{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:03:48Z","timestamp":1785503028738,"version":"3.56.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a rare and diagnostically challenging entity in children, adolescents, and young adults. Although ALCL accounts for a meaningful subset of young patients diagnosed with non-Hodgkin lymphoma, the vast majority of cases are ALK-positive, while ALK-negative disease is seen predominantly in older adults. As a result, pediatric-specific data are limited to small series and case reports, with treatment strategies often extrapolated from adult peripheral T-cell lymphoma or pediatric ALK-positive ALCL clinical trials. Despite morphologic overlap with ALK-positive ALCL, ALK-negative ALCL is biologically heterogeneous, with recurrent alterations involving\n                    <jats:italic>DUSP22<\/jats:italic>\n                    ,\n                    <jats:italic>TP63<\/jats:italic>\n                    ,\n                    <jats:italic>JAK\/STAT<\/jats:italic>\n                    pathway genes,\n                    <jats:italic>TYK2<\/jats:italic>\n                    ,\n                    <jats:italic>ROS1<\/jats:italic>\n                    ,\n                    <jats:italic>ERBB4<\/jats:italic>\n                    , and other potential molecular drivers. These alterations may have prognostic and therapeutic implications, but their frequency and significance in children and adolescents remain incompletely defined. Accurate diagnosis of ALK-negative ALCL requires expert hematopathology review, with integration of morphology, immunophenotype, and molecular testing. Emerging therapeutic approaches include CD30-directed therapy,\n                    <jats:italic>JAK\/STAT<\/jats:italic>\n                    pathway inhibition, and checkpoint blockade. This review summarizes the diagnostic, biologic, and therapeutic challenges affecting young patients with ALK-negative ALCL and the healthcare teams that care for them. We highlight the need for further collaborative and multidisciplinary work, systematic molecular profiling, and consideration of this group in future clinical trials to ultimately advance care for this group of pediatric and adolescent cancer patients.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1898680","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:19:22Z","timestamp":1785500362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ALK-negative anaplastic large cell lymphoma in pediatric and adolescent patients: a mini-review"],"prefix":"10.3389","volume":"16","author":[{"given":"Kaitlin J.","family":"Devine","sequence":"first","affiliation":[{"name":"Division of Oncology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]},{"name":"Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Stokke","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Los Angeles, Cancer and Blood Disease Institute, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay F.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]},{"name":"Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Northwestern University Feinberg School of Medicine","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-04-571091","article-title":"ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes","volume":"124","author":"Parrilla Castellar","year":"2014","journal-title":"Blood J Am Soc Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184667","article-title":"ALK-negative anaplastic large cell lymphoma: current concepts and molecular pathogenesis of a heterogeneous group of large T-cell 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