Poorly Differentiated Intestinal-Type Gastric Adenocarcinoma Mimicking Diffuse-Type Gastric Cancer (Linitis Plastica): The Diagnostic Utility of E-Cadherin Immunohistochemistry.
Year: 2026
Type: article
Study design: Case Report
Abstract: Background: The histological classification of gastric cancer into intestinal and diffuse types carries significant prognostic and therapeutic implications. While poorly cohesive carcinomas typically characterize the diffuse type with loss of E-cadherin expression, poorly differentiated intestinal-type adenocarcinomas can occasionally display discohesive architectural features, creating diagnostic dilemmas on small mucosal biopsies. Case Presentation: A 75-year-old male presented with progressive dysphagia and a clinical suspicion of gastric malignancy. Preoperative computed tomography revealed distal esophageal wall thickening, retroperitoneal lymphadenopathy, and moderate ascites. Intraoperative findings identified a gastric mass resembling linitis plastica extending into the distal esophagus. Initial mucosal biopsies showed lamina propria infiltration by small, discohesive malignant cells, initially favoring a poorly cohesive / diffuse-type gastric carcinoma. However, outside consultation and confirmatory immunohistochemical profiling revealed that the tumor cells were strongly and diffusely positive for E-cadherin, alongside nuclear expression of CDX2 and partial positivity for CK20, definitively establishing the diagnosis of a poorly differentiated intestinal-type gastric adenocarcinoma. Conclusion: Discohesive growth patterns in gastric biopsies should not automatically default to diffuse-type carcinoma. Comprehensive immunohistochemistry—specifically robust E-cadherin preservation and CDX2 expression—is essential to accurately classify poorly differentiated gastric adenocarcinomas and guide appropriate clinical management. Keywords Gastric Adenocarcinoma, Intestinal-Type, Poorly Differentiated, Diffuse-Type mimic, E-Cadherin, CDX2, Gastrointestinal Pathology. Introduction Gastric cancer remains a leading cause of cancer-related mortality globally. According to the classic Laurén classification, gastric adenocarcinomas are broadly divided into two main histologic subtypes: intestinal-type, which typically forms cohesive glands and is associated with environmental risk factors, and diffuse-type, characterized by infiltrating discohesive signet-ring or small cells, often linked to genetic predispositions (such as CDH1 germline mutations). In routine clinical practice, small mucosal pinch biopsies of infiltrative gastric tumors can exhibit overlapping architectural patterns. Poorly differentiated intestinal-type adenocarcinomas frequently lose glandular formation and display discohesive sheets, mimicking signet-ring cell or poorly cohesive carcinomas (diffuse type). Distinguishing between these entities is crucial, as their molecular pathways, responses to targeted therapies, and metastatic behaviors differ. Immunohistochemistry utilizing epithelial markers, caudal-type homeobox 2 (CDX2), and cell-adhesion molecules like E-cadherin provides a reliable roadmap for resolving diagnostic ambiguities. Case Presentation Clinical History and Imaging Findings A 75-year-old male presented with complaints of progressive dysphagia. Preoperative abdominal CT scans revealed marked distal esophageal wall thickening concerning for a malignant process, accompanied by multiple retroperitoneal lymphadenopathies and moderate ascites. Intraoperative exploratory findings demonstrated a prominent gastric mass resembling linitis plastica involving the gastric body and extending into the distal third of the esophagus, alongside Grade 2 esophageal candidiasis. Macroscopic Pathology Endoscopic mucosal biopsies of the gastric lesion yielded multiple minute, off-white tissue fragments measuring up to $0.2 \times 0.1 \times 0.1 \text{ cm}$, which were entirely submitted for histopathologic examination. Initial Histopathology Microscopic inspection via Hematoxylin and Eosin (H&E) demonstrated gastric mucosa extensively infiltrated by an invasive malignant epithelial neoplasm. The tumor comprised small-to-medium-sized discohesive cells with hyperchromatic, irregular nuclei infiltrating the lamina propria individually and in small clusters, accompanied by mucosal ulceration and active chronic inflammation. Based on the discohesive architecture, the initial institutional report favored a poorly cohesive gastric carcinoma (WHO classification) / diffuse-type gastric adenocarcinoma (Laurén classification). Confirmatory Immunohistochemical Profiling To definitively characterize the lineage and assess cell adhesion status, specialized immunohistochemical stains were performed: E-Cadherin: Showed strong and diffuse membranous positivity throughout the infiltrating malignant cells, confirming retained intercellular adhesion and pointing toward an intestinal phenotype. CDX2: Diffusely positive, confirming intestinal lineage differentiation. CK20: Partial focal positivity. CD7: Patchy expression. The retention of strong E-cadherin expression combined with robust CDX2 positivity effectively ruled out a diffuse-type (CDH1-deficient) gastric cancer, establishing the definitive diagnosis of a Poorly Differentiated Gastric Adenocarcinoma, Intestinal-Type. Discussion The differentiation between intestinal and diffuse gastric carcinomas is vital for understanding tumor biology and epidemiology. While intestinal-type tumors typically arise through a well-defined multistep cascade (chronic gastritis, atrophy, intestinal metaplasia, dysplasia, carcinoma) and form recognizable tubular or glandular structures, poorly differentiated variants can lose gland formation entirely. When a gastric biopsy reveals discohesive single cells or small nests infiltrating the lamina propria, pathologists must consider both poorly cohesive carcinoma (diffuse type) and solid variants of poorly differentiated intestinal-type adenocarcinoma. Relying solely on H&E morphology in small biopsy fragments can lead to misclassification. E-Cadherin is a calcium-dependent transmembrane glycoprotein crucial for epithelial cell-to-cell adhesion. In diffuse-type gastric cancer (specifically hereditary diffuse gastric cancer and sporadic equivalents), CDH1 mutations or promoter hypermethylation typically result in the complete loss of membranous E-cadherin expression. Conversely, intestinal-type gastric carcinomas retain intact E-cadherin expression, reflecting their epithelial/glandular heritage even when poorly differentiated. The addition of CDX2 further substantiates intestinal differentiation. In this patient, immunohistochemistry successfully corrected the initial impression, providing accurate classification for targeted oncologic planning. Conclusions Poorly differentiated intestinal-type gastric adenocarcinoma can exhibit discohesive growth patterns on mucosal biopsies, closely simulating diffuse-type gastric carcinoma. E-cadherin immunohistochemistry is an indispensable diagnostic biomarker that differentiates between intestinal-type (retained membranous expression) and diffuse-type (aberrant loss of expression) gastric cancers. Accurate subtyping through targeted immunohistochemical panels ensures precise clinicopathologic diagnosis and optimal therapeutic stratification. Figure Captions Figure 1 (Microfotografía - H&E, Low Power): Low-power histologic view of the gastric mucosal biopsy showing extensive mucosal infiltration by an invasive malignant epithelial neoplasm with associated surface ulceration (H&E, 40x). Figure 2 (Microfotografía - H&E, High Power): High-power magnification highlighting infiltrating atypical epithelial cells with hyperchromatic irregular nuclei and discohesive arrangements within the lamina propria (H&E, 200x). References Laurén P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965;64:31-49. Carneiro F, et al. Molecular pathology of gastric cancer, with particular reference to the histopathological subtypes. J Pathol. 2004;203(3):757-767. Karpeh MS, et al. A comparison of metastatic spread in specific histologic types of gastric cancer. Cancer. 2001;92(12):3064-3069. Schulick RD, et al. E-cadherin expression in gastric and esophageal cancers. Ann Surg Oncol. 1999;6(8):760-766.
Author: Milanés Sánchez, José Luis
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7225378367