Colorectal Signet-ring Cell Carcinoma Research Articles

Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma.

Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. To provide an updated overview of risk factors, prognosis, and management of CSRCC. A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.

Individualized prediction of conditional survival for colorectal signet-ring cell carcinoma patients.

Conditional survival (CS) considers the time already survived after surgery and may provide additional survival information. The authors sought to construct and validate novel conditional survival nomograms for the prediction of conditional overall survival (OS) and cancer-specific survival (CSS) of colorectal signet-ring cell carcinoma (SRCC) patients. Patients diagnosed with stage I-III SRCC between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The formula calculating CS was: CS(x|y) = S(x+y)/S(x), where S(x) represents the survival at x years. CS nomograms were then constructed to predict the 5-year conditional OS and CSS, followed by internal validation. A total of 944 colorectal SRCC patients were finally identified in this study. The 5-year OS and CSS improved gradually with additional survival time. Univariate and multivariate Cox regression analysis conducted in training set revealed that age, race, T stage, LNR, and perineural invasion were independent risk factors for both OS and CSS. Two nomograms with considerable predictive ability were successfully constructed [area under the curve (AUC) for OS: 0.788; AUC for CSS: 0.847] and validated (AUC for OS: 0.773; AUC for CSS: 0.799) for the prediction of 5-year OS and CSS, based on the duration of 1-4 years post-surgery survival. The probability of achieving 5-year OS and 5-year CSS in colorectal SRCC patients improved gradually with additional time. Conditional nomograms considering survival time will be more reliable and informative for risk stratification and postoperative follow-up.

Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes.

Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

A novel log odds of positive lymph nodes–based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study

PurposeConsidering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan–Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis.ResultsA total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III–IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients.ConclusionThe integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Spatial Epidemiology of Signet-ring Cell Colorectal Cancer in India.

Signet-ring cell colorectal carcinoma (SRCC) is an extremely aggressive yet uncommon histologic subtype of colorectal cancer (CRC) with an unknown etiology. There is a stark difference in the prevalence of signet cancers between Western countries and the Indian subcontinent; however, India itself is a vast and diverse country with variable cancer incidence. To study the spatial epidemiology of SRCC in India for identifying regions with high prevalence. This retrospective study included all patients diagnosed with colorectal adenocarcinoma at Tata Memorial Hospital, the largest colorectal cancer referral unit in India, between January 2020 and December 2022. Geocoding based on the location of the residence was done to map the incidences. Comparisons were performed between the proportion of signet cell and non-signet colorectal cancers. A total of 4100 patients with colon or rectal adenocarcinomas were included, of which signet cell histology was found in 624 (15%) patients. SRCC accounted for the highest proportions of CRCs in the Central (19%) and Northern (19%) regions, and the lowest in the North-Eastern (10%) and Western (12%) regions of India (P < 0.001), with non-overlapping confidence intervals. Compared with patients with non-signet CRCs, those with SRCC more commonly had colon cancers (22% vs. 17%; P = 0.003) and belonged to a lower socioeconomic background (67% vs. 59%; P < 0.001). This study found that SRCCs accounted for a significant proportion of CRC cases in India, but there was no substantial disparity in distribution across regions.

A nomogram for the prediction of survival for colorectal signet ring cell carcinoma after surgery: A population-based study.

The aim was to construct and verify a nomogram-based assessment of cancer-specific survival (CSS) in patients with colorectal signet ring cell carcinoma after surgery. Patients were collected from Surveillance, Epidemiology, and End Results program between 2004 and 2015. Independent prognostic indicators were determined in the training cohort by Cox regression model. We identified 2217 eligible patients, who were further categorized into the training set (n = 1693) as well as the validation set (n = 524). Multivariate analysis revealed that age at diagnosis, gender, grade, tumor size, T stage, N stage, and M stage were independent predictive indicators. Then, the above 7 predictive factors were incorporated into a nomogram model to assess CSS, which showed good calibration and discrimination capacities in both sets. Both internal and external calibration plot diagrams revealed that the actual results were consistent with the predicted outcomes. The time-independent area under the curves for 3-year and 5-year CSS in the nomogram were larger than American Joint Committee on Cancer and Surveillance, Epidemiology, and End Results summary stage system. Moreover, decision curve analysis indicated the clinical utility of the nomogram. The nomogram demonstrated favorable predictive accuracy of survival in colorectal signet ring cell carcinoma patients after surgery, which should be further confirmed before clinical implementation.

