Submucosal-dominant, stricture-type rectosigmoid adenocarcinoma with false-negative biopsies: a case report

Submucosal-dominant, stricture-type rectosigmoid adenocarcinoma with false-negative biopsies: a case report | 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 Submucosal-dominant, stricture-type rectosigmoid adenocarcinoma with false-negative biopsies: a case report Yuejun Han, Zhi Chen, Xiangping Wu, Ketao Jin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8383724/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Endoscopic biopsy is the standard for diagnosing colorectal cancer. However, infiltrative tumors presenting as annular strictures may yield non-diagnostic samples, risking significant treatment delay. Case presentation: An 82-year-old man presented with loose stools and hematochezia. Colonoscopy revealed a tight, non-traversable rectosigmoid stricture; repeated mucosal biopsies were negative for malignancy. Contrast-enhanced computed tomography (CT) demonstrated concerning features, including circumferential mural thickening, luminal narrowing, and small pericolic nodules. Due to persistent high clinicoradiologic suspicion despite negative biopsies, the patient underwent laparoscopic low anterior resection. Final histopathology confirmed a moderately-to-poorly differentiated adenocarcinoma, staged as pT3N1c, with lymphovascular invasion, perineural invasion, and intermediate tumor budding. Conclusions This case highlights the diagnostic limitations of superficial mucosal biopsy in submucosal-dominant, stricturing colorectal lesions. It underscores the critical importance of multidisciplinary, probability-driven decision-making when histologic findings contradict strong clinical and imaging evidence of malignancy. In such scenarios, proceeding to timely surgical resection is paramount to avoid progression to emergency presentation and to facilitate appropriate adjuvant therapy. Colorectal cancer False-negative biopsy Diagnostic dilemma Stricture Multidisciplinary team Tumor deposits Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Colorectal cancer (CRC) ranks as the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide( 1 ). In 2022, it accounted for approximately 9.6% of global cancer incidence and 9.3% of cancer deaths( 2 ). Obstructing or near-obstructing tumors represent a clinically challenging subgroup, often diagnosed at more advanced stages and associated with poorer outcomes, particularly when management occurs under emergency conditions( 3 , 4 ). Accurate and timely preoperative diagnosis is therefore essential to optimize treatment pathways and survival. While colonoscopic forceps biopsy is the first-line modality for tissue diagnosis, its sensitivity is notably reduced in stenotic or infiltrative tumors that proliferate beneath a deceptively normal-appearing mucosa. A recent large cohort study reported initial sampling error—defined as benign or non-diagnostic histology in ultimately confirmed cancers—in approximately 22.6% of cases, a factor independently associated with prolonged time to definitive surgery( 5 ). Earlier studies on neoplastic polyps similarly documented false-negative biopsy rates of up to 18.5% when compared with final surgical specimens, highlighting the inherent limitations of superficial sampling( 6 ). Contemporary clinical guidelines, including those from the National Comprehensive Cancer Network (NCCN), emphasize the need for prompt evaluation of obstructing or highly suspicious strictures. They advocate for diagnostic escalation—through repeat or deeper sampling, advanced endoscopic techniques, or direct resection—when histologic results are discordant with compelling clinicoradiologic evidence of malignancy( 7 ). We present a case involving a short-segment, circumferential rectosigmoid stricture characterized by repeatedly negative biopsies but high radiologic suspicion, which was ultimately confirmed as a pT3N1c adenocarcinoma. This scenario epitomizes a high-stakes diagnostic dilemma and demonstrates the value of a pragmatic, multidisciplinary approach where integrative clinical and imaging assessment rightfully overrides falsely reassuring biopsy findings. Case presentation An 82-year-old man presented with a one-month history of loose stools and one week of frank hematochezia. He reported no associated abdominal pain, weight loss, or fever. Physical examination was notable only for the presence of fresh blood on digital rectal examination. Routine laboratory investigations, including complete blood count and coagulation profile, were within normal limits. Serum tumor markers were not elevated (carcinoembryonic antigen < 1.7 ng/mL; CA 19 − 9: 2.8 U/mL). A non-contrast chest CT scan revealed no evidence of distant metastases. A contrast-enhanced abdominal CT demonstrated a short-segment, circumferential wall thickening at the rectosigmoid junction with significant luminal narrowing and the presence of small pericolic nodules suspicious for regional lymph node involvement (Fig. 1 ). Subsequent colonoscopy identified a fixed, annular, non-traversable stricture without an exophytic mass (Fig. 2 ). Multiple mucosal biopsies were obtained from the stricture site; all