Marsh Michael N, Heal Calvin J
Luton and Dunstable Hospitals University NHS Trust, and Wolfson College, University of Oxford, Linton Road, Oxford OX2 6UD, UK.
Centre for Biostatistics, Faculty of Biology, Academic Health Science Centre, University of Manchester, Manchester M13 9PL, UK.
Nutrients. 2017 Feb 28;9(3):213. doi: 10.3390/nu9030213.
The evolving history of the small intestinal biopsy and its interpretation-and misinterpretations-are described in this paper. Certain interpretative errors in the technical approaches to histological assessment are highlighted-even though we may never be rid of them. For example, mucosal "flattening" does not reduce individual villi to their cores, as still seems to be widely believed. Neither is the mucosa undergoing an atrophic process-since it can recover structurally. Rather, the intestinal mucosa manifests a vast hypertrophic response resulting in the formation of large plateaus formed from partially reduced villi and their amalgamation with the now increased height and width of the inter-villous ridges: this is associated with considerable increases in crypt volumes. Sections through mosaic plateaus gives an erroneous impression of the presence of stunted, flat-topped villi which continues to encourage both the continued use of irrelevant "atrophy" terminologies and a marked failure to perceive what random sections through mosaic plateaus actually look like. While reviewing the extensive 40+ year literature on mucosal analysis, we extracted data on intraepithelial lymphocytes (IEL) counts from 607 biopsies, and applied receiver-operating characteristic (ROC)-curve analysis. From that perspective, it appears that counting IEL/100 enterocyte nuclei in routine haematoxylin and eosin (H&E) sections provides the most useful discriminator of celiac mucosae at histological level, with an effective cut-off of 27 IEL, and offering a very high sensitivity with few false negatives. ROC-curve analysis also revealed the somewhat lesser accuracies of either CD3+ or γδ+ IEL counts. Current official guidelines seem to be somewhat inadequate in clearly defining the spectrum of gluten-induced mucosal pathologies and how they could be optimally interpreted, as well as in promoting the ideal manner for physicians and pathologists to interact in interpreting intestinal mucosae submitted for analysis. Future trends should incorporate 3-D printing and computerised modelling in order to exemplify the subtle micro-anatomical features associated with the crypt-villus interzone. The latter needs precise delineation with use of mRNA in-section assays for brush border enzymes such as alkaline phosphate and esterase. Other additional approaches are needed to facilitate recognition and interpretation of the features of this important inter-zone, such as wells, basins and hypertrophic alterations in the size of inter-villous ridges. The 3-D computerised models could considerably expand our understandings of the microvasculature and its changes-in relation both to crypt hypertrophy, in addition to the partial attrition and subsequent regrowth of villi from the inter-villous ridges during the flattening and recovery processes, respectively.
本文描述了小肠活检的发展历程及其解读——以及误读。文中强调了组织学评估技术方法中的某些解读错误——尽管我们可能永远无法摆脱这些错误。例如，黏膜“扁平”并非如人们普遍认为的那样，使单个绒毛只剩下其核心部分。黏膜也并非处于萎缩过程——因为它在结构上可以恢复。相反，肠道黏膜表现出巨大的肥大反应，导致形成由部分变矮的绒毛及其与现在增高增宽的绒毛间嵴融合而成的大平台：这与隐窝体积的显著增加有关。穿过镶嵌平台的切片会给人一种存在发育不良、平顶绒毛的错误印象，这继续促使人们持续使用不相关的“萎缩”术语，并且明显无法认识到穿过镶嵌平台的随机切片实际是什么样子。在回顾40多年来关于黏膜分析的大量文献时，我们从607份活检样本中提取了上皮内淋巴细胞（IEL）计数数据，并应用了受试者操作特征（ROC）曲线分析。从这个角度来看，在常规苏木精和伊红（H&E）切片中计数IEL/100个肠上皮细胞核，在组织学水平上是区分乳糜泻黏膜最有用的指标，有效临界值为27个IEL，假阴性很少，灵敏度很高。ROC曲线分析还显示CD3 +或γδ + IEL计数的准确性略低。当前的官方指南在明确界定麸质诱导的黏膜病变谱及其最佳解读方式，以及促进医生和病理学家在解读送检分析的肠道黏膜时的理想互动方式方面，似乎有些不足。未来的趋势应该包括3D打印和计算机建模，以例证与隐窝 - 绒毛中间区相关的细微微观解剖特征。后者需要使用针对诸如碱性磷酸酶和酯酶等刷状缘酶的mRNA切片检测进行精确描绘。还需要其他额外的方法来促进对这个重要中间区特征的识别和解读，比如凹陷、池以及绒毛间嵴大小的肥大改变。3D计算机模型可以极大地扩展我们对微血管系统及其变化的理解——这与隐窝肥大有关，此外还分别与绒毛在扁平化和恢复过程中从绒毛间嵴的部分磨损和随后再生有关。
