Mesalazine-Induced Temporary Remission of Colonic Ulcers in Primary Intestinal NK/T-Cell Lymphoma: A Case Report and Literature Review

Mesalazine-Induced Temporary Remission of Colonic Ulcers in Primary Intestinal NK/T-Cell Lymphoma: 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 Mesalazine-Induced Temporary Remission of Colonic Ulcers in Primary Intestinal NK/T-Cell Lymphoma: A Case Report and Literature Review Feifei Ding, Yinhua Feng, Xiang Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7699265/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 Purpose We present a rare case of short-term healing of colonic ulcers caused by Primary Intestinal NK/T-cell Lymphoma following mesalazine treatment. Methods Clinical, endoscopic, and pathological data from a patient treated at the Second Hospital of Lanzhou University were retrospectively analyzed. Literature on mesalazine was reviewed to explore potential mechanisms underlying ulcer healing in Primary Intestinal NK/T-cell Lymphoma. Clinical trial number: not applicable. Results A 21-year-old female presented with recurrent fever and colonic ulcers, pathologically confirmed as Primary Intestinal NK/T-cell Lymphoma. After six months of oral mesalazine (4 g/day), colonoscopy revealed ulcer healing, accompanied by resolution of abdominal pain and fever. The patient’s family declined further chemotherapy. Unfortunately, 1 year later, she was hospitalized for colonic perforation, underwent emergency surgery, and received postoperative chemotherapy.The patient died 2 years after the surgery. Conclusion This case suggests that mesalazine may induce transient mucosal healing in Primary Intestinal NK/T-cell Lymphoma-associated ulcers, potentially masking disease progression. Clinicians should remain vigilant and conduct long-term follow-up even if mesalazine treatment is effective for colonic ulcers. Mesalazine Intestinal NK/T-cell Lymphoma colonic ulcers Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Extranodal NK/T-cell lymphoma (ENKTL) is a rare lymphoid malignancy of NK- or T-cell origin that demonstrates nearly universal association with Epstein-Barr virus (EBV) infection. The disease most frequently involves the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate)[ 1 ]. As a distinct subtype of non-Hodgkin lymphoma, ENKTL shows marked geographic predilection, with significantly higher incidence in Asian populations compared to Western countries (male predominance noted)[ 2 ]. Primary intestinal involvement by ENKTL represents an uncommon clinical presentation. The nonspecific nature of its symptoms, physical findings, and endoscopic features often leads to misdiagnosis as inflammatory bowel disease (IBD)[ 3 ]. We present a diagnostically challenging case initially managed as ulcerative colitis that subsequently revealed intestinal ENKTL. Remarkably, the patient demonstrated short-term colonic ulcer healing following mesalazine therapy - a phenomenon not previously documented in ENKTL literature. This unexpected therapeutic response might mislead clinicians in diagnosing the disease. Case report A 21-year-old female first presented in 2017 with a 10-year history of recurrent fever, abdominal pain, and oral aphthous ulcers. She had previously been diagnosed with ulcerative colitis and was intermittently treated with mesalazine. Notably, her symptoms consistently recurred upon discontinuation of the medication. Upon admission, her body weight was 45 kg, with a body mass index (BMI) of 17.57 kg/m². Vital signs were stable, and no significant enlargement of superficial lymph nodes was noted. Abdominal examination revealed tenderness localized to the lower abdomen. Laboratory tests demonstrated markedly elevated inflammatory markers, including a C-reactive protein (CRP) level of 133 mg/L. Epstein-Barr virus (EBV) serology was positive.Colonoscopy performed on August 10, 2017, revealed multiple irregular ulcers scattered throughout the ileocecal region and ascending colon (Fig. 1 ). Histopathological examination showed dense lymphocytic infiltration (Fig. 2 ). Immunohistochemical analysis revealed strong expression of CD3, CD7, and TIA-1, with a Ki-67 proliferative index of 40%. The lymphoid infiltrate was negative for CD4, CD8, CD20, CD5 (Fig. 3 ). Regrettably, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were not performed at the time. Based on the histomorphology, immunophenotypic profile, and positive EBV serology, primary intestinal natural killer (NK)/T-cell lymphoma was considered. Although the clinical and pathological findings were highly suggestive of this