Xu Zhengfan, Theisen Brian K, Chang Qing, Schultz Daniel, Ahsan Beena U
Henry Ford Health, Detroit, MI, USA.
Henry Ford Health, Detroit, MI, USA; Michigan State University College of Human Medicine, East Lansing, MI, USA.
Hum Pathol. 2024 Dec;154:105710. doi: 10.1016/j.humpath.2024.105710. Epub 2024 Dec 21.
The morphologic diagnosis of colorectal carcinoma (CRC) is typically straight forward. However, there are certain subtypes of CRC that pose diagnostic challenges for daily practice due to sometimes overlapping morphologic and immunohistochemical features. These subtypes include poorly differentiated adenocarcinoma NOS, in the absence of conventional morphology (PDA-NOS), large cell neuroendocrine carcinoma (LCNEC), medullary carcinoma (MC), undifferentiated carcinoma (UC) and lymphoepithelioma-like carcinoma (LELC). This study aims to see if there is a survival difference between poorly differentiated variants of CRC, as well as other clinicopathological features that may affect prognosis. Additionally, we analyzed interobserver agreement among gastrointestinal pathologists (GP) at our institution in subclassifying poorly differentiated CRC. All consecutive patients with the diagnoses of PDA-NOS, MC, LCNEC, UC and LELC between July 2018 and July 2023 were included. Cox proportional regression test was used for multivariate analysis, while log-rank and Kaplan-Meier tests were used for univariate and survival analyses. Out of the same cohort of patients, 58 samples identified and reviewed by 3 GI-subspecialty-trained pathologists who were asked to assign the cases as PDA-NOS, LCNEC, MC, UC and LELC. Interobserver agreement was analyzed using Fleiss Kappa. Of the total 77 patients, 63 were PDA-NOS, 3 were LCNEC, 6 were MC, 4 were UC and 1 was LELC patients. Multivariate analysis using Cox proportional regression showed that tumor size (p = 0.001, HR = 1.22, 95% CI 1.08-1.38), patient age (p = 0.001, HR 1.73, 95% CI 1.24-2.40), and M stage (p = 0.02, HR 2.22, 95% CI 1.14-4.32) were significantly associated with worse OS. For the 58 cases analyzed, 3 GP agreed on 42 (72%) cases. The most common diagnosis was PDA-NOS and for 33 (57%) agreement was unanimous. There was moderate agreement (k 0.41-0.60) between all 3 GP. Our study evaluated the challenges associated with histological evaluation of colon cancers with poorly differentiated morphologies. Among the diagnoses considered in the study, MC and LCNEC had different prognostic implications compared to PDA-NOS and UC. Additionally, our GP showed moderate interobserver agreement, indicating that some level of variability in diagnosing poorly differentiated CRC subtypes may be inevitable.
结直肠癌（CRC）的形态学诊断通常较为简单直接。然而，由于形态学和免疫组化特征有时重叠，某些CRC亚型给日常实践带来了诊断挑战。这些亚型包括缺乏传统形态学特征的低分化腺癌（PDA-NOS）、大细胞神经内分泌癌（LCNEC）、髓样癌（MC）、未分化癌（UC）和淋巴上皮瘤样癌（LELC）。本研究旨在探讨CRC低分化变体之间是否存在生存差异，以及其他可能影响预后的临床病理特征。此外，我们分析了本机构胃肠道病理学家（GP）在对低分化CRC进行亚分类时的观察者间一致性。纳入了2018年7月至2023年7月期间所有连续诊断为PDA-NOS、MC、LCNEC、UC和LELC的患者。多变量分析采用Cox比例回归检验，单变量和生存分析采用对数秩检验和Kaplan-Meier检验。在同一队列患者中，58个样本由3名接受胃肠道亚专业培训的病理学家进行识别和评估，他们被要求将病例分类为PDA-NOS、LCNEC、MC、UC和LELC。使用Fleiss Kappa分析观察者间一致性。在总共77例患者中，63例为PDA-NOS，3例为LCNEC，6例为MC，4例为UC，1例为LELC患者。使用Cox比例回归进行的多变量分析显示，肿瘤大小（p = 0.001，HR = 1.22，95% CI 1.08 - 1.38）、患者年龄（p = 0.001，HR 1.73，95% CI 1.24 - 2.40）和M分期（p = 0.02，HR 2.22，95% CI 1.14 - 4.32）与较差的总生存期显著相关。对于分析的58例病例，3名GP在42例（72%）上达成一致。最常见的诊断是PDA-NOS，33例（57%）的诊断一致。所有3名GP之间存在中度一致性（k 0.41 - 0.60）。我们的研究评估了低分化形态结肠癌组织学评估相关的挑战。在本研究考虑的诊断中，与PDA-NOS和UC相比，MC和LCNEC具有不同的预后意义。此外，我们的GP显示出中度的观察者间一致性，表明在诊断低分化CRC亚型时一定程度的变异性可能是不可避免的。
