Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma

Abstract

Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005–2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

Consensus on the pathological definition and classification of poorly cohesive gastric carcinoma

“…Currently, one can only speculate that the cumulative effect of the adverse behaviours of intestinal and diffuse-type gastric carcinoma is responsible for the greater biological aggressiveness of mixed-type gastric carcinoma compared to "pure" intestinal and diffuse gastric carcinoma [26][27][28][29][30][31][32][33]. The level of existing evidence is too low for a definitive conclusion.…”

Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications

“…Mixed GC, defined by a dual pattern of differentiationglandular/solid (intestinal) and isolated-cell carcinoma (diffuse) -carried, in a multivariate analysis, significantly worse prognosis than the 2 main types of the Laurén classification [18,27]. As further proof, several authors demonstrated that mixed GCs display more aggressive features than "pure" intestinal and diffuse GCs, including larger tumour size, deeper invasion, lymphatic invasion, and lymph node metastases [27][28][29][30][31]. Interestingly, mixed GC shows a dual metastatic pattern (hematogenous metastases and peritoneal dissemination with lymph node metastases), suggesting a cumulative effect of the adverse behaviours of intestinal and diffuse-type GC [32].…”

“…The recognition of this morphological entity is important, as it carries a bad prognosis compared to intestinal and diffuse GC (see Morphological Heterogeneity of GC, above). However, previous studies have shown that preoperative endoscopic biopsies have a limited value in predicting the presence of both components [29,31,87]. This is a clear example of how ITH may limit the correct pathological diagnosis and patient prognostic evaluation.…”

Endoscopic management of patients with early gastric cancer before and after endoscopic resection: A review

“…Second, mixed‐type EGC can be simply classified as predominantly differentiated (MD) or predominantly undifferentiated (MU) types. Various studies have investigated the risk of LNM in these two types of EGC . Mita and Shimoda compared the clinicopathological features of submucosal differentiated EGC with and without LNM, and found that the rate of LNM in mixed EGC was higher, which was further identified in the multivariate analysis .…”