Signet Ring Cell Carcinoma Of Colon Research Articles

Signet-ring cell carcinoma of the transverse colon in a 10-year-old girl: A case report

BACKGROUND Signet-ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer. The incidence of primary colonic SRCC is relatively rare in pediatric patients, with a limited number of reported cases currently available. The prognosis for this specific tumor type is unfavorable, and the preoperative diagnosis presents challenges, potentially leading to misdiagnosis. This case report describes the diagnosis of primary SRCC in the colon of a 10-year-old girl. CASE SUMMARY The patient was admitted to the hospital due to abdominal pain and vomiting. A computed tomography scan revealed an irregular mass with soft tissue density in her transverse colon, showing uneven density and multiple calcifications. The patient underwent surgical resection of the affected bowel and lymph node dissection, which was confirmed by pathological examination to be SRCC infiltrating both nerves and the entire intestinal wall. Additionally, tumor thrombus formation was observed in blood vessels and lymphatic vessels, multiple cancerous nodules were found in the omentum, and metastasis to 18 of 26 mesenteric lymph nodes examined. Immunohistochemistry for mismatch repair gene protein demonstrated microsatellite stability. No mutations in KRAS , NRAS , BRAF , or PIK3CA genes were detected through molecular pathology analysis. After surgery, she received standard chemotherapy for 8 cycles without tumor progression or other abnormalities during a 12-month follow-up period. CONCLUSION Primary colonic SRCC is a rare malignant tumor with atypical clinical symptoms, and timely identification and intervention are crucial for improving the prognosis.

The tumor immune microenvironment features and their prognostic value in rectal and sigmoid colon signet-ring cell carcinoma.

3544 Background: Signet-ring cell carcinoma (SRCC) of the rectum and sigmoid colon is a rare and highly malignant challenge in clinical practice. Although high PD-1+CD8+ tumor-infiltrating lymphocyte (TIL) infiltration has been reported as a positive prognostic factor in gastric cancer, pancreatic cancer, etc., its role in colorectal SRCC remains unclear. This study aims to explore the immune landscape of colorectal SRCC and its prognostic implications. Methods: The study included 34 patients with stage II-IV SRCC of the rectum and sigmoid colon. The immune contextures of tumor tissues were characterized using multiplex immunofluorescence assays and compared with a cohort of 57 cases of stage II-IV AC. The ratio density and spatial distribution of CD3+, CD8+, PD-1+, PD-L1+ cells, M1/M2 macrophages, and NK cells were quantitively analyzed in both parenchymal (p) and interstitial (i) regions. Characteristics of immune cell infiltration and their prognostic value for long-term survival were investigated in SRCC cases. Results: Compared to AC, SRCC exhibited significantly higher infiltration of CD8+ and CD3+ iTILs in the interstitial region (P=0.00024; P=0.00321, respectively) and elevated CD8+ pTILs infiltration in tumor parenchyma (P=0.041). Conversely, parenchymal infiltration of TILs co-expressing PD-1 was significantly lower in SRCC than AC (PD-1+CD8+ pTILs: P=0.00035; PD-1+CD3+ pTILs: P=5.0e-05). SRCC showed significantly lower infiltration of M1 macrophages in both parenchyma and interstitium (P=0.0035; P=5.4e-09, respectively), lower interstitial infiltration of M2 macrophages (P=1.5e-05), and a borderline lower parenchymal infiltration of M2 macrophages (P=0.0522), compared to AC. Additionally, patients with high parenchymal or interstitial infiltration of PD-1+CD8+ TILs exhibited significantly longer DFS (P=0.00024; P=0.0041, respectively) and OS (P=0.011; P=0.0044, respectively) than those with low infiltration. Multivariate analysis indicated that the level of PD-1+CD8+ pTILs infiltration is an independent prognostic factor for DFS, being independent of CEA levels and TNM stage (P = 0.018; P = 0.02, respectively). Among patients with normal CEA level or of stage II-III, high level of PD-1+CD8+ pTILs infiltration was still associated with significantly improved DFS (P<0.0001; P=0.00018, respectively) and OS (P=0.00021; P<0.0001, respectively). Conclusions: SRCC of rectum and sigmoid colon exhibits distinct immune profiles compared to conventional AC, characterized by higher infiltration of CD8+ and CD3+ TILs, but lower infiltration of PD-1+CD8+ TILs. The unique immune landscape in SRCC, particularly the level of PD-1+CD8+ TILs infiltration and its positive predictive value for DFS and OS, provides new perspectives for immune-based stratification and therapeutic strategies for this clinically significant cancer subtype.

