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肾上腺皮质肿瘤的诊断方法(五)

2020-1-7 15:58| 发布者: admin| 查看: 205| 评论: 0

摘要: Ki67 labeling index has been shown to be prognostically significant in ACCs (discussed later). The Helsinki scoring system, proposed in 2015 and subsequently validated in a later series, has incorpora ...

Ki67 labeling index has been shown to be prognostically significant in ACCs (discussed later). The Helsinki scoring system, proposed in 2015 and subsequently validated in a later series, has incorporated the role of the Ki67 labeling index into its criteria for malignancy along with mitotic rate (>5 per 50 high-power fields) and presence/absence of necrosis. The Helsinki system uses a weighted-point system: 5 points are awarded if necrosis is present and 3 points are awarded if more than 5 mitoses are seen in 50 high-power fields. The value of the Ki67 index (percentage positive tumor nuclei from hot spots) is used as the third scoring component. A score greater than 8.5 indicates a malignant lesion. Of note, the Ki67 index should be evaluated in the area of highest proliferative activity; no visual assessment is allowed, and, ideally, the evaluation should be done by an automated image analysis software nuclear algorithm. The Italian validation series included oncocytic (mixed and pure tumors) and myxoid ACCs in addition to conventional ACCs. In this validation cohort, oncocytic ACCs (diagnosed based on the Lin-Weiss-

Bisceglia criteria) had a Helsinki score ranging from 3 to 79. Although there were only a few myxoid tumors from which to draw a reliable conclusion, the Helsinki score of 19 or greater captured a significant proportion of aggressive forms of oncocytic ACCs. In a recent multicenter French cohort, the diagnostic performance of the Helsinki scoring scheme in oncocytic ACTs was not as good as other schemes, but the Helsinki score was more useful in the prediction of poor prognostic subgroups of oncocytic ACCs. These findings have pointed out the diagnostic limitations of this scoring system; however, further studies are still needed to expand the diagnostic limitations of this scheme.

Ki67增殖指数在ACCs中具有预测意义(稍后讨论)。Helsinki评分系统于2015年提出,随后在一个系列研究中得到验证,该系统将Ki67标记指数的作用纳入恶性肿瘤的标准中,同时考虑核分裂象(每50个高倍视野>5个)和是否存在坏死。Helsinki系统采用加权积分制:如果出现坏死,得5分;50个高倍视野中发现5个以上核分裂象,得3分。Ki67指数(热点肿瘤细胞核阳性百分率)作为第三个评分指标。分数大于8.5表示恶性病变。值得注意的是,Ki67指数应在增殖活性最高的区域进行评估;不允许进行视觉评估,理想情况下,评估应通过自动图像分析软件核算法进行。意大利验证系列包括嗜酸细胞(混合和纯肿瘤)和黏液样ACCs以及经典型ACCs。在这个验证队列中,嗜酸细胞ACCs(根据Lin-Weiss-Bisceglia标准诊断)Helsinki得分在3到79之间。尽管只有少数黏液样肿瘤可以得出可靠的结论,但Helsinki评分为19分或更高的患者中,有相当比例的嗜酸细胞ACCs具有侵袭性。在最近的一个多中心法国队列中,Helsinki评分方案对嗜酸细胞ACTs的诊断效果不如其他方案,但Helsinki评分对预测嗜酸细胞ACCs预后不良亚组更有用。这些发现指出了该评分系统的诊断局限性,但仍需进一步研究以扩大该方案的诊断局限性。

Although rare, pediatric ACTs often represent a diagnostic conundrum because it has been shown that some histologic features typically associated with malignancy in adult adrenocortical neoplasms do not necessarily correlate with poor outcome in pediatric patients. Although this may partially be related to differences in application of some cardinal features of malignancy among diagnosticians, the Wieneke system was devised to better delineate benign from malignant ACTs in the pediatric setting. The Wieneke system incorporates some traditional prognostic variables (atypical mitoses, vascular invasion, capsular invasion, tumor necrosis, mitotic rate >15 per 20 highpower fields) into its scoring algorithm, in addition to gland size and weight as well as tumor involvement of local structures, including vena cava and other extra-adrenal structures. When 4 parameters are met, a diagnosis of pediatric ACC can be made. An assignment of uncertain malignant potential can be made with a score of 3, whereas a score of 1 or 2 is thought to suggest a benign course. This approach to pediatric ACTs has also been evaluated in subsequent series.

