明细胞腺癌(clear cell adenocarcinoma cancer,CCAC)是宫颈腺癌中一种罕见的病理类型。报道[3]显示,CCAC的发病率约占宫颈腺癌的4%。长期以来,对CCAC的研究主要集中在个案。因此,本文对其病因、临床表现、治疗及预后进行了综述。
1 病因
CCAC的发病与其宫内暴露于乙烯雌酚有关。乙烯雌酚曾被用于治疗孕早期的先兆流产[4]。直到1971年,Herbst等[5]认为阴道CCAC的发生与乙烯雌酚有关,乙烯雌酚被才停止使用。乙烯雌酚使得CCAC发生率增加近40倍[6]。其次,不同于宫颈鳞状细胞癌及其他宫颈腺癌,高危型人乳头瘤病毒(HR-HPV)感染不是其主要病因,HR-HPV导致的宫颈癌会过表达p16INK4a,同时低表达p53[7]。Kocken等[8]对28例诊断为CCAC的患者检测HR-HPV的同时检测p16INK4a及p53表达,发现HR-HPV阳性患者13例,其中过表达p16INK4a同时低表达或不表达p53的患者只有3例,提示尽管CCAC患者HR-HPV患病率很高,但HR-HPV并不是其病因。
2 临床表现
CCAC的临床表现与宫颈鳞癌基本相同,但不论患者是否曾暴露于乙烯雌酚,其发病年龄的高峰均在15~29岁及40~54岁[9]。由于其发病年龄的双峰性,有很大一部分CCAC患者在诊断时为幼女或尚未生育[9-11],这与文献[12]报道的宫颈鳞状细胞癌随着妊娠和分娩次数增加,其患宫颈癌的概率增加不同。Smith等[10]的大规模流行病学调查显示,88例CCAC患者中有57例表现为阴道不规则出血,11例表现为性交疼痛。这与我国统计的早期表现为阴道不同程度的出血及阴道排液基本相同[13-14]。
3 诊断
宫颈细胞学涂片是筛查宫颈癌的重要手段,联合HPV可以提高检出率[15]。宫颈细胞学涂片也是筛查CCAC的手段,但其阳性检出率较低。有研究[16-17]对546例CCAC患者进行检查,发现有49%的患者曾行细胞学检查,其中仅65%的为阳性。因此,在临床上应联合超声、阴道镜下活检,甚至是宫颈锥切术,以明确诊断。大体上,大部分CCAC患者发现时,其肿瘤直径<4 cm,且以内生型为主,镜下根据癌组织的排列可分为管状囊性癌、乳头状癌、实质性癌,其中以管状囊性癌多见[16-21]。
4 治療方案
由于CCAC发病率低,因此缺乏规范化的治疗方案。Huo等[4]的研究认为,CCAC发病年龄具有双峰性,对于尚未生育患者的治疗方式应与常规治疗有所不同。早期CCAC首选治疗方式仍为根治性子宫切除+盆腔淋巴结切除[9]。对早期宫颈鳞状细胞癌行根治性宫颈切除与根治性子宫切除比较,其生存率无明显差异,提示对于渴望保留生育功能的CCAC患者也可考虑行根治性宫颈切除[22]。早在1979年,Herbst等[23]曾尝试对166例Ⅰ期CCAC患者采取四种不同的治疗方案。其后,2014年Jiang等[9]收治的32例CCAC患者中早期25例,其中3例行保留生育功能的手术,术后分别随访8、16、54个月,均未见复发。以上报道说明,对早期且渴望保留生育功能的CCAC患者,可根据其个体考虑行根治性宫颈切除或宫颈锥切术[24]。但行保留生育功能手术后,需考虑流产及早产的风险,Pareja等[25]的大样本回顾性分析显示,经历宫颈根治术的患者的生育率为24%。
5 预后
国内外对于CCAC与宫颈鳞癌的5年生存率报道无明显差异。Reich等[26]的研究中,Ⅰ期CCAC患者的5年生存率为67%,与宫颈腺癌的77%及宫颈鳞癌的80%比较,其生存率较低,但差异无统计学意义。Thomas等[27]认为CCAC本身并不是独立的危险因素,该研究的34例CCAC患者早期(Ⅰ~ⅡA期)3年生存率为91%,晚期(Ⅲ~Ⅳ期)3年生存率为22%。而国内报道的19例患者中,11例接受手术的早期患者(ⅠA~ⅡA期)随访92~140个月仅有2例有术后病理高危因素者死亡[28]。协和医院的28例患者中,早期患者的5年生存率也高达80.8%。这些研究均提示,CCAC本身并不是预后不良的危险因素,而其与肿瘤的大小、浸润肌层的深度、脉管癌栓、淋巴结转移情况有关[29-30]。
综上所述,CCAC是一种罕见的宫颈恶性肿瘤,其发病率低,治疗方案与宫颈鳞状细胞癌基本相同,但也要注意综合个体化治疗。早发现、早治疗,并对患者密切随访,以降低CCAC的发病率,提高CCAC患者的生存率。
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(收稿日期:2018-04-25 本文编辑:王 蕾)