were reported as negative for malignancy. Given the persistently high radiological suspicion and the characteristic endoscopic appearance of the stricture, the case was reviewed at a multidisciplinary tumor board (MDT). Consensus was reached to proceed with definitive surgical management. The patient subsequently underwent an uncomplicated laparoscopic low anterior resection. Pathological findings Gross examination of the resected specimen revealed a firm, annular stricture measuring 2.5 × 2.5 × 2.0 cm (Fig. 3 ). Histopathological analysis confirmed a moderately-to-poorly differentiated adenocarcinoma infiltrating through the muscularis propria into the pericolorectal tissue, consistent with pT3 staging (Fig. 4 A, B). All surgical margins were negative for tumor involvement. Examination of nine retrieved lymph nodes showed no evidence of metastasis (0/9). However, three discrete tumor deposits were identified in the pericolic fat, meeting the criteria for pN1c staging according to the American Joint Committee on Cancer (AJCC) 8th edition. Additional high-risk pathological features included lymphovascular invasion, perineural invasion, and intermediate tumor budding (Bd2). Immunohistochemical profiling demonstrated proficient mismatch repair (pMMR) status, diffuse strong nuclear overexpression of p53 (mutant pattern), a high Ki-67 proliferation index (~ 70%), and a CK20+/CDX2+/SATB2+/CK7- immunophenotype. HER2 expression was scored as 1+ (negative). Outcomes and follow-up The patient's postoperative recovery was uneventful, and he was discharged on the seventh postoperative day. In light of the final stage IIIB (pT3N1c) disease and the presence of multiple adverse pathological features, adjuvant chemotherapy with CapeOx (capecitabine plus oxaliplatin) was recommended. The patient remains under regular oncologic surveillance. Discussion This report underscores a well-recognized yet challenging diagnostic scenario in colorectal surgery: an infiltrative adenocarcinoma exhibiting submucosal-dominant growth that results in a fibrotic annular stricture while sparing the overlying mucosa. In such lesions, standard endoscopic forceps biopsies are prone to sampling error, often failing to capture the underlying desmoplastic tumor component and yielding false-negative results despite a high pre-test probability of malignancy( 5 , 6 ). The endoscopic finding of a rigid, non-traversable stricture should itself be considered a significant "red flag." When this is corroborated by CT findings such as concentric mural thickening, luminal narrowing, and pericolic nodules, the post-test probability of cancer becomes sufficiently high to warrant definitive management rather than repeated, likely futile, superficial biopsies( 8 – 11 ). The definitive histology in this case confirmed an aggressive tumor biology (pT3N1c with lymphovascular invasion, perineural invasion, and intermediate budding) characteristic of an infiltrative growth pattern. Tumor deposits, as identified here, carry established adverse prognostic significance independent of lymph node metastasis count. Their integration into staging and risk assessment refines stratification, particularly for stage III disease, and informs adjuvant therapy decisions( 12 , 13 ). The MDT-driven decision to proceed directly to planned resection was crucial. It likely averted an emergency presentation—a situation consistently linked with inferior long-term survival—and allowed for timely initiation of stage-appropriate adjuvant therapy( 14 , 15 ). Clinical implications and a proposed management pathway Based on this experience, we propose a structured approach for managing similar cases of suspicious colorectal strictures with non-diagnostic biopsies: Immediate Integrated Risk Stratification: Systematically combine endoscopic features (fixed, tight, non-traversable stricture), cross-sectional imaging findings (circumferential wall thickening, pericolic stranding/nodules), and clinical context (bleeding, obstructive symptoms). These objective high-risk features should be formally documented in the MDT record. Escalated Tissue Acquisition (When Feasible and Safe): If the anatomy permits, employ techniques to obtain deeper tissue samples. This may include using larger-capacity or cap-assisted biopsy forceps, or targeting the edge of the stricture. Intra-procedural consultation with pathology can help assess sample adequacy( 6 , 11 ). Endoscopic ultrasound-guided sampling is an option in select cases but is often technically challenging in near-obstructive distal rectal lesions. Timely Definitive Surgical Management: If adequate deep sampling is not feasible or persists in being non-diagnostic, and the integrated clinicoradiologic suspicion remains high, proceeding to planned oncologic resection under MDT guidance is justified. This strategy aims to prevent harmful treatment delays and the need for higher-risk emergency surgery( 14 , 15 ). Multidisciplinary Reconciliation and Process Improvement: Structured post-operative debriefings involving endoscopists, radiologists, surgeons, and pathologists are valuable. They help reconcile diagnostic discrepancies, establish local consensus thresholds for surgical