Propensity-Score Matched Analysis of Survival Outcomes of Adjuvant Therapy in Stage II-III Signet-Ring Cell Carcinoma of the Colon

BackgroundColonic signet ring cell carcinoma (SRCC) is a mucinous adenocarcinoma subtype often associated with poor prognosis. This study assessed the survival benefits of adjuvant therapy after curative resection of stage II-III colonic SRCC. MethodsThis was a retrospective analysis of outcomes of adjuvant therapy in colonic SRCC using National Cancer Database (2010-2019) data. Patients who received adjuvant therapy were matched to those who did not use the nearest neighbor propensity-score matching. The primary outcome was 5-year overall survival (OS). ResultsThe unmatched cohort included 3530 patients. Patients who received adjuvant therapy were significantly younger, more often male, and more often had Charlson scores 0-1, left-sided cancers, stage III disease, lymphovascular invasion, and perineural invasion. The matched cohort included 958 patients (53.6% female); 479 received adjuvant therapy and 479 did not. Adjuvant therapy was associated with longer mean OS (39.9 vs. 29.2 months; P < .001). Survival benefit of adjuvant therapy was evident in stage III disease (37.5 vs. 24.7 months; P < .001), right-sided colon cancer (40.2 vs. 27.7 months; P < .001), and transverse colon cancer (40.6 vs. 31.1 months; P = .002), but not stage II disease (52.1 vs. 53.1 months; P = .694) or left-sided colon cancer (35.8 vs. 32.6 months; P = .417). Independent predictors of improved OS were adjuvant therapy (HR: 0.539; P < .001), laparoscopic surgery (HR: 0.829; P = .001), robotic-assisted surgery (HR: 0.63; P = .007), and number of harvested lymph nodes (HR: 0.976; P < .001). ConclusionsAdjuvant therapy was associated with improved OS in stage III, right-sided, and transverse colon SRCC. The survival benefit of adjuvant therapy in stage II and left-sided colon SRCC was limited.

Comparative analysis of tumor biology and prognosis in mucinous and signet-ring cell colon cancers versus classical adenocarcinoma.

Background: Limited information is currently available on the natural history and prognosis of two distinct histological subtypes of adenocarcinoma (AC) in the colon: mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC). Therefore, the aim of this study is to examine the clinicopathological characteristics of colon MAC and SRCC, comparing them to classical AC, using a large cohort of cases from the United States. Methods: Patients diagnosed with colon AC, MAC, or SRCC from the SEER database between 2000 and 2018 were included in our study. Incidence trends, patient demographics, tumor characteristics, treatment, and survival were analyzed. Results: In our study, we analyzed a total of 310,813 patients with colon cancers, including 271,382 cases of classical AC, 34,750 cases of MAC, and 4,681 cases of SRCC. Over the study period, we observed a decline in the age-adjusted incidence rates of colon AC, MAC, and SRCC. Notably, the MAC and SRCC cohorts differed significantly from AC in terms of patient characteristics, tumor locations, and treatment patterns. Patients with MAC and SRCC had poorer survival outcomes compared to those with AC. Factors associated with worse survival included older age, male sex, poorly differentiated tumors, advanced stage, and the presence of MAC or SRCC histology. On the other hand, surgical intervention was associated with improved survival. Conclusion: Our study underscores the significance of recognizing the distinct features and outcomes associated with different histological subtypes of colon cancer. Further research is warranted to delve into the underlying biological traits that contribute to these differences and to develop more tailored treatment strategies.

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.

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.

