{"paper_id":"2c9d69e5-2412-486b-9dab-bbefafff303a","body_text":"Aggressive Rectal Signet Ring Cell Carcinoma Presenting With Extensive Lymph Node Metastasis A Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Aggressive Rectal Signet Ring Cell Carcinoma Presenting With Extensive Lymph Node Metastasis A Case Report and Literature Review Olga Salam Ramahi, Yahya Kayed AbuJwaid, Kareem Istetieh, Shaker Nayeif Sehweil, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8936056/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Signet ring cell carcinoma (SRCC) of the colorectum is a rare and biologically aggressive subtype of adenocarcinoma, characterized by diffuse infiltrative growth, abundant intracytoplasmic mucin, and an unfavorable prognosis. Owing to its nonspecific clinical presentation, the disease is frequently diagnosed at an advanced stage. We report the case of a 63-year-old male with a strong family history of malignancy who presented with progressive abdominal distension, altered bowel habits, mucus discharge, and significant unintentional weight loss. Notably, he denied rectal bleeding or tenesmus. Colonoscopic evaluation revealed a near-obstructing circumferential lesion at the rectosigmoid region, and histopathological analysis confirmed a poorly differentiated signet ring cell carcinoma. Despite normal tumor markers and absence of distant metastases on imaging, the patient demonstrated extensive regional lymph node involvement. The patient underwent total mesorectal excision with colorectal anastomosis and protective diverting ileostomy. Final pathology revealed transmural tumor invasion with lymphovascular involvement and metastases in 14 of 18 resected lymph nodes (pT3N2). This case highlights the insidious presentation and aggressive regional spread of colorectal SRCC, even in the absence of classical alarm symptoms or elevated tumor markers. It underscores the importance of maintaining a high index of suspicion and supports consideration of individualized, and potentially more extensive, surgical approaches in selected patients with this rare histologic subtype. Signet ring cell carcinoma Rectal cancer Colorectal cancer Total mesorectal excision Lymph node metastasis Case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Colorectal cancer is one of the most common malignancies worldwide, yet it encompasses a spectrum of histological subtypes with distinct clinical behaviors and prognostic implications. Among these, signet ring cell carcinoma (SRCC) represents an exceptionally rare entity, accounting for less than 1% of all colorectal cancers ( 1 ). This variant is defined histologically by tumor cells containing abundant intracytoplasmic mucin that displaces the nucleus to the periphery, producing the characteristic “signet ring” morphology. Although more frequently encountered in the stomach, SRCC of the colorectum—particularly when arising in the rectum—is uncommon, biologically aggressive, and often diagnosed at an advanced stage ( 2 ). The clinical course of colorectal SRCC differs markedly from that of conventional adenocarcinoma. Patients typically present with nonspecific symptoms, including vague abdominal pain, alterations in bowel habits, anorexia, or progressive weight loss ( 3 ). Because these manifestations overlap with benign gastrointestinal conditions, diagnosis is frequently delayed until obstructive symptoms or systemic deterioration occur. Radiological findings such as colonic wall thickening may raise suspicion; however, histological confirmation remains essential. Several studies have reported that, at the time of diagnosis, the majority of colorectal SRCC cases already demonstrate advanced disease, with regional lymph node involvement and, in many cases, distant metastases ( 4 ). Prognosis in colorectal SRCC is significantly worse than in conventional adenocarcinoma. Population-based analyses have consistently demonstrated inferior survival outcomes, with reported five-year survival rates of approximately 25–30%, compared with nearly 60% for non-signet ring colorectal cancer ( 5 ). This unfavorable prognosis is thought to reflect the tumor’s aggressive biological behavior, including diffuse submucosal infiltration, early lymphovascular spread, and a propensity for peritoneal dissemination. Management of rectal SRCC remains challenging. Surgical resection is considered the cornerstone of treatment; however, high rates of early nodal involvement and circumferential resection margin positivity complicate curative intent surgery. Although chemoradiotherapy constitutes an integral component of standard rectal cancer management, SRCC has been reported to exhibit limited responsiveness to conventional treatment regimens. Consequently, increasing attention has been directed toward multimodal treatment strategies, aggressive surgical planning, and the potential role of neoadjuvant or molecularly guided therapies in selected patients ( 6 ). In this case report, we describe a 63-year-old male with a strong family history of malignancy who presented with progressive obstructive symptoms and was subsequently diagnosed with poorly differentiated rectal signet ring cell carcinoma. This case is notable for the extensive regional lymph node involvement and the decision to pursue total mesorectal excision (TME) rather than a standard low anterior resection (LAR), highlighting the ongoing clinical dilemma regarding the optimal surgical approach for this aggressive histologic subtype. By contextualizing this case within the existing literature, we aim to underscore the diagnostic, therapeutic, and prognostic challenges associated with rectal SRCC and to contribute to the limited body of reported cases. Case Presentation A 63-year-old male with a strong family history of malignancy presented with a two-month history of progressive abdominal distension, alternating constipation and diarrhea, recurrent nausea, mucus discharge, and unintentional weight loss of approximately 9 kg over the same period. He denied rectal bleeding, tenesmus, nocturnal symptoms, or vomiting. The patient had no known chronic medical illnesses and no known drug allergies. He