前列腺癌gleason评分课件

前列腺癌Gleason分级 Gleason Grading of Prostatic Carcinoma Gleason Grading of Prostatic Carcinoma 2009.4.122009.4.12 Pathology Department of Johns Hopkins Hospital l/prostate Gleason分级意义 lGleason分级与生物学行为和预后关联良好，成为制定 前列腺癌治疗方案的重要参考指标。 l美国全国综合肿瘤网（NCCN）推荐的前列腺癌治疗 指南中， Gleason分级、PSA水平和肿瘤分期是决定治 疗方案的最重要的指标。 l2004年WHO泌尿与生殖系统肿瘤分类已将Gleason分 级/评分正式纳入。 Overview of Gleason Grading l l Gleason Gleason 分级系统有分级系统有 2 2个特征：个特征： l l 1 1 、该、该分级系统是建立在组织结构分级系统是建立在组织结构 构型基础上，构型基础上， 而不而不考虑细胞学（细考虑细胞学（细 胞核）特征。根据组织学结构特点胞核）特征。根据组织学结构特点 分为分为5 5种不同的组织学结构构型（种不同的组织学结构构型（ patternpattern）或称级别（或称级别（gradegrade） ， 其其分化程度递减，分化程度递减，pattern pattern （gradegrade ） 1 1 分化最好，分化最好，pattern pattern （gradegrade） 5 5 分化最差。分化最差。 l l 2 2、 分级并不是建立在肿瘤中分化分级并不是建立在肿瘤中分化 最差的构型上，最差的构型上， Gleason Gleason 认为大多认为大多 数前列腺癌都是多种组织学构型，数前列腺癌都是多种组织学构型， 发现前列腺癌的预后是介于其主要发现前列腺癌的预后是介于其主要 结构和次要结构之间。结构和次要结构之间。 Gleason分级/评分原则（1） l l GleasonGleason分级评分是结构类型评分分级评分是结构类型评分 l l Gleason Gleason 分级系统：分级系统： GleasonGleason评分主要结构类型（级评分主要结构类型（级 别）别）+ + 次要结构类型（级别）次要结构类型（级别） ，获得，获得 一个一个 Gleason Gleason scorescore，如：如： Gleason grade 3 + 4 = 7. Gleason grade 3 + 4 = 7. l l 评分范围评分范围 2 2 1010，最低为最低为 1+ 1 1+ 1 = = 2 2，最高为，最高为 5 + 5 5 + 5 = = 10 10 Gleason分级原则（2） l l 只有一种只有一种GleasonGleason结构类型的前列腺癌，主要结构类型的前列腺癌，主要 结构类型和次要结构类型视为相同，结构类型和次要结构类型视为相同，如：如： Gleason grade 3+3=6Gleason grade 3+3=6 l l 具有具有3 3种种GleasonGleason patternpattern且最高级别成分最少且最高级别成分最少 时，在报告中加注说明。时，在报告中加注说明。 Gleason Pattern 1 l l Gleason pattern 1Gleason pattern 1： 由由界限清楚的、大致呈圆形的、界限清楚的、大致呈圆形的、 膨胀性生长的结节组成，结节内的腺体为中等大小、膨胀性生长的结节组成，结节内的腺体为中等大小、 圆形或卵圆形腺体，形状和大小基本一致，腺体排列圆形或卵圆形腺体，形状和大小基本一致，腺体排列 紧密、背靠背，间质很少，但每个腺体是独立的、互紧密、背靠背，间质很少，但每个腺体是独立的、互 不融合，腺体不浸润邻近的正常前列腺组织。不融合，腺体不浸润邻近的正常前列腺组织。 胞浆丰胞浆丰 富淡染（不作为分级评估条件）。富淡染（不作为分级评估条件）。 Well-formed glands of Well-formed glands of adenocarcinomaadenocarcinoma growing in a tight nodule consistent with growing in a tight nodule consistent with Gleason score Gleason score 1+2=3.1+2=3.（WHO:1+1WHO:1+1） More uniformly sized glands (left) are consistent with pattern 1 where as large More uniformly sized glands (left) are consistent with pattern 1 where as large variably sized glands (right) are typical of pattern 2. variably sized glands (right) are typical of pattern 2. Uniform loosely-packed glands with pale to clear cytoplasm larger than typical Gleason Uniform loosely-packed glands with pale to clear cytoplasm larger than typical Gleason pattern 3 pattern 3 adenocarcinomaadenocarcinoma. The focus would be consistent with Gleason score 2+1=3. . The focus