膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座.pptx

介绍介绍n n近年来，WHO和国际抗癌协会（UICC）分别对膀胱癌组织学分级、TNM分期法进行了一些主要改动和修订n n欧洲泌尿外科医师协会也适时推出了膀胱癌新版指南-Guidelines on TaT1(Non-muscle invasive)bladder cancer。n n在我国，中华医学会泌尿外科学分会肿瘤学组正在着手制订膀胱癌诊疗治疗指南。膀胱癌诊疗治疗指南。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第1页主要分期（Stage)和分级（Grade)标准Grade Grade n nBergkvistBergkvist分级法分级法n n19651965n n改良改良BergkvistBergkvist法法77（19871987）n n世界卫生组织世界卫生组织(WHO)(WHO)n nWHO 1973WHO 1973n nWHO/ISUP 1998 WHO/ISUP 1998 ConsensusConsensusn n WHO 1999WHO 1999n nWHO WHO StageStagen n国际癌控制中心国际癌控制中心UICCUICC(Union International Union International Contre le CancerContre le Cancer，19981998，)TNMTNM分期法为标准分期法为标准 3 3，4 4n n美国美国Jewett-Strong-Jewett-Strong-MarshallMarshall分期法分期法 （AJCCAJCC）膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第2页膀胱尿路上皮癌组织学分级膀胱尿路上皮癌组织学分级n n被覆尿路上皮统称为尿路上皮(urothelium)。n n传统上将尿路上皮称为移行上皮14,当前在文件上和习惯上这两个名词经常交替使用。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第3页膀胱癌组织学分级膀胱癌组织学分级n n 膀胱肿瘤恶性程度以级（grade）来表示。n n关于膀胱癌分级，国际上有不少版本，综合于（表1）。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第4页Grading systemWHO 1973,1999 WHO 1973,1999 WHO/ISUP 1998 Consensus,WHO Papilloma Papilloma Papilloma Papilloma TCC grade 1 TCC grade 1 Papillary urothelial neoplasm of low malignant Papillary urothelial neoplasm of low malignant potential(PUNLMP potential(PUNLMP)Urothelial carcinoma low grade Urothelial carcinoma low grade TCC grade 2 TCC grade 2 Urothelial carcinoma high grade Urothelial carcinoma high grade TCC grade 3 TCC grade 3膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第5页历史发展和演变历史发展和演变n nWHO 1973 Classification 1973年WHO提出，方法简单，便于分类，主要是依据肿瘤细胞核间变程度，将膀胱尿路上皮癌分为3级，分化良好、中度分化和分化不良，用grade 1、2、3或grade、分别表示。当前依然广泛使用（WHO1999相同）。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第6页历史发展和演变历史发展和演变n n19981998年，世界卫生组织（年，世界卫生组织（WHOWHO）和国际泌尿病理）和国际泌尿病理协会（协会（ISUPISUP）提出了非浸润性膀胱癌新分类。以）提出了非浸润性膀胱癌新分类。以后，后，年年WHOWHO正式出版了这一新分类方法（表正式出版了这一新分类方法（表1 1）。）。n n本新分类法应用特殊细胞学和结构学标准，对膀本新分类法应用特殊细胞学和结构学标准，对膀胱癌各个级别有详尽描述。能够在网页胱癌各个级别有详尽描述。能够在网页www.pathology.jhu.edu/bladderwww.pathology.jhu.edu/bladder查到各级膀胱说明例查到各级膀胱说明例证。这个分级法把尿路上皮肿瘤分为低度恶性潜证。这个分级法把尿路上皮肿瘤分为低度恶性潜能（能（PUNLMPPUNLMP）、低级和高级尿路上皮癌。）、低级和高级尿路上皮癌。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第7页Urothelial Papilloma n nUrothelial papilloma is defined as discrete papillary Urothelial papilloma is defined as discrete papillary growth with a central fibrovascular cores lined by growth with a central fibrovascular cores lined by urothelium of normal thickness and cytology.There urothelium of normal thickness and cytology.There is no need for counting the number of cell layers.is no need for counting the number of cell layers.