Gleason分级系统.doc

此文档收集于网络，如有侵权，请联系网站删除Gleason分级系统（Gleason Grading System）Gleason分级系统由Dr. Donald F. Gleason创建于1 966年，以全部肿瘤的分化程度并兼顾生长方式及间质浸润状态为基础,根据相当低放大倍数下前列腺癌腺泡的生长形式而定的，不需要细胞学特征就可的出结论。癌肿分为最常见与次常见的生长型。因为这两种不同的生长形式影响预后。每型的分值为1-5。Gleason评分就是把最常见的癌肿生长形式组织学分级数加上次常见的组织学分级数之和，形成预后的组织分级常数(5级10分制)。Gleason分级与前列腺癌患者的死亡率问呈非常好的线性关系，说明Gleason分级能很好地预测患者的预后状况。如果一个癌肿只有一致的组织学生长形式，那么最常见和次常见的生长形式积分一样。Gleason积分一般在2分到10分之间。分化最好者，为1+1+2分。最差者，为5+5=10分。如主要类型为三级计3分，次要类型为四级计4分则此例前列腺癌的分级为七级计7分，表示为：Gleason评分34(总计7分)。 值得一提的是使用Gleason分级不管主要类型与次要类型的分级是多少，只要两者的和相同其预后即相类似。如Gleason评分25与Gleason评分34或Gleason评分为52等，其最后的评分均为7分。Gleason分级和WHO的分级可以统一起来应用，一般将Gleason2、3、4级划为WHO的高分化腺癌Gleason5、6、7、8级划为中分化腺癌Gleason8、9、10级为低分化腺癌。评分越高，肿瘤恶性度越高，预后越差。Gleason评分为8-10分时，肿瘤为非激素依赖性的比率较大。 Gleason 1:癌肿极罕见。其边界很清楚，膨胀型生长，几乎不侵犯基质，癌腺泡很简单，多为圆形，中度大小，紧密排列，其胞浆与良性上皮细胞胞浆很相近。肿瘤由排列紧密、大小相同的腺体构成，腺上皮为单层四角形上皮细胞。这些腺体形成的肿瘤结节常为圆形，对周边的组织有挤压，易和BPH的肿瘤性结节及非典型增生的结节相混淆。故强调诊断1级前列腺癌必须找到几个含有明显的核仁(直径应大于lum)的细胞。1级癌的多数病例腺体背靠背地密集排列，但少数腺体排列很疏松。癌灶多数很小，少数也有很弥漫的。一些病理学家称l级癌为腺病。Gleason 2:癌肿很少见，多发生在前列腺移行区，癌肿边界不很清楚，癌腺泡被基质分开，呈简单圆形，大小可不同，可不规则，疏松排列。与1级癌相比，2级癌腺体的大小和形状不一，肿瘤结节边缘腺体浸润间质的现象较明显。Gleason Pattern 2Gleason 3:癌肿最常见，多发生在前列腺外周区，最重要的特征是侵润性生长，癌腺泡大小不一，形状各异，核仁大而红，胞浆多程碱性。又分为3A、3B、3C，恶性度以3C最恶，3B次之。3级癌较2级癌腺体的形状和大小变化更大，部分腺体呈多角形、梭形或扭曲形，细胞较l、2级的嗜碱性强。肿瘤结节的边缘不整齐，腺体对间质的浸润更明显。3A与3B的不同点只在肿瘤腺体的大小上，3A腺体中等偏大，3B的腺体小且有些是由成簇的细胞组成有较小的腺腔或没有腺腔。3C为乳头状或筛状肿瘤且边缘整齐，一些作者习惯上称此类型为导管癌或子宫内膜样癌。3A，3B和3C之所以分为一组是因为它们常一同出现且有相似的预后。 Gleason Pattern 3 Gleason 4：又分成4A、4B两级。癌肿分化差，侵润性生长，癌腺泡不规则融合在一起，形成微小乳头状或筛状，核仁大而红，胞浆可程碱性或灰色反应。肿瘤可为小腺泡状、筛状或乳头状，但边缘参差不齐且较3C有明显的浸润现象。4A由暗细胞组成，4B由透明细胞组成，两者常同存且恶性度相似。4级易误诊为3级或2级。4级腺体的结构可以相似且细胞分化可以很好，但腺管却呈融合状。部分区域可以看到4级与3B及5B的移行关系诊断时需仔细辨别。 Gleason Pattern 4 Gleason 5:癌肿分化极差，边界可为规则或不规则状，伴勤润性生长，生长形式为片状单一细胞型或者是粉刺状癌型，伴有坏死，癌细胞核大，核仁大而红，胞浆染色可有变化。又分为5A和5B两亚型。5A很象粉刺样癌，呈乳头状或筛状结构，边缘整齐，但中心区域灶状坏死。5A很象3C但后者没有坏死。5B为弥漫性小细胞癌，边缘不清，浸润明显，只少数分散的腺腔形成提示是腺癌。Gleason Pattern 5 少数肿瘤分化程度可有三种、四种乃至五种，按Gleason分级都归结为两种，方法为； (1)若分级最低(分化最好)的肿瘤所占的体积小于整个肿瘤的5%，则将该分级忽略不计。 (2)若高、中、低分级的肿瘤共存且每一种都占肿瘤体积的5%以上，则删去中分级，记录高、低分级。 (3)若分级最高的肿瘤的体积小于总体积的5，而其他两级肿瘤所占的比例较大，则删去分级最高的。 (4)若分级最高的肿瘤所占体积多于5，而其他分级中的其中之一所占比例较大，则将比例最大的肿瘤的分级记为主要类型，而将分级最高的记为次要类型。 (5)若三种分级并不连续，如l、2、4，则记录分级最高的两种。 Gleason分级的缺点是只根据肿瘤的组织结构分级，不考虑细胞学类型，而后者可能也是与预后有关的重要因素之一。另一个不足是可重复性会因病理学家掌握的尺度不同而有很大差异。在前列腺癌组织中,PSA表达与Gleason分级呈相反趋势,即分化差的前列腺癌表达较低,甚至不表达。穿刺后的Gleason评分往往低于大体标本。一般认为,活检标本Gleason评分越高,与对应的根治性切除术标本Gleason评分吻合率就越高,穿刺活检的指导意义就更准确;活检标本Gleason评分低,则吻合率低,而对应的根治性切除术标本Gleason评分却不一定低,穿刺活检的指导意义就欠准确。造成低估的主要因素有:(1) Gleason评分系统相邻级别之间腺体结构的两可性;(2)穿刺标本的部位局限,有时遗漏高分级癌组织区域;(3)根治术标本量大,增加了高评分的机会;(4)病理医师低估穿刺活检标本Gleason评分的主观倾向性。前列腺癌的准确分期是对其进行有效治疗的重要手段,分期偏低可影响治疗效果和使病人承受不必要的经济负担,分期过高可能错过前列腺癌治愈的机会,因此进行治疗前相对准确的分期可提高疗效和改善病人的生活质量。lesaon评分比血清PSA及穿刺阳性针数百分率能更好的预测前列腺癌的分期。