ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.
Adolescent
Adult
Anaplastic Lymphoma Kinase
/ analysis
Child
Child, Preschool
Female
Histiocytic Disorders, Malignant
/ complications
Humans
Infant
Male
Nervous System Diseases
/ etiology
Oncogene Proteins, Fusion
/ analysis
Protein Kinase Inhibitors
/ therapeutic use
Retrospective Studies
Young Adult
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
13 01 2022
13 01 2022
Historique:
received:
19
07
2021
accepted:
18
10
2021
pubmed:
3
11
2021
medline:
8
3
2022
entrez:
2
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34727172
pii: S0006-4971(21)01821-8
doi: 10.1182/blood.2021013338
pmc: PMC8759533
doi:
Substances chimiques
KIF5B-ALK fusion protein, human
0
Oncogene Proteins, Fusion
0
Protein Kinase Inhibitors
0
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
256-280Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA259260
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2022 by The American Society of Hematology.
Références
Nature. 2019 Mar;567(7749):521-524
pubmed: 30867592
Int J Surg Pathol. 2021 Aug;29(5):543-549
pubmed: 33243034
Mod Pathol. 2019 Jun;32(6):830-843
pubmed: 30626916
JAMA Oncol. 2018 Mar 1;4(3):384-388
pubmed: 29188284
Blood. 2020 May 28;135(22):1929-1945
pubmed: 32187362
Blood. 2017 Sep 14;130(11):1377-1380
pubmed: 28667012
Pediatr Blood Cancer. 2021 Nov;68(11):e29227
pubmed: 34245207
Mod Pathol. 2019 May;32(5):598-608
pubmed: 30573850
Nat Med. 2019 Dec;25(12):1839-1842
pubmed: 31768065
Nat Immunol. 2020 Jan;21(1):1-7
pubmed: 31831887
Am J Surg Pathol. 2021 Jan;45(1):35-44
pubmed: 33177341
Am J Surg Pathol. 2021 Mar 1;45(3):347-355
pubmed: 32826530
Am J Hematol. 2021 May 1;96(5):E146-E150
pubmed: 33539584
Lung Cancer. 2015 May;88(2):231-4
pubmed: 25736571
Mod Pathol. 2018 May;31(5):753-762
pubmed: 29327718
Blood. 2014 Sep 4;124(10):1655-8
pubmed: 24982505
Blood. 2014 Nov 6;124(19):3016-9
pubmed: 25150293
Leukemia. 2007 Feb;21(2):201-6
pubmed: 17170732
Blood Adv. 2017 Feb 14;1(6):357-366
pubmed: 28553668
Oncologist. 2021 Jul;26(7):e1263-e1272
pubmed: 33904632
Clin Cancer Res. 2019 Nov 15;25(22):6662-6670
pubmed: 31358542
Blood. 2014 May 15;123(20):3152-5
pubmed: 24652991
Blood. 2016 Nov 24;128(21):2533-2537
pubmed: 27729324
Virchows Arch. 2017 Oct;471(4):467-489
pubmed: 28695297
Mol Cytogenet. 2019 Jun 17;12:27
pubmed: 31236139
J Clin Oncol. 2019 Nov 1;37(31):2857-2865
pubmed: 31513482
Blood. 2014 Nov 6;124(19):3007-15
pubmed: 25202140
Haematologica. 2019 Nov;104(11):e534-e536
pubmed: 31371408
Mod Pathol. 2017 Oct;30(10):1367-1377
pubmed: 28664935
JCO Precis Oncol. 2021 May 03;5:
pubmed: 34036223
Turk Patoloji Derg. 2021;37(2):172-177
pubmed: 33973641
Haematologica. 2018 Apr;103(4):e177-e180
pubmed: 29472347
Mod Pathol. 2015 Jul;28(7):904-12
pubmed: 25857825
Haematologica. 2020 Apr;105(4):951-960
pubmed: 31439678
Am J Surg Pathol. 2022 Mar 1;46(3):344-352
pubmed: 34482333
J Am Acad Dermatol. 2020 Aug 18;:
pubmed: 32822792
Pediatr Blood Cancer. 2020 Jul;67(7):e28381
pubmed: 32383820
Neuro Oncol. 2020 Jul 7;22(7):979-992
pubmed: 31950179
Leukemia. 2003 Dec;17(12):2257-317
pubmed: 14671650
Cancer Discov. 2014 Aug;4(8):889-95
pubmed: 24875859
Cancer Discov. 2016 Feb;6(2):154-65
pubmed: 26566875
JAMA Oncol. 2017 Sep 1;3(9):1253-1256
pubmed: 28253394
Am J Surg Pathol. 2005 Jan;29(1):21-8
pubmed: 15613853
Am J Surg Pathol. 2019 Jan;43(1):93-101
pubmed: 29877921
Clin Cancer Res. 2019 Dec 15;25(24):7294-7302
pubmed: 31506385
Leuk Lymphoma. 2021 May;62(5):1234-1238
pubmed: 33353436
Am J Surg Pathol. 2003 May;27(5):579-93
pubmed: 12717244
Blood. 2013 Feb 28;121(9):1495-500
pubmed: 23258922
Acta Haematol. 2021;144(2):218-221
pubmed: 32721959
Oncologist. 2017 Dec;22(12):1444-1450
pubmed: 29079636
Virchows Arch. 2021 Dec;479(6):1079-1083
pubmed: 33825946
Blood. 2008 Oct 1;112(7):2965-8
pubmed: 18660380
Am J Hematol. 2018 May;93(5):E114-E117
pubmed: 29396850
BMJ Case Rep. 2018 Mar 7;2018:
pubmed: 29514838
Br J Haematol. 2016 Sep;174(6):887-98
pubmed: 27273725
Blood. 2012 Sep 27;120(13):2700-3
pubmed: 22879539
Genes Chromosomes Cancer. 2015 Jun;54(6):361-8
pubmed: 25899310
Br J Haematol. 2018 Jan;180(1):150-153
pubmed: 27711968
Pediatr Dev Pathol. 2018 Sep-Oct;21(5):449-455
pubmed: 29224419
Br J Haematol. 2018 Nov;183(4):608-617
pubmed: 30421536
Blood. 2016 Jun 2;127(22):2672-81
pubmed: 26966089
Pediatr Blood Cancer. 2013 Feb;60(2):175-84
pubmed: 23109216
Am J Surg Pathol. 2019 Aug;43(8):1156
pubmed: 31021856
Lancet Oncol. 2017 Feb;18(2):e113-e125
pubmed: 28214412
Nat Rev Cancer. 2011 Jul 07;11(8):558-72
pubmed: 21734724
Ann Oncol. 2016 Sep;27 Suppl 3:iii4-iii15
pubmed: 27573755
Lancet. 2021 Jul 10;398(10295):157-170
pubmed: 33901419
Virchows Arch. 2021 Apr;478(4):779-783
pubmed: 33011863
Clin Cancer Res. 2019 Aug 1;25(15):4712-4722
pubmed: 31028088
Neuropathol Appl Neurobiol. 2021 Oct;47(6):878-881
pubmed: 34048085
Acta Neuropathol. 2019 Aug;138(2):335-337
pubmed: 31119374
Int J Pediatr Otorhinolaryngol. 2019 Nov;126:109585
pubmed: 31351348
Acta Neuropathol Commun. 2019 Nov 4;7(1):168
pubmed: 31685033
Blood. 2010 Sep 16;116(11):1919-23
pubmed: 20519626
Mod Pathol. 2007 May;20(5):592-603
pubmed: 17396140
JCI Insight. 2017 Feb 9;2(3):e89473
pubmed: 28194436