was an active smoker with a history of approximately 20 pack-years and denied alcohol consumption. His past surgical history included previous disc surgery and cardiac catheterization in 2021 without reported complications. Four years earlier, in 2021, a screening colonoscopy had been performed and showed no significant findings. With the recent onset of obstructive gastrointestinal symptoms, initial evaluation during the current presentation included an abdominal X-ray ( Fig. 1 ), which demonstrated multiple air–fluid levels suggestive of bowel obstruction. A contrast-enhanced abdominal CT scan revealed features consistent with large bowel obstruction, including marked thickening of the colonic wall ( Fig. 2 ). Laboratory investigations showed a normal complete blood count, with a white blood cell count of 5 ×10⁹/L, hemoglobin level of 13.1 g/dL, mean corpuscular volume of 85 fL, and platelet count of 161 ×10⁹/L. Renal and liver function tests were within normal limits, including creatinine 0.66 mg/dL, BUN 12.8 mg/dL, AST 22.5 U/L, ALT 26 U/L, ALP 35 U/L, and total bilirubin 0.6 mg/dL. Inflammatory markers were elevated, with a C-reactive protein level of 17.76 mg/L. Serum tumor markers, including carcinoembryonic antigen (CEA 3.26 ng/mL), CA 19 − 9 (8.83 U/mL), and CA 15 − 3 (22 U/mL), were all within normal ranges. Given persistent obstructive symptoms, the patient underwent a diagnostic colonoscopy in April 2025. The procedure revealed a circumferential, tight stricture located at the rectosigmoid region, approximately 18 cm from the anal verge, causing near-subtotal obstruction and preventing safe advancement of the colonoscope beyond the lesion. Multiple biopsies were obtained. Due to the severity of the obstruction, a fully uncovered metallic colonic stent measuring 10 cm in length and 2.2 cm in diameter was deployed across the stricture to restore luminal patency. Histopathological examination of the biopsy specimens (aggregate 1.0 × 1.0 × 0.2 cm of soft tissue fragments) demonstrated a poorly differentiated signet ring cell carcinoma of colorectal origin (Fig. 3 and Fig. 4 ). Microscopic examination revealed diffuse infiltration by poorly cohesive malignant cells containing abundant intracytoplasmic mucin with peripherally displaced nuclei, consistent with signet ring morphology. No well-formed glandular structures were identified. A prominent desmoplastic stromal reaction was observed. Immunohistochemical staining showed positivity for CK20, focal positivity for CDX2, and negativity for CK7. Further staging with MRI of the chest and pelvis revealed no evidence of distant metastatic disease. Following decompression with the metallic stent and histologic confirmation of malignancy, the patient underwent total mesorectal excision with colorectal anastomosis and creation of a protective diverting ileostomy. Gross examination of the surgical specimen revealed a large tumor measuring 7 × 5 × 1.5 cm. Histopathological analysis demonstrated tumor invasion extending through the muscularis propria into the perirectal tissues, with evidence of lymphovascular invasion. Of 18 regional lymph nodes retrieved, 14 were positive for metastatic carcinoma, corresponding to a pathological stage of pT3N2. Following surgery, the patient had an uncomplicated postoperative recovery and was subsequently referred to the multidisciplinary oncology team. Given the pathological stage (pT3N2) and extensive nodal involvement, adjuvant treatment was recommended. The patient completed a course of adjuvant radiotherapy without significant acute complications. At follow-up visits, he reported good functional recovery, with no new gastrointestinal symptoms. Clinical assessment and available follow-up evaluations showed no evidence of disease recurrence at the time of reporting. This case illustrates a rare histologic subtype of colorectal cancer presenting with subacute obstructive symptoms and advanced disease, emphasizing the complex diagnostic and therapeutic course associated with signet ring cell carcinoma. Discussion Signet ring cell carcinoma (SRCC) of the colorectum is a rare and highly aggressive histologic subtype of adenocarcinoma, representing less than 1% of all colorectal malignancies ( 1 ). Patients with SRCC often present with nonspecific symptoms such as altered bowel habits, abdominal distension, weight loss, and abdominal pain, frequently leading to delayed diagnosis ( 7 ). In the present case, the patient was found to have a near-obstructing circumferential rectal lesion, histologically confirmed as poorly differentiated SRCC with extensive lymph node involvement (14 out of 18 lymph nodes positive), corresponding to a pathological stage of pT3N2. This presentation is consistent with previously reported patterns in which colorectal SRCC is commonly diagnosed at an advanced stage and is associated with inferior survival outcomes compared with conventional adenocarcinoma ( 8 ). Surgical resection remains the cornerstone of treatment for localized disease ( 9 ). In this case, total mesorectal excision (TME) was performed rather than a standard low anterior resection (LAR), with the aim of achieving wider circumferential margins and more comprehensive lymph node clearance. This surgical approach was guided by the recognized tendency of SRCC for diffuse infiltration and extensive lymphatic spread, rather than by histology-specific surgical guidelines. The role of adjuvant and neoadjuvant therapies in colorectal SRCC remains an area of ongoing debate. Although chemotherapy and radiotherapy constitute standard components of treatment for conventional colorectal adenocarcinoma, several retrospective studies have reported limited responsiveness in SRCC ( 6 , 9 ). Nevertheless, neoadjuvant chemoradiation has been shown to improve local control in rectal cancer, and adjuvant chemotherapy is generally recommended for stage III disease ( 10 ). The relatively poor treatment response observed in SRCC has been linked, in the literature, to distinct molecular characteristics, including higher rates of microsatellite instability (MSI), BRAF mutations, and epithelial–mesenchymal