would be consistent with Gleason score 2+1=3. Where the glands in the lower right are more uniform in size consistent with pattern 1, Where the glands in the lower right are more uniform in size consistent with pattern 1, glands in the upper left and top are more variable in size consistent with pattern 2. glands in the upper left and top are more variable in size consistent with pattern 2. Gleason Pattern 1注意点 l l 非常少见，通常在癌的移行区可以见到非常少见，通常在癌的移行区可以见到 l l 如果存在，通常与肿瘤如果存在，通常与肿瘤pattern 2pattern 2伴随，而且与伴随，而且与pattern 2pattern 2差差 异并不是那么严谨异并不是那么严谨, , 因为两种因为两种 patterns patterns 有有类似的预后。类似的预后。 l l 针吸活检中不应诊断针吸活检中不应诊断pattern 1pattern 1，因为因为pattern 1pattern 1结节通常比结节通常比 穿刺针大，其边界难以确定。穿刺针大，其边界难以确定。 l l 活检中如果见到由数个肿瘤腺体组成的、周围有间质的小活检中如果见到由数个肿瘤腺体组成的、周围有间质的小 团病灶，通常是团病灶，通常是 patternpattern 3 3，因为因为pattern 1pattern 1不不形成几个腺体形成几个腺体 组成的小病灶。组成的小病灶。 Gleason Pattern 2 l l Gleason pattern 2Gleason pattern 2：由边界比较清楚的结节组成，结由边界比较清楚的结节组成，结 节内腺体结构和大小较一致，腺体也是保持单个独立节内腺体结构和大小较一致，腺体也是保持单个独立 ，但，但与与pattern 1pattern 1 比，比，腺体不是很一致，腺体之间距离腺体不是很一致，腺体之间距离 增加，排列较松散，可以局部肿瘤性腺体向周围前列增加，排列较松散，可以局部肿瘤性腺体向周围前列 腺组织微小浸润。同腺组织微小浸润。同pattern 1pattern 1一样一样, , 腺体普遍比腺体普遍比 pattern 3 pattern 3 大。大。 腺体圆形或卵圆形，有开放的腔，腺腺体圆形或卵圆形，有开放的腔，腺 体较圆滑而不像体较圆滑而不像 pattern 3pattern 3成角。与成角。与 pattern 1pattern 1一样一样, , pattern 2 pattern 2 胞浆通常丰富淡染。胞浆通常丰富淡染。 Pattern 2 Pattern 2 在癌在癌移行区移行区 通常能见到，但并不是一定能见到。通常能见到，但并不是一定能见到。 Well-circumscribed nodule consisting of glands of relatively uniform size and shape with Well-circumscribed nodule consisting of glands of relatively uniform size and shape with minimal infiltration into surrounding benign prostate tissue. Gleason score 2+2=4. minimal infiltration into surrounding benign prostate tissue. Gleason score 2+2=4. l l The glands are round or oval and have open The glands are round or oval and have open luminalumina. The glands are smoothly rounded, not . The glands are smoothly rounded, not angular. They are separated by strands of angular. They are separated by strands of stromastroma not exceeding the diameter of an not exceeding the diameter of an acinusacinus. . The diameter of the glands does not vary much and The diameter of the glands does not vary much and microglandsmicroglands (glands with very fine (glands with very fine calibrecalibre) are very sparse.) are very sparse. l l The glands are round or oval and have The glands are round or oval and have luminalumina. In this example, the glands are so regular and tightly . In this example, the glands are so regular and tightly clustered that