diagnosis, the patient and her family declined conventional chemotherapy. Interestingly, she reported symptomatic improvement with oral mesalazine at a dose of 4 g daily. A follow-up colonoscopy on March 5, 2018, revealed complete mucosal healing of previously documented ulcers (Fig. 4 ), accompanied by resolution of systemic symptoms including fever and abdominal pain. Mesalazine was continued as maintenance therapy, and the patient remained clinically stable for nearly one year. However, in February 2019, she was urgently admitted with acute abdominal pain. Imaging studies identified colonic perforation, necessitating emergency surgical intervention. After postoperative recovery, she was referred to hematology and initiated on systemic chemotherapy. In March 2020, she developed a nasal mass. Histopathological analysis confirmed the diagnosis of extranodal NK/T-cell lymphoma involving the nasal cavity( Pathological findings are provided in the Supplementary Materials ). Despite receiving intensive treatment, the disease progressed, and the patient ultimately succumbed to the illness in 2021. Discussion Primary intestinal NK/T-cell lymphoma (INKTL) represents an exceptionally rare clinical entity, with only limited cases reported in the literature. The pathogenesis of NK/T-cell lymphomas involves critical roles of genetic alterations and Epstein-Barr virus (EBV) infection. Molecular studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway as being intimately associated with extranodal NK-cell lymphoma pathogenesis. STAT3 mutations promote phosphorylation and transcriptional activation of STAT3. The activated STAT3 upregulates PD-L1 expression, and the increased PD-L1 binds to programmed death-1 (PD-1), inhibiting T cell activation and signal transduction, thereby promoting tumor cell survival. Enhancer of zeste homolog 2 (EZH2) is aberrantly overexpressed in extranodal NK/T-cell lymphoma (ENKTL) and contributes to its pathogenesis. Epstein-Barr virus (EBV) downregulates non-homologous end-joining factor 1 (NHEJ1), a crucial DNA repair factor in the non-homologous end joining (NHEJ) pathway that mediates double-strand break repair. This disruption of NHEJ1 impairs genomic stability and promotes the development of ENKTL[ 2 ]. Mesalazine is a 5-aminosalicylic acid (5-ASA) drug, which has been widely used in the treatment of inflammatory bowel disease at present. The existing evidence indicates that 5-aminosalicylic acid is one of the safest and most commonly used treatment modalities for inflammatory bowel disease. The mechanism of action is still not fully understood. It has been reported that the mechanism of 5-aminosalicylic acid in the treatment of inflammatory bowel disease may be to inhibit the secretion of pro-inflammatory molecules, such as leukotrienes, prostaglandins, and some cytokines, similar to activating peroxisome proliferator-activated receptor γ (PPARγ)[ 4 ]. 5-ASA exerts local anti-inflammatory effects on the intestinal mucosa by inhibiting lipoxygenase and cyclooxygenase to reduce leukotriene and prostaglandin production. It functions as a free radical scavenger that suppresses inflammatory mediators and interferes with nuclear factor-κB (NF-κB) activity, thereby inhibiting transcription of pro-inflammatory cytokines. Additionally, 5-ASA suppresses lymphocyte function as well as macrophage and natural killer cell activities[ 5 ]. Mesalazine may be involved in inhibiting the development of colorectal cancer by inhibiting COX-dependent and COX-independent pathways[ 6 ]. The cellular responses mediated by molecular interactions between JAK and STAT play a pivotal role in maintaining intestinal homeostasis and regulating inflammatory processes. Molecular agents that disrupt these interactions have shown promising therapeutic efficacy in the management of inflammatory bowel disease (IBD)[ 7 ]. 5-aminosalicylic acid (5-ASA) reduces the levels of activated STAT1 in the nuclei of HT-29 cells[ 8 , 9 ].Thus, we hypothesize that mesalazine may promote the healing of intestinal ulcers caused by NK/T-cell lymphoma (INKTL) through partial inhibition of the JAK/STAT pathway, although current evidence is lacking and further investigation is required. Additionally, for patients with colonic ulcers that respond clinically to mesalazine treatment, clinicians should maintain close follow-up to confirm the definitive diagnosis. Declarations Author contributions Feifei Ding participated in the collection of case data, literature review, and drafting of the manuscript. Yinhua Feng was responsible for literature review and edited the