Enteroblastic and Hepatoid Colorectal Carcinomas are Aggressive Cancers With a Distinctive Immunophenotype, While Clear Cell Carcinoma Appears to Represent Clear Cell Change in Conventional Colorectal Cancer.
Publication/Presentation Date
4-21-2026
Abstract
Enteroblastic, hepatoid, and clear cell carcinomas are rare subtypes of colorectal carcinoma (CRC) with histologic and immunohistochemical (IHC) overlap. We assessed 37 CRCs that possibly represent these subtypes. Provisional criteria for each subtype, along with case photomicrographs and IHC data, were circulated among the authors to provide diagnostic interpretations. Based on plurality consensus, the carcinomas were classified as enteroblastic (n=13), hepatoid (n=6), and clear cell (n=18). Unanimous agreement was reached in 18% (3 clear cell, 3 hepatoid). Interobserver analysis revealed a mean pairwise Cohen κ of 0.63 (range: 0.32 to 0.91), with the hepatoid subtype eliciting the greatest consensus. Clear cell areas were the most likely to intermix with areas of conventional CRC (P< 0.001). Seven patients (20%) had inflammatory bowel disease (mostly linked to enteroblastic CRC). Twenty-three of 34 patients (68%) had nodal metastasis, and 12 (32%) had distant metastasis (mostly to the liver) at presentation. Median recurrence-free survival was 17 months, with enteroblastic cases the most likely to recur (54%, P=0.015). Median follow-up length was 27 months, with 14 patients (40%) dying of disease (representing 7 enteroblastic, 4 hepatoid, and 3 clear cell CRC). Mutations were identified in TP53 (n=8), APC (n=3), FBXW7 (n=2), and KRAS (n=1). Inflammatory bowel disease significantly worsened recurrence-free survival on multivariate analysis, while distant metastasis significantly worsened both recurrence-free and overall survival on multivariate analysis. Enteroblastic, hepatoid, and clear cell CRC demonstrate morphologic and IHC overlap, leading to interobserver variability in diagnosis. Given potential differences in clinical correlations and outcomes, more refined criteria are likely necessary.
ISSN
1532-0979
Published In/Presented At
Khan, F., Polydorides, A. D., Paulsen, J. D., Chen, W., Vazzano, J., Huber, A., Papke, D., Jr, Sharifai, N., Stashek, K., Ruz-Caracuel, I., Allende, D., McHugh, K., Shia, J., Longacre, T. A., Dhall, D., Makhoul, E., Lee, M. J., Collins, K., Ulbright, T. M., Zhang, M. L., … Gonzalez, R. S. (2026). Enteroblastic and Hepatoid Colorectal Carcinomas are Aggressive Cancers With a Distinctive Immunophenotype, While Clear Cell Carcinoma Appears to Represent Clear Cell Change in Conventional Colorectal Cancer. The American journal of surgical pathology, 10.1097/PAS.0000000000002555. Advance online publication. https://doi.org/10.1097/PAS.0000000000002555
Disciplines
Medicine and Health Sciences
PubMedID
42012857
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article