Signet Ring Cell Colorectal and Appendiceal Cancer: A Small Signet Ring Cell Component Is Also Associated with Poor Outcome

Abstract

Background: Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size.

Methods: All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist.

Results: Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively.

Conclusions: The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.

Keywords: appendiceal cancer; colorectal cancer; peritoneal metastases; signet ring cells.

Figure 1

Scatterplot of signet ring cell component (%) and extracellular mucin component (%) in colorectal and appendiceal cancer (n = 51). Group 1 ≥ 50% signet ring cells, any extracellular mucin component; Group 2 ≤ 50% signet ring cells, <50% extracellular mucin; Group 3 ≤ 50% signet ring cells, ≥50% extracellular mucin.

Figure 2

The primary tumour localization of signet ring cell colorectal and appendiceal cancer. Colours represent histopathological characteristics of the primary tumour (signet ring cell component or extracellular mucin component). In four patients, the exact localization of the primary tumour was unknown.

Figure 3

The sites of synchronous metastases in patients with stage IV colorectal and appendiceal cancer, separated into signet ring cell tumours (n = 26) and non-signet ring cell tumours (n = 515). The colour grading indicates if patients had one or multiple sites of metastases. In cases of multiple sites, the patient was included in two or more sites.

Figure 4

(a) Overall survival (OS) for patients with signet ring cell tumours and non-signet ring cell tumours. (b) OS in patients with adenocarcinoma (AC), mucinous adenocarcinoma (MAC), and signet ring cell tumours. Only patients with information on extracellular mucin were included. (c) OS in patients with adenocarcinoma (AC), mucinous adenocarcinoma (MAC), and signet ring cells ≥50% or <50% of the tumour tissue. (d) Signet ring cell tumour patients separated based on the extent of signet ring cells and extracellular mucin: Group 1 ≥ 50% signet ring cells, any extracellular mucin component; Group 2 ≤ 50% signet ring cells, <50% extracellular mucin; Group 3 ≤ 50% signet ring cells, ≥50% extracellular mucin.

Figure 5

(a) Recurrence-free survival in patients with adenocarcinoma (AC), mucinous adenocarcinoma (MAC), and signet ring cell tumours. Only patients with information on extracellular mucin were included. (b) Patients with signet ring cell tumours were categorized based on signet ring cells comprising ≥50% or <50% of the tumour tissue.