title: A malignant inflammatory myofibroblastic tumor of the hypopharynx harboring the 3a/b variants of theEML4-ALKfusion gene.
abstract: Inflammatory myofibroblastic tumors (IMT) in the head and neck region are rare neoplasms that generally mimic benign/low-grade neoplasms. Overexpression of anaplastic lymphoma kinase (ALK) has been reported in 50% of IMT cases, secondary toALKactivation by structural rearrangements in theALKgene, which results in a fusion protein with echinoderm microtubule associated protein like 4 (EML4) in ~20% of cases. The present study describes a case of a 74-year-old woman with a malignant IMT in the right posterior hypopharynx harboring a previously unreported chromosomal rearrangement resulting inEML4andALKgene fusion. Strong ALK immunoreactivity was observed in neoplastic cells, while fluorescentin situhybridization combined with fluorescent fragment analysis and direct sequencing identified the first case of the 3a/b variants of theEML4-ALKfusion gene in IMT. The results of the current study highlight the uncommon occurrence of ALK-positive IMT in the head/neck region and demonstrate the importance of integrating different molecular methodologies to identify unequivocal gene fusion characterization.
authors.affiliation: Laboratory of Oncology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.affiliation: Pathologic Anatomy Unit, University Hospital Policlinico, I-41124 Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Laboratory of Oncology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Trombetta
authors.affiliation: Laboratory of Oncology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: La Torre
authors.affiliation: Unit of Pathology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Leonarda
authors.initials: L
authors.lastname: Di Candia
authors.affiliation: Pathologic Anatomy Unit, University Hospital Policlinico, I-41124 Modena, Italy.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Mengoli
authors.affiliation: Laboratory of Oncology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sparaneo
authors.affiliation: Laboratory of Oncology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.affiliation: Unit of Pathology, Scientific Institute for Research and Healthcare, Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
keywords: anaplastic lymphoma kinase; echinoderm microtubule associated protein like 4; fusion variants; inflammatory myofibroblastic tumor; molecular markers