transition–related alterations such as CDH1 and SMAD4 loss ( 11 ). Compared with published series, the present case is notable for an exceptionally high nodal burden, despite the absence of distant metastatic disease on preoperative imaging. This finding highlights the potential for radiologic underestimation of disease extent in SRCC and underscores the importance of individualized surgical decision-making when aggressive histologic features are identified. In summary, colorectal SRCC represents a biologically distinct and clinically challenging entity. Early suspicion, adequate endoscopic sampling, and careful surgical planning are critical components of management. This case emphasizes the need for multidisciplinary evaluation and supports consideration of more extensive surgical approaches in selected patients with rectal SRCC, while acknowledging the current limitations of evidence guiding such decisions. Conclusion The clinical course of colorectal signet ring cell carcinoma is frequently characterized by delayed diagnosis and adverse outcomes due to its rarity, aggressive biology, and nonspecific presentation. This case illustrates how SRCC may initially mimic benign gastrointestinal conditions before manifesting as an advanced, locally invasive malignancy with extensive nodal involvement. Despite normal tumor markers and unremarkable metastatic imaging, the disease demonstrated aggressive regional spread. While surgical resection remains central to management, the optimal extent of surgery and the role of intensified multimodal therapy in rectal SRCC remain uncertain. Further prospective studies and collaborative registries are required to clarify optimal treatment strategies and improve patient outcomes. Literature review Prevalence: Rectal signet ring cell carcinoma is an exceedingly rare malignancy, accounting for approximately 0.7% of rectal cancers and about 0.9% of colorectal carcinomas overall ( 1 ). Other studies report a broader range of 0.1–2.4% for SRCC among all colorectal cancers, reflecting heterogeneity in study populations and diagnostic criteria ( 6 ). Stage at Diagnosis and Metastatic Rate: SRCC is most commonly diagnosed at an advanced stage. Data from the SEER database indicate that approximately 33% of patients present with distant metastases, compared with 20% among non-signet ring adenocarcinomas ( 1 ). Additional comparative studies have reported that up to 90% of rectal SRCC cases are stage III or IV at diagnosis ( 12 ), with multiple retrospective cohorts demonstrating advanced-stage presentation rates ranging from 75% to 91% ( 7 ). Survival Outcomes: Survival outcomes in SRCC are consistently inferior to those of conventional adenocarcinoma. The reported 5-year relative survival for rectal SRCC is approximately 24.9%, compared with 59.8% for non-signet ring colorectal cancers ( 1 ). Median survival has been reported at approximately 16.8 months, markedly lower than that observed in typical adenocarcinomas ( 1 ). Other population-based datasets have reported comparable results, with variations between colonic and rectal SRCC and across geographic regions ( 13 ). Lymph Node and Peritoneal Spread: SRCC is frequently poorly differentiated and exhibits aggressive behavior, with a high incidence of lymphovascular invasion and a recognized propensity for peritoneal dissemination. Precise estimates of dissemination rates vary across studies, reflecting differences in staging and reporting methodologies ( 6 ). Geographic Variation: While SRCC remains rare globally, higher reported incidences have been described in certain Middle Eastern cohorts, including rates of approximately 5% in Egypt and up to 18.5% in Jordan and Lebanon. These findings are likely influenced by referral bias, institutional case series, and regional diagnostic practices rather than true population-level incidence ( 6 ). Regional (Palestine) Data: A review of indexed medical literature revealed no published cases of primary rectal signet ring cell carcinoma from Palestine. This likely reflects underreporting rather than absence of disease and underscores the rarity of documented cases in the local context. Abbreviations SRCC Signet ring cell carcinoma CRC Colorectal cancer TME Total mesorectal excision LAR Low anterior resection CEA Carcinoembryonic antigen CT Computed tomography MRI Magnetic resonance imaging CRP C–reactive protein MSI Microsatellite instability Declarations Acknowledgements: None. Data availability: All data generated or analysed during this study are included in this published article. Funding: No funding sources are available. Ethics Approval The requirement of ethical approval for this study was waived by the Institutional Review Board of Al-Quds University in accordance with the Declaration of Helsinki. Consent to participate Written informed consent for participation was obtained from the patient. Consent to publish Written informed consent for publication was obtained from the patient. Competing interests: The authors declare no competing interests. Contributions: Olga Salam Ramahi contributed to the clinical management of the patient, data collection, literature review, manuscript drafting, and critical revision of the manuscript. Yahya Kayed AbuJwaid contributed to the clinical management of the patient, data collection, literature review, manuscript drafting, and supervision of the work. Kareem Istetieh contributed to manuscript drafting. Shaker Nayeif Sehweil and Sahar Ayyad contributed to supervision of the study. All authors read and approved the final version of the manuscript. References Benesch MGK, Mathieson A. Epidemiology of Signet Ring Cell Adenocarcinomas. Cancers. 2020;12(6):1544. https://doi.org/10.3390/cancers12061544 . Fu KI, Sano Y, Kato S, Saito H, Ochiai A, Fujimori T, Saito Y, Matsuda T, Fujii T, Yoshida S. Primary signet-ring cell carcinoma of the colon at early stage: A case report and a review of the literature. World J Gastroenterol. 2006;12(21):3446–9. https://doi.org/10.3748/wjg.v12.i21.3446 . Nitsche U, Zimmermann A, Späth C, Müller T, Maak M, Schuster T, Slotta-Huspenina J, Käser SA, Michalski CW, Janssen K-P, Friess H, Rosenberg R, Bader FG. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg. 2013;258(5):775–83. https://doi.org/10.1097/SLA.0b013e3182a69f7e . Hyngstrom JR, Hu CY, Xing Y, You YN, Feig BW, Skibber JM, Rodriguez-Bigas MA, Cormier JN, Chang GJ. Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol. 2012;19(9):2814–21. https://doi.org/10.1245/s10434-012-2321-7 . Chen JS, Hsieh PS, Chiang JM, Yeh CY, Tsai WS, Tang R, Changchien CR, Wu RC. Clinical outcome of signet ring cell carcinoma and mucinous adenocarcinoma of the colon. Chang Gung Med J. 2010;33(1):51–7. Nuytens F, Drubay V, Eveno C, Renaud F, Piessen G. Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma. World J Gastrointest Oncol. 2024;16(5):2141–58. https://doi.org/10.4251/wjgo.v16.i5.2141 . Weng MT, Chao KH, Tung CC, Chang HC, Shih IL, Lin BR, Shieh MJ, Shun CT, Wong JM, Wei SC. Characteristics of primary signet ring cell carcinoma of colon and rectum: a case control study. BMC Gastroenterol. 2022;22(1):173. https://doi.org/10.1186/s12876-022-02258-1 . Chen W, Cai H, Chen K, Liu X, Jiang W, Li S, Zhang Y, Chen Z, Guan G. The prognostic significance of different proportion of signet-ring cells of colorectal carcinoma. Bosnian J basic Med Sci. 2022;22(1):124–30. https://doi.org/10.17305/bjbms.2021.5856 . Tamhankar AS, Ingle P, Engineer R, Bal M, Ostwal V, Saklani A. Signet ring colorectal carcinoma: Do we need to improve the treatment algorithm? World J Gastrointest Oncol. 2016;8(12):819–25. https://doi.org/10.4251/wjgo.v8.i12.819 . Zhao Z, Yan N, Pan S, et al. The value of adjuvant chemotherapy in stage II/III colorectal signet ring cell carcinoma. Sci Rep. 2020;10:14126. https://doi.org/10.1038/s41598-020-70985-0 . Puccini A, Poorman K, Catalano F, Seeber A, Goldberg RM, Salem ME, Shields AF, Berger MD, Battaglin F, Tokunaga R, Naseem M, Zhang W, Philip PA, Marshall JL, Korn WM, Lenz HJ. Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets. Oncogene. 2022;41(26):3455–60. https://doi.org/10.1038/s41388-022-02350-6 . Chen JS, Hsieh PS, Hung SY, Tang R, Tsai WS, Changchien CR, Lin PY, Wang JY, Yeh CY. Clinical significance of signet ring cell rectal carcinoma. Int J Colorectal Dis. 2004;19(2):102–7. https://doi.org/10.1007/s00384-003-0515-y . An Y, Zhou J, Lin G, Wu H, Cong L, Li Y, Qiu X, Shi W. Clinicopathological and molecular characteristics of colorectal signet ring cell carcinoma: A review. Pathol Oncol Res. 2021;27:1609859. https://doi.org/10.3389/pore.2021.1609859 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 14 May, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers invited by journal 17 Apr, 2026 Editor invited by journal 20 Mar, 2026 Editor assigned by journal 10 Mar, 2026 Submission checks completed at journal 09 Mar, 2026 First submitted to journal 09 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-8936056\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":627948901,\"identity\":\"b1021a70-20bc-48e9-9c24-4a9cc6685fc7\",\"order_by\":0,\"name\":\"Olga Salam Ramahi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Olga\",\"middleName\":\"Salam\",\"lastName\":\"Ramahi\",\"suffix\":\"\"},{\"id\":627948903,\"identity\":\"0b3e0db2-74cf-4a93-9633-51fe7f429d26\",\"order_by\":1,\"name\":\"Yahya Kayed 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17:12:48\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":46590,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eContrast-enhanced abdominal computed tomography showing marked circumferential colonic wall thickening with features of large bowel obstruction.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8936056/v1/0cb238207d7789245045f4de.jpg\"},{\"id\":107870650,\"identity\":\"daeb0019-b49c-4770-b6bc-c3514622573d\",\"added_by\":\"auto\",\"created_at\":\"2026-04-27 07:40:15\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":243475,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eHematoxylin and eosin (H\\u0026amp;E) stain demonstrating diffuse infiltration by poorly cohesive malignant cells with abundant intracytoplasmic mucin and peripherally displaced nuclei, consistent with signet ring cell morphology.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8936056/v1/8bdf60cfee19187051158b4e.jpg\"},{\"id\":107870744,\"identity\":\"2533abee-1c80-4abe-bcd8-c56011e65425\",\"added_by\":\"auto\",\"created_at\":\"2026-04-27 07:40:31\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":155128,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eHigher magnification view (H\\u0026amp;E stain) highlighting individual signet ring cells with prominent mucin vacuoles and absence of well-formed glandular structures within a desmoplastic stromal background.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"image4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8936056/v1/65bbdad612701e1fba8399d7.jpg\"},{\"id\":108181084,\"identity\":\"11854bee-cbbc-4517-9d3e-3da941caf590\",\"added_by\":\"auto\",\"created_at\":\"2026-04-30 08:57:06\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":951331,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8936056/v1/fce55766-8a47-48f1-b3a3-c5b6178b1d07.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Aggressive Rectal Signet Ring Cell Carcinoma Presenting With Extensive Lymph Node Metastasis A Case Report and Literature Review\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eColorectal cancer is one of the most common malignancies worldwide, yet it encompasses a spectrum of histological subtypes with distinct clinical behaviors and prognostic implications. Among these, signet ring cell carcinoma (SRCC) represents an exceptionally rare entity, accounting for less than 1% of all colorectal cancers (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). This variant is defined histologically by tumor cells containing abundant intracytoplasmic mucin that displaces the nucleus to the periphery, producing the characteristic \\u0026ldquo;signet ring\\u0026rdquo; morphology. Although more frequently encountered in the stomach, SRCC of the colorectum\\u0026mdash;particularly when arising in the rectum\\u0026mdash;is uncommon, biologically aggressive, and often diagnosed at an