Gleason Grading System for Prostate CancerIntroduction: Once the diagnosis of adenocarcinoma (cancer) is made, it is important to determine the histologic grade of the tumor .i.e. the degree of aggressiveness of the tumor. Low-grade tumors progress slowly whereas high-grade tumors grow rapidly and may have adverse outcome. The histologic grade is assigned by observing the degree of differentiation of the tumor cells and glands .i.e. the extent to which tumor cells and glands formed by them resemble normal prostate cells and glands. Well-differentiated cancers closely mimic the architecture of normal prostate glands. They are slow growing and less dangerous. Moderately-differentiated cancers show features and biologic behavior intermediate between well-differentiated and poorly-differentiated cancers. They are the most commonly seen pattern. Poorly-differentiated or undifferentiated cancers often do not form recognizable glands, are rapidly growing, and can be fatal. Gleason Grading System: The Gleason Grading System is the most widely used and accepted system for grading prostate cancer. It was devised by Dr. Donald F. Gleason and is based on the architectural patterns of cancer glands observed by the pathologist under the microscope. Dr. Gleason provided a simplified diagram that is used by pathologists throughout the world for assigning grades. Five Gleason grades are recognized (Grade 1 through 5) ?with Grade 1 being the most well-differentiated cancer (slow-growing) and Grade 5 being the most poorly-differentiated cancer (rapidly growing). Gleason grade 1 is rarely, if ever, seen in needle biopsies since the tiny caliber of the biopsy needle does not sample the entire tumor nodule. Grade 1 pattern is generally seen in cancers arising in the transition zone of the prostate. The Five Gleason Grades Grade 1: The least common pattern, especially in needle biopsies. Consists of a circumscribed mass of evenly placed uniform glands that closely resemble normal prostate glandsGrade 2: Cancer glands are similar to those seen in Grade 1 but do not form a circumscribed mass. There may be slight variation in size, shape, and spacing of the glands. The glands can be seen infiltrating (spreading) through the surrounding stroma. Grade 3: The most common pattern showing considerable variation in size, shape, and spacing of the glands. Irregular infiltration of the surrounding stroma may impart a ragged appearance to the cancer focus when seen at low-magnification under the microscope. Grade 4: The most important feature of this grade is fusion of glands forming an anastomosing network punctuated by glandular lumens. Glands are no longer recognized as individual units.Grade 5: The cancer cells form solid sheets and clusters or may infiltrate the prostate as individual cells. Necrosis may be present. There is no attempt at gland formation by cancer. To account for the heterogeneity of prostate cancer, the pathologist assigns the primary grade (the most common pattern) and secondary grade (the next most common pattern) to each tumor. Gleason