Prognostic value of tumor-infiltrating lymphocytes in signet-ring cell carcinoma of the rectum and sigmoid colon.

e15079 Background: Signet-ring cell carcinoma (SRCC) of rectum and sigmoid colon is an extremely rare subtype of colorectal cancer (CRC) with very poor prognosis. Tumor-infiltrating lymphocytes (TILs) signify the host immune response to tumors, which were reported to predict survival outcomes of patients with various cancer types. In this study, we aimed to characterize TILs and mutational features of SRCC of rectum and sigmoid colon as well as their correlations with the clinicopathological parameters and survival outcomes. Methods: 28 patients with stage II-IV SRCC of rectum and sigmoid colon were included, in which 12 patients had tumors with ≥50% signet-ring cells (SRCs) and 16 had tumors with &lt;50% SRCs. Targeted next generation sequencing using a 1,021-gene panel was used to investigate the genetic alterations of tumor tissue. Multiplex immunofluorescence assays were performed to visualize TILs. TILs within cancer cell nests (iTILs) and in cancer stroma (sTILs) were counted separately. The correlations of TILs with survival outcomes were analyzed in stage II/III patients who underwent the radical resection. Results: Somatic alterations were detected in all the 28 cases. The most frequently mutated genes included TP53, APC and SMAD4, occurring in 68%, 36% and 36% of cases, respectively. BRAF mutation were detected in only one patient (3.6%). The median tumor mutational burden (TMB) was 4.80 (range, 0.96-42.24) muts/Mb. Three patients (10.7%) were with microsatellite instability-high (MSI-H) status and a high TMB of more than 10 muts/Mb. Patients with stage IV tumors have significantly lower PD-1+ CD8+ iTILs and sTILs (p=0.018 for both), CD8+ iTILs (p=0.022), and PD-1+ iTILs (p=0.013) levels than those with stage II/III tumors. Tumors with ≥ 50% SRCs showed lower levels of CD8+ sTILs than those with &lt; 50% SRCs (p=0.046). Patients with CEA&gt;5.0 ng/ml showed significantly lower levels of PD-1+ CD8+ iTILs than those with CEA≤5.0 ng/ml (p=0.015). Moreover, significantly lower levels of PD-1+ CD8+ sTILs (p=0.036) were observed in tumors that appeared as long circumferential thickening of the bowel wall with stenosis compared to those did not. Multivariate analysis indicated that patients with high PD-1+ CD8+ iTILs and sTILs levels had significantly better disease-free survival (DFS) than those with low PD-1+ CD8+ iTILs and sTILs levels (not reached vs. 22 months for both; p=0.008 and 0.003, respectively). High PD-1+ CD3+ sTILs levels were associated with significantly longer overall survival (OS) compared to low levels (not reached vs. 39 months, p=0.034). No correlation between MSI or TMB and DFS or OS was observed in this small cohort. Conclusions: Our results demonstrated that PD-1+ CD8+ iTILs and sTILs are powerful independent predictors of survival outcomes in patients with resectable SRCC of rectum and sigmoid colon. Further investigations in larger cohorts are needed to validate our findings.

Superior survival in right-sided versus left-sided colon signet ring cell carcinoma

This study aimed to explore the association of tumor sidedness with the prognosis of patients with colon signet ring cell carcinoma (SRCC). Eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with left-sided colon SRCC and those with right-sided lesions. A total of 2660 patients were included, among them, 1983 (74.5%) had right-sided colon SRCC. Compared to patients with left-sided colon SRCC, those who had the right-sided colon SRCC showed higher proportion of white race, female, aged ≥ 65 years, receiving total colectomy and ≥ 4 regional lymph node dissection; while had lower proportion of advanced AJCC stage. Besides, right-sided patients exhibited superior 5-year CSS (32.74% vs. 25.89%, P = 0.001) and OS (27.38% vs. 23.02%, P = 0.024) rates compared with left-sided ones. Multivariate analysis revealed that tumor sidedness was an independent prognostic factor. To be specific, patients with right-sided colon SRCC showed better CSS (HR: 0.873; 95% CI 0.777–0.981; P = 0.023) and OS (HR: 0.838; 95% CI 0.753–0.965; P = 0.002). Moreover, subgroup analysis demonstrated superior CSS and OS for right-sided patients in most subgroups. Tumor sidedness was an independent prognostic indicator for colon SRCC. Besides, patients with right-sided colon SRCC have superior prognosis than those with left-sided lesions.

