Jass Jeremy R
Department of Pathology, McGill University, Montreal, Quebec, Canada.
Fam Cancer. 2004;3(2):93-100. doi: 10.1023/B:FAME.0000039849.86008.b7.
Morphological features may serve as diagnostically useful markers of colorectal cancer (CRC) with the microsatellite instability-high (MSI-H) phenotype. The most important of these are lymphocytic infiltration, mucin secretion and poor differentiation. These features are apparent in both sporadic MSI-H CRC and CRC occurring in the context of hereditary non-polyposis colorectal cancer (HNPCC). There is now strong evidence that that the two principal subtypes of MSI-H CRC evolve through different pathways. Sporadic MSI-H CRC orginate within serrated polyps with BRAF mutation and DNA methylation while CRC in HNPCC arise within conventional adenomas in which there is frequent mutation of APC or beta -catenin and/or K- ras. These early differences in pathogenesis translate into multiple morphological distinctions in the cancers developing through the two pathways. Lymphocytic infiltration, tumour budding (de-differentiation), and co-existing adenomas are more evident in HNPCC while mucin secretion, poor differentiation, tumour heterogeneity and glandular serration, and co-existing serrated polyps are more evident in sporadic MSI-H CRC. Sporadic MSI-H CRC are also characterized by cytoplasmic eosinophilia and nuclei that are large, round, vesicular and contain a prominent nucleolus while in HNPCC the cytological features recapitulate the basophilia and nuclear characteristics of conventional adenomas. In practice, lymphocytic infiltration is the most sensitive marker of MSI-H status in both sporadic CRC and HNPCC. The crucial distinction between HNPCC and sporadic MSI-H CRC should be achieved by means of all available data including family history, age at onset of malignancy and molecular features. There is increasing evidence that genetic factors may predispose to DNA methylation. This can result in familial clustering of MSI-H CRC in which the underlying mechanism is methylation of hMLH1 rather than germline mutation. Morphological features can assist is distinguishing such families from bona fide HNPCC families which they closely mimic.
形态学特征可能是具有微卫星高度不稳定（MSI-H）表型的结直肠癌（CRC）的诊断有用标志物。其中最重要的是淋巴细胞浸润、黏液分泌和低分化。这些特征在散发性MSI-H CRC和遗传性非息肉病性结直肠癌（HNPCC）背景下发生的CRC中均很明显。现在有强有力的证据表明，MSI-H CRC的两种主要亚型通过不同途径演变。散发性MSI-H CRC起源于具有BRAF突变和DNA甲基化的锯齿状息肉，而HNPCC中的CRC则起源于常规腺瘤，其中APC或β-连环蛋白和/或K-ras频繁发生突变。这些发病机制的早期差异转化为通过这两种途径发展的癌症中的多种形态学差异。淋巴细胞浸润、肿瘤芽生（去分化）和共存腺瘤在HNPCC中更明显，而黏液分泌、低分化、肿瘤异质性和腺管锯齿状以及共存锯齿状息肉在散发性MSI-H CRC中更明显。散发性MSI-H CRC的特征还包括细胞质嗜酸性和大的、圆形的、泡状的且含有突出核仁的细胞核，而在HNPCC中，细胞学特征再现了常规腺瘤的嗜碱性和核特征。在实践中，淋巴细胞浸润是散发性CRC和HNPCC中MSI-H状态最敏感的标志物。HNPCC和散发性MSI-H CRC之间的关键区别应通过所有可用数据来实现，包括家族史、恶性肿瘤发病年龄和分子特征。越来越多的证据表明遗传因素可能易导致DNA甲基化。这可导致MSI-H CRC的家族聚集，其潜在机制是hMLH1甲基化而非种系突变。形态学特征有助于将此类家族与它们紧密模仿的真正HNPCC家族区分开来。