散在乳头状肿瘤，其中央有中心纤维血管关键，散在乳头状肿瘤，其中央有中心纤维血管关键，排列着正常厚度，正常细胞尿路上皮。不需计排列着正常厚度，正常细胞尿路上皮。不需计数细胞层次。数细胞层次。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第8页Papillary Urothelial Neoplasm of Low Malignant PotentialPapillary Urothelial Neoplasm of Low Malignant Potential n nPapillary urothelial neoplasm of low malignant potential is a papillary Papillary urothelial neoplasm of low malignant potential is a papillary urothelial lesion with an orderly arrangement of cells within papillae with urothelial lesion with an orderly arrangement of cells within papillae with minimal architectural abnormalities and minimal nuclear atypia minimal architectural abnormalities and minimal nuclear atypia irrespective of the number of cell layers.The urothelium in papillary irrespective of the number of cell layers.The urothelium in papillary urothelial neoplasms of low malignant potential is much thicker than in urothelial neoplasms of low malignant potential is much thicker than in papillomas and/or the nuclei are significantly enlarged and somewhat papillomas and/or the nuclei are significantly enlarged and somewhat hyperchromatic.Mitotic figures are infrequent in papillary urothelial hyperchromatic.Mitotic figures are infrequent in papillary urothelial neoplasms of low malignant potential,and usually confined to the basal neoplasms of low malignant potential,and usually confined to the basal layer.layer.n n低度恶性潜能尿路上皮癌指乳头状尿路上皮损害，乳头状低度恶性潜能尿路上皮癌指乳头状尿路上皮损害，乳头状肿瘤细胞排列有序，结构轻度异常，细胞核轻度间变，可肿瘤细胞排列有序，结构轻度异常，细胞核轻度间变，可不考虑细胞层次数目。低度恶性潜能尿路上皮癌比乳头状不考虑细胞层次数目。低度恶性潜能尿路上皮癌比乳头状瘤细胞层次显著多，和瘤细胞层次显著多，和/或细胞核轻微增大，染色质增多，或细胞核轻微增大，染色质增多，有丝分裂相偶见，通常限于基底层。有丝分裂相偶见，通常限于基底层。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第9页Low-grade Papillary Urothelial CarcinomaLow-grade Papillary Urothelial Carcinoma n nLow-grade papillary urothelial carcinomas are characterized by Low-grade papillary urothelial carcinomas are characterized by an overall orderly appearance but with easily recognizable an overall orderly appearance but with easily recognizable variation of architectural and or cytologic features even at variation of architectural and or cytologic features even at scanning magnification.Variation of polarity and nuclear size,scanning magnification.Variation of polarity and nuclear size,shape,and chromatin texture comprise the minimal but shape,and chromatin texture comprise the minimal but definitive cytologic atypia.Mitotic figures are infrequent and definitive cytologic atypia.Mitotic figures are infrequent and usually seen in the lower half,but may be seen at any level of the usually seen in the lower half,but