title: (Secondary) solid tumors in thyroid cancer patients treated with the multi-kinase inhibitor sorafenib may present diagnostic challenges.
abstract: BACKGROUND
  Sorafenib is an orally active multikinase tyrosine kinase inhibitor (TKI) that targets B-type Raf kinase (BRAF), vascular endothelial growth factor receptors (VEGFR) 1 and 2, and rearranged during transfection (RET), inducing anti-angiogenic and pro-apoptotic actions in a wide range of solid tumors. A side effect of sorafenib is the occurrence of cutaneous squamous tumors.
  
  
  METHODS
  Here we describe three patients with a history of sorafenib treatment for advanced radioactive iodine refractory papillary thyroid cancer (two with a BRAF c.1799 T > A and one carrying a rare c.1799-1801het_delTGA mutation) who presented with secondary non-cutaneous lesions. The first patient was diagnosed with a squamous cell carcinoma (SCC) of the tongue, the second patient with a primary adenocarcinoma of the lung, and the third with a SCC originating from the cricoid. Secondary analysis was required to show that the latter two presentations were in fact recurrent thyroid cancer.
  
  
  CONCLUSIONS
  These findings suggest that drugs such as sorafenib may induce metaplasia/clonal divergence of metastatic thyroid cancer and thus cause diagnostic misclassification. Furthermore, sorafenib is potentially involved in the tumorigenesis of secondary non-cutaneous SCC. These observations should now be confirmed in larger series of patients treated with drugs such as sorafenib.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.|Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tatiana C
authors.initials: TC
authors.lastname: Schneider
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kapiteijn
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan W A
authors.initials: JWA
authors.lastname: Smit
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacobus J M
authors.initials: JJM
authors.lastname: van der Hoeven
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. j.morreau@lumc.nl.
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C117307:KRAS protein, human; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)