ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition-Reference-Cited by-同舟云学术

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

Published:2022-01-13 Issue:2 Volume:139 Page:256-280
ISSN:0006-4971
Container-title:Blood
language:en
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Author:

Kemps Paul G.¹²^ORCID,Picarsic Jennifer³^ORCID,Durham Benjamin H.⁴⁵^ORCID,Hélias-Rodzewicz Zofia⁶⁷^ORCID,Hiemcke-Jiwa Laura²^ORCID,van den Bos Cor²⁸^ORCID,van de Wetering Marianne D.²⁸,van Noesel Carel J. M.⁹^ORCID,van Laar Jan A. M.¹⁰¹¹^ORCID,Verdijk Robert M.¹²^ORCID,Flucke Uta E.¹³^ORCID,Hogendoorn Pancras C. W.¹^ORCID,Woei-A-Jin F. J. Sherida H.¹⁴^ORCID,Sciot Raf¹⁵^ORCID,Beilken Andreas¹⁶^ORCID,Feuerhake Friedrich¹⁷^ORCID,Ebinger Martin¹⁸^ORCID,Möhle Robert¹⁹,Fend Falko²⁰^ORCID,Bornemann Antje²⁰,Wiegering Verena²¹^ORCID,Ernestus Karen²²,Méry Tina²³,Gryniewicz-Kwiatkowska Olga²⁴^ORCID,Dembowska-Baginska Bozenna²⁴^ORCID,Evseev Dmitry A.²⁵^ORCID,Potapenko Vsevolod²⁶²⁷^ORCID,Baykov Vadim V.²⁸^ORCID,Gaspari Stefania²⁹^ORCID,Rossi Sabrina³⁰^ORCID,Gessi Marco³¹^ORCID,Tamburrini Gianpiero³²^ORCID,Héritier Sébastien³³^ORCID,Donadieu Jean⁷³³^ORCID,Bonneau-Lagacherie Jacinthe³⁴,Lamaison Claire³⁵,Farnault Laure³⁶^ORCID,Fraitag Sylvie³⁷^ORCID,Jullié Marie-Laure³⁸^ORCID,Haroche Julien³⁹,Collin Matthew⁴⁰^ORCID,Allotey Jackie³¹,Madni Majid⁴¹,Turner Kerry⁴²^ORCID,Picton Susan⁴³,Barbaro Pasquale M.⁴⁴^ORCID,Poulin Alysa⁴⁵,Tam Ingrid S.⁴⁵^ORCID,El Demellawy Dina⁴⁶^ORCID,Empringham Brianna⁴⁷^ORCID,Whitlock James A.⁴⁷,Raghunathan Aditya⁴⁸^ORCID,Swanson Amy A.⁴⁸,Suchi Mariko⁴⁹^ORCID,Brandt Jon M.⁵⁰,Yaseen Nabeel R.⁵¹,Weinstein Joanna L.⁵²^ORCID,Eldem Irem⁵³^ORCID,Sisk Bryan A.⁵³^ORCID,Sridhar Vaishnavi⁵⁴,Atkinson Mandy⁵⁴,Massoth Lucas R.⁵⁵^ORCID,Hornick Jason L.⁵⁶^ORCID,Alexandrescu Sanda⁵⁶⁵⁷^ORCID,Yeo Kee Kiat⁵⁸^ORCID,Petrova-Drus Kseniya⁵^ORCID,Peeke Stephen Z.⁵⁹^ORCID,Muñoz-Arcos Laura S.⁶⁰^ORCID,Leino Daniel G.³^ORCID,Grier David D.³^ORCID,Lorsbach Robert³,Roy Somak³^ORCID,Kumar Ashish R.⁶¹⁶²^ORCID,Garg Shipra³¹,Tiwari Nishant³¹,Schafernak Kristian T.³¹,Henry Michael M.⁶³^ORCID,van Halteren Astrid G. S.²⁶⁴^ORCID,Abla Oussama⁴⁷^ORCID,Diamond Eli L.⁶⁵^ORCID,Emile Jean-François⁶⁷^ORCID