advanced stage (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eThe clinical course of colorectal SRCC differs markedly from that of conventional adenocarcinoma. Patients typically present with nonspecific symptoms, including vague abdominal pain, alterations in bowel habits, anorexia, or progressive weight loss (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Because these manifestations overlap with benign gastrointestinal conditions, diagnosis is frequently delayed until obstructive symptoms or systemic deterioration occur. Radiological findings such as colonic wall thickening may raise suspicion; however, histological confirmation remains essential. Several studies have reported that, at the time of diagnosis, the majority of colorectal SRCC cases already demonstrate advanced disease, with regional lymph node involvement and, in many cases, distant metastases (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003ePrognosis in colorectal SRCC is significantly worse than in conventional adenocarcinoma. Population-based analyses have consistently demonstrated inferior survival outcomes, with reported five-year survival rates of approximately 25\\u0026ndash;30%, compared with nearly 60% for non-signet ring colorectal cancer (\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). This unfavorable prognosis is thought to reflect the tumor\\u0026rsquo;s aggressive biological behavior, including diffuse submucosal infiltration, early lymphovascular spread, and a propensity for peritoneal dissemination.\\u003c/p\\u003e \\u003cp\\u003eManagement of rectal SRCC remains challenging. Surgical resection is considered the cornerstone of treatment; however, high rates of early nodal involvement and circumferential resection margin positivity complicate curative intent surgery. Although chemoradiotherapy constitutes an integral component of standard rectal cancer management, SRCC has been reported to exhibit limited responsiveness to conventional treatment regimens. Consequently, increasing attention has been directed toward multimodal treatment strategies, aggressive surgical planning, and the potential role of neoadjuvant or molecularly guided therapies in selected patients (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eIn this case report, we describe a 63-year-old male with a strong family history of malignancy who presented with progressive obstructive symptoms and was subsequently diagnosed with poorly differentiated rectal signet ring cell carcinoma. This case is notable for the extensive regional lymph node involvement and the decision to pursue total mesorectal excision (TME) rather than a standard low anterior resection (LAR), highlighting the ongoing clinical dilemma regarding the optimal surgical approach for this aggressive histologic subtype. By contextualizing this case within the existing literature, we aim to underscore the diagnostic, therapeutic, and prognostic challenges associated with rectal SRCC and to contribute to the limited body of reported cases.\\u003c/p\\u003e\"},{\"header\":\"Case Presentation\",\"content\":\"\\u003cp\\u003eA 63-year-old male with a strong family history of malignancy presented with a two-month history of progressive abdominal distension, alternating constipation and diarrhea, recurrent nausea, mucus discharge, and unintentional weight loss of approximately 9 kg over the same period. He denied rectal bleeding, tenesmus, nocturnal symptoms, or vomiting. The patient had no known chronic medical illnesses and no known drug allergies. He was an active smoker with a history of approximately 20 pack-years and denied alcohol consumption. His past surgical history included previous disc surgery and cardiac catheterization in 2021 without reported complications.\\u003c/p\\u003e \\u003cp\\u003eFour years earlier, in 2021, a screening colonoscopy had been performed and showed no significant findings. With the recent onset of obstructive gastrointestinal symptoms, initial evaluation during the current presentation included an abdominal X-ray ( Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e), which demonstrated multiple air\\u0026ndash;fluid levels suggestive of bowel obstruction. A contrast-enhanced abdominal CT scan revealed features consistent with large bowel obstruction, including marked thickening of the colonic wall ( Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eLaboratory investigations showed a normal complete blood count, with a white blood cell count of 5 \\u0026times;10⁹/L, hemoglobin level of 13.1 g/dL, mean corpuscular volume of 85 fL, and platelet count of 161 \\u0026times;10⁹/L. Renal and liver function tests were within normal limits, including creatinine 0.66 mg/dL, BUN 12.8 mg/dL, AST 22.5 U/L, ALT 26 U/L, ALP 35 U/L, and total bilirubin 0.6 mg/dL. Inflammatory markers were elevated, with a C-reactive protein level of 17.76 mg/L. Serum tumor markers, including carcinoembryonic antigen (CEA 3.26 ng/mL), CA 19\\u0026thinsp;\\u0026minus;\\u0026thinsp;9 (8.83 U/mL), and CA 15\\u0026thinsp;\\u0026minus;\\u0026thinsp;3 (22 U/mL), were all within normal ranges.\\u003c/p\\u003e \\u003cp\\u003eGiven persistent obstructive symptoms, the patient underwent a diagnostic colonoscopy in April 2025. The procedure revealed a circumferential, tight stricture located at the rectosigmoid region, approximately 18 cm from the anal verge, causing near-subtotal obstruction and preventing safe advancement of the colonoscope beyond the lesion. Multiple biopsies were obtained. Due to the severity of the obstruction, a fully uncovered metallic colonic stent measuring 10 cm in length and 2.2 cm in diameter was deployed across the stricture to restore luminal patency.\\u003c/p\\u003e \\u003cp\\u003eHistopathological examination of the biopsy specimens (aggregate 1.0 \\u0026times; 1.0 \\u0026times; 0.2 cm of soft tissue fragments) demonstrated a poorly differentiated signet ring cell carcinoma of colorectal origin (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e and Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). Microscopic examination revealed diffuse infiltration by poorly cohesive malignant cells containing abundant intracytoplasmic mucin with peripherally displaced nuclei, consistent with signet ring morphology. No well-formed glandular structures were identified. A prominent desmoplastic stromal reaction was observed. Immunohistochemical staining showed positivity for CK20, focal positivity for CDX2, and negativity for CK7.