manuscript for grammar. Xiang Wang supervised the study, and reviewed and edited the final manuscript. Compliance with ethical standards Conflict of interest The authors have no competing interests to declare that are relevant to the content of this article Institutional review board statement The publication of this case report was approved by the Ethics Committee of Lanzhou University Second Hospital Informed consent statement Consent for publication was obtained from the patient's father as the legal next-of-kin. Funding The authors did not receive support from any organization for the submitted work. Data Availability All data generated or analyzed during this study are included in this published article (and its supplementary information files). References Wood PB, Parikh SR, Krause JR. Extranodal NK/T-cell lymphoma, nasal type. Proc (Bayl Univ Med Cent). 2011;24(3):251-4.https://doi.org/10.1080/08998280.2011.11928727. Thida AM, Gohari P. Extranodal NK-Cell Lymphoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559207/ Jayakumar P, Singh L, Ahuja V, Yadav R, Mallick S. Primary Intestinal NK/T-cell Lymphoma Masquerading as Crohn's Disease: A Report of Two Cases. Cureus. 2025;17(1):e77056.https://doi.org/10.7759/cureus.77056. Desreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid - new evidence. Aliment Pharmacol Ther. 2006;24 Suppl 1:2-9.https://doi.org/10.1111/j.1365-2036.2006.03069.x. Tavares Junior AG, de Araújo JTC, Meneguin AB, Chorilli M. Characteristics, Properties and Analytical/Bioanalytical Methods of 5-Aminosalicylic Acid: A Review. Crit Rev Anal Chem. 2022;52(5):1000-14.https://doi.org/10.1080/10408347.2020.1848516. Słoka J, Madej M, Strzalka-Mrozik B. Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules. 2023;28(13).https://doi.org/10.3390/molecules28135081. Salas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S, et al. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17(6):323-37.https://doi.org/10.1038/s41575-020-0273-0. Serra D, Rufino AT, Mendes AF, Almeida LM, Dinis TC. Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach. PLoS One. 2014;9(10):e109048.https://doi.org/10.1371/journal.pone.0109048. Serra D, Paixão J, Nunes C, Dinis TC, Almeida LM. Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: comparison with 5-aminosalicylic acid. PLoS One. 2013;8(9):e73001.https://doi.org/10.1371/journal.pone.0073001. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7699265","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":527496815,"identity":"1b40fa7c-1303-461b-8d4c-724f9229281e","order_by":0,"name":"Feifei Ding","email":"","orcid":"","institution":"Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Feifei","middleName":"","lastName":"Ding","suffix":""},{"id":527496817,"identity":"61acbfa6-1543-46bd-89ed-7320114bbbce","order_by":1,"name":"Yinhua Feng","email":"","orcid":"","institution":"Lanzhou 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02:35:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":275586,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological examination demonstrates dense lymphocytic infiltration at different magnifications: (a) (HE, ×40), (b) (HE, ×100), (c) (HE, ×200), and (d) (HE, ×400).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7699265/v1/0cf6840b84930e2d5d7e58f5.png"},{"id":93541649,"identity":"0475475e-adac-4218-9064-b880bf937b20","added_by":"auto","created_at":"2025-10-15 02:35:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":508839,"visible":true,"origin":"","legend":"\u003cp\u003eImmunohistochemical staining shows tumor cells positive for CD3(a), CD7(d), and cytotoxic granule-associated protein (TIA-1) (f), and negative for CD4(c), CD8(e), CD20(h), CD5(b), The Ki-67 proliferation index is 40%(g).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7699265/v1/b8eb22bd559fed5808004529.png"},{"id":93539542,"identity":"375c27a3-444f-4faf-8820-4656e8c690e2","added_by":"auto","created_at":"2025-10-15 02:19:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":155234,"visible":true,"origin":"","legend":"\u003cp\u003eFollow-up colonoscopy after approximately six months of mesalazine treatment shows complete healing of ulcers in the ileocecal region(a) and ascending colon(b).