| Literature DB >> 34727172 |
Paul G Kemps1,2, Jennifer Picarsic3, Benjamin H Durham4,5, Zofia Hélias-Rodzewicz6,7, Laura Hiemcke-Jiwa2, Cor van den Bos2,8, Marianne D van de Wetering2,8, Carel J M van Noesel9, Jan A M van Laar10,11, Robert M Verdijk12, Uta E Flucke13, Pancras C W Hogendoorn1, F J Sherida H Woei-A-Jin14, Raf Sciot15, Andreas Beilken16, Friedrich Feuerhake17, Martin Ebinger18, Robert Möhle19, Falko Fend20, Antje Bornemann20, Verena Wiegering21, Karen Ernestus22, Tina Méry23, Olga Gryniewicz-Kwiatkowska24, Bozenna Dembowska-Baginska24, Dmitry A Evseev25, Vsevolod Potapenko26,27, Vadim V Baykov28, Stefania Gaspari29, Sabrina Rossi30, Marco Gessi31, Gianpiero Tamburrini32, Sébastien Héritier33, Jean Donadieu7,33, Jacinthe Bonneau-Lagacherie34, Claire Lamaison35, Laure Farnault36, Sylvie Fraitag37, Marie-Laure Jullié38, Julien Haroche39, Matthew Collin40, Jackie Allotey31, Majid Madni41, Kerry Turner42, Susan Picton43, Pasquale M Barbaro44, Alysa Poulin45, Ingrid S Tam45, Dina El Demellawy46, Brianna Empringham47, James A Whitlock47, Aditya Raghunathan48, Amy A Swanson48, Mariko Suchi49, Jon M Brandt50, Nabeel R Yaseen51, Joanna L Weinstein52, Irem Eldem53, Bryan A Sisk53, Vaishnavi Sridhar54, Mandy Atkinson54, Lucas R Massoth55, Jason L Hornick56, Sanda Alexandrescu56,57, Kee Kiat Yeo58, Kseniya Petrova-Drus5, Stephen Z Peeke59, Laura S Muñoz-Arcos60, Daniel G Leino3, David D Grier3, Robert Lorsbach3, Somak Roy3, Ashish R Kumar61,62, Shipra Garg31, Nishant Tiwari31, Kristian T Schafernak31, Michael M Henry63, Astrid G S van Halteren2,64, Oussama Abla47, Eli L Diamond65, Jean-François Emile6,7.
Abstract
ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.Entities:
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Year: 2022 PMID： 34727172 PMCID： PMC8759533 DOI： 10.1182/blood.2021013338
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113