intervention, and refine shared decision-making processes that incorporate patient preferences. Conclusion and Limitations The findings and recommendations from a single case report have inherent limitations in generalizability. However, the clear diagnostic sequence—from endoscopy and imaging to final pathology—provides a practical, illustrative model for managing such discrepant data in clinical practice. Prospective, multi-center studies are warranted to quantify the incremental diagnostic yield of advanced biopsy techniques in stricturing lesions and to validate specific imaging "red flags" that could reliably justify direct surgical intervention in cases of biopsy-negative colorectal stenosis. Abbreviations AJCC American Joint Committee on Cancer CA 19 − 9 Carbohydrate Antigen 19 − 9 CEA Carcinoembryonic Antigen CRC Colorectal Cancer CT Computed Tomography MDT Multidisciplinary Team pMMR Proficient Mismatch Repair Declarations Ethics approval and consent to participate: The studies involving humans were approved by Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (Ethical Review No. 2025-KLS-961-01). The studies were conducted in accordance with the local legislation and institutional requirements. Consent for publication: Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. Competing interests: The authors declare that they have no competing interests. Funding: This work was supported by Science and Technology Department of the State Administration of Traditional Chinese Medicine of China - Zhejiang Province Joint Construction Project (grant no. GZY-ZJ-KJ-24098 to K.T.J.). Author Contribution K.J., Y.H., and Z.C. conceived the report and collected the clinical data. X.W. performed the histopathological analysis and interpretation. Y.H. drafted the initial manuscript. All authors critically reviewed, revised, and approved the final version of the manuscript. Acknowledgements: We acknowledge the valuable contributions of the multidisciplinary tumor board in the management of this case. Data Availability The de-identified clinical data supporting this report are available from the corresponding author upon reasonable request. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. Xi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021;14(10):101174. Zhou H, Jin Y, Wang J, Chen G, Chen J, Yu S. Comparison of short-term surgical outcomes and long-term survival between emergency and elective surgery for colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2023;38(1):41. Xu Z, Becerra AZ, Aquina CT, Hensley BJ, Justiniano CF, Boodry C, et al. Emergent Colectomy Is Independently Associated with Decreased Long-Term Overall Survival in Colon Cancer Patients. J Gastrointest Surg. 2017;21(3):543–53. Johnson G, Hershorn O, Singh H, Park J, Helewa RM. Sampling error in the diagnosis of colorectal cancer is associated with delay to surgery: a retrospective cohort study. Surg Endosc. 2022;36(7):4893–902. Absar MS, Haboubi NY. Colonic neoplastic polyps: biopsy is not efficient to exclude malignancy. The Trafford experience. Tech Coloproctol. 2004;8(Suppl 2):s257–60. Benson AB, Venook AP, Adam M, Chang G, Chen YJ, Ciombor KK et al. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(2 D). 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The prognostic impact of tumor deposits in colorectal cancer: More than just N1c. Cancer. 2024;130(23):4052–60. Cohen R, Shi Q, Meyers J, Jin Z, Svrcek M, Fuchs C, et al. Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)(☆). Ann Oncol. 2021;32(10):1267–75. McArdle CS, Hole DJ. Emergency presentation of colorectal cancer is associated with poor 5-year survival. Br J Surg. 2004;91(5):605–9. Arnarson O, Syk I, Butt ST. Who should operate patients presenting with emergent colon cancer? A comparison of short- and long-term outcome depending on surgical sub-specialization. World J Emerg Surg. 2023;18(1):3. Additional Declarations No competing interests reported. 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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-8383724","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":570272463,"identity":"ebca4036-8cc6-4a65-acd5-e7db9a45f16e","order_by":0,"name":"Yuejun Han","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","correspondingAuthor":false,"prefix":"","firstName":"Yuejun","middleName":"","lastName":"Han","suffix":""},{"id":570272464,"identity":"6ea316ad-5149-4931-b9b6-75bfa6b95a2e","order_by":1,"name":"Zhi 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05:28:39","extension":"xml","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":47457,"visible":true,"origin":"","legend":"","description":"","filename":"dc5a2a0dc66f4bdea8a003bae66f3dea1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/48527436e8d3b6c4c9e1c2b5.xml"},{"id":100004868,"identity":"19f68e90-1dd4-4c64-9dfb-6d2e9e6436b0","added_by":"auto","created_at":"2026-01-12 05:28:39","extension":"html","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":54337,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/630a9c255f00f8bf67b3f580.html"},{"id":100004814,"identity":"283756b6-c03b-43e9-87ec-c9cb00eb650b","added_by":"auto","created_at":"2026-01-12 05:28:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1087280,"visible":true,"origin":"","legend":"\u003cp\u003eContrast-enhanced axial CT image of the pelvis. Red arrows indicate the short-segment circumferential mural thickening at the rectosigmoid junction with associated luminal narrowing and small pericolic nodules.