may be seen at any level of the urothelium.It is important to recognize that there may be a urothelium.It is important to recognize that there may be a spectrum of cytologic and architectural abnormalities within a spectrum of cytologic and architectural abnormalities within a single lesion,such that the entire lesion should be examined,single lesion,such that the entire lesion should be examined,with the highest grade of abnormality noted.with the highest grade of abnormality noted.n n低级乳头状尿路上皮癌低级乳头状尿路上皮癌 整体排列整齐。高倍视野下细胞整体排列整齐。高倍视野下细胞特征和结构有显著变异，极向和细胞核大小、形状、染色特征和结构有显著变异，极向和细胞核大小、形状、染色质改变即使不是很显著，但又必定细胞病变。有丝分裂相质改变即使不是很显著，但又必定细胞病变。有丝分裂相少见。少见。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第10页High-grade Papillary Urothelial CarcinomaHigh-grade Papillary Urothelial Carcinoma n nHigh-grade papillary urothelial carcinomas are characterized High-grade papillary urothelial carcinomas are characterized by a predominantly or totally disorderly appearance at low by a predominantly or totally disorderly appearance at low magnification.The disorder results from both architectural magnification.The disorder results from both architectural and cytologic abnormalities.Architecturally,cells appear and cytologic abnormalities.Architecturally,cells appear irregularly clustered and the epithelium is disorganized.irregularly clustered and the epithelium is disorganized.Cytologically,there is a spectrum of pleomorphism ranging Cytologically,there is a spectrum of pleomorphism ranging from moderate to marked.The nuclear chromatin tends to be from moderate to marked.The nuclear chromatin tends to be clumped and nucleoli may be prominent.Mitotic figures,clumped and nucleoli may be prominent.Mitotic figures,including atypical forms,are frequently seen at all levels including atypical forms,are frequently seen at all levels of the urothelium.There is an option in the diagnosis of of the urothelium.There is an option in the diagnosis of high-grade papillary urothelial carcinoma to comment on high-grade papillary urothelial carcinoma to comment on whether there is marked nuclear anaplasiawhether there is marked nuclear anaplasia.n n 高级乳头状尿路上皮癌高级乳头状尿路上皮癌 在低倍显微镜下有显著，或完全在低倍显微镜下有显著，或完全排列紊乱。细胞学和结构有显著异常。结构上，细胞不规排列紊乱。细胞学和结构有显著异常。结构上，细胞不规则成簇状，上皮排列紊乱。细胞学，中度到严重多型性，则成簇状，上皮排列紊乱。细胞学，中度到严重多型性，核染色质成堆，核仁显著。有丝分裂相，在各层尿路上皮核染色质成堆，核仁显著。有丝分裂相，在各层尿路上皮中可见。中可见。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第11页n n总之，1998/WHO 分类法有3个主要改变。n n不再使用分级系统（没有不再使用分级系统（没有GG）；）；n n提出提出PUNLAMP(PUNLAMP(低度恶性潜能低度恶性潜能)概念；概念；n n 认为全部非浸润性认为全部非浸润性 High gradeHigh grade 癌与浸润性一癌与浸润性一样有一样特征（遗传性上不稳定）。样有一样特征（遗传性上不稳定）。n n鉴于当前这两种分类法仍在广泛使用，EAU推荐当前WHO 1973,两个版本能够同时使用；直到证实年愈加合理。