the pattern comes close to grade 1. However, for grade 1 it is required that the focus has a clustered that the pattern comes close to grade 1. However, for grade 1 it is required that the focus has a rounded outline, which is not possible to determine in this magnification. Furthermore, the glands of grade 1 rounded outline, which is not possible to determine in this magnification. Furthermore, the glands of grade 1 should be of equal size and round, not oval as in this case. Grade 1 is very rare and should be avoided. Notice should be of equal size and round, not oval as in this case. Grade 1 is very rare and should be avoided. Notice the the intraluminalintraluminal crystalloids, typical of grades 1 - 2. crystalloids, typical of grades 1 - 2. Gleason Pattern 2注意点 l l 与与pattern 1pattern 1类似，由于类似，由于Gleason pattern 2Gleason pattern 2边边 界在针吸活检中难以确定，在针吸活检中诊断界在针吸活检中难以确定，在针吸活检中诊断 pattern 2pattern 2应慎重，活检中由数个肿瘤腺体组成应慎重，活检中由数个肿瘤腺体组成 的小团病灶，也不是的小团病灶，也不是pattern 2pattern 2，通常是通常是 patternpattern 3 3。 Gleason Pattern 3 (1) l l Gleason pattern 3Gleason pattern 3对邻近非肿瘤前列腺组织有明显的浸润是其突出的特点对邻近非肿瘤前列腺组织有明显的浸润是其突出的特点 。 pattern 3pattern 3腺体的形状和大小明显不一致，常常是拉长或成角，在较宽的腺体的形状和大小明显不一致，常常是拉长或成角，在较宽的 间质中杂乱浸润成长，与间质中杂乱浸润成长，与pattern 4pattern 4比，比， pattern 3pattern 3的腺体仍保持独立。的腺体仍保持独立。 l l 比比Gleason pattern 1 or 2Gleason pattern 1 or 2腺体通常较小腺体通常较小 (“(“microglandsmicroglands”) ”) ，但是部分腺体但是部分腺体 可以为中等到大的腺体可以为中等到大的腺体 ， l l pattern 3pattern 3可以形成筛状结构。这些筛状结构的腺体比良性前列腺体稍大，可以形成筛状结构。这些筛状结构的腺体比良性前列腺体稍大， 外形轮廓较规则外形轮廓较规则。 与与pattern 4pattern 4 不同，不同， pattern 3 pattern 3 筛状结构腺体必须是独立筛状结构腺体必须是独立 的、的、 导管内筛状结构增生和前列腺导管腺癌。导管内筛状结构增生和前列腺导管腺癌。 l l Gleason pattern 3Gleason pattern 3 微小浸润几乎总是伴随着微小浸润几乎总是伴随着 pattern 3pattern 3 的筛状结构。的筛状结构。 l l 胞浆常常嗜双色胞浆常常嗜双色 ，这有助于与这有助于与 patterns 1 patterns 1 和和 2 2 鉴别。鉴别。 Gleason score 3+3=6 with well-formed individual discrete glandular Gleason score 3+3=6 with well-formed individual discrete glandular unitsunits. . Small focus of Gleason score 3+3=6 with an infiltrative pattern between Small focus of Gleason score 3+3=6 with an infiltrative pattern between benign glands.benign glands. Irregular, jagged glands. Medium size glands are mixed with fine-Irregular, jagged glands. Medium size glands are mixed with fine-calibrecalibre, dissecting , dissecting aciniacini. The . The Gleason grading is based on architecture and not cellular morphology, but the Gleason grading is based on architecture and not cellular morphology, but the basophiliabasophilia of the of the cytoplasm in this case