\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/5074de7a78612f4dafda56ae.png"},{"id":100004813,"identity":"1640813f-da2e-49cd-830b-2956dd893e92","added_by":"auto","created_at":"2026-01-12 05:28:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":898157,"visible":true,"origin":"","legend":"\u003cp\u003eColonoscopic image showing the fixed, annular, and non-traversable rectosigmoid stricture. No exophytic mass is visible.\u003c/p\u003e","description":"","filename":"Fig.2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/b561beb43e44fdf777be9b76.jpg"},{"id":100004817,"identity":"3d20a921-56a9-497e-a0e1-504113e4b7cf","added_by":"auto","created_at":"2026-01-12 05:28:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6451279,"visible":true,"origin":"","legend":"\u003cp\u003eGross pathological specimen of the resected rectosigmoid segment. A: External view of the firm, annular stricture (yellow arrow). B: Opened view of the specimen, yellow arrow revealing the stenotic lumen and submucosal tumor (scale: 2.5 × 2.5 × 2.0 cm).\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/c79bc440eef50841df26bfb8.png"},{"id":100004816,"identity":"1f707aaf-ebf1-4b20-94e9-614275627ad4","added_by":"auto","created_at":"2026-01-12 05:28:38","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":2979917,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological and immunohistochemical findings. A: Hematoxylin and eosin (H\u0026amp;E) staining at low magnification (7×) demonstrating tumor infiltration beyond the muscularis propria, consistent with pT3 staging. B: H\u0026amp;E staining at higher magnification (40×) highlighting the desmoplastic stromal reaction and foci of intermediate tumor budding (Bd2). C: Immunohistochemistry for p53 showing a diffuse, strong nuclear staining pattern (mutant pattern). D: Immunohistochemistry for Ki-67 indicating a high proliferation index (approximately 70%).\u003c/p\u003e","description":"","filename":"Fig.4.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/691c6104564617961fe00945.jpg"},{"id":101195134,"identity":"5302844f-4b61-46c6-88bf-3a74ee5b3699","added_by":"auto","created_at":"2026-01-27 07:58:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":12735888,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8383724/v1/2a8fb335-c5fb-44a4-a04d-44fabe670936.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Submucosal-dominant, stricture-type rectosigmoid adenocarcinoma with false-negative biopsies: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eColorectal cancer (CRC) ranks as the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2022, it accounted for approximately 9.6% of global cancer incidence and 9.3% of cancer deaths(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Obstructing or near-obstructing tumors represent a clinically challenging subgroup, often diagnosed at more advanced stages and associated with poorer outcomes, particularly when management occurs under emergency conditions(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Accurate and timely preoperative diagnosis is therefore essential to optimize treatment pathways and survival.\u003c/p\u003e \u003cp\u003eWhile colonoscopic forceps biopsy is the first-line modality for tissue diagnosis, its sensitivity is notably reduced in stenotic or infiltrative tumors that proliferate beneath a deceptively normal-appearing mucosa. A recent large cohort study reported initial sampling error\u0026mdash;defined as benign or non-diagnostic histology in ultimately confirmed cancers\u0026mdash;in approximately 22.6% of cases, a factor independently associated with prolonged time to definitive surgery(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Earlier studies on neoplastic polyps similarly documented false-negative biopsy rates of up to 18.5% when compared with final surgical specimens, highlighting the inherent limitations of superficial sampling(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Contemporary clinical guidelines, including those from the National Comprehensive Cancer Network (NCCN), emphasize the need for prompt evaluation of obstructing or highly suspicious strictures. They advocate for diagnostic escalation\u0026mdash;through repeat or deeper sampling, advanced endoscopic techniques, or direct resection\u0026mdash;when histologic results are discordant with compelling clinicoradiologic evidence of malignancy(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe present a case involving a short-segment, circumferential rectosigmoid stricture characterized by repeatedly negative biopsies but high radiologic suspicion, which was ultimately confirmed as a pT3N1c adenocarcinoma. This scenario epitomizes a high-stakes diagnostic dilemma and demonstrates the value of a pragmatic, multidisciplinary approach where integrative clinical and imaging assessment rightfully overrides falsely reassuring biopsy findings.