A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application.

Colon signet-ring cell carcinoma (SRCC) is a rare type of malignant dedifferentiated adenocarcinomas, and is associated with poor survival. However, an in-depth study of the biological features of SRCC is hindered by the lack of a reliable in vitro model of colon SRCC. Thus, the establishment of cell cultures from SRCC has become the most challenging task. Here, by harnessing the power of the organoid culture system, we describe the establishment of a human colon SRCC organoid line from a surgical sample from one patient with colon SRCC. The colon SRCC organoid line, YQ-173, was characterized for morphology, histology, ultrastructure and chromosome stability levels, showing that it resembles the histological and growth characteristics of the original tumor cells; xenografts were used to show that it also has a high tumor formation rate. RNA sequencing of YQ-173 compared with the normal tissue verified its mucinous nature. Capture-based targeted DNA sequencing combined with drug screening based on a bespoke 88 compound library identified that JAK2 might be a treatment target. An in vitro drug screening found that AT9283 and Pacritinib could be effective JAK2 inhibitors, which was consistent with the in vivo xenograft response. We report, for the first time, the establishment of an SRCC organoid line allowing in-depth study of SRCC biology, as well as a strategy to assess in vitro drug testing in a personalized fashion.

A Novel Human Colon Signet-Ring Cell Carcinoma Organoid Line: Establishment, Characterization and Application

Background: Colon signet-ring cell carcinoma (SRCC) is a rare type of malignant dedifferentiated adenocarcinomas, and associated with poor survival. However, an in-depth study of the biological features of colon SRCC is hampered by lack of in vitro model. Our study was designed to establish and characterize cell cultures from SRCC for further translational and biological research. Methods: By harnessing the power of organoid culture system, we established a human colon SRCC organoid line from surgical sample of one patient with colon SRCC. The organoid line was characterized at the morphology, histology, ultrastructure, chromosome stability level and its tumorigenic ability was verified by xenografts. Capture-based targeted DNA sequencing combining with drug screen based on a bespoke 88 compound library identified the possible target and the treatment response was confirmed by in vivo organoid system and in vitro xenografts. Findings: Our data showed that the colon SRCC organoid line, YQ-173, resemble histological and growth characteristics of the original tumor cells and have high tumor formation rate. DNA sequencing indicated JAK2 might be the treatment target. In vitro drug screen found that AT9283 and Pacritinib could be the effective JAK2 inhibitors, which was consistent with in vivo xenografts' response. Interpretation: We report, for the first time, the establishment of SRCC organoid line allowing in-depth study of SRCC biology, as well as a strategy to assess in vitro drug testing in a personalized fashion. Funding: This work was supported by National Natural Science Foundation of China (31470826, 31670858, 81672374), Science and Technology Commission of Shanghai Municipality (16411966300), and Shanghai Sailing Program (19YF1409500). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: The tissue was obtained with informed consent for experimentation with the patient and this study was approved by the ethical committee of Fudan University Shanghai Cancer Center. All animal experiments were performed according to the guidelines for the care and use of laboratory animals and were approved by Institutional Animal Care and Use Committee of Fudan University.