is common in grade 3 as opposed to grade 2, which more often features a cytoplasm in this case is common in grade 3 as opposed to grade 2, which more often features a light staining cytoplasm.light staining cytoplasm. Gleason score 3+3=6 Gleason score 3+3=6 with minor Gleason score 3+3=6 with minor cribriformcribriform component component CribriformCribriform Gleason score 3+3=6 with scattered small individual non- Gleason score 3+3=6 with scattered small individual non- cribriformcribriform Gleason pattern 3. Gleason pattern 3. Gleason Pattern 3注意点 l l Gleason Pattern 3Gleason Pattern 3是是国外针穿活检和手术切除标本中最常国外针穿活检和手术切除标本中最常 见的结构类型（而国内见的结构类型（而国内Pattern 3Pattern 3和和4 4均常见）。均常见）。 l l 筛状结构须与筛状结构须与PatternPattern 4 4的筛状结构鉴别，后者特点是腺的筛状结构鉴别，后者特点是腺 体融合。体融合。 l l 穿活检中，在良性腺体间查见少量肿瘤腺体浸润，是穿活检中，在良性腺体间查见少量肿瘤腺体浸润，是 Pattern 3Pattern 3的的特点，不要误认为是特点，不要误认为是Pattern 2Pattern 2。 Gleason Pattern 4 l l Gleason pattern 4Gleason pattern 4 特点是腺体融合。特点是腺体融合。分为分为4a4a和和4b4b l l 4a 4a 融合腺体不规则、互相吻合，呈链状、巢状或团块状（无腺腔融合腺体不规则、互相吻合，呈链状、巢状或团块状（无腺腔 结构），偶尔可以有腺腔、筛状或乳头状结构形成，并浸润间质结构），偶尔可以有腺腔、筛状或乳头状结构形成，并浸润间质 ； 融合腺体内偶尔可以包含几束残余间质，使腺体看起来象部分融合腺体内偶尔可以包含几束残余间质，使腺体看起来象部分 独立的，独立的， 融合腺体周边可以呈扇贝状。融合腺体周边可以呈扇贝状。 l l 融合腺体不常见的一个变型是类似于肾细胞癌，即胞浆透亮、核融合腺体不常见的一个变型是类似于肾细胞癌，即胞浆透亮、核 小而深染的肿瘤细胞形成的片状结构，小而深染的肿瘤细胞形成的片状结构， 即即4b4b，又称为又称为 “ “hypernephromatoidhypernephromatoid“ pattern “ pattern 。 Gleason score 4+4=8.Gleason score 4+4=8. Fused more poorly-formed glands of pattern 4 consistent with Gleason score 4+4=8. Both fusion of glands and solid strands are seen.Both fusion of glands and solid strands are seen. Poorly-formed fused glands of Gleason score 4+4=8. Detached Detached cribriformcribriform glands of pattern 4. Despite its small size, the tumor is Gleason glands of pattern 4. Despite its small size, the tumor is Gleason score 4+4=8.score 4+4=8. Irregular cribriform glands of pattern 4 resulting in Gleason score 4+4=8. Irregular cribriform glands of Gleason score 4+4=8. Irregular cribriform glands of Gleason score 4+4=8. Gleason patterns 3 (left) and 4 (right) Gleason pattern 3 (lower right) and 4 (upper left).Gleason pattern 3 (lower right) and 4 (upper left). Gleason Pattern 4 注意点 l l 融合腺体形成的结节须与融合腺体形成的结节须与PatternPattern 2 2鉴别，后者结节形态规则，结节内每鉴别，后者结节形态规则，结节内每 一腺体是分开、独立的。一腺体是分开、独立的。 l l pattern 4 pattern 4 的筛状腺体即有大的筛状腺体，包括筛片状，又有伴有不规则的筛状腺体即有大的筛状腺体，包括筛片状，又有伴有不规则 浸润边缘的小筛状腺体，后者要与浸润边缘的小筛状腺体，后者要与 pattern 3 pattern 3 筛状腺体区别。筛状腺体区别。4a4a的筛状的筛状 结构须与结构须与3c3c的筛状结构鉴别，的筛状结构鉴别， 4a4a腺体融合形成的具有筛状结构是较小的腺体融合形成的具有筛状结构是较小的 、界限清楚的、外形光滑圆钝的腔内形成。