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eAn 82-year-old man presented with a one-month history of loose stools and one week of frank hematochezia. He reported no associated abdominal pain, weight loss, or fever. Physical examination was notable only for the presence of fresh blood on digital rectal examination. Routine laboratory investigations, including complete blood count and coagulation profile, were within normal limits. Serum tumor markers were not elevated (carcinoembryonic antigen\u0026thinsp;\u0026lt;\u0026thinsp;1.7 ng/mL; CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9: 2.8 U/mL).\u003c/p\u003e \u003cp\u003eA non-contrast chest CT scan revealed no evidence of distant metastases. A contrast-enhanced abdominal CT demonstrated a short-segment, circumferential wall thickening at the rectosigmoid junction with significant luminal narrowing and the presence of small pericolic nodules suspicious for regional lymph node involvement (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Subsequent colonoscopy identified a fixed, annular, non-traversable stricture without an exophytic mass (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Multiple mucosal biopsies were obtained from the stricture site; all were reported as negative for malignancy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGiven the persistently high radiological suspicion and the characteristic endoscopic appearance of the stricture, the case was reviewed at a multidisciplinary tumor board (MDT). Consensus was reached to proceed with definitive surgical management. The patient subsequently underwent an uncomplicated laparoscopic low anterior resection.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePathological findings\u003c/h2\u003e \u003cp\u003eGross examination of the resected specimen revealed a firm, annular stricture measuring 2.5 \u0026times; 2.5 \u0026times; 2.0 cm (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Histopathological analysis confirmed a moderately-to-poorly differentiated adenocarcinoma infiltrating through the muscularis propria into the pericolorectal tissue, consistent with pT3 staging (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA, B). All surgical margins were negative for tumor involvement. Examination of nine retrieved lymph nodes showed no evidence of metastasis (0/9). However, three discrete tumor deposits were identified in the pericolic fat, meeting the criteria for pN1c staging according to the American Joint Committee on Cancer (AJCC) 8th edition. Additional high-risk pathological features included lymphovascular invasion, perineural invasion, and intermediate tumor budding (Bd2). Immunohistochemical profiling demonstrated proficient mismatch repair (pMMR) status, diffuse strong nuclear overexpression of p53 (mutant pattern), a high Ki-67 proliferation index (~\u0026thinsp;70%), and a CK20+/CDX2+/SATB2+/CK7- immunophenotype. HER2 expression was scored as 1+ (negative).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcomes and follow-up\u003c/h3\u003e\n\u003cp\u003eThe patient's postoperative recovery was uneventful, and he was discharged on the seventh postoperative day. In light of the final stage IIIB (pT3N1c) disease and the presence of multiple adverse pathological features, adjuvant chemotherapy with CapeOx (capecitabine plus oxaliplatin) was recommended. The patient remains under regular oncologic surveillance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis report underscores a well-recognized yet challenging diagnostic scenario in colorectal surgery: an infiltrative adenocarcinoma exhibiting submucosal-dominant growth that results in a fibrotic annular stricture while sparing the overlying mucosa. In such lesions, standard endoscopic forceps biopsies are prone to sampling error, often failing to capture the underlying desmoplastic tumor component and yielding false-negative results despite a high pre-test probability of malignancy(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The endoscopic finding of a rigid, non-traversable stricture should itself be considered a significant \"red flag.\" When this is corroborated by CT findings such as concentric mural thickening, luminal narrowing, and pericolic nodules, the post-test probability of cancer becomes sufficiently high to warrant definitive management rather than repeated, likely futile, superficial biopsies(\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe definitive histology in this case confirmed an aggressive tumor biology (pT3N1c with lymphovascular invasion, perineural invasion, and intermediate budding) characteristic of an infiltrative growth pattern. Tumor deposits, as identified here, carry established adverse prognostic significance independent of lymph node metastasis count. Their integration into staging and risk assessment refines stratification, particularly for stage III disease, and informs adjuvant therapy decisions(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The MDT-driven decision to proceed directly to planned resection was crucial. It likely averted an emergency presentation\u0026mdash;a situation consistently linked with inferior long-term survival\u0026mdash;and allowed for timely initiation of stage-appropriate adjuvant therapy(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eClinical implications and a proposed management pathway\u003c/h3\u003e\n\u003cp\u003eBased on this experience, we propose a structured approach for managing similar cases of suspicious colorectal strictures with non-diagnostic biopsies:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eImmediate Integrated Risk Stratification: Systematically combine endoscopic features (fixed, tight, non-traversable stricture), cross-sectional imaging findings (circumferential wall thickening, pericolic stranding/nodules), and clinical context (bleeding, obstructive symptoms). These objective high-risk features should be formally documented in the MDT record.