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eFurther staging with MRI of the chest and pelvis revealed no evidence of distant metastatic disease.\\u003c/p\\u003e \\u003cp\\u003eFollowing decompression with the metallic stent and histologic confirmation of malignancy, the patient underwent total mesorectal excision with colorectal anastomosis and creation of a protective diverting ileostomy. Gross examination of the surgical specimen revealed a large tumor measuring 7 \\u0026times; 5 \\u0026times; 1.5 cm. Histopathological analysis demonstrated tumor invasion extending through the muscularis propria into the perirectal tissues, with evidence of lymphovascular invasion. Of 18 regional lymph nodes retrieved, 14 were positive for metastatic carcinoma, corresponding to a pathological stage of pT3N2.\\u003c/p\\u003e \\u003cp\\u003eFollowing surgery, the patient had an uncomplicated postoperative recovery and was subsequently referred to the multidisciplinary oncology team. Given the pathological stage (pT3N2) and extensive nodal involvement, adjuvant treatment was recommended. The patient completed a course of adjuvant radiotherapy without significant acute complications. At follow-up visits, he reported good functional recovery, with no new gastrointestinal symptoms. Clinical assessment and available follow-up evaluations showed no evidence of disease recurrence at the time of reporting.\\u003c/p\\u003e \\u003cp\\u003eThis case illustrates a rare histologic subtype of colorectal cancer presenting with subacute obstructive symptoms and advanced disease, emphasizing the complex diagnostic and therapeutic course associated with signet ring cell carcinoma.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eSignet ring cell carcinoma (SRCC) of the colorectum is a rare and highly aggressive histologic subtype of adenocarcinoma, representing less than 1% of all colorectal malignancies (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Patients with SRCC often present with nonspecific symptoms such as altered bowel habits, abdominal distension, weight loss, and abdominal pain, frequently leading to delayed diagnosis (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eIn the present case, the patient was found to have a near-obstructing circumferential rectal lesion, histologically confirmed as poorly differentiated SRCC with extensive lymph node involvement (14 out of 18 lymph nodes positive), corresponding to a pathological stage of pT3N2. This presentation is consistent with previously reported patterns in which colorectal SRCC is commonly diagnosed at an advanced stage and is associated with inferior survival outcomes compared with conventional adenocarcinoma (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eSurgical resection remains the cornerstone of treatment for localized disease (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e). In this case, total mesorectal excision (TME) was performed rather than a standard low anterior resection (LAR), with the aim of achieving wider circumferential margins and more comprehensive lymph node clearance. This surgical approach was guided by the recognized tendency of SRCC for diffuse infiltration and extensive lymphatic spread, rather than by histology-specific surgical guidelines.\\u003c/p\\u003e \\u003cp\\u003eThe role of adjuvant and neoadjuvant therapies in colorectal SRCC remains an area of ongoing debate. Although chemotherapy and radiotherapy constitute standard components of treatment for conventional colorectal adenocarcinoma, several retrospective studies have reported limited responsiveness in SRCC (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e). Nevertheless, neoadjuvant chemoradiation has been shown to improve local control in rectal cancer, and adjuvant chemotherapy is generally recommended for stage III disease (\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e). The relatively poor treatment response observed in SRCC has been linked, in the literature, to distinct molecular characteristics, including higher rates of microsatellite instability (MSI), BRAF mutations, and epithelial\\u0026ndash;mesenchymal transition\\u0026ndash;related alterations such as CDH1 and SMAD4 loss (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003eCompared with published series, the present case is notable for an exceptionally high nodal burden, despite the absence of distant metastatic disease on preoperative imaging. This finding highlights the potential for radiologic underestimation of disease extent in SRCC and underscores the importance of individualized surgical decision-making when aggressive histologic features are identified.\\u003c/p\\u003e \\u003cp\\u003eIn summary, colorectal SRCC represents a biologically distinct and clinically challenging entity. Early suspicion, adequate endoscopic sampling, and careful surgical planning are critical components of management. This case emphasizes the need for multidisciplinary evaluation and supports consideration of more extensive surgical approaches in selected patients with rectal SRCC, while acknowledging the current limitations of evidence guiding such decisions.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eThe clinical course of colorectal signet ring cell carcinoma is frequently characterized by delayed diagnosis and adverse outcomes due to its rarity, aggressive biology, and nonspecific presentation. This case illustrates how SRCC may initially mimic benign gastrointestinal conditions before manifesting as an advanced, locally invasive malignancy with extensive nodal involvement. Despite normal tumor markers and unremarkable metastatic imaging, the disease demonstrated aggressive regional spread. While surgical resection remains central to management, the optimal extent of surgery and the role of intensified multimodal therapy in rectal SRCC remain uncertain. Further prospective studies and collaborative registries are required to clarify optimal treatment strategies and improve patient outcomes.