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

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.