{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:14Z","timestamp":1789624994570,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Comprehensive molecular profiling is now routinely performed in newly diagnosed non\u2010small cell lung carcinomas (NSCLCs) to identify actionable genomic alterations. Although numerous molecular abnormalities have been described in lung carcinomas, rare and unexpected gene fusions may create significant diagnostic challenges, particularly when they are characteristically associated with tumours of different lineages. To our knowledge, this is the first reported case of a primary lung squamous cell carcinoma harbouring an in\u2010frame\n                    <jats:italic>PAX8::PPAR\u03b3<\/jats:italic>\n                    fusion with a concurrent FGFR2 exon 7 missense mutation (p.W290C). An 80\u2010year\u2010old man with a smoking history exceeding 50\u2009years presented with a rapidly enlarging PET\u2010avid right upper lobe pulmonary mass. Bronchial brushing cytology demonstrated a hypercellular malignant neoplasm composed of pleomorphic squamoid cells with hyperchromatic nuclei, dense cytoplasm and extensive necrosis. Cell block material showed squamous morphology and diffuse p40 positivity, supporting squamous differentiation. Reflex next\u2010generation sequencing identified an FGFR2 exon 7 missense mutation (p.W290C; c.870G&gt;C) and targeted RNA fusion analysis demonstrated an in\u2010frame\n                    <jats:italic>PAX8::PPAR\u03b3<\/jats:italic>\n                    fusion resulting from a t(2;3)(q13;p25.2) translocation. Because\n                    <jats:italic>PAX8::PPAR\u03b3<\/jats:italic>\n                    rearrangements are strongly associated with follicular thyroid neoplasms, extensive clinicoradiologic and immunohistochemical correlation was performed to exclude metastatic thyroid carcinoma. Imaging studies showed no thyroid lesion or residual thyroid tissue, and tumour cells were negative for thyroglobulin, TTF\u20101 and PAX8. Correlation of the clinical history, radiologic findings, cytomorphology, immunophenotype and molecular profile supported the diagnosis of primary lung squamous cell carcinoma. This case expands the molecular spectrum of lung squamous cell carcinoma and highlights the importance of integrated cytopathologic, immunohistochemical, molecular and radiologic evaluation when unexpected gene fusions are identified in cytology specimens.\n                  <\/jats:p>","DOI":"10.1111\/cyt.70130","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:23:47Z","timestamp":1789622627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung Squamous Cell Carcinoma Harbouring a Novel\n                    <i>PAX8::PPAR\u03b3<\/i>\n                    Fusion and a\n                    <scp>FGFR2<\/scp>\n                    Exon 7 Missense Mutation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2804-4104","authenticated-orcid":false,"given":"Maria F.","family":"Gonzalez","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center Williams P. Clements Jr. University Hospital  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Butka","sequence":"additional","affiliation":[{"name":"PGY3 Temple University Hospital  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0476-357X","authenticated-orcid":false,"given":"Anjali","family":"Seth","sequence":"additional","affiliation":[{"name":"Molecular Pathology Laboratory, Fox Chase Cancer Center, Department of Pathology Genomic Cancer Institute  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Cancer Stat Facts: Lung and Bronchus Cancer \u201cSurveillance Epidemiology and End Results (SEER) Program National Cancer Institute \u201d 2026 https:\/\/seer.cancer.gov\/statfacts\/html\/lungb.html."},{"key":"e_1_2_11_3_1","volume-title":"Thoracic Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2021"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.lungcan.2025.108550","article-title":"Comprehensive Molecular Profiling of Advanced NSCLC Using NGS: Prevalence of Druggable Mutations and Clinical Trial Opportunities in the ATLAS Study","volume":"204","author":"Serna\u2010Blasco R.","year":"2025","journal-title":"Lung Cancer"},{"issue":"9","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1089\/thy.2024.0216","article-title":"FGFR Alterations in Thyroid Carcinoma: A Novel Class of Primary Drivers With Significant Therapeutic Implications and Secondary Molecular Events Potentially Mediating Resistance in Thyroid Malignancy","volume":"34","author":"Sabbagh M. F.","year":"2024","journal-title":"Thyroid"},{"issue":"4","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/PAI.0b013e3182025f66","article-title":"Expression of PAX8 in Normal and Neoplastic Tissues: A Comprehensive Immunohistochemical Study","volume":"19","author":"Tacha D. T.","year":"2011","journal-title":"Applied Immunohistochemistry & Molecular Morphology"},{"issue":"4","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1210\/jc.2017-02533","article-title":"Pioglitazone Therapy of PAX8\u2010PPAR\u03b3 Fusion Protein Thyroid Carcinoma","volume":"103","author":"Giordano T. J.","year":"2018","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"issue":"5","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.17931","article-title":"Peroxisome Proliferator\u2010Activated Receptors as Therapeutic Target for Cancer","volume":"28","author":"Wang Y.","year":"2024","journal-title":"Journal of Cellular and Molecular Medicine"},{"key":"e_1_2_11_9_1","volume-title":"Endocrine and Neuroendocrine Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2025"},{"issue":"7417","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature11404","article-title":"Comprehensive Genomic Characterization of Squamous Cell Lung Cancers","volume":"489","author":"Cancer Genome Atlas Research Network","year":"2012","journal-title":"Nature"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1514471","article-title":"Case Report: High\u2010Grade Serous Tubo\u2010Ovarian Carcinoma With FGFR2::IQCG Fusion and Insights Into Targetability","volume":"14","author":"Sono R.","year":"2024","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_11_12_1","unstructured":"Genomenon \u201cFGFR2 W290C: Gene Variant Detail. Cancer Knowledgebase (CKB) \u201d 2026 https:\/\/ckb.genomenon.com\/geneVariant\/show?geneVariantId=3773."}],"container-title":["Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70130","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cyt.70130","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:23:50Z","timestamp":1789622630000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.70130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":11,"alternative-id":["10.1111\/cyt.70130"],"URL":"https:\/\/doi.org\/10.1111\/cyt.70130","archive":["Portico"],"relation":{},"ISSN":["0956-5507","1365-2303"],"issn-type":[{"value":"0956-5507","type":"print"},{"value":"1365-2303","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"2026-02-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cyt.70130"}}