Early Images of Colorectal Signet Ring Cell Carcinoma.

Early Images of Colorectal Signet Ring Cell Carcinoma.

Clinicopathologic and prognostic factors of patients with T3/T4 colorectal signet ring cell carcinoma: a population-based study

BackgroundTo evaluate cancer-specific survival (CSS) and construct a nomogram to predict the CSS of patients with colorectal signet ring cell carcinoma (SRCC).MethodsThe data for patients with colorectal SRCC from 2000 to 2019 was identified from Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to minimize bias between SRCC and adenocarcinoma patients. Kaplan–Meier method and log-rank test were used to estimate the CSS. A nomogram was constructed based on the independent prognostic factors identified by univariate and multivariate Cox proportional hazards regression analyses. The model was evaluated by receiver operating characteristic (ROC) curves and calibration plots.ResultsPoor CSS was more common in patients with colorectal SRCC, especially in patients with T4/N2 stage, tumor size > 80 mm, grade III-IV, and chemotherapy. Age, T/N stage, and tumor size > 80 mm were identified as independent prognostic indicators. And a prognostic nomogram was constructed and validated as an accurate model for the CSS of patients with colorectal SRCC by ROC curves and calibration plots.ConclusionPatients with colorectal SRCC have a poor prognosis. And the nomogram was expected to be effective in predicting the survival of patients with colorectal SRCC.

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

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. 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. 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. 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.

Diagnosis and Progression of Rectal Signet Ring Cell Carcinoma in a 15 Year Old Lebanese Boy: A Case Report

Introduction: Colorectal cancer (CRC) is a rare entity in children and adolescents compared to adults. In the young, it is mostly detected in the right and transverse parts of the colon. Among the variants of CRC are the uncommon Signet Ring Cell Carcinoma (SRCC) which has a late presentation and pessimistic prognosis. Patients are asymptomatic for a long time and suddenly develop changes in bowel habits or obstruction. Case Report: A 15-year-old boy with no known health issues presented with recent rectorrhagia and weight loss. He was stable but pale with abdominal tenderness and no rectal mass on digital rectal examination (DRE). Colonoscopy unveiled a 13 centimeters segment of circumferential ulcerated blackish mucosa extending from the upper rectum to the rectosigmoid junction. Pathology studies revealed SRCC of the rectum and sigmoid. Metastatic workup showed rectosigmoid wall thickening and denoted the tumor a stage IV with ascites and intraperitoneal implants. Palliative treatment with chemotherapy was initiated, and a follow-up CT was done later to assess disease progression and response to treatment. The disease had worsened and the patient deteriorated. Conclusion: In children, colorectal SRCC is scarce and usually presents at a late stage due to the lack of characteristic symptoms and findings. It is then usually missed by physicians and not considered in the differential thus delaying the diagnosis and rendering the prognosis poorer. To improve the outcome, pediatricians ought to keep CRC in mind when facing obstructive symptoms or refractory abdominal pain.

Prognostic value of log odds of positive lymph nodes, lymph node ratio, and N stage in patients with colorectal signet ring cell carcinoma: A retrospective cohort study.

Little attention has been paid in the prognosis of colorectal signet ring cell carcinoma (SRCC). This study aims to explore the predictive capacity of log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in the prognosis of patients with colorectal SRCC. A retrospective cohort study was designed, and data were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Data on demographic characteristics, clinicopathological features, and treatment were extracted. Outcomes were overall survival (OS) and cancer-specific survival (CSS). Association of LODDS, LNR, and pN stage with OS and CSS were explored using Cox proportional hazard model and Cox competing risk model, respectively, with results showing as hazard ratio and 95% confidence interval (CI). Predictive performance of LODDS, LNR, and pN stage in OS and CSS was assessed by calculating C-index. A total of 2,198 patients were included in this study. LODDS, LNR, and pN stage were associated with the OS and CSS of colorectal SRCC patients (all P < 0.05). LODDS showed a good performance in the OS (C-index: 0.704, 95% CI: 0.690-0.718), which was superior to LNR (C-index: 0.657, 95% CI: 0.643-0.671) and pN stage (C-index: 0.643, 95% CI: 0.629-0.657). The C-index of LODDS, LNR, and pN stage for CSS was 0.733 (95% CI: 0.719-0.747), 0.713 (95% CI: 0.697-0.729), and 0.667 (95% CI: 0.651-0.683), respectively. LODDS displayed a better predictive capacity in the OS and CSS than LNR and pN stage, indicating that LODDS may be effective to predict the prognosis of colorectal SRCC in the clinic.