、界限清楚的、外形光滑圆钝的腔内形成。 l l 区别区别pattern 3 pattern 3 和和 pattern 4 pattern 4 很重要，因为这常常是区别很重要，因为这常常是区别Gleason score Gleason score 6 6 和和Gleason score 7 Gleason score 7 ，后者预后更差。后者预后更差。 l l 在针穿活检中，筛状癌的碎片意味着一个大的筛状腺体或伴有少许间质在针穿活检中，筛状癌的碎片意味着一个大的筛状腺体或伴有少许间质 的片块，这是的片块，这是pattern 4pattern 4 特有的。特有的。 Gleason Pattern 5 l l Gleason pattern 5 Gleason pattern 5 肿瘤已没有腺体分化，腺腔结构几肿瘤已没有腺体分化，腺腔结构几 乎完全消失，而是由实性片状、条索状或单个肿瘤细胞乎完全消失，而是由实性片状、条索状或单个肿瘤细胞 组成组成。肿瘤巢团肿瘤巢团 中央伴有中心性（粉刺样）坏死。中央伴有中心性（粉刺样）坏死。 l l 是否有筛状结构存在争议，因为筛状结构被认为是是否有筛状结构存在争议，因为筛状结构被认为是 Gleason pattern 4Gleason pattern 4 ，但在，但在筛状结构中如果出现粉刺样筛状结构中如果出现粉刺样 坏死是坏死是 Gleason pattern 5Gleason pattern 5。 Gleason score 5+5=10.Gleason score 5+5=10. Solid sheets of cells consistent with Gleason score 5+5=10. l l The field is dominated by solid strands and single cell invasion, another variant of grade 5. An The field is dominated by solid strands and single cell invasion, another variant of grade 5. An occasional lumen can be identified. The cells have a more abundant and light-staining cytoplasm occasional lumen can be identified. The cells have a more abundant and light-staining cytoplasm compared to the previous example. However, the amount of cytoplasm is not a defining criterion compared to the previous example. However, the amount of cytoplasm is not a defining criterion for grade 5.for grade 5. lSolid strands and single cell invasion dominate the scene. Small focus of individual cells consistent with Gleason score 5+5=10. Solid sheets of epithelial cells with Solid sheets of epithelial cells with comedocomedo necrosis (arrow). necrosis (arrow). ComedoComedo necrosis is by definition grade 5. necrosis is by definition grade 5. ComedoComedo necrosis must not be necrosis must not be misenterpretedmisenterpreted as a lumen filled with secretion. Conversely, necrotic cells are required as a lumen filled with secretion. Conversely, necrotic cells are required for for comedocomedo necrosis, not just flocculent secretions that may simulate necrosis, not just flocculent secretions that may simulate comedocomedo necrosis. necrosis. Gleason Pattern 5注意点 l l 4 4腺体融合，腺腔结构可能难以辨认，特别是切片较厚腺体融合，腺腔结构可能难以辨认，特别是切片较厚 时，须仔细观察，以与时，须仔细观察，以与5 5的实性结构区别。的实性结构区别。 l l 其他级别肿瘤腺腔中可出现嗜酸性分泌物、中性粒细其他级别肿瘤腺腔中可出现嗜酸性分泌物、中性粒细 胞等，需与胞等，需与5 5的肿瘤性坏死鉴别。的肿瘤性坏死鉴别。 l l 单个肿瘤细胞分散浸润，切片染色太淡时，容易忽略单个肿瘤细胞分散浸润，切片染色太淡时，容易忽略 。 