{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:57:43Z","timestamp":1747184263729,"version":"3.40.5"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epidermal growth factor receptor <jats:bold>(<\/jats:bold>EGFR)\u2010tyrosine kinase inhibitor (TKI) resistance may be acquired via genotypic and\/or phenotypic transformations. Herein, we report an extremely uncommon case with sequential small cell transformation and EGFR T790M mutation, in an elderly female with <jats:italic>EGFR<\/jats:italic> exon 21 L858R\u2010mutant lung adenocarcinoma, following treatment with a first\u2010generation EGFR\u2010TKI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case<\/jats:title><jats:p>A 67\u2010year\u2010old female never\u2010smoker presented with a cough and dyspnoea of 2\u2009months' duration. Computerised tomography revealed a 39\u2009mm lesion in the upper lobe of the right lung with pleural effusion. Pleural fluid cytology revealed metastatic lung adenocarcinoma, and <jats:italic>EGFR<\/jats:italic> testing revealed exon 21 L858R mutation. She was started on gefitinib. After a progression\u2010free survival of 31\u2009months, she presented with disease progression and multiple extra\u2010thoracic metastases. Fine needle aspiration cytology of a chest wall lesion revealed metastatic small cell carcinoma. <jats:italic>EGFR<\/jats:italic> testing on this aspirate revealed persistent L858R mutation only. In view of small cell transformation, chemotherapy (etoposide and carboplatin) was administered. After 4\u2009months, ascitic fluid cytology revealed metastatic adenocarcinoma with persistent L858R mutation and an acquired T790M mutation (both detected on liquid biopsy as well) indicating amplification of the adenocarcinoma clone and regression of the small cell carcinoma clone. She was then initiated on osimertinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The index case highlights the significance of serial <jats:italic>EGFR<\/jats:italic> genotyping along with repeated tissue and\/or blood sampling in the prompt detection of genetic and phenotypic resistance mechanisms to EGFR\u2010TKIs. Furthermore, it lends evidence in support of the upfront treatment approaches targeting the heterogeneity of acquired EGFR\u2010TKI resistance mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cyt.13168","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T18:10:16Z","timestamp":1658513416000},"page":"732-737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sequential small cell transformation and <scp>T790M<\/scp> mutation in an epidermal growth factor\u2010mutant lung adenocarcinoma: A rare occurrence with significant management implications"],"prefix":"10.1111","volume":"33","author":[{"given":"Malvika","family":"Shastri","sequence":"first","affiliation":[{"name":"Department of Cytology and Gynecological Pathology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2159-4325","authenticated-orcid":false,"given":"Parikshaa","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Cytology and Gynecological Pathology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-1955","authenticated-orcid":false,"given":"Nalini","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Cytology and Gynecological Pathology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Navneet","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Postgraduate Institute of Medical Education and Research  Chandigarh 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