Department of Haematology and Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
SAHMRI Colorectal Node, Basil Hetzel Institute, Woodville South, Australia.
Crit Rev Clin Lab Sci. 2021 Sep;58(6):369-384. doi: 10.1080/10408363.2021.1881756. Epub 2021 Feb 11.
Primary appendiceal neoplasms (ANs) comprise a heterogeneous group of tumors. The pathology and classification of ANs have been controversial, and thus, a new classification of these neoplasms was published in the World Health Organization (WHO) classification of tumors (5th edition, 2019). However, immunohistochemistry (IHC) features of epithelial ANs are not explained in this edition and the limited data on the molecular pathology of these tumors shows inconsistent findings in various studies. It would be useful to identify biomarkers appropriate for each subtype to better aid in treatment selection. Therefore, we reviewed the literature to investigate what is known of the molecular pathology and IHC features of the most frequently diagnosed pathological subtypes of epithelial ANs based on the recent classification. The inconsistencies in research findings regarding the IHC features and molecular pathology of ANs could be due to differences in the number of samples and their collection and preparation as well as to the lack of a universally accepted classification system for these neoplasms. However, the literature shows that epithelial ANs typically stain positive for MUC2, CK20, and CDX2 and that the expression of SATB2 protein could be used as a biomarker for appendix tumor origin. Low-grade appendiceal mucinous neoplasms tend to have mutations in and but are usually wild-type for , , and . Conversely, appendiceal adenocarcinomas are frequently found with mutations in , , , , and , and have significant nuclear expression of β-catenin, loss of nuclear or nuclear and cytoplasmic expression of SMAD4, and loss of cytoplasmic membranous expression of E-cadherin. Goblet cell carcinomas (GCCs) typically stain positive for keratin and mucin markers and are frequently mutated in and chromatin-modifier genes, but they tend to be wild-type for , , , and The expression of CK7 and SATB2 proteins is usually negative in appendiceal neuroendocrine neoplasms and they lack the mutations in common cancer-associated genes including , , , and The available data suggest that GCCs have distinct molecular and immunohistochemical features and that they have characteristics more in common with adenocarcinoma than classical neuroendocrine tumors. In addition, MSI does not seem to have a role in the pathogenesis of epithelial ANs because they are rarely detected in these tumors. Finally, hereditary predisposition may have a role in the development of ANs because heterozygous , and germline mutations have recently been identified in low and high grades ANs.
原发性阑尾肿瘤（ANs）是一组异质性肿瘤。ANs 的病理学和分类一直存在争议，因此，世界卫生组织（WHO）在 2019 年的肿瘤分类（第 5 版）中发布了新的分类。然而，该版本并未解释上皮性 ANs 的免疫组织化学（IHC）特征，并且关于这些肿瘤的分子病理学的有限数据表明，在各种研究中发现的结果不一致。确定适用于每种亚型的生物标志物将有助于更好地辅助治疗选择。因此，我们复习了文献，以根据最近的分类调查最常诊断的上皮性 ANs 病理亚型的分子病理学和 IHC 特征。ANs 的 IHC 特征和分子病理学研究结果的不一致可能是由于样本数量及其采集和准备的差异以及这些肿瘤缺乏普遍接受的分类系统所致。然而，文献表明，上皮性 ANs 通常对 MUC2、CK20 和 CDX2 呈阳性染色，SATB2 蛋白的表达可用作阑尾肿瘤起源的生物标志物。低级别阑尾黏液性肿瘤倾向于具有 和 突变，但通常为野生型 、 、 。相反，阑尾腺癌常发现 、 、 、 、 突变，β-连环蛋白核表达明显，SMAD4 核或核质表达缺失，E-钙黏蛋白质膜表达缺失。杯状细胞癌（GCCs）通常对角蛋白和黏蛋白标志物呈阳性染色，并且在 以及染色质修饰基因中经常发生突变，但它们通常为野生型 、 、 、 。阑尾神经内分泌肿瘤的 CK7 和 SATB2 蛋白表达通常为阴性，并且缺乏常见的癌症相关基因中的突变，包括 、 、 、 。现有数据表明，GCCs 具有独特的分子和免疫组织化学特征，并且与经典神经内分泌肿瘤相比，它们具有更多的特征与腺癌相似。此外，微卫星不稳定性（MSI）似乎在上皮性 ANs 的发病机制中没有作用，因为这些肿瘤中很少检测到 MSI。最后，遗传易感性可能在 ANs 的发生中起作用，因为最近在低级别和高级别 ANs 中发现了杂合性 、 和 种系突变。
