Very well-differentiated gastric carcinoma of intestinal type: analysis of diagnostic criteria

Abstract

Very well-differentiated gastric adenocarcinoma of intestinal type is a rare variant of gastric cancer characterized by low-grade nuclear atypia, and for which the diagnostic criteria and clinical behavior are not fully established. This study presents a detailed histologic, immunohistochemical, and clinical analysis of 21 cases. Nuclear atypia was mild in all cases. Characteristic architectural features of this gastric adenocarcinoma variant were pit and glandular anastomosis, spiky glands, distended glands, discohesive cells, abortive glands, and glandular outgrowth. At least three of these features were present in all the cases. Retrospective review of preoperative biopsies in 18 patients revealed that half of the biopsies were originally reported as negative or indeterminate for malignancy. On the basis of immunohistochemical stains for intestinal (MUC2, CD10, and CDX-2) and gastric (MUC5AC and MUC6) markers, 11 (52%) cases had an intestinal immunophenotype and 10 (48%) cases had a mixed immunophenotype. Foci of discohesive neoplastic cells, indicating dedifferentiation toward a poorly cohesive carcinoma, were observed exclusively in neoplasms of mixed immunophenotype (n=5). All patients with follow-up but one were alive without disease at a mean of 19 months (range 1-60 months). One individual with a pT4 tumor with associated poorly cohesive carcinoma died of disease. In summary, very well-differentiated gastric adenocarcinomas are diagnostically challenging. Architectural features are critical to making the diagnosis. Cases with pure intestinal immunophenotype have not been associated with transformation into poorly cohesive carcinoma, and appear to behave as biologically low grade. Those with mixed immunophenotype appear more likely to dedifferentiate and behave more aggressively.

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients

“…From the pathologic point of view, the upgrade frequency from HGN at initial EFB to carcinoma in final ESD specimens is the highest in the cohort, illustrating an urgent need for establishment of diagnostic criteria for carcinoma among pathologists with limited small EFB tissues. For example, very well differentiated adenocarcinoma is rarely diagnosed in EFB in China and requires further investigations in Chinese patients to minimize the under-diagnosis rate at initial EFS [23].…”

Distinct expression profile of key molecules in crawling-type early gastric carcinoma

“…Crawling-type adenocarcinoma (CRA) is a rare variant of gastric cancer (GC) that is characterized by low-grade nuclear atypia and irregularly fused glands [1,2]. The characteristic histological details are as follows: (1) cytologically low-grade or extremely well-differentiated tumor cells resembling intestinal metaplasia; (2) growth in architecturally tortuous, branching, anastomosing, distending, abortive and spiky patterns with glandular outgrowth; and (3) topographically, tumor glands distributed predominantly in the middle third of the stomach with occasional signet-ring cells [2]. In prior literature, the distinguishing architectural features were referred to as a ''shaking-hands structure,'' ''WHYX pattern,'' and ''crawling type'' [1,3,4].…”

Clinicopathology of Early Gastric Carcinoma: An Update for Pathologists and Gastroenterologists

“…In histopathology, most early tubular adenocarcinomas originate in the isthmus/neck of a gastric unit along the lesser curvature in the distal stomach [13,20]. A pathologic diagnosis of early tubular adenocarcinoma requires 2 essential histology features [20,21,22]: (1) nuclear dysplastic changes with hyperchromasia, nuclear enlargement in the size of 3-4 naïve small lymphocytes, high nuclear-to-cytoplasmic ratio, marked pleomorphism, increased mitotic figures with atypical forms, prominent nucleoli, and cellular immaturity; and (2) architectural abnormalities with a spectrum of growth patterns at low power view, such as anastomosing, fusing, branching, cribriforming, budding, back-to-back crowding, microcysts, disunion, spiky glands with sharp projections, single cell clusters, abortive glands, and necrotic debris in the gland lumens. Recognition of the morphologic characteristics of early tubular adenocarcinoma is crucial in small biopsies to guide patient triage and management, as most patients with early tubular adenocarcinoma are treated by endoscopic, rather than surgical resection in East Asian countries.…”