Metastatic Gastric Cancer Presenting as Periorbital Edema

A 53 year old male presented with recent labs and imaging concerning for periorbital cellulitis. The patient was initially admitted by ophthalmology and managed with antibiotics. He displayed minimal improvement with antibiotics, leading to the addition of systemic steroids. His condition deteriorated the following day when he developed hematemesis. Antibiotics were therefore escalated with the addition of IV Pantoprazole, and steroids were discontinued. EGD showed a large, non-bleeding ulcer with a visible vessel in the gastric body. Small, clean-based ulcers were also seen in the body and antrum. Diffuse, friable mucosa was noted throughout the stomach and biopsies were taken due to concern for malignancy. Right orbital biopsy and CT chest/abdomen/pelvis was also ordered to further evaluate for malignancy. CT showed bilateral pulmonary emboli, retroperitoneal soft tissue infiltrates, and bladder and colonic wall thickening. The patient's hematemesis recurred, necessitating repeat EGD with epinephrine injections and bipolar cautery in order to achieve hemostasis. Gastric biopsies revealed invasive and poorly differentiated Signet Ring Cell Carcinoma (SRCC) with a background of severe ulcerated gastritis and H. pylori. Antibiotics were de-escalated and tailored to treat H. Pylori. Colonoscopy was performed given CT findings of circumferential stenosis within the ascending and transverse colon. Colonic and right orbit biopsies were consistent with metastatic SRCC. The patient was discharged home after the initial work up with future plans for orbital radiation, chemotherapy initiation, and repeat EGD. The number of cases of gastric SRCC has steadily increased over the last few decades, despite an overall decline in incidence in gastric cancer worldwide. SRCC is a distinct diffuse-type gastric adenocarcinoma based on its histological and clinical features. Patients typically present in advanced stages and carry a poor prognosis. Synchronous SRCC is rare, although the colon appears to be the most common synchronous cancer associated with gastric SRCC. Gastric SRCC has a predilection for metastasis to the peritoneum, lung, bladder, and in rare cases the optic nerve. H. Pylori may be associated with SRCC; treatment of H. Pylori improves mucosal healing and may aid in interventional therapies. This case represents a unique presentation of an advanced stage synchronous gastric and colonic SRCC.2661_A Figure 1. Periorbital edema of the right eye.2661_B Figure 2. Malignant ulcer with visible vessel and active bleeding. Friable mucosa surrounding ulcer.2661_C Figure 3. Orbital biopsy showing metastatic signet ring cell carcinoma (H&E, 400x).

Prognosis and efficiency of adjuvant therapy in resected colon signet-ring cell carcinoma

Prognosis and efficiency of adjuvant therapy in resected colon signet-ring cell carcinoma

Prognosis and efficiency of adjuvant therapy in resected colon signet-ring cell carcinoma

Background: Colon signet-ring cell carcinoma (SRCC) is associated with poor survival compared with other histologic subtypes such as adenocarcinoma (AC) and mucinous adenocarcinoma (MC). This present study analyzed the prognosis factors of SRCC and assessed whether the adjuvant therapy could supply benefit for SRCC with different regimens. Methods: Data on 82,606 colon cancer patients who received surgery in the period 1992–2005 was included in this population-based study. The survival benefit was evaluated using a Cox proportional hazards model and propensity score (PS)-matched techniques. Results: SRCC was found in 779 (0.9%) patients who were more frequently in stage III and IV colon cancer than other subtypes. The 5-year survival of SRCC patients were 30.1% (95% CI, 26.7–33.5) which was significantly lower compared with 51.6% (95% CI, 51.3–52.0) for AC and 48.8% (95% CI, 47.8–49.8) for MC. For patients in stage II, there was no significantly difference between chemo group and no-chemo group in all histologic subtypes. The results in stage III showed that 5-FU based adjuvant chemotherapy for AC and SRCC patients could improve overall survival (OS) which could be further enhanced by adding oxaliplatin. The similar benefit was found in stage IV patients. However, there was no significantly difference between different therapy regimens in stage IV SRCC patients. Conclusions: Although the prognosis of patients with colon SRCC was pessimistic, the effective role of adjuvant therapy for OS was still observed in stage III SRCC patients who received surgery. Similarly, patients with stage IV SRCC could also gain benefit from systemic therapy.

Metastatic Gastric Signet Ring Cell Carcinoma Mimicking Crohnʼs Disease

Signet-ring cell carcinoma (SRCC) is an adenocarcinoma characterized by mucin-producing cells and most commonly arises in the stomach. Colonic SRCC can share features of colitis, including long segments of concentric bowel wall thickening and ulcerated mucosa with regions of sparing. We describe a rare case of metastatic gastric SRCC mimicking Crohn’s disease. Our patient underwent 2 colonoscopies, and biopsies revealed chronic active inflammation with no evidence of malignancy. The diagnosis of SRCC was only made after colectomy was performed for recurrent bowel obstruction.