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7699265/v1/faad3f7ab835140b03bbe667.png"},{"id":96363967,"identity":"1a3edaa0-563f-446b-961d-8f86ec89362e","added_by":"auto","created_at":"2025-11-20 10:08:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1582454,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7699265/v1/caa3630d-2a53-4a49-a52d-2653b1304c4d.pdf"},{"id":93541139,"identity":"99d55b03-c186-43bf-83b8-942f6a7fbe2e","added_by":"auto","created_at":"2025-10-15 02:27:36","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2100295,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-7699265/v1/7769e3c9ddd0a27ad37a93d1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mesalazine-Induced Temporary Remission of Colonic Ulcers in Primary Intestinal NK/T-Cell Lymphoma: A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eExtranodal NK/T-cell lymphoma (ENKTL) is a rare lymphoid malignancy of NK- or T-cell origin that demonstrates nearly universal association with Epstein-Barr virus (EBV) infection. The disease most frequently involves the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. As a distinct subtype of non-Hodgkin lymphoma, ENKTL shows marked geographic predilection, with significantly higher incidence in Asian populations compared to Western countries (male predominance noted)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePrimary intestinal involvement by ENKTL represents an uncommon clinical presentation. The nonspecific nature of its symptoms, physical findings, and endoscopic features often leads to misdiagnosis as inflammatory bowel disease (IBD)[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We present a diagnostically challenging case initially managed as ulcerative colitis that subsequently revealed intestinal ENKTL. Remarkably, the patient demonstrated short-term colonic ulcer healing following mesalazine therapy - a phenomenon not previously documented in ENKTL literature. This unexpected therapeutic response might mislead clinicians in diagnosing the disease.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 21-year-old female first presented in 2017 with a 10-year history of recurrent fever, abdominal pain, and oral aphthous ulcers. She had previously been diagnosed with ulcerative colitis and was intermittently treated with mesalazine. Notably, her symptoms consistently recurred upon discontinuation of the medication.\u003c/p\u003e\n\u003cp\u003eUpon admission, her body weight was 45 kg, with a body mass index (BMI) of 17.57 kg/m\u0026sup2;. Vital signs were stable, and no significant enlargement of superficial lymph nodes was noted. Abdominal examination revealed tenderness localized to the lower abdomen. Laboratory tests demonstrated markedly elevated inflammatory markers, including a C-reactive protein (CRP) level of 133 mg/L. Epstein-Barr virus (EBV) serology was positive.Colonoscopy performed on August 10, 2017, revealed multiple irregular ulcers scattered throughout the ileocecal region and ascending colon (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Histopathological examination showed dense lymphocytic infiltration (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Immunohistochemical analysis revealed strong expression of CD3, CD7, and TIA-1, with a Ki-67 proliferative index of 40%. The lymphoid infiltrate was negative for CD4, CD8, CD20, CD5 (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Regrettably, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were not performed at the time.\u003c/p\u003e\n\u003cp\u003eBased on the histomorphology, immunophenotypic profile, and positive EBV serology, primary intestinal natural killer (NK)/T-cell lymphoma was considered.\u003c/p\u003e\n\u003cp\u003eAlthough the clinical and pathological findings were highly suggestive of this diagnosis, the patient and her family declined conventional chemotherapy. Interestingly, she reported symptomatic improvement with oral mesalazine at a dose of 4 g daily. A follow-up colonoscopy on March 5, 2018, revealed complete mucosal healing of previously documented ulcers (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e), accompanied by resolution of systemic symptoms including fever and abdominal pain. Mesalazine was continued as maintenance therapy, and the patient remained clinically stable for nearly one year.\u003c/p\u003e\n\u003cp\u003eHowever, in February 2019, she was urgently admitted with acute abdominal pain. Imaging studies identified colonic perforation, necessitating emergency surgical intervention. After postoperative recovery, she was referred to hematology and initiated on systemic chemotherapy. In March 2020, she developed a nasal mass. Histopathological analysis confirmed the diagnosis of extranodal NK/T-cell lymphoma involving the nasal cavity( Pathological findings are provided in the Supplementary Materials ). Despite receiving intensive treatment, the disease progressed, and the patient ultimately succumbed to the illness in 2021.