S2190 A Case of Colorectal Signet Ring Cell Carcinoma Presenting as Ulcerative Recto-Sigmoiditis and Stricture

Introduction: Signet ring cell carcinoma accounts for about one percent of all colorectal cancers. It is an aggressive subtype of adenocarcinomas with the tendency for intramural spread and peritoneal carcinomatosis. Here, we reported a middle-aged male with circumferential colonic stenosis and inconclusive histology, found to have stage 4 colorectal signet ring cell carcinoma (SRCC). Case Description/Methods: A 41-year-old male without significant past medical history was referred to a gastroenterology clinic with bright red blood per rectum. Colonoscopy showed ulcerative recto-sigmoiditis with rectal bleeding, and there was stricture in the rectum, in the recto-sigmoid colon, and from anus to descending colon (Figure A). Biopsy was obtained from the stricture. The pathology revealed granulation tissue and abundant fibrinopurulent exudate showing small clusters, and individual atypical cells stained positive for CDX-2 immunostain. Unfortunately, the patient subsequently lost follow-up. Three months later, the patient was hospitalized for small bowel obstruction. CT showed markedly enlarged heterogeneous and edematous rectum, an abnormal mass within the posterior pelvis/rectum, retroperitoneal and pelvic lymphadenopathy with thickening and nodularity of the peritoneum. Biopsy was obtained from an inguinal lymph node with histological examination showing metastatic adenocarcinoma composed of poorly cohesive signet-ring cells (Figure B). Immunostains revealed that the neoplastic cells were strongly and diffusely positive for CDX2 and CK20 while negative for CK7, confirming a colorectal primary. Accordingly, the diagnosis of colorectal signet ring cell carcinoma was made. Discussion: The colonoscopic findings of colorectal SRCC could be nonspecific as diffuse circumferential thickening, stricture, or ulcerations. Typical pathological features may not appear on the initial biopsy sample. Immunohistochemical testing could help increase diagnostic yield and early identification of cancer cells. Our case hallmarked the importance of close follow-up for abnormal diffuse stricture and ulcerations in the colorectal area. These lesions may need to be rebiopsied, co-screened with abdominal imaging, and undergo an immunohistochemical investigation to characterize pathology further.Figure 1.: A: Colonoscopy: An intrinsic inflammatory circumferential fibrosis friable severe stenosis measuring 20cm (in length) * 9 mm (inner diameter) was found in the rectum, in the recto-sigmoid colon, and from anus to descending colon. B: Hematoxylin & eosin stain of tissue from lymph node showed metastatic adenocarcinoma composed of poorly cohesive signet-ring cells.

Predictors of Long-Time Survivors in Nonmetastatic Colorectal Signet Ring Cell Carcinoma: A Large Population-Based Study.

Background Colorectal signet ring cell carcinoma (SRCC) is a rare and distinct subtype of colorectal cancer (CRC), with extremely poor prognosis and aggressive tumor biological behavior. In this study, we aimed to analyze the clinicopathological characteristics and to identify the independent predictors of long-time survivors (LTSs) of nonmetastatic colorectal SRCC. Methods Patients diagnosed with nonmetastatic colorectal SRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared and analyzed the clinicopathological characteristics between LTSs (patients survived over 5 years) and non-LTSs (patients survived of or less than 5 years). Afterwards, multivariate logistic regression analysis was used to identify independent predictors of LTSs, which were further used to construct a nomogram model to predict the probability of being LTSs. Results We enrolled 2050 patients with nonmetastatic colorectal SRCC, consisting of 1441 non-LTSs and 609 LTSs. Multivariate logistic regression analysis revealed that race, marital status, tumor infiltration, lymph node involvement, and primary tumor treatment were independent predictors of LTSs. In addition, these five parameters were incorporated into a nomogram model to predict the probability of being LTSs. In terms of the model performance, the calibration curve revealed good agreement between observed and predicted probability of LTSs, and receiving operator characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion Collectively, we analyzed and profiled the clinicopathological characteristics of LTSs in patients with nonmetastatic colorectal SRCC. Race, marital status, T stage, N stage, and primary tumor treatment were independent predictors of LTSs.

Colorectal signet-ring cell carcinoma treated with FOLFOX plus panitumumab.

