{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:08:28Z","timestamp":1789016908748,"version":"build-2803163510"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies in which the primary tumor site remains unidentified despite comprehensive diagnostic evaluation. Accurate determination of tissue origin is essential for guiding treatment and improving clinical outcomes. The Canhelp\n                      <jats:sup>\u00ae<\/jats:sup>\n                      -Origin gene expression profiling (GEP) assay, combined with specific immunohistochemical markers, has emerged as a valuable tool for identifying the origin of metastatic carcinomas. However, its clinical application in challenging cases, particularly those with atypical presentation and limited lineage-specific markers, warrants further documentation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We present a case of a patient with right axillary metastatic carcinoma, in which the primary site remained undetermined after extensive imaging and initial immunohistochemical workup. Integrated application of the Canhelp\n                      <jats:sup>\u00ae<\/jats:sup>\n                      -Origin GEP assay and immunohistochemical staining for lineage-specific markers, including TRPS1 and SOX10 (+), supported a probable diagnosis of metastatic triple-negative breast cancer, though melanoma and synovial sarcoma could not be fully excluded given overlapping immunophenotype and limited available tissue for additional confirmatory molecular testing. The patient subsequently received an AC-based chemotherapy regimen combined with immunotherapy and sequential radiotherapy. According to RECIST 1.1 criteria, the therapeutic effect was confirmed as complete response (CR), with complete remission of axillary and cervical lymph node metastases. Notably, treatment response is non-specific and cannot serve as retrospective proof of tumor tissue-of-origin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case highlights the potential adjunct value of the Canhelp\n                      <jats:sup>\u00ae<\/jats:sup>\n                      -Origin assay in identifying the tissue of origin in CUP and underscores the supportive diagnostic role of TRPS1 immunohistochemistry in triple-negative breast cancer. These findings demonstrate the clinical utility of an integrated diagnostic strategy for the probabilistic classification of CUP, supporting its potential to guide effective treatment decisions in this challenging clinical setting.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1920276","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:28:59Z","timestamp":1789014539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnosis and management of axillary lymph node metastasis from an unknown primary carcinoma: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Motong","family":"Xu","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Qiu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.5552","article-title":"Cancer of unknown primary: a review on clinical guidelines in the development and targeted management of patients with the unknown primary site","volume":"11","author":"Qaseem","year":"2019","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1186\/s12885-023-11563-1","article-title":"Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China","volume":"23","author":"Ren","year":"2023","journal-title":"BMC Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16213568","article-title":"A comprehensive review of Trps1 as a diagnostic immunohistochemical marker for primary breast carcinoma: latest insights and diagnostic pitfalls","volume":"16","author":"Georgescu","year":"2024","journal-title":"Cancers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2020.12.001","article-title":"The role of molecular profiling in the diagnosis and management of metastatic undifferentiated cancer of unknown primary(\u2606): molecular profiling of metastatic cancer of unknown primary","volume":"38","author":"Dermawan","year":"2021","journal-title":"Semin Diagn Pathol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s00428-014-1545-2","article-title":"Gene expression profiling in patients with carcinoma of unknown primary site: from translational research to standard of care","volume":"464","author":"Hainsworth","year":"2014","journal-title":"Virchows Archiv Int J Pathol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2020-0234","article-title":"Defining a distinct immunotherapy eligible subset of patients with cancer of unknown primary using gene expression profiling with the 92-gene assay","volume":"25","author":"Raghav","year":"2020","journal-title":"Oncologist"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.Crc-25-0171","article-title":"Gpsai: a clinically validated AI tool for tissue of origin prediction during routine tumor profiling","volume":"5","author":"Ghani","year":"2025","journal-title":"Cancer Res Commun"},{"key":"B8","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12967-022-03318-6","article-title":"Clinical validation of a 90-gene expression test for tumor tissue of origin diagnosis: a large-scale multicenter study of 1417 patients","volume":"20","author":"Sun","year":"2022","journal-title":"J Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2020.06.005","article-title":"Development and clinical validation of a 90-gene expression assay for identifying tumor tissue origin","volume":"22","author":"Ye","year":"2020","journal-title":"J Mol Diagnostics JMD"},{"key":"B10","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1186\/s12967-019-2082-1","article-title":"90-gene signature assay for tissue origin diagnosis of brain metastases","volume":"17","author":"Zheng","year":"2019","journal-title":"J Transl Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00354","article-title":"Gene expression profiling for diagnosis of triple-negative breast cancer: a multicenter, retrospective cohort study","volume":"9","author":"Wang","year":"2019","journal-title":"Front Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2012.43.3755","article-title":"Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon Research Institute","volume":"31","author":"Hainsworth","year":"2013","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1097\/pap.0000000000000409","article-title":"Trps1, a new promising marker for assessment of distant metastatic breast cancer","volume":"30","author":"McIntire","year":"2023","journal-title":"Adv Anatomic Pathol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13000-025-01623-4","article-title":"Trichorhinophalangeal syndrome type 1 (Trps1) in breast pathology: diagnostic utility and pitfalls","volume":"20","author":"Hashmi","year":"2025","journal-title":"Diagn Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2025.152480","article-title":"The diagnostic significance of immunohistochemical expression of Sox10 and Trps1 in triple negative breast cancer","volume":"78","author":"Elgohary","year":"2025","journal-title":"Ann Diagn Pathol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2024.01.003","article-title":"Diagnostic utility and sensitivities of matrix Gla protein (Mgp), Trps1 and Gata3 in breast cancer: focusing on metastatic breast cancer, invasive breast carcinoma with special features, and salivary gland-type tumours","volume":"56","author":"Wu","year":"2024","journal-title":"Pathology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/pas.0000000000002213","article-title":"Trps1 is a highly sensitive marker for breast cancer: a tissue microarray study evaluating more than 19,000 tumors from 152 different tumor entities","volume":"48","author":"Lennartz","year":"2024","journal-title":"Am J Surg Pathol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/pgp.0000000000001042","article-title":"Trps1 is consistently expressed in hidradenoma papilliferum","volume":"44","author":"Velthof","year":"2025","journal-title":"Int J Gynecological Pathol Off J Int Soc Gynecological Pathologists"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-024-00746-6","article-title":"Diagnostic utility of a 90-gene expression assay (Canhelp-Origin) for patients with metastatic cancer with an unclear or unknown diagnosis","volume":"29","author":"Qi","year":"2025","journal-title":"Mol Diagnosis Ther"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1920276\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:28:59Z","timestamp":1789014539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1920276\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":19,"alternative-id":["10.3389\/fonc.2026.1920276"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1920276","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"article-number":"1920276"}}