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary intestinal NK/T-cell lymphoma (INKTL) represents an exceptionally rare clinical entity, with only limited cases reported in the literature. The pathogenesis of NK/T-cell lymphomas involves critical roles of genetic alterations and Epstein-Barr virus (EBV) infection. Molecular studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway as being intimately associated with extranodal NK-cell lymphoma pathogenesis. STAT3 mutations promote phosphorylation and transcriptional activation of STAT3. The activated STAT3 upregulates PD-L1 expression, and the increased PD-L1 binds to programmed death-1 (PD-1), inhibiting T cell activation and signal transduction, thereby promoting tumor cell survival. Enhancer of zeste homolog 2 (EZH2) is aberrantly overexpressed in extranodal NK/T-cell lymphoma (ENKTL) and contributes to its pathogenesis. Epstein-Barr virus (EBV) downregulates non-homologous end-joining factor 1 (NHEJ1), a crucial DNA repair factor in the non-homologous end joining (NHEJ) pathway that mediates double-strand break repair. This disruption of NHEJ1 impairs genomic stability and promotes the development of ENKTL[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMesalazine is a 5-aminosalicylic acid (5-ASA) drug, which has been widely used in the treatment of inflammatory bowel disease at present. The existing evidence indicates that 5-aminosalicylic acid is one of the safest and most commonly used treatment modalities for inflammatory bowel disease. The mechanism of action is still not fully understood. It has been reported that the mechanism of 5-aminosalicylic acid in the treatment of inflammatory bowel disease may be to inhibit the secretion of pro-inflammatory molecules, such as leukotrienes, prostaglandins, and some cytokines, similar to activating peroxisome proliferator-activated receptor γ (PPARγ)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. 5-ASA exerts local anti-inflammatory effects on the intestinal mucosa by inhibiting lipoxygenase and cyclooxygenase to reduce leukotriene and prostaglandin production. It functions as a free radical scavenger that suppresses inflammatory mediators and interferes with nuclear factor-κB (NF-κB) activity, thereby inhibiting transcription of pro-inflammatory cytokines. Additionally, 5-ASA suppresses lymphocyte function as well as macrophage and natural killer cell activities[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Mesalazine may be involved in inhibiting the development of colorectal cancer by inhibiting COX-dependent and COX-independent pathways[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe cellular responses mediated by molecular interactions between JAK and STAT play a pivotal role in maintaining intestinal homeostasis and regulating inflammatory processes. Molecular agents that disrupt these interactions have shown promising therapeutic efficacy in the management of inflammatory bowel disease (IBD)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. 5-aminosalicylic acid (5-ASA) reduces the levels of activated STAT1 in the nuclei of HT-29 cells[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].Thus, we hypothesize that mesalazine may promote the healing of intestinal ulcers caused by NK/T-cell lymphoma (INKTL) through partial inhibition of the JAK/STAT pathway, although current evidence is lacking and further investigation is required. Additionally, for patients with colonic ulcers that respond clinically to mesalazine treatment, clinicians should maintain close follow-up to confirm the definitive diagnosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eFeifei Ding participated in the collection of case data, literature review, and drafting of the manuscript. Yinhua Feng was responsible for literature review and edited the manuscript for grammar. Xiang Wang supervised the study, and reviewed and edited the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with ethical standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003eThe authors have no competing interests to declare that are relevant to the content of this article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional review board statement\u0026nbsp;\u003c/strong\u003eThe publication of this case report was approved by the Ethics Committee of Lanzhou University Second Hospital\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent statement\u0026nbsp;\u003c/strong\u003eConsent for publication was obtained from the patient\u0026apos;s father as the legal next-of-kin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThe authors did not receive support from any organization for the submitted work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003eAll data generated or analyzed during this study are included in this published article (and its supplementary information files).