肝母细胞瘤新辅助化疗方案的治疗效应:形态学和免疫组织化学研究

2011-05-06

出处:Am J Surg Pathol. 2010 Mar;34(3):287-99. 作者:Wang LL, Filippi RZ, Zurakowski D, Archibald T, Vargas SO, Voss SD, Shamberger RC, Davies K, Kozakewich H, Perez-Atayde AR.PMID:20118773译者: F1000因子:8 评级:

出处:Am J Surg Pathol. 2010 Mar;34(3):287-99.
作者:Wang LL, Filippi RZ, Zurakowski D, Archibald T, Vargas SO, Voss SD, Shamberger RC, Davies K, Kozakewich H, Perez-Atayde AR.
PMID:20118773
译者: F1000因子:8 评级:必读

    肿瘤切除术前的新辅助化疗方案现已成为了肝母细胞瘤(HB)的一项主要治疗手段。化疗后的典型组织学改变是导致肿瘤坏死和纤维化。我们观察发现,HBs患者经化疗后会发生此前从未报道过的组织形态学变化。在此,我们报道了一项为期15年的回顾性研究,其中包含22例接受了儿童肿瘤协作组推荐新辅助化疗方案的HBs患儿。回顾内容包括患儿的医疗记录、诊断影像以及组织病理学结果。HBs病灶区域中除了有化疗后特征性的坏死和纤维化之外,其三分之二的区域内还存在类似非肿瘤性肝组织的细胞结构分化(细胞成熟),四分之一的区域内具有类似肝细胞癌的组织改变。细胞核内是否表达β-连环蛋白和角蛋白,有助于区分残余肿瘤组织和来自非肿瘤性肝组织的“成熟细胞”,也有助于外科手术边缘的评估。统计分析显示,化疗前后影像学上肿瘤较大、病理检查中肿瘤较大以及肿瘤侵及血管是转移性病灶的显著单变量预测因子,然而,化疗前影像学上的肿瘤大小及肿瘤侵及血管两因素,也是转移病灶的显著独立预测因子(多因素logistic 回归分析)。化疗后多灶性、范围更大的坏死以及肝细胞癌样形态改变与转移性病灶相关,但是这种相关关系尚不具备统计学意义上的显著性。

Neoadjuvant chemotherapy followed by resection has become the mainstay in the treatment of hepatoblastoma (HB). The changes after chemotherapy typically result in tumor necrosis and a fibrohistiocytic response. We have observed that treated HBs undergo additional morphologic changes that have not been described. Herein, we report a 15-year retrospective study of HBs in 22 children who received neoadjuvant chemotherapy according to the Children's Oncology Group protocols. The medical records, diagnostic imaging, and histopathology were reviewed. Besides treated HBs having characteristic necrosis and fibrohistiocytic response, two-thirds had areas of cytoarchitectural differentiation ("maturation") mimicking non-neoplastic liver, and a quarter had alterations mimicking hepatocellular carcinoma. Nuclear expression of beta-catenin and keratin profiles were useful in distinguishing residual tumor with "maturation" from non-neoplastic liver and therefore in the assessment of surgical margins. Statistical analysis revealed that larger pretreatment and posttreatment imaged tumor size, larger tumor size at pathologic examination, and vascular invasion were significant univariate predictors of metastatic disease, whereas pretreatment imaged tumor size and vascular invasion were also significant independent predictors (multivariate logistic regression analysis). Multifocality, greater posttreatment necrosis and hepatocellular carcinoma-like morphology were more often associated with metastatic disease, but did not reach statistical significance.


专家点评
Piotr Czauderna
Medical University of Gdansk, Poland

I found this paper very interesting because it presents the rarely discussed problem of comparison of the pre- and post-chemotherapy hepatoblastoma (HB) specimens, with some important clinical conclusions. The authors showed that treated HBs show maturation areas mimicking non-neoplastic liver, which may make recognition of the clear resection margin in post-operative chemotherapy-exposed tumors a difficult issue.

What can help is immunohistochemistry and specific staining for beta-catenin and keratin, particularly cytokeratin (CK)7, which differentiates normal liver from the tumoral tissue. CK7 was uniformly negative in tumor cells, while in non-neoplastic liver only cholangioles and bile ducts were immunoreactive. Another interesting finding was that chemotherapy induced in HBs architectural alterations which resembled hepatocellular carcinoma (HCC) (HCC-like lesions) and differed from a standard macrotrabecular HB pattern. Recognition of this change in post-treatment HB is of potential importance as it may lead to an incorrect change of the diagnosis from HB into HCC. It was also more commonly associated with metastasizing/relapsing tumors. Hence, its detection may help to reveal an unfavorable prognosis.

专家评价:

       我认为这篇论文非常有趣,因为它阐述了目前研究甚少的、肝母细胞瘤(HB)样本化疗前后的比较问题,并得出了一些重要的临床结论。作者发现,化疗后的 HBs病灶具有类似非肿瘤性肝组织的成熟组织区,这使得我们在接受过化疗的术后肿瘤病灶内很难清晰地辨别外科手术的切除边缘。

       通过对β-连环蛋白和角蛋白[尤其是细胞角蛋白(CK)7]进行免疫组织化学分析和特殊染色,有助于区分正常肝组织和肿瘤组织。细胞角蛋白 (CK)7在肿瘤细胞中均呈阴性,而在非肿瘤性肝组织中只有毛细胆管和胆管细胞中有CK7免疫染色。另一个有趣的发现是,化疗诱发的HBs结构改变与肝细胞癌(HCC)相似(也称HCC样病变),而与标准的巨粱型HB形态不同。在化疗后的HB病灶中正确识别上述形态变化可能是十分重要的,因为它可能会导致医师将HB误诊为HCC。上述形态改变也多见于转移性或复发性肿瘤病灶中。因此,识别该形态学变化也有助于预测患者的不良预后。

点评专家
Piotr Czauderna
Medical University of Gdansk, Poland

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