Beneath HMGA2 alterations in pleomorphic adenomas: Pathological, immunohistochemical, and molecular insights

Ziyad Alsugair,P Schultz,J Michel,G Mineur,C Queiros,Marick Laé,L De Gabory,M Tassart,E Saada,R Taouachi,N Vulquin,S Mirafzal,S Guihard,L Digue,X Leroy,P Boisselier,J Frandon,A Houessinon,C Boulagnon-Rombi,C Ala-Eddine,B Devauchelle,A Siegfried,F Coste,F.R Ferrand,N Saroul,J.P Cristofari,J.P Cottier,Claire Castain,A Lapierre,C Galy,A Modesto,S Wong,C Dupin,C Castain,K Benezery,L Ramin,R.J Bensadoun,J.-M.prades J.-M.Prades,C Page,D Franetti,S Hans,J Pestre,J Lacau Saint Guily,O Choussy,H De Kermadec,B Verillaud,M Laadhari,M Lae,J.-P Marie,A Prevost,G Malouf,Marie-Delphine Lanic,M Doré,S Faivre,C Linassier,F Rolland,Anne Sudaka,E De Monès,S Vergez,M.-C Kaminsky,M Lefevre,S Duflo,A Lagrange,C Evrard,M Wassef,M Juliéron,J.M Constans,M Lapeyre,Anne-Catherine Baglin,N Pham Dang,E Fabiano,N Fakhry,Franck Tirode,F Sacino,D Bodmer,B Lallemant,J.-C Merol,P Ceruse,A Rahmani,F Kolb,A Siegfried,E Eker,Daniel Pissaloux,Charles Lépine,M Onea,L Webert,O Casiraghi,Onea Mihaela,Pierre Philouze,E Brenet,S Renard,G Dolivet,I Wagner,V Bastit,M Lesnik,S Salas,C Bertolus,N Benzerdjeb,A Coutte,A Simonaggio,S Molinier-Blossier,P Philouze,B Barry,Jonathan Lopez,Anne Champagnac,M Volondat,Valérie Costes-Martineau,D Cupissol,C Majoufre,C Marchand,B Baujat,E Babin,G Lefebvre,A Coste,M Bernadach,F Nguyen,B Toussaint,E Uro Coste,M Hourseau,E Cassagnau,C Halimi,G Valette,X Dufour,G Calais,J.P Delord,C Le Tourneau,Françoise Descotes,C Jeanne,S Kreps,Philippe Céruse,D Chevalier,T Van Den Abbele,T Maurina,V Costes,F Clatot,C Even,K Aubry,A Varoquaux,C Pouliquen,E Musat,P Herman,M Timar David,J Delgrande,H Orliac,Michel Wassef,P Maingon,G Poissonnet,R Jankowski,L Laccoureye,A Biet,A Villepelet,C.A Righini,S Camby,P Lang,V Strunski,L Bozec,Y Lelonge,F.R Obongo-Anga,M Lamuraglia,X Liem,C Pons,H Mirghani,O Malard,L Gilain,A Rambeau,Nazim Benzerdjeb,S Morinière,C Bach,F Jegoux,S Xu-Shan,A.Bozorg Grayeli,V Calugaru,A.C Baglin,H Gauthier,F Mouawad,Emmanuelle Uro-Coste,R Kaci,C Badoual,S Guillerm,O Sterkers,M Garcier,J Castelli,J.thariat J.Thariat,A.Lasne Cardon,G Noel,S Testelin,F Huguet,A Moya-Plana,E Vauleon,L Muller,O Mauvais,L Brugel,F Lagarde,V Patron,R Garrel,F Chabolle,Maxime Fieux,A Sudaka,A Timochenko,E Jadaud,J Villa

doi:10.1016/j.humpath.2024.105633

Abstract

AimsMost salivary gland neoplasms are distinguished by specific recurrent gene fusions. Recently, a subset of pleomorphic adenomas (PAs) originated from the parotid gland harboring the HMGA2:WIF1 fusion was described with a canalicular adenoma-like morphology and a greater propensity for recurrence and carcinomatous transformation. Methods and resultsThis study delineates the clinicopathological attributes of 54 cases of PAs exhibiting HMGA2 alterations, predominantly characterized by the HMGA2:WIF1 fusion, alongside a comparative analysis of their morphological and immunohistochemical profiles. The cohort consisted of 23 females and 31 males (n = 54), mean age was 56.7 (25–84), tumors predominantly originated from the parotid gland (94.4%, 51/54), with 3 cases from seromucous glands (5.6%). Mean tumor size was 2.6 cm (0.8–7.5). No clinical difference (demographic, follow-up) was observed among histological subsets (conventional, hybrid, and pure). Complete excision was performed in all cases, with follow-up data available for 41% (22/54) of patients, showing 13.6% of recurrence (3/22) between 5 and 8 months. Various histological growth patterns were identified, with the pure hypercellular monomorphic subset being the most prevalent. The HMGA2:WIF1 gene was identified in all subsets without any particular predominance. Novel gene partners of HMGA2 were identified, comprising NRXN1, INPP4B, MSRB3, PHLDA1, and FLJ41278. ConclusionsThe present study reports that the HMGA2:WIF1 gene fusion was present in all subsets of PAs without significant predominance. However, further investigations are warranted to explore the relationship between histological subsets of PAs and the molecular alterations underlying them.

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