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eEscalated Tissue Acquisition (When Feasible and Safe): If the anatomy permits, employ techniques to obtain deeper tissue samples. This may include using larger-capacity or cap-assisted biopsy forceps, or targeting the edge of the stricture. Intra-procedural consultation with pathology can help assess sample adequacy(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Endoscopic ultrasound-guided sampling is an option in select cases but is often technically challenging in near-obstructive distal rectal lesions.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTimely Definitive Surgical Management: If adequate deep sampling is not feasible or persists in being non-diagnostic, and the integrated clinicoradiologic suspicion remains high, proceeding to planned oncologic resection under MDT guidance is justified. This strategy aims to prevent harmful treatment delays and the need for higher-risk emergency surgery(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eMultidisciplinary Reconciliation and Process Improvement: Structured post-operative debriefings involving endoscopists, radiologists, surgeons, and pathologists are valuable. They help reconcile diagnostic discrepancies, establish local consensus thresholds for surgical intervention, and refine shared decision-making processes that incorporate patient preferences.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e"},{"header":"Conclusion and Limitations","content":"\u003cp\u003eThe findings and recommendations from a single case report have inherent limitations in generalizability. However, the clear diagnostic sequence\u0026mdash;from endoscopy and imaging to final pathology\u0026mdash;provides a practical, illustrative model for managing such discrepant data in clinical practice. Prospective, multi-center studies are warranted to quantify the incremental diagnostic yield of advanced biopsy techniques in stricturing lesions and to validate specific imaging \"red flags\" that could reliably justify direct surgical intervention in cases of biopsy-negative colorectal stenosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAJCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Joint Committee on Cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCA 19\u0026thinsp;\u0026minus;\u0026thinsp;9\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCarbohydrate Antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9\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\"\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\"\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\"\u003eMDT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultidisciplinary Team\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003epMMR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProficient Mismatch Repair\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003eThe studies involving humans were approved by Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (Ethical Review No. 2025-KLS-961-01). The studies were conducted in accordance with the local legislation and institutional requirements.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and any accompanying images.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by Science and Technology Department of the State Administration of Traditional Chinese Medicine of China - Zhejiang Province Joint Construction Project (grant no. GZY-ZJ-KJ-24098 to K.T.J.).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eK.J., Y.H., and Z.C. conceived the report and collected the clinical data. X.W. performed the histopathological analysis and interpretation. Y.H. drafted the initial manuscript. All authors critically reviewed, revised, and approved the final version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eWe acknowledge the valuable contributions of the multidisciplinary tumor board in the management of this case.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe de-identified clinical data supporting this report are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXi Y, Xu P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol. 2021;14(10):101174.