Colorectal signet-ring cell carcinoma treated with FOLFOX plus panitumumab.

Metastatic Breast Signet-Ring Cell Carcinoma from a Colonic Primary: Review of a Rare Case Report

Introduction: Colonic signet-ring cell carcinoma is a distinctive rare subtype of adenocarcinoma with a predilection for early metastasis. Among the rare extramammary metastatic adenocarcinomas to the breast, colonic signet-ring cell carcinomas constitute a small percentage. The distinction of a primary from a secondary breast signet-ring cell carcinoma is indispensable since it may result in different therapeutic approaches. Here we presented a rare case of metastatic breast signet-ring cell carcinoma from a rectal origin and review its distinctive histopathologic features. Case Presentation: A 37-year-old woman presented with a breast mass 3 months after undergoing low anterior resection surgery to remove a rectal mass, diagnosed as signet-ring cell carcinoma. Histopathologic examination of the core needle breast mass biopsy revealed tumor cells with signet-ring cell cytomorphology. The performed immunohistochemistry confirmed carcinoma of colonic origin. Conclusions: Colorectal signet-ring cell carcinoma is a rare and aggressive tumor. Its metastatic spread is most seen in the intra-abdominal area, with seldom reported cases of breast metastasis. Histologically, it can mimic a primary breast carcinoma, especially if no prior history of colonic origin exists. Accurate diagnosis is important since these two entities carry different therapeutic management. Proper immunophenotyping, obtaining a thorough clinical history and imaging studies facilitate a correct diagnosis.

S1736 A Case of Primary Signet Ring Cell Carcinoma in a Colon Polyp on Routine Colonoscopy

Introduction: Colon polyp size contributes significantly to the assigned surveillance interval for prevention of colorectal carcinoma (CRC). Polyps ≤5-mm generally have a negligible risk of malignancy and colonic invasion (< 1%) and are often amenable to standard endoscopic resection. We present a patient undergoing her index average risk screening colonoscopy found to have rare colorectal primary signet ring cell carcinoma (SRCC) in a 5-mm polyp, necessitating surgery. Case Description/Methods: A 52-year-old Hispanic female with hypertension presented for her first routine screening colonoscopy. She denied a family history of gastrointestinal malignancy and was otherwise asymptomatic. A 5-mm, Paris Is sessile polyp was noted in the sigmoid colon (Image 1a) and was resected en-bloc with a cold snare. Histology showed poorly differentiated, invasive adenocarcinoma with signet ring cells (Image 1d). A staging abdominopelvic CT scan did not reveal pathologic lymphadenopathy or distant metastatic disease. Based on the histological findings and imaging, the patient returned for a flexible sigmoidoscopy to tattoo the lesion, and then underwent robotic-assisted laparoscopic sigmoid colectomy. There was no evidence of malignancy in the surgical pathology specimen. Discussion: SRCC is an epithelial malignancy with prominent intracytoplasmic mucin typically found in gastric glandular cells. Colorectal primary SRCC is a rare clinical entity accounting for 1% of all CRCs. It is often detected at an advanced stage, and therefore its overall prognosis is worse than other types of CRC. Risk factors for lymph node metastasis in pT1 polyps invading the submucosa include deep submucosal invasion for sessile lesions, poor differentiation, lymphovascular invasion, rectal location, tumor budding/mucinous tumors and the presence of either positive or indeterminate resection margins. The decision regarding surgical intervention after endoscopic resection of pT1 colorectal polyps is a complex one and depends upon the risk of residual cancer in the bowel wall and metastatic spread to adjacent or remote lymph nodes. Studies suggest that endoscopic resection before surgical resection of a high-risk pT1 CRC has no adverse effects on morbidity and mortality. In SRCC, factors such as advanced age, higher tumor grading and size, primary tumor location and nodal involvement are significantly correlated with a poor prognosis, thus, as seen in our patient, immediate colectomy provides the highest chance of survival.Figure 1.: A computed tomography scan of the abdomen exhibited diffuse fluid-filled dilatation of the colon with wall thickening and peri-colonic haziness, most prominent in the sigmoid colon and rectum. Chronic bilateral hydronephrosis and chronic cystitis were present as well.

Trends in the Incidence and Survival Rates of Colorectal Signet-Ring Cell Carcinoma in the South Korean Population: Analysis of the Korea Central Cancer Registry Database.