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第12页膀胱癌分期膀胱癌分期 n n膀胱肿瘤分期指肿瘤浸润深度及转移情况，是判断膀胱肿瘤预后最有价值参数。n n当前有两种主要分期方法。n n一个是美国一个是美国Jewett-Strong-MarshallJewett-Strong-Marshall分期法和美国分期法和美国癌症联合会分期法，癌症联合会分期法，n n另一个为国际抗癌协会另一个为国际抗癌协会(The International Union(The International Union Against CancerAgainst Cancer，UICCUICC)TNMTNM分期法。分期法。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第13页膀胱癌分期膀胱癌分期 n n这两种国际上流行分类或分期系统已经历经半个世纪发展和演变，虽日趋完善，仍还有不少争议和不尽人意之处，有待于深入完善。n n当前普遍采取国际抗癌协会年第6版TNM分期法（表2）。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第14页 膀胱癌膀胱癌TNM分期分期n n依据膀胱镜检验、影像学所见、经尿道电切及组织病理学检验，能够把膀胱癌分为浅表性膀胱癌（Tis,Ta,T1)和浸润性膀胱癌(T2以上)两大组。n n浅表性膀胱癌指局限于黏膜层乳头状肿瘤（Ta）或已经侵入固有膜T1期膀胱癌。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第15页 膀胱癌膀胱癌TNM分期分期 n n局限于黏膜层扁平状原位癌，即使也属于浅表性膀胱癌，但与低级别Ta和T1期膀胱癌显著不一样；原位癌分化差，属于高度恶性肿瘤。n n它可能是浸润性膀胱癌前身，假如不治疗，比绝大多数浅表性膀胱癌病变进展几率要高得多22。n n所以，应该将原位癌与浅表性膀胱癌加以区分。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第16页n n表表2 2 膀胱癌膀胱癌 TNM TNM 分期分期T(原发肿瘤)TX 原发肿瘤无法评定T0 无原发肿瘤证据Ta 非浸润性乳头状癌Tis 原位癌(扁平癌)T1 肿瘤侵入上皮下结缔组织T2 肿瘤侵犯肌层 T2a 肿瘤侵犯浅肌层(内侧半)T2b 肿瘤侵犯深肌层(外侧半)T3 肿瘤侵犯膀胱周围组织 T3a 显微镜下发觉 T3b 肉眼所见(膀胱外肿块)T4 肿瘤侵犯以下任一器官或组织，如前列腺、子宫、阴道、盆壁和腹壁 T4a 肿瘤侵犯前列腺、子宫、或阴道 T4b 肿瘤侵犯盆壁或腹壁膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第17页膀胱癌膀胱癌TNM分期分期-N分期分期n nN(淋巴结)n nNX NX 区域淋巴结无法评定区域淋巴结无法评定n nN0 N0 无区域淋巴结转移无区域淋巴结转移n nN1 N1 单个淋巴结转移，最大径小于或等于单个淋巴结转移，最大径小于或等于2 cm2 cmn nN2 N2 单个淋巴结转移，最大径大于单个淋巴结转移，最大径大于2 cm 2 cm 但小于但小于 5 cm 5 cm，或多个淋巴结转移，最大径小于，或多个淋巴结转移，最大径小于5 cm5 cmn nN3 N3 淋巴结转移，最大径超出淋巴结转移，最大径超出 5 cm5 cm膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第18页膀胱癌膀胱癌TNM分期分期-M分期分期n nM 远处转移n nMX MX 远处转移无法评定远处转移无法评定n nM0 M0 无远处转移无远处转移n nM1 M1 远处转移远处转移膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第19页膀胱癌膀胱癌TNM分期注意事项分期注意事项n nT分期 n nTUR TUR 和双合诊：和双合诊：TURTUR时时,要切到深肌层或膀胱要切到深肌层或膀胱周围脂肪组织，以识别膀胱癌浸润深度。在男周围脂肪组织，以识别膀胱癌浸润深度。在男性，必须取前列腺尿道部活检；女性，膀胱颈性，必须取前列腺尿道部活检；女性，膀胱颈部要取活检。另外，在经尿道膀胱癌电切前后，部要取活检。另外，在经尿道膀胱癌电切前后，做双合诊识别有没有可扪及肿块，或了解肿瘤做双合诊识别有没有可扪及肿块，或了解肿瘤是否与骨盆壁固定。是否与骨盆壁固定。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第20页膀胱癌膀胱癌TNM分期分期n n影像学：影像学检验目标是识别局部肿瘤范围，影像学：影像学检验目标是识别局部肿瘤范围，了解淋巴结和其它器官转移情况。假如考虑膀了解淋巴结和其它器官转移情况。假如考虑膀胱癌为浸润性癌，应该进行影像学检验。胱癌为浸润性癌，应该进行影像学检验。n n1 1）静脉法肾盂造影（）静脉法肾盂造影（IVPIVP）：发觉肾积水提醒预后）：发觉肾积水提醒预后不良不良2525 。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第21页膀胱癌膀胱癌TNM分期分期n n 2)CT:CT2)CT:CT检验不能准确地域分限于器官和膀胱外检验不能准确地域分限于器官和膀胱外扩散膀胱癌，扩散膀胱癌，CTCT发觉和膀胱切除标本符合率为发觉和膀胱切除标本符合率为65-65-80%80%26,2726,27。n n 3)3)核磁共振核磁共振 (MRI)(MRI)MRI MRI诊疗价值与诊疗价值与CTCT相同，相同，MRIMRI不不能识别膀胱周围脂肪微小转移病变，分期误差约为能识别膀胱周围脂肪微小转移病变，分期误差约为30%30%2828，2929 。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第22页膀胱癌膀胱癌TNM分期分期n n 2.N分期分期n n CTCT和和 MRIMRI对淋巴结为转移漏诊率高达对淋巴结为转移漏诊率高达70%70%2727，30,3130,31。