{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T07:59:48Z","timestamp":1767945588629,"version":"3.49.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive mature T-cell non-Hodgkin lymphoma. Its typical characteristics include positive CD30 and ALK expression detected by immunohistochemistry, and it is often accompanied by ALK gene translocation, among which the chromosomal translocation t (2;5) is the most common. This disease predominantly affects young individuals, with extranodal involvement being relatively common. However, cases involving the digestive tract are relatively rare. We report a rare case of a 14-year-old female with ALK+ALCL presenting with fever and peripheral blood leukocytosis as initial manifestations and complicated by diffuse involvement of the entire gastrointestinal tract. The patient showed significant remission having completed 4 chemotherapy sessions. In further studies, RNA sequencing confirmed the presence of\n                    <jats:italic>NPM1::ALK<\/jats:italic>\n                    gene fusion in this case; whole-exome sequencing (WES) detected somatic mutations in multiple genes of the JAK-STAT pathway (including\n                    <jats:italic>JAK1, PTPN6, MTOR<\/jats:italic>\n                    , and\n                    <jats:italic>TYK2<\/jats:italic>\n                    ). It is noteworthy that such genetic alterations are more commonly observed in ALK-negative anaplastic large cell lymphoma (ALK-ALCL) but are less commonly reported in ALK+ALCL.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2025.1709110","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:35Z","timestamp":1767940595000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: diffuse entire gastrointestinal tract involvement of ALK-positive anaplastic large cell lymphoma harboring JAK-STAT pathway mutations in an adolescent with leukemoid reaction"],"prefix":"10.3389","volume":"15","author":[{"given":"Sizhe","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sha","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1365-2141.2005.05735.x","article-title":"The impact of age and gender on biology, clinical features and treatment outcome of non-hodgkin lymphoma in childhood and adolescence","volume":"131","author":"Burkhardt","year":"2005","journal-title":"Br J Haematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071650","article-title":"Anaplastic large cell lymphoma: molecular pathogenesis and treatment","volume":"14","author":"Zhang","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V49.5.845.845","article-title":"Demonstration of granulopoietic factor(S) in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue","volume":"49","author":"Asano","year":"1977","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-717793","article-title":"Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target","volume":"129","author":"Werner","year":"2017","journal-title":"Blood"},{"key":"B6","article-title":"Alk+ Lymphoma: clinico-pathological findings and outcome","volume":"93","author":"Falini","year":"1999","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3681","article-title":"Cd30(+) anaplastic large cell lymphoma: A review of its histopathologic, genetic, and clinical features","volume":"96","author":"Stein","year":"2000","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0037-1963(03)00138-0","article-title":"Systemic and primary cutaneous anaplastic large cell lymphomas","volume":"40","author":"Kadin","year":"2003","journal-title":"Semin Hematol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112679","article-title":"Primary gastrointestinal T\/nk cell lymphoma","volume":"13","author":"Kim","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153295","article-title":"Paraneoplastic leukemoid reaction: case report and review of the literature","volume":"217","author":"Abukhiran","year":"2021","journal-title":"Pathol Res Pract"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2006.04.004","article-title":"An update on the etiology and diagnostic evaluation of a leukemoid reaction","volume":"17","author":"Sakka","year":"2006","journal-title":"Eur J Intern Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13127","article-title":"Leukemoid reaction: A 21st-century cohort study","volume":"42","author":"Portich","year":"2020","journal-title":"Int J Lab Hematol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/10668969221137518","article-title":"Anaplastic large-cell lymphoma involving gastrointestinal tract: A clinicopathologic study of 25 cases of a rare tumor at a rare site","volume":"31","author":"Ud Din","year":"2023","journal-title":"Int J Surg Pathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0661-RA","article-title":"Gastrointestinal tract lymphomas","volume":"145","author":"Alvarez-Lesmes","year":"2021","journal-title":"Arch Pathol Lab Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4253\/wjge.v7.i10.928","article-title":"Rare gastrointestinal lymphomas: the endoscopic investigation","volume":"7","author":"Vetro","year":"2015","journal-title":"World J Gastrointest Endosc"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.17235\/reed.2024.10644\/2024","article-title":"A case of mantle cell lymphoma with involvement of the entire gastrointestinal tract - multiple endoscopic findings","volume":"117","author":"Zhang","year":"2024","journal-title":"Rev Esp Enferm Dig"},{"key":"B17","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3892\/ol.2024.14496","article-title":"Mantle cell lymphoma characterized by numerous diffuse polypoid lesions along the entire digestive tract: A case report","volume":"28","author":"Cheng","year":"2024","journal-title":"Oncol Lett"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880395","article-title":"Early phase of intestinal mantle cell lymphoma: A report of two cases associated with advanced colonic adenocarcinoma","volume":"14","author":"Kanehira","year":"2001","journal-title":"Mod Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2019-206340","article-title":"Paraneoplastic leukemoid reactions induced by cytokine-secreting tumours","volume":"73","author":"Abukhiran","year":"2020","journal-title":"J Clin Pathol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-014-1557-3","article-title":"Anaplastic large cell lymphoma with paraneoplastic neutrophilia: an association between il-17 elevation and aggressive disease progression","volume":"99","author":"Sueki","year":"2014","journal-title":"Int J Hematol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"477\u201385","DOI":"10.3324\/haematol.2017.177972","article-title":"Blood cytokine concentrations in pediatric patients with anaplastic lymphoma kinase-positive anaplastic large cell lymphoma","volume":"103","author":"Kn\u00f6rr","year":"2018","journal-title":"Haematologica"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1241532","article-title":"Updates in pathobiological aspects of anaplastic large cell lymphoma","volume":"13","author":"Wu","year":"2023","journal-title":"Front Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10040107","article-title":"The pathological spectrum of systemic anaplastic large cell lymphoma (Alcl)","volume":"10","author":"Montes-Mojarro","year":"2018","journal-title":"Cancers (Basel)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300744","article-title":"Malignant transformation of cd4+ T lymphocytes mediated by oncogenic kinase npm\/alk recapitulates il-2-induced cell signaling and gene expression reprogramming","volume":"191","author":"Marzec","year":"2013","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41375-024-02468-4","article-title":"Comprehensive genomic analysis reveals molecular heterogeneity in pediatric alk-positive anaplastic large cell lymphoma","volume":"39","author":"Shaw","year":"2025","journal-title":"Leukemia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/s41392-023-01468-7","article-title":"Evolving cognition of the jak-stat signaling pathway: autoimmune disorders and cancer","volume":"8","author":"Xue","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.650295","article-title":"Ruxolitinib, a jak1\/2 inhibitor, ameliorates cytokine storm in experimental models of hyperinflammation syndrome","volume":"12","author":"Huarte","year":"2021","journal-title":"Front Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12081910","article-title":"Pathogenic and prognostic roles of paraneoplastic leukocytosis in cervical cancer: can genomic-based targeted therapies have a role? A literature review and an emblematic case report","volume":"12","author":"Madeddu","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174256","article-title":"Cytokines, genetic lesions and signaling pathways in anaplastic large cell lymphomas","volume":"13","author":"Merlio","year":"2021","journal-title":"Cancers (Basel)"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1709110\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:37Z","timestamp":1767940597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1709110\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":29,"alternative-id":["10.3389\/fonc.2025.1709110"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1709110","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]},"article-number":"1709110"}}