Survival in signet ring cell carcinoma varies based on primary tumor location: a Surveillance, Epidemiology, and End Results database analysis

ABSTRACTBackground: The aim of this study was to investigate the survival of patients with signet ring cell carcinoma (SRCC) based on primary tumor location.Methods: Patient data were obtained from the Surveillance, Epidemiology, and End Results database (1988–2012) with ≥200 cases per tumor location. Cox regression analysis was used to investigate prognostic factors of cause-specific survival (CSS).Results: We identified 24,171 patients. Of the patients, 63.4% had gastric SRCC, followed by colon (18.2%), esophageal (5.0%), rectal (3.5%), lung (3.1%), pancreatic (1.8%), breast (1.5%), bladder (1.3%), small intestine (1.1%), and gallbladder SRCC (1.0%). The 5-year CSS was 22.1%, 69.0%, 33.2%, 28.1%, 24.8%, 16.1%, 13.6%, 12.6%, 11.0%, 6.4% in patients with gastric, breast, colon, rectum, bladder, small intestine, esophageal, gallbladder, lung, and pancreatic SRCC, respectively (P < 0.001). Multivariate analyses showed that the primary tumor location was an independent prognostic factor of survival. Patients with lung, small intestine, and bladder SRCC had a comparable CSS to gastric SRCC, while breast and colorectal SRCC had better survival than gastric SRCC. Esophageal, gallbladder, and pancreatic SRCC were significantly associated with poor CSS compared with gastric SRCC.Conclusion: Our study suggests a major difference in survival of SRCC based on the primary tumor locations.

Metastatic Gastric Signet Ring Cell Carcinoma Mimicking Crohnʼs Disease

Background: Signet-ring cell carcinoma (SRCC) is a rare adenocarcinoma characterized by mucin producing cells that commonly arises in the stomach. Here we describe the first case of metastatic gastric SRCC mimicking Crohn's disease (CD). Case: A 40 year-old Puerto-Rican man without significant medical history presented to another facility with 3 months of abdominal pain, associated with loose brown stool, and 20 lbs. weight loss. Stool studies were negative and computed tomography (CT) revealed thickening of the transverse and descending colon. Colonoscopy showed marked mucosal inflammation with stenosis starting at 30 cm from the anal verge and extending to the distal transverse colon. Biopsies were negative for malignancy. Over the course of a year the patient was repeatedly admitted for obstructive symptoms. Due to concern for inflammatory bowel disease (IBD), mesalamine and high dose prednisone therapy was initiated and later escalated to azathioprine and infliximab with minimal relief. Subsequent imaging and colonoscopy showed no significant changes beyond a few terminal ileum ulcers. At our institution, magnetic resonance enterography (MRE) showed a thickened transverse colon without the previously noted mesenteric stranding. The patient underwent a total colectomy with ileorectal anastomosis. Pathology revealed a poorly differentiated carcinoma with signet-ring cell features involving the hepatic flexure, transverse, and proximal descending colon. Immunohistochemical staining favored metastatic disease. Upper endoscopy confirmed the suspected gastric origin. Discussion: Primary gastric signet-ring cell carcinoma is an uncommon diagnosis that presents at a younger age and often late in the disease course. Colonic SRCC can share features of colitis including long segments of concentric bowel wall thickening and ulcerated mucosa with regions of sparing. Our patient underwent two colonoscopies with biopsies showing no evidence of malignancy. This misdiagnosis is likely due to endoscopic sampling error and resulted in treatment for presumed CD. The diagnosis of SRCC was only made after the colectomy was performed. Our case typifies some of the challenges of endoscopists and pathologists in detecting colonic neoplasia in younger populations which impacts survival. Physicians need to have a higher index of suspicion for malignancy in patients with presumed IBD that present with high-risk strictures, and are refractory to conventional treatment.Figure 1Figure 2

