Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 256-280 |
| Number of pages | 25 |
| Journal | Blood |
| Volume | 139 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 13 Jan 2022 |
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Blood, Vol. 139, No. 2, 13.01.2022, p. 256-280.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - ALK-positive histiocytosis
T2 - a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition
AU - Kemps, Paul G.
AU - Picarsic, Jennifer
AU - Durham, Benjamin H.
AU - Hélias-Rodzewicz, Zofia
AU - Hiemcke-Jiwa, Laura
AU - van den Bos, Cor
AU - van de Wetering, Marianne D.
AU - van Noesel, Carel J. M.
AU - van Laar, Jan A. M.
AU - Verdijk, Robert M.
AU - Flucke, Uta E.
AU - Hogendoorn, Pancras C. W.
AU - Woei-A-Jin, F. J. Sherida H.
AU - Sciot, Raf
AU - Beilken, Andreas
AU - Feuerhake, Friedrich
AU - Ebinger, Martin
AU - Möhle, Robert
AU - Fend, Falko
AU - Bornemann, Antje
AU - Wiegering, Verena
AU - Ernestus, Karen
AU - Méry, Tina
AU - Gryniewicz-Kwiatkowska, Olga
AU - Dembowska-Baginska, Bozenna
AU - Evseev, Dmitry A.
AU - Potapenko, Vsevolod
AU - Baykov, Vadim V.
AU - Gaspari, Stefania
AU - Rossi, Sabrina
AU - Gessi, Marco
AU - Tamburrini, Gianpiero
AU - Héritier, S. bastien
AU - Donadieu, Jean
AU - Bonneau-Lagacherie, Jacinthe
AU - Lamaison, Claire
AU - Farnault, Laure
AU - Fraitag, Sylvie
AU - Jullié, Marie-Laure
AU - Haroche, Julien
AU - Collin, Matthew
AU - Allotey, Jackie
AU - Madni, Majid
AU - Turner, Kerry
AU - Picton, Susan
AU - Barbaro, Pasquale M.
AU - Poulin, Alysa
AU - Tam, Ingrid S.
AU - el Demellawy, Dina
AU - Empringham, Brianna
AU - Whitlock, James A.
AU - Raghunathan, Aditya
AU - Swanson, Amy A.
AU - Suchi, Mariko
AU - Brandt, Jon M.
AU - Yaseen, Nabeel R.
AU - Weinstein, Joanna L.
AU - Eldem, Irem
AU - Sisk, Bryan A.
AU - Sridhar, Vaishnavi
AU - Atkinson, Mandy
AU - Massoth, Lucas R.
AU - Hornick, Jason L.
AU - Alexandrescu, Sanda
AU - Yeo, Kee Kiat
AU - Petrova-Drus, Kseniya
AU - Peeke, Stephen Z.
AU - Muñoz-Arcos, Laura S.
AU - Leino, Daniel G.
AU - Grier, David D.
AU - Lorsbach, Robert
AU - Roy, Somak
AU - Kumar, Ashish R.
AU - Garg, Shipra
AU - Tiwari, Nishant
AU - Schafernak, Kristian T.
AU - Henry, Michael M.
AU - van Halteren, Astrid G. S.
AU - Abla, Oussama
AU - Diamond, Eli L.
AU - Emile, Jean-François
N1 - Funding Information: P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143). Funding Information: The authors acknowledge the International Rare Histiocytic Disorders Registry (IRHDR, ClinicalTrial.gov number NCT02285582), which included some patients described in this study. The authors thank Chris Woods (Lead Analyst, Imaging Informatics) and the Research Pathology Laboratory at Cincinnati Children's Hospital Medical Center, John DeCoteau (molecular pathologist) at University of Saskatchewan, Sven van Kempen (senior laboratory technician) and Lennart Kester (clinical molecular biologist in pathology in training) at Princess M?xima Center for Pediatric Oncology, and Demi van Egmond (laboratory technician), Tom van Wezel (clinical molecular biologist in pathology), and Arjen Cleven (pathologist) at Leiden University Medical Center for technical assistance. The authors thank Els Wauters (pulmonologist and respiratory oncologist) at University Hospitals Leuven, Andreas Rosenwald (pathologist) at the Institute of Pathology of the University of W?rzburg, and Bipin Mathew (pathologist) at Leeds Teaching Hospitals for clinical care and/or diagnostics of patients described in this study. The authors thank Les Laboratoires Servier for allowing the use of their medical illustrations (Servier Medical Art, https://smart.servier.com) in the visual abstract. Figure 6 was created with BioRender.com. P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143). Publisher Copyright: © 2022 American Society of Hematology
PY - 2022/1/13
Y1 - 2022/1/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122787125&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/blood.2021013338
DO - https://doi.org/10.1182/blood.2021013338
M3 - Article
C2 - 34727172
SN - 0006-4971
VL - 139
SP - 256
EP - 280
JO - Blood
JF - Blood
IS - 2
ER -