State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments

Figures & data

Figure 1 WHO classification of all types of gastric tumors, including signet ring cell carcinoma.

Figure 2 Genes with most frequent alterations in signet ring cell carcinoma.

Figure 3 Proposed management algorithm for patients with SRCC.

Abbreviation: SRCC, signet ring cell carcinoma; MDT, multidisciplinary team; ESR, endoscopic submucosal dissection.

Table 1 Characteristics of different studies, indicating the observed treatment effects in SRCC patients

Study characteristics	Treatment type	Treatment effects	Reference
822 EGC lesions from 789 probands: 498 differentiated cancer, 65 weakly differentiated cancer, 91 signet ring cells, 26 weakly differentiated with SRCC, 41 mixed, 10 medullary cancers, and 91 weakly cohesive cancers were investigated	Endoscopic treatment	Postoperation biopsies showed the aggressiveness of SRCC in EGC, and the results displayed that SRCC is not more aggressive than differentiated cancer and may be considered a candidate for endoscopic treatment	Kang et al, 2017^Citation50
A retrospective study was performed on 12 cases of early signet ring cell gastric cancer with average age of 61 years. Majority of the lesions were stage T1a (83%), some were also T1b (17%). The mean lesion size was 1.4 cm	Magnification endoscopy with narrow band imaging	Using standard endoscopy, all probands displayed a pale, flat lesion without occurrence of mucosal abnormality, like elevation, ulceration, or depression. Investigating magnification endoscopy with NBI, irregularities in the glands and microvasculature consistent with early gastric cancer were characteristic within the observed group. Additionally, “stretch sign”, an elongation or expansion of the architectural structure was detected	Phalanusitthepha et al, 2015^Citation66
The main goal of the study was to assess the factors related to incomplete resection in signet ring cell early gastric cancer; a retrospective analysis was conducted on 126 patients, who had undergone endoscopic submucosal dissection between 2007 and 2012	Endoscopic submucosal dissection	Multivariate analysis highlighted that large tumor size was the only important factor related to incomplete resection. Moreover, large tumor size was the only significant factor concerning endoscopic size underestimation. The rate of endoscopic size underestimation was preferably higher in tumors with a size ≥20 mm	Kim et al, 2014^Citation67
Among 3,010 patients operated on for GA, patients with pTis or pT1 tumors were chosen and compared between the SRCC and non-SRCC groups. The main goal was to compare the 5-year survival rate between groups	Total gastrectomy	SRCC morphologic subtype is not a negative prognostic factor in early GC in comparison to more advanced GC; better survival could be related to the younger age of SRCC patients	Gronnier et al, 2013^Citation49
The retrospective study encompassed 769 patients with gastric carcinoma who underwent gastrectomy, including 42.4% with early gastric cancer and 57.6% with advanced gastric cancer	Subtotal gastrectomy	Patients with SRCC displayed close clinicopathological features with undifferentiated histology; the survival of SRCC cases reflected a better prognosis in patients with undifferentiated GC; among AGC patients, SRCC patients had a worse prognosis than other cell types	Kwon et al, 2014^Citation34
Study of patients with early gastric cancer with differentiated and signet ring-cell histology undergoing surgery was performed	Gastrectomy	Patients with early gastric cancer with signet ring celltype histology can be best treated by gastrectomy with lymph node dissection	Lee et al, 2010^Citation46
The study was done on a cohort of 618 patients randomized during surgery to subtotal (315) or total (303) gastrectomy, with no intraperitoneal or distant spread, no less than 6 cm from the proximal edge of the tumou to the cardia, and it was possible to remove the tumor entirely	Total and subtotal gastrectomy	Both types of gastrectomy have similar survival probability; however, the authors suggested that subtotal gastrectomy might be a better option, which has been associated with an improved nutritional status and quality of life	Bozzetti et al, 1999^Citation68

Abbreviations: AGC, advanced gastric cancer; EGC, early gastric cancer; GA, gastric adenocarcinoma; NBI, narrow band imaging; pTI, tumor invades lamina propria or submucosa; pTis, carcinoma in situ: intraepithelial tumor without invasion of the lamina propria/high grade dysplasia; SRCC, signet ring cell carcinoma.

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