score is obtained by adding the two values. As a rule, the secondary grade should comprise at least 5% of the cancer. Examples of Gleason Score: The lowest possible Gleason score is 1+1=2 when both the primary and secondary patterns are Grade 1. The highest possible Gleason score is 5+5=10 when both the primary and secondary patterns are Grade 5 The most commonly observed Gleason score is 3+3=6. If the biopsies show a tiny focus of cancer with features of Gleason grade 4 and no secondary pattern, the Gleason score would be 4+4=8 (the primary grade is simply doubled). Should tiny foci of cancer in needle biopsies be graded?Nowadays, the pathologists are increasingly making diagnosis on tiny foci of cancer in needle biopsies. Due to small tumor volume a secondary pattern may not be observed. In such cases, the primary grade is simply doubled (as shown in the example above). Gleason grading should be applied to all positive biopsies irrespective of the amount of cancer. Studies have shown that overall the correlation of Gleason scores between biopsies and prostatectomy specimens is good. However, it should be understood that the Gleason score of a tiny focus of cancer in a needle biopsy may not be reflective of the overall tumor due to sampling issues. About 30% to 45% of such cases are undergraded when compared to the Gleason grade in the radical prostatectomy specimen. Is cancer with Gleason score of 3+4=7 different from 4+3=7?If the biopsies show 60% Gleason grade 3 and the remaining 40% is Gleason grade 4, the Gleason score is 3+4=7. If 60% of the cancer is Gleason grade 4 and 40% is Gleason grade 3, the Gleason score is (4+3=7). In a study of patients with Gleason score 7 treated by radical prostatectomy, the primary Gleason pattern (4 vs 3) showed a significant correlation with other histologic and clinical predictors of disease progression; however, in a multivariate analysis along with pre-operative PSA, tumor volume, surgical margin status, extraprostatic extension, status of seminal vesicle involvement, and lymph node metastases, the primary Gleason pattern was not an independent predictor of disease progression. (Herman CM et al. Primary Gleason pattern as a predictor of disease progression in Gleason score 7 prostate cancer: a multivariate analysis of 823 men treated with radical prostatectomy. American Journal of Surgical Pathology 2001 May; 25(5):657-60. What about tertiary Gleason patterns observed in needle biopsies?When tertiary (third most common) and quaternary (fourth most common) patterns are observed in needle biopsies, they are usually ignored unless they are of higher grade. If three histologic grades are present and 2nd and 3rd grade are roughly equal in proportions, the higher grade is chosen to assign Gleason score. For e.g. if biopsies show 60% Grade 3, 20% Grade 2, and 20% Grade 4, the Gleason score would be