\\u003c/p\\u003e\\n\\u003ch3\\u003eLiterature review\\u003c/h3\\u003e\\n\\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePrevalence:\\u003c/h2\\u003e \\u003cp\\u003eRectal signet ring cell carcinoma is an exceedingly rare malignancy, accounting for approximately 0.7% of rectal cancers and about 0.9% of colorectal carcinomas overall (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Other studies report a broader range of 0.1\\u0026ndash;2.4% for SRCC among all colorectal cancers, reflecting heterogeneity in study populations and diagnostic criteria (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eStage at Diagnosis and Metastatic Rate:\\u003c/h3\\u003e\\n\\u003cp\\u003eSRCC is most commonly diagnosed at an advanced stage. Data from the SEER database indicate that approximately 33% of patients present with distant metastases, compared with 20% among non-signet ring adenocarcinomas (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Additional comparative studies have reported that up to 90% of rectal SRCC cases are stage III or IV at diagnosis (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e), with multiple retrospective cohorts demonstrating advanced-stage presentation rates ranging from 75% to 91% (\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eSurvival Outcomes:\\u003c/h2\\u003e \\u003cp\\u003eSurvival outcomes in SRCC are consistently inferior to those of conventional adenocarcinoma. The reported 5-year relative survival for rectal SRCC is approximately 24.9%, compared with 59.8% for non-signet ring colorectal cancers (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Median survival has been reported at approximately 16.8 months, markedly lower than that observed in typical adenocarcinomas (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Other population-based datasets have reported comparable results, with variations between colonic and rectal SRCC and across geographic regions (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eLymph Node and Peritoneal Spread:\\u003c/h3\\u003e\\n\\u003cp\\u003eSRCC is frequently poorly differentiated and exhibits aggressive behavior, with a high incidence of lymphovascular invasion and a recognized propensity for peritoneal dissemination. Precise estimates of dissemination rates vary across studies, reflecting differences in staging and reporting methodologies (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003ch3\\u003eGeographic Variation:\\u003c/h3\\u003e\\n\\u003cp\\u003eWhile SRCC remains rare globally, higher reported incidences have been described in certain Middle Eastern cohorts, including rates of approximately 5% in Egypt and up to 18.5% in Jordan and Lebanon. These findings are likely influenced by referral bias, institutional case series, and regional diagnostic practices rather than true population-level incidence (\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eRegional (Palestine) Data:\\u003c/h2\\u003e \\u003cp\\u003eA review of indexed medical literature revealed no published cases of primary rectal signet ring cell carcinoma from Palestine. This likely reflects underreporting rather than absence of disease and underscores the rarity of documented cases in the local context.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eSRCC\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eSignet ring cell carcinoma\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCRC\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eColorectal cancer\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eTME\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eTotal mesorectal excision\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eLAR\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eLow anterior resection\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCEA\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eCarcinoembryonic antigen\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCT\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eComputed tomography\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eMRI\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eMagnetic resonance imaging\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eCRP\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eC\\u0026ndash;reactive protein\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e \\u003cdiv class=\\\"Term\\\"\\u003eMSI\\u003c/div\\u003e \\u003cdiv class=\\\"Description\\\"\\u003e \\u003cp\\u003eMicrosatellite instability\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u003cbr\\u003e\\u003c/strong\\u003eNone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability:\\u003cbr\\u003e\\u003c/strong\\u003eAll data generated or analysed during this study are included in this published article.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003cbr\\u003e\\u003c/strong\\u003eNo funding sources are available.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics Approval\\u0026nbsp;\\u003cbr\\u003e\\u003c/strong\\u003eThe requirement of ethical approval for this study was waived by the Institutional Review Board of Al-Quds University in accordance with the Declaration of Helsinki.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent to participate\\u003cbr\\u003e\\u003c/strong\\u003eWritten informed consent for participation was obtained from the patient.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent to publish\\u003cbr\\u003e\\u003c/strong\\u003eWritten informed consent for publication was obtained from the patient.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests:\\u003cbr\\u003e\\u003c/strong\\u003eThe authors declare no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eContributions:\\u003cbr\\u003e\\u003c/strong\\u003eOlga Salam Ramahi contributed to the clinical management of the patient, data collection, literature review, manuscript drafting, and critical revision of the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003eYahya Kayed AbuJwaid contributed to the clinical management of the patient, data collection, literature review, manuscript drafting, and supervision of the work.