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWood PB, Parikh SR, Krause JR. Extranodal NK/T-cell lymphoma, nasal type. Proc (Bayl Univ Med Cent). 2011;24(3):251-4.https://doi.org/10.1080/08998280.2011.11928727.\u003c/li\u003e\n\u003cli\u003eThida AM, Gohari P. Extranodal NK-Cell Lymphoma. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559207/\u003c/li\u003e\n\u003cli\u003eJayakumar P, Singh L, Ahuja V, Yadav R, Mallick S. Primary Intestinal NK/T-cell Lymphoma Masquerading as Crohn\u0026apos;s Disease: A Report of Two Cases. Cureus. 2025;17(1):e77056.https://doi.org/10.7759/cureus.77056.\u003c/li\u003e\n\u003cli\u003eDesreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid - new evidence. Aliment Pharmacol Ther. 2006;24 Suppl 1:2-9.https://doi.org/10.1111/j.1365-2036.2006.03069.x.\u003c/li\u003e\n\u003cli\u003eTavares Junior AG, de Ara\u0026uacute;jo JTC, Meneguin AB, Chorilli M. Characteristics, Properties and Analytical/Bioanalytical Methods of 5-Aminosalicylic Acid: A Review. Crit Rev Anal Chem. 2022;52(5):1000-14.https://doi.org/10.1080/10408347.2020.1848516.\u003c/li\u003e\n\u003cli\u003eSłoka J, Madej M, Strzalka-Mrozik B. Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules. 2023;28(13).https://doi.org/10.3390/molecules28135081.\u003c/li\u003e\n\u003cli\u003eSalas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S, et al. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17(6):323-37.https://doi.org/10.1038/s41575-020-0273-0.\u003c/li\u003e\n\u003cli\u003eSerra D, Rufino AT, Mendes AF, Almeida LM, Dinis TC. Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach. PLoS One. 2014;9(10):e109048.https://doi.org/10.1371/journal.pone.0109048.\u003c/li\u003e\n\u003cli\u003eSerra D, Paix\u0026atilde;o J, Nunes C, Dinis TC, Almeida LM. Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: comparison with 5-aminosalicylic acid. PLoS One. 2013;8(9):e73001.https://doi.org/10.1371/journal.pone.0073001.\u003c/li\u003e\n\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":"Mesalazine, Intestinal NK/T-cell Lymphoma, colonic ulcers","lastPublishedDoi":"10.21203/rs.3.rs-7699265/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7699265/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eWe present a rare case of short-term healing of colonic ulcers caused by Primary Intestinal NK/T-cell Lymphoma following mesalazine treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eClinical, endoscopic, and pathological data from a patient treated at the Second Hospital of Lanzhou University were retrospectively analyzed. Literature on mesalazine was reviewed to explore potential mechanisms underlying ulcer healing in Primary Intestinal NK/T-cell Lymphoma. Clinical trial number: not applicable.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA 21-year-old female presented with recurrent fever and colonic ulcers, pathologically confirmed as Primary Intestinal NK/T-cell Lymphoma. After six months of oral mesalazine (4 g/day), colonoscopy revealed ulcer healing, accompanied by resolution of abdominal pain and fever. The patient\u0026rsquo;s family declined further chemotherapy. Unfortunately, 1 year later, she was hospitalized for colonic perforation, underwent emergency surgery, and received postoperative chemotherapy.The patient died 2 years after the surgery.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis case suggests that mesalazine may induce transient mucosal healing in Primary Intestinal NK/T-cell Lymphoma-associated ulcers, potentially masking disease progression. Clinicians should remain vigilant and conduct long-term follow-up even if mesalazine treatment is effective for colonic ulcers.\u003c/p\u003e","manuscriptTitle":"Mesalazine-Induced Temporary Remission of Colonic Ulcers in Primary Intestinal NK/T-Cell Lymphoma: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 02:19:31","doi":"10.21203/rs.3.rs-7699265/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":"70f035a9-a023-4057-8d78-0b577a984fdb","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-19T09:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-15 02:19:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7699265","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7699265","identity":"rs-7699265","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}