Objective: Signet-ring cell carcinoma (SRCC) is a rare histopathological subtype of colorectal cancer (CRC) constituting approximately 1% of CRC cases. This study analyzed the incidence and survival rates of colorectal SRCC. Methods: We analyzed the incidence and survival rates of colorectal SRCCs based on patients’ data of the Korea Central Cancer Registry. Results: The age-standardized incidence rates of colon and rectum SRCC in 2017 were 0.17 and 0.07 individuals per 100,000, respectively. Between 1993 and 2017, the 1-, 2-, 3-, 4-, and 5-year relative survival rates of patients with colon SRCC were 65.6%, 49.0%, 38.9%, 34.9%, and 33.0%, respectively, while those of patients with rectum SRCC were 69.6%, 47.8%, 38.5%, 32.8%, and 29.4%, respectively. According to the Surveillance, Epidemiology, and End Results summary stages, the 5-year relative survival rates of colon SRCC between 1993 and 2017 were 70.4% for the localized stage, 41.0% for the regional stage, and 7.0% for the distant stage, while those for rectum SRCC were 60.7%, 34.4, and 3.3%, respectively. Conclusions: Although the incidence of colorectal SRCC is extremely low in South Korea, it has been increasing in recent decades. As the prognosis of colorectal SRCC is extremely poor; clinicians should be aware of the differential diagnosis of SRCC in colorectal cancer cases.

Clinicopathological and Molecular Characteristics of Colorectal Signet Ring Cell Carcinoma: A Review.

Colorectal signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC) with unique characteristics. Due to the limited researches on it, a comprehensive and in-depth understanding of this subtype is still lacking. In this article, we summarize the clinicopathological features and molecular characteristics of colorectal SRCC based on a literature review. Clinically, SRCC has been associated with young age, proximal site preference, advanced tumor stage, high histological grade, high rate of lymph node involvement, frequent peritoneal metastasis, and a significantly poor prognosis. Regarding molecular characteristics, in SRCC, the mutation burden of the classic signaling pathways that include WNT/β-catenin, RAS/RAF/MAPK, and PI3K/AKT/mTOR signaling pathways are generally reduced. In contrast, some genes related to the “epithelial-mesenchymal transition (EMT) process” and the “stem cell properties”, including RNF43, CDH1, and SMAD4, as well as the related TGF-β signaling pathway have been observed more frequently altered in SRCC than in conventional adenocarcinoma (AC). In many studies but not in others, SRCC showed a higher frequency of BRAF mutation, microsatellite instability-high (MSI-H) and CpG island methylator phenotype (CIMP) positive status compared to AC. It has been proposed that colorectal SRCC consists of two subtypes, in which the MSI+/CIMP+/BRAF +/CD3+/PD-L1+ hypermethylated genotype is more common in the proximal colon, and may represent the potential candidate for immunotherapy. Understanding the special molecular mechanisms related to the aggressive biology of SRCC is of great importance, which may provide a theoretical basis for the development of more targeted and effective treatments for this refractory disease.

The prognostic significance of different proportion of signet-ring cells of colorectal carcinoma.

While the prognosis of patients with partial signet-ring cell carcinoma (PSRCC) has been rarely reported, colorectal signet-ring cell carcinoma (SRCC) has been associated with poor prognosis. The aim of this study was to analyze the prognosis of patients with different signet-ring cell (SRC) composition and establish a prediction model. A total of 91 patients with SRC component were included in the study. These patients were divided into two groups: SRCC group (SRC composition >50%; n = 41) and PSRCC group (SRC composition ≤50%; n = 50). COX regression model was used to identify independent prognostic factors for overall survival (OS). A predictive nomogram was established and compared with the 7th American Joint Committee on Cancer (AJCC) staging system. After a median follow-up of 16 months, no significant difference in OS was observed in either group. Pre-operative carcinoembryonic antigen level, pN stage, M stage, pre-operative ileus, and adjuvant chemotherapy were independent prognostic risk factors for OS (p < 0.05). A nomogram for predicting the OS of colorectal SRCC was established with a C-index of 0.800, and it showed better performance than that of the 7th AJCC staging system (p < 0.001). In summary, the ratio of SRC component was not an independent prognostic factor of the OS. Those patients with <50% of SRC component should be given the same clinical attention. A predictive nomogram for survival based on five independent prognostic factors was developed and showed better performance than the 7th AJCC staging system. This resulted to be helpful for individualized prognosis prediction and risk assessment.