Gleason分级/评分的报告 l l 针穿活检标本（针穿活检标本（corecore）：）：左右各左右各3 core3 core （1 1） GleasonGleason评分主要结构类型（级别）评分主要结构类型（级别）+ +次要结构类型（级别）次要结构类型（级别） （2 2）具有）具有3 3种种Gleason PatternsGleason Patterns且最高级别成分数量最少时，多数倾向：主且最高级别成分数量最少时，多数倾向：主 要结构要结构 类型（级别）类型（级别）+ +最高结构类型（级别）最高结构类型（级别） （3 3）原则上避免做出）原则上避免做出1+11+12 2或或2+22+24 4评分，因为评分，因为Pattern1Pattern1或或2 2在在针穿活检标本中难针穿活检标本中难 以观察到以观察到 （4 4）同一患者同一次穿刺活检各条前列腺组织中癌分级不一时，）同一患者同一次穿刺活检各条前列腺组织中癌分级不一时，建议建议综合评分综合评分 （5 5）数次穿刺活检其）数次穿刺活检其Gleason PatternsGleason Patterns又不一致时，又不一致时，建议建议取数次活检评分的均值或取数次活检评分的均值或 取最高评分结果取最高评分结果 l l TURPTURP标本标本(chip)(chip)：按照标准的按照标准的GleasonGleason分级分级/ /评分方法评分方法 主要结构类型（级别）主要结构类型（级别）+ +次要结构类型（级别）次要结构类型（级别） l l 根治性手术标本：根治性手术标本： （1 1）主要结构类型（级别）主要结构类型（级别）+ +次要结构类型（级别）次要结构类型（级别） （2 2）具有）具有3 3种种Gleason PatternsGleason Patterns且最高级别成分数量最少时，在报告中加注说明且最高级别成分数量最少时，在报告中加注说明 Gleason分级评分适用范围 l l 绝大部分前列腺癌，即经典的腺泡型腺癌绝大部分前列腺癌，即经典的腺泡型腺癌 l l 前列腺癌变异型（前列腺癌变异型（variantsvariants）分级尚未统一，下列原则分级尚未统一，下列原则 供参考：供参考： 导管腺癌导管腺癌 4 4（有坏死者为（有坏死者为 5 5），部分为），部分为 3 3 黏液腺癌黏液腺癌 4 4 印戒细胞癌印戒细胞癌 5 5 泡沫腺腺癌泡沫腺腺癌 3 3 或或 4 4 假增生型腺癌假增生型腺癌 2 2 或或 3 3 ，偶尔，偶尔 4 4 萎缩型腺癌萎缩型腺癌 3 3 肉瘤样癌肉瘤样癌 5 5 Gleason分级评分不适用范围 l l 小细胞癌小细胞癌 l l 鳞状细胞癌鳞状细胞癌 l l 腺鳞癌腺鳞癌 l l 基底细胞癌基底细胞癌 l l 腺样囊性癌腺样囊性癌 l l 移行细胞癌移行细胞癌 预后 l l Gleason Gleason 分级分级/ /评分系统是评估前列腺癌预后的最好指标之一评分系统是评估前列腺癌预后的最好指标之一 l l 从治疗和预后的角度可划分为从治疗和预后的角度可划分为4 4组：组： 2 24 4：高分化，：高分化， 5 56 6： 7 7： 8 81010：低分化。：低分化。 l l 病理医师应尽量给出准确评分，而不是笼统地将之归入某一组病理医师应尽量给出准确评分，而不是笼统地将之归入某一组 。 Examples of pathology reports of core biopsies（1 ）: l l 1): Core biopsies from the prostate.1): Core biopsies from the prostate. l l 2): 5 mm cancer Gleason grade 3, focally 42): 5 mm cancer Gleason grade 3, focally 4 l l 3): 2 mm cancer grade 33): 2 mm cancer grade 3 l l 5): 7 mm cancer grade 3, focally 25): 7 mm cancer grade 3, focally 2 l l 1, 4 and 6): Prostate tissue without 1, 4 and 6): Prostate tissue without atypiaatypia l l Diagnosis: Prostate cancer Gleason sum 3 + 3 = Diagnosis: Prostate cancer Gleason sum 3 + 3 = 6. Cancer in biopsy 2, 3, and 5.6. Cancer in biopsy 2, 3, and 5. l l (Focal deviations of grade have been ignored (Focal deviations of grade have been ignored according to the 5% rule.)according to the 5% rule.) Examples of pathology reports of core biopsies（2 ）: l l Core biopsies from the prostate.Core biopsies from the prostate. l l 2): 5 mm cancer Gleason grade 3 - 42): 5 mm cancer Gleason grade 3 - 4 l l 3): 2 mm cancer grade 43): 2 mm cancer grade 4 l l 5): 7 mm cancer grade 4, focally 35): 7 mm cancer grade 4, focally 3 l l 6): 3 mm cancer grade 3, focally 26): 3 mm cancer grade 3, focally 2 l l 1 and 4): Prostate tissue without 1 and 4): Prostate tissue without atypiaatypia l l Diagnosis: Prostate cancer Gleaso