\\u003c/p\\u003e\\n\\u003cp\\u003eKareem Istetieh contributed to manuscript drafting.\\u003c/p\\u003e\\n\\u003cp\\u003eShaker Nayeif Sehweil and Sahar Ayyad contributed to supervision of the study.\\u003c/p\\u003e\\n\\u003cp\\u003eAll authors read and approved the final version of the manuscript.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eBenesch MGK, Mathieson A. 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Sci Rep. 2020;10:14126. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1038/s41598-020-70985-0\\u003c/span\\u003e\\u003cspan address=\\\"10.1038/s41598-020-70985-0\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePuccini A, Poorman K, Catalano F, Seeber A, Goldberg RM, Salem ME, Shields AF, Berger MD, Battaglin F, Tokunaga R, Naseem M, Zhang W, Philip PA, Marshall JL, Korn WM, Lenz HJ. Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets. 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Int J Colorectal Dis. 2004;19(2):102\\u0026ndash;7. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.1007/s00384-003-0515-y\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s00384-003-0515-y\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAn Y, Zhou J, Lin G, Wu H, Cong L, Li Y, Qiu X, Shi W. Clinicopathological and molecular characteristics of colorectal signet ring cell carcinoma: A review. Pathol Oncol Res. 2021;27:1609859. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://doi.org/10.3389/pore.2021.1609859\\u003c/span\\u003e\\u003cspan address=\\\"10.3389/pore.2021.1609859\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"discover-medicine\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"\",\"sideBox\":\"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)\",\"snPcode\":\"44337\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/44337/3\",\"title\":\"Discover Medicine\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Discover Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Signet ring cell carcinoma, Rectal cancer, Colorectal cancer, Total mesorectal excision, Lymph node metastasis, Case report\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8936056/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8936056/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eSignet ring cell carcinoma (SRCC) of the colorectum is a rare and biologically aggressive subtype of adenocarcinoma, characterized by diffuse infiltrative growth, abundant intracytoplasmic mucin, and an unfavorable prognosis. Owing to its nonspecific clinical presentation, the disease is frequently diagnosed at an advanced stage.\\u003c/p\\u003e \\u003cp\\u003eWe report the case of a 63-year-old male with a strong family history of malignancy who presented with progressive abdominal distension, altered bowel habits, mucus discharge, and significant unintentional weight loss. Notably, he denied rectal bleeding or tenesmus. Colonoscopic evaluation revealed a near-obstructing circumferential lesion at the rectosigmoid region, and histopathological analysis confirmed a poorly differentiated signet ring cell carcinoma. Despite normal tumor markers and absence of distant metastases on imaging, the patient demonstrated extensive regional lymph node involvement.\\u003c/p\\u003e \\u003cp\\u003eThe patient underwent total mesorectal excision with colorectal anastomosis and protective diverting ileostomy. Final pathology revealed transmural tumor invasion with lymphovascular involvement and metastases in 14 of 18 resected lymph nodes (pT3N2).\\u003c/p\\u003e \\u003cp\\u003eThis case highlights the insidious presentation and aggressive regional spread of colorectal SRCC, even in the absence of classical alarm symptoms or elevated tumor markers. It underscores the importance of maintaining a high index of suspicion and supports consideration of individualized, and potentially more extensive, surgical approaches in selected patients with this rare histologic subtype.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Aggressive Rectal Signet Ring Cell Carcinoma Presenting With Extensive Lymph Node Metastasis A Case Report and Literature Review\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-04-26 17:12:44\",\"doi\":\"10.21203/rs.3.rs-8936056/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"reviewerAgreed\",\"content\":\"269642806556638012748969044591756608798\",\"date\":\"2026-05-14T20:39:41+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"8956404428268434386629942555232381192\",\"date\":\"2026-04-22T18:33:26+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-04-17T11:45:54+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvited\",\"content\":\"\",\"date\":\"2026-03-20T07:36:43+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-03-10T18:29:57+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-03-09T23:50:36+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Discover Medicine\",\"date\":\"2026-03-09T19:32:58+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"discover-medicine\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"\",\"sideBox\":\"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)\",\"snPcode\":\"44337\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/44337/3\",\"title\":\"Discover Medicine\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Discover Series\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"691bef97-904d-4dac-8f57-c3c9110b0d99\",\"owner\":[],\"postedDate\":\"April 26th, 2026\",\"published\":true,\"recentEditorialEvents\":[{\"type\":\"reviewerAgreed\",\"content\":\"269642806556638012748969044591756608798\",\"date\":\"2026-05-14T20:39:41+00:00\",\"index\":79,\"fulltext\":\"\"}],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-04-26T17:12:44+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-04-26 17:12:44\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8936056\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8936056\",\"identity\":\"rs-8936056\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}