Colonic carcinoma metastatic to the left testis, epididymis &amp; spermatic cord

A 27 yr old man was admitted to the department of Surgery, Wenzhou Central Hospital, Wenzhou, Zhejiang, PR China, in May 2014 with a complaint of left scrotal swelling for 15 years. He had a history of signet-ring cell carcinoma of the splenic flexure colon (Fig. 1) and underwent radical left hemicolectomy in December 2010, during which a preoperative computed tomography (CT) showed the only hydrocele of tunica vaginalis in the left scrotum (Fig. 2A). The current physical examination revealed mild left testicular tenderness with hydrocele of the testis. Routine laboratory tests revealed no abnormality. The ultrasonography of the left testis done prior to refrerral to our hospital showed testis spermatic cord hydrocele complicating local thickening of the tunica vaginalis and testicular microlithiasis-like lesions. CT (Fig. 2B) diagnosis was left testis tumour and hydrocele of tunica vaginalis. The patient underwent a left radical orchiectomy. Histopathological examination and immunohistochemistry (IHC) staining (Fig. ​(Fig.3A3A-​-D)D) revealed metastatic colonic signet-ring cell carcinoma of the left testis (Fig ​(Fig4A,4A, ​,B),B), epididymis (Fig. 4C) and spermatic cord (Fig. 4D). The patient was followed up for nine months after his surgery. He showed no evidence of other regional metastatic colonic carcinoma.

Colorectal signet-ring cell carcinoma: Responsive to adjuvant chemotherapy but still a poor prognosis.

529 Background: Colorectal signet-ring cell carcinoma (SRCC) has been associated with a poor survival compared to mucinous adenocarcinoma (MC) and the common adenocarcinoma (AC). Prognostic impact of tumor localization is unknown and efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyses prognostic impact of SRCC and determines whether SRCC patients benefit from adjuvant chemotherapy for colon cancer equally compared with AC. Methods: Data on 196,757 patients with CRC in the Netherlands in the period 1989 and 2010 was included in this nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. Results: SRCC was found in 1.0% of CRC patients. SRCC patients presented more frequently with stage III or IV disease than AC (75.2% versus 43.6%, P&lt;0.0001) and SRCC was more frequently found in the proximal colon (57.7% versus 32.0%, P&lt;0.0001). SRCC patients had a poor 5-year relative survival of 31% in colon and 20% in the rectum compared to 57% and 59% in AC (P&lt;0.0001). This poorer survival for SRCC was found in stage II, III and IV. In comparison with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. Conclusions: Prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but colonic SRCC patients seem to benefit from adjuvant chemotherapy equally compared with AC. Reduced efficacy of adjuvant chemotherapy therefore does not seem to explain the poor outcome in SRCC patients. We recommend to adhere to adjuvant treatment guidelines for all histological subtypes, but encourage clinical trials to take histological subtype into account for stratification.

Critical Analysis of 33 Patients with Peritoneal Carcinomatosis Secondary to Colorectal and Appendiceal Signet Ring Cell Carcinoma

Primary signet-ring cell carcinoma (SRC) of colorectal and appendiceal origin is a rare entity with an aggressive biology and clinical behavior. The majority of patients develop peritoneal carcinomatosis (PC) early in the disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may potentially improve survival. An observational study of 33 patients with SRC of colorectal or appendiceal origin was identified through a retrospective review of two peritoneal surface malignancy databases between January 1997 and December 2008. Survival analysis was performed using the Kaplan-Meier method. Thirty-three patients (18 women (55%); mean age at diagnosis of carcinomatosis, 49 (standard deviation = 12) years) were identified to have SRC, with 15 cases of colorectal and 18 of appendiceal origin. For patients with colonic SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 13 and 18 months (P = 0.75). For patients with appendiceal SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 27 and 15 months (P = 0.12). There seems to be less survival benefits after a complete CRS and HIPEC as a curative treatment for PC from colorectal SRC compared with that for non-SRC colorectal adenocarcinoma. However, in patients with appendiceal SRC, long-term survival is a reality after treatment.

Primary Stomach and Colon Signet Ring Cell Carcinoma Immunohistochemical Staining Patterns Using CDX2, MUC2 and Muc6

Primary Stomach and Colon Signet Ring Cell Carcinoma Immunohistochemical Staining Patterns Using CDX2, MUC2 and Muc6