三维。三维MRI MRI 可能比较灵敏，但现有经验有可能比较灵敏，但现有经验有限。正电子发射断层摄影术（限。正电子发射断层摄影术（Positron emission Positron emission tomography tomography，PET)PET)，腹腔镜淋巴结切除价值有腹腔镜淋巴结切除价值有待深入探讨。待深入探讨。n n当前，淋巴结切除活检是惟一能够排除淋巴结当前，淋巴结切除活检是惟一能够排除淋巴结转移方法。转移方法。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第23页膀胱癌膀胱癌TNM分期分期n nM分期分期 在制订治疗方案之前，必须确定是否存在远处转移。n n全部病人必须行胸部X线检验，n n假如怀疑骨骼受累应行骨扫描检验，假如骨扫描发觉可疑病变，能够做MRI能够确定骨转移病变32。n nB超能够发觉肝脏转移。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第24页浅表性膀胱癌浅表性膀胱癌-高危高危/低危概念低危概念 n n 浅表性膀胱癌在早期治疗后（TUR或膀胱部分切除）主要问题是肿瘤复发和进展。n n绝大多数浅表性膀胱癌发展为浸润性膀胱癌几绝大多数浅表性膀胱癌发展为浸润性膀胱癌几率不高，但高分级率不高，但高分级T1G3T1G3膀胱复发进展率高达膀胱复发进展率高达50%50%3434，3535 。n n一些临床和病理参数能够预测膀胱癌复发和进一些临床和病理参数能够预测膀胱癌复发和进展危险展危险36363838 。这些原因被称为浅表性膀胱癌这些原因被称为浅表性膀胱癌预后原因。预后原因。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第25页浅表性膀胱癌浅表性膀胱癌-高危高危/低危概念低危概念 与膀胱癌复发相关原因，按照主要性排列以下：n n1.1.初诊时肿瘤数目。初诊时肿瘤数目。n n2.2.以前复发率，以前复发率，3 3个月复发率。个月复发率。n n3.3.肿瘤大小，肿瘤愈大，复发危险就愈高肿瘤大小，肿瘤愈大，复发危险就愈高n n4.4.肿瘤间变程度。肿瘤间变程度。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第26页浅表性膀胱癌浅表性膀胱癌-高危高危/低危概念低危概念膀胱癌间变程度和膀胱癌间变程度和T T分类是最主要判断疾病进展参分类是最主要判断疾病进展参数。数。膀胱颈部肿瘤比其它部位肿瘤预后差膀胱颈部肿瘤比其它部位肿瘤预后差3939 。按照预后原因，能够把浅表性膀胱癌分为低危、按照预后原因，能够把浅表性膀胱癌分为低危、高危和中度危险高危和中度危险3 3组。组。1.1.低危肿瘤：单个肿瘤、低危肿瘤：单个肿瘤、Ta,G1 Ta,G1 直径小于直径小于3cm3cm。2.2.高危肿瘤：高危肿瘤：T1,G3,T1,G3,多灶性或频繁复发，多灶性或频繁复发，TISTIS3.3.中度危险：全部其它肿瘤、中度危险：全部其它肿瘤、Ta-T1,G1-G2,Ta-T1,G1-G2,多灶多灶性，直径大于性，直径大于3 3厘米。厘米。膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第27页参考文件参考文件n n1.Mostofi FK,Sorbin LH,Torloni H.Histologic typing of 1.Mostofi FK,Sorbin LH,Torloni H.Histologic typing of urinary bladder tumours.International classification of tumours,urinary bladder tumours.International classification of tumours,No 10.WHO,Geneva,1973.No 10.WHO,Geneva,1973.n n2.World Health Organization.Histologic typing of urinary 2.World Health Organization.Histologic typing of urinary bladder tumours.International classification of tumours,No 10.bladder tumours.International classification of tumours,No 10.Second editionSecond edition，Geneva,1999.Geneva,1999.n n3.UICC International Union Against Cancer.In:TNM 3.UICC International Union Against Cancer.In:TNM Classification of Malignant Tumours 4th ed.(Hermanck P,Sobin Classification of Malignant Tumours 4th ed.(Hermanck P,Sobin LH eds).Springer-Verlag,Philadelphia,Berlin,1998,pp 135LH eds).Springer-Verlag,Philadelphia,Berlin,1998,pp 135137.137.n n4.Sobin DH and Witteking Ch(eds).TNM Classification of 4.Sobin DH and Witteking Ch(eds).TNM Classification of Malignant Tumours.6th edn.Wiley-Liss:New York,.Malignant Tumours.6th edn.Wiley-Liss:New York,.膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第28页参考文件参考文件n n5.Fleshner NE,Herr HW,Stewart AK,Murphy GP,Mettlin C,5.Fleshner NE,Herr HW,Stewart AK,Murphy GP,Mettlin C,Menck HR.The National Cancer Data Base report on bladder Menck HR.The National Cancer Data Base report on bladder carcinoma.Cancer,1996,78(7):1505-1513carcinoma.Cancer,1996,78(7):1505-1513n n6.6.顾方六顾方六.尿路上皮肿瘤诊疗和治疗尿路上皮肿瘤诊疗和治疗.见：吴阶平主编见：吴阶平主编.吴阶吴阶平泌尿外科学平泌尿外科学,济南：山东科学技术出版社，济南：山东科学技术出版社，959-980959-980n n7.Kantor AF,Hartge P,Hoover RN,Fraumeni JF Jr.7.Kantor AF,Hartge P,Hoover RN,Fraumeni JF Jr.Epidemiological characteristics of squamous cell carcinoma and Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder.Cancer Res 1988;48(13):3853-5.adenocarcinoma of the bladder.Cancer Res 1988;48(13):3853-5.n n8.Lynch CF,Cohen MB.Urinary system.Cancer,1995,8.Lynch CF,Cohen MB.Urinary system.Cancer,1995,75(Suppl):316-329.75(Suppl):316-329.膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第29页参考文件参考文件n n9.Bennett JK,Wheatly JK,Walton KN.10-year experience with adenocarcinoma of the bladder.J Urol 1984,131:262-263.n n10.Nielsen K,Nielsen KK.Adenocarcinoma in exstrophy of the bladder-the last case in Scandinavia?A case report and review of the literature.J Urol,1983,130:1180-1182.膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第30页参考文件参考文件n n11.Costello AJ,Tiptaft RC,England HR,et al:Squamous cell 11.Costello AJ,Tiptaft RC,England HR,et al:Squamous cell carcinoma of the bladder.Urology 1984;23:234.carcinoma of the bladder.Urology 1984;23:234.n n12.Kantor AF,Hartge P,Hoover RN,et al:Epidemiological 12.Kantor AF,Hartge P,Hoover RN,et al:Epidemiological characteristics of characteristics of squamous cell carcinoma and squamous cell carcinoma and adenocarcinoma of the bladder.Cancer Res 1988;48:3853-3855adenocarcinoma of the bladder.Cancer Res 1988;48:3853-3855n n13.13.El-Bolkainy MN,El-Bolkainy MN,Chu EW,(eds)Chu EW,(eds)：Detection of bladder Detection of bladder cancer associated with schistosomiasis.The National Cancer cancer associated with schistosomiasis.The National Cancer Institute,Institute,CairoCairo University.University.ALAL-Ahram-Ahram Press,Press,CairoCairo,1981,1981 n n14.Melicow MM.Histological study of vesical urothelium 14.Melicow MM.Histological study of vesical urothelium intervening between gross tumours in total cystectomy.J Urol intervening between gross tumours in total cystectomy.J Urol 1952;68:261-279 1952;68:261-279 膀胱尿路上皮癌恶性程度分级和浸润程度分期的进展专家讲座第31页参考文件参考文件n n15.15.Bergkvist ABergkvist A,Ljungqvist ALjungqvist A,Moberger GMoberger G.Classification of.Classification of bladder tumours based on the cellular pattern.Preliminary report b