虽然很少见,但儿童ACTs往往是一个诊断难题,因为已经证明,一些与成人肾上腺皮质肿瘤的恶性相关的典型组织学特征,并不一定与儿童患者的不良预后相关。虽然这可能部分地与诊断者在应用恶性肿瘤的一些基本特征方面的差异有关,但Wieneke系统的设计是为了更好地描述儿童患者的良性和恶性ACTs。Wieneke系统将一些传统的预后变量(非典型核分裂象、血管侵犯、包膜侵犯、肿瘤坏死、核分裂象>15/20高倍视野)纳入其评分算法中,此外还包括腺体大小和重量以及肿瘤侵犯局部结构,包括腔静脉和其他肾上腺外结构。当满足4个参数时,可诊断为儿童ACC。3分为恶性潜能未定,而1分或2分被认为是良性的过程。这种儿童ACTs的判断方法也在随后的研究中进行了评估。

It has been the observation of our team members that areas suggestive of adenoma-tocarcinoma tumor progression exist in some ACTs (O.M., author observation). Moreover, ACA-like low-proliferative regions can be seen admixed with nodular areas with high-grade proliferation. These lesions can be particularly challenging for diagnosticians, especially when limited representative sampling was performed from the tumor. Even so, there are very rare ACTs that are in a diagnostic gray zone and, in those cases, some diagnosticians use the term atypical or borderline adrenocortical neoplasm, whereas others apply the term ACT of uncertain malignant potential (UMP) for similar presentations. When the rare diagnosis of an ACT-UMP is being considered, additional sections should be submitted of the entire periphery of the tumor along with the central portion, and a diligent search including serial/ deeper sections should be conducted to evaluate for features of malignancy. The diagnostic workup of an ACT is no longer restricted to conventional histomorphology. There are several immunohistochemical biomarkers that can be useful in establishing a diagnosis of malignancy. Similarly, the diagnosis and prognostication of ACC is now possible when applying various molecular biology techniques in the evaluation of an ACT (discussed later).

我们的团队成员观察到,在某些ACTs中存在腺瘤样癌进展的区域(O.M.,作者观察)。此外,ACA样低增殖区可与高增殖结节区混合。对于诊断者来说,这些病变尤其具有挑战性,特别是当从肿瘤中进行有限的代表性取样时。即使如此,也有非常少见的ACTs是在一个诊断灰色区域,在这些情况下,一些诊断医师使用术语非典型或交界性肾上腺皮质肿瘤,而其他相似的表现ACT应用恶性潜能未定(UMP)这个术语。当考虑到少见的ACT-UMP诊断时,应在肿瘤的整个边缘和中心部分提交额外的切片,并应进行包括系列/深层切片在内的仔细观察,以评估恶性肿瘤的特征。一个ACT的诊断不再局限于传统的组织形态学。有几种免疫组织化学生物标记物可用于确定恶性肿瘤的诊断。类似地,当应用各种分子生物学技术来评估一个ACT时(稍后讨论),现在ACC的诊断和预后预测是可能的。

Once a diagnosis of malignancy has been established, ACCs are further categorized as high grade or low grade based on mitotic counts from hot spots, depending on whether up to 20 (low grade) or more than 20 mitoses (high grade) are seen per 50 high-power fields. This approach stems from the original article by Weiss and colleagues, but this has been adopted in the past decade in several practices given its prognostic significance. Volante and colleagues also showed that ACCs can be further prognosticated combining tumor stage and mitotic activity (≤9 per 50 high-power fields vs >9 per 50 high-power fields). Mete and colleagues also showed that the cutoff of 10 mitoses per 50 high-power fields had a better performance in the correlation of disease-free survival in ACCs.

一旦诊断恶性肿瘤,根据热点区核分裂象计数,ACCs被分为高级别或低级别,这取决于每50HPF是否出现20个(低级别)或超过20个(高级别)的核分裂象。这种方法源于Weiss和他的同事们最初的文章,但是考虑到它的预测意义,在过去十年中在一些实践中采用了这种方法。Volante和他的同事们还发现,结合肿瘤分期和核分裂象(≤9/50HPF vs >9/50HPF),可以进一步预测ACCs生物学行为。Mete及其同事还发现,在ACCs无病生存的相关性方面,核分裂象10个/50HPF是作为具有更好预后的一个阈值。

In practice, most ACCs are easily separated from ACAs, especially when they are widely invasive and highly proliferative. Overall, it has been reported that vascular invasion (see Fig. 17), defined as tumor cells invading through a vessel wall and/or intravascular tumor cells admixed with thrombus, is the strongest diagnostic parameter and predictive of poor outcome, and thus it is reasonable to suggest that every case should be thoroughly scrutinized to rule this finding in or out, even in cases that are obviously malignant.

实际上,大多数ACCs很容易与ACAs鉴别,尤其是当它们具有广泛的侵袭性和高度增殖性时。总的来说,有报道称,血管侵犯(见图17)是指肿瘤细胞通过血管壁和/或血管内肿瘤细胞与血栓混合侵入,是最强的诊断参数和不良预后的预测,因此,有理由建议对每一个病例进行彻底的检查,以排除这一发现,即使是在明显恶性的病例中。

~~~未完待续~~~

作者简介

慧海拾穗,主治医师。

从事儿童病理诊断,对淋巴造血、软组织和泌尿生殖系统肿瘤有着浓厚的兴趣

座右铭:《为病寻理》就要爱病理 !


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