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou H, Jin Y, Wang J, Chen G, Chen J, Yu S. Comparison of short-term surgical outcomes and long-term survival between emergency and elective surgery for colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis. 2023;38(1):41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu Z, Becerra AZ, Aquina CT, Hensley BJ, Justiniano CF, Boodry C, et al. Emergent Colectomy Is Independently Associated with Decreased Long-Term Overall Survival in Colon Cancer Patients. J Gastrointest Surg. 2017;21(3):543\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson G, Hershorn O, Singh H, Park J, Helewa RM. Sampling error in the diagnosis of colorectal cancer is associated with delay to surgery: a retrospective cohort study. Surg Endosc. 2022;36(7):4893\u0026ndash;902.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbsar MS, Haboubi NY. Colonic neoplastic polyps: biopsy is not efficient to exclude malignancy. The Trafford experience. Tech Coloproctol. 2004;8(Suppl 2):s257\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenson AB, Venook AP, Adam M, Chang G, Chen YJ, Ciombor KK et al. Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(2 D).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eExpert Panel on, Gastrointestinal I, Korngold EK, Moreno C, Kim DH, Fowler KJ, Cash BD, et al. ACR Appropriateness Criteria(R) Staging of Colorectal Cancer: 2021 Update. J Am Coll Radiol. 2022;19(5S):S208\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNerad E, Lahaye MJ, Maas M, Nelemans P, Bakers FC, Beets GL, et al. Diagnostic Accuracy of CT for Local Staging of Colon Cancer: A Systematic Review and Meta-Analysis. AJR Am J Roentgenol. 2016;207(5):984\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShkurti J, van den Berg K, Tissier RLM, van der Mierden S, Lahaye MJ, Beets-Tan RGH et al. Diagnostic accuracy of CT for identifying high-risk colon cancer: a systematic review and meta-analysis. Eur Radiol. 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerlitsch M, Hassan C, Bisschops R, Bhandari P, Dinis-Ribeiro M, Risio M, et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy. 2024;56(7):516\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhutiani N, Peacock O, Uppal A, Hu CY, Bednarski BK, Taggart MW, et al. The prognostic impact of tumor deposits in colorectal cancer: More than just N1c. Cancer. 2024;130(23):4052\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen R, Shi Q, Meyers J, Jin Z, Svrcek M, Fuchs C, et al. Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)(☆). Ann Oncol. 2021;32(10):1267\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcArdle CS, Hole DJ. Emergency presentation of colorectal cancer is associated with poor 5-year survival. Br J Surg. 2004;91(5):605\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArnarson O, Syk I, Butt ST. Who should operate patients presenting with emergent colon cancer? A comparison of short- and long-term outcome depending on surgical sub-specialization. World J Emerg Surg. 2023;18(1):3.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorectal cancer, False-negative biopsy, Diagnostic dilemma, Stricture, Multidisciplinary team, Tumor deposits","lastPublishedDoi":"10.21203/rs.3.rs-8383724/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8383724/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEndoscopic biopsy is the standard for diagnosing colorectal cancer. However, infiltrative tumors presenting as annular strictures may yield non-diagnostic samples, risking significant treatment delay.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eAn 82-year-old man presented with loose stools and hematochezia. Colonoscopy revealed a tight, non-traversable rectosigmoid stricture; repeated mucosal biopsies were negative for malignancy. Contrast-enhanced computed tomography (CT) demonstrated concerning features, including circumferential mural thickening, luminal narrowing, and small pericolic nodules. Due to persistent high clinicoradiologic suspicion despite negative biopsies, the patient underwent laparoscopic low anterior resection. Final histopathology confirmed a moderately-to-poorly differentiated adenocarcinoma, staged as pT3N1c, with lymphovascular invasion, perineural invasion, and intermediate tumor budding.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case highlights the diagnostic limitations of superficial mucosal biopsy in submucosal-dominant, stricturing colorectal lesions. It underscores the critical importance of multidisciplinary, probability-driven decision-making when histologic findings contradict strong clinical and imaging evidence of malignancy. In such scenarios, proceeding to timely surgical resection is paramount to avoid progression to emergency presentation and to facilitate appropriate adjuvant therapy.\u003c/p\u003e","manuscriptTitle":"Submucosal-dominant, stricture-type rectosigmoid adenocarcinoma with false-negative biopsies: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 05:28:30","doi":"10.21203/rs.3.rs-8383724/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6dd73e1d-76c4-4c47-a795-68c8fa5e4378","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-18T18:09:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 05:28:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8383724","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8383724","identity":"rs-8383724","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}