Affiliation:

1. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;

2. Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;

3. Division of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

4. Human Oncology and Pathogenesis Program, Department of Medicine, and

5. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY;

6. Department of Pathology, Ambroise Paré Hospital, Assistance Publique–Hôpitaux de Paris, Boulogne, France;

7. EA4340-Biomarqueurs et Essais Cliniques en Cancérologie et Onco-Hématologie, Versailles Saint-Quentin-en-Yvelines University, Boulogne, France;

8. Department of Pediatric Oncology, Emma Children’s Hospital, and

9. Department of Pathology, Amsterdam University Medical Centers, Amsterdam, The Netherlands;

10. Department of Internal Medicine and Immunology, and

11. Section of Clinical Immunology, Department of Immunology, and

12. Department of Pathology, Erasmus Medical Center University Medical Center Rotterdam, Rotterdam, The Netherlands;

13. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands;

14. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium;

15. Department of Pathology, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium;

16. Department of Pediatric Hematology and Oncology, and

17. Department of Pathology, Hannover Medical School, Hannover, Germany;

18. Department I – General Pediatrics, Children’s Hospital, Hematology and Oncology,

19. Department of Hematology and Oncology, and

20. Department of Pathology and Neuropathology and Comprehensive Cancer Center, University Hospital Tuebingen, Tuebingen, Germany;

21. Department of Oncology, Hematology and Stem Cell Transplantation, University Children’s Hospital Würzburg, Würzburg, Germany;

22. Department of Pathology, University of Würzburg and Comprehensive Cancer Center Mainfranken, Würzburg, Germany;

23. Division of Pediatric Hematology and Oncology, Department of Pediatrics, Klinikum Chemnitz, Chemnitz, Germany;

24. Department of Oncology, Children’s Memorial Health Institute, Warsaw, Poland;

25. Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia;

26. Department of Hematology and Oncology, Municipal Educational Hospital N°31, Saint Petersburg, Russia;

27. Department of Bone Marrow Transplantation and

28. Department of Pathology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia;

29. Department of Hematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children’s Hospital Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy;

30. Pathology Unit, Laboratories Department, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy;

31. Department of Pathology and

32. Department of Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;

33. Department of Pediatric Hematology and Oncology, Trousseau Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France;

34. Department of Pediatric Onco-Hematology and

35. Department of Pathology, Rennes University Hospital, Rennes, France;

36. Department of Hematology, La Conception, University Hospital of Marseille, Marseille, France;

37. Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France;

38. Department of Pathology, University Hospital of Bordeaux, Bordeaux, France;

39. Department of Internal Medicine, University Hospital La Pitié-Salpêtrière Paris, French National Reference Center for Histiocytoses, Assistance Publique–Hôpitaux de Paris, Paris, France;

40. Newcastle upon Tyne Hospitals, Newcastle upon Tyne, United Kingdom;

41. Department of Pediatric Hematology and Oncology, Nottingham University Hospitals, Nottingham, United Kingdom;

42. Department of Histopathology and

43. Department of Pediatric Oncology, Leeds Children’s Hospital, Leeds, United Kingdom;

44. Department of Hematology, Queensland Children’s Hospital, Brisbane, QLD, Australia;

45. Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada;

46. Department of Pathology, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada;

47. Department of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada;

48. Division of Anatomic Pathology, Mayo Clinic Rochester, Rochester, MN;

49. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI;

50. Department of Pediatric Oncology, Hospital Sisters Health System St Vincent Children’s Hospital, Green Bay, WI;

51. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL;

52. Department of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL;

53. Department of Pediatric Hematology and Oncology, St Louis Children’s Hospital, Washington University in St Louis, St Louis, MO;

54. Department of Pediatric Hematology and Oncology, Carilion Children’s Pediatric Hematology and Oncology, Roanoke, VA;

55. Department of Pathology, Massachusetts General Hospital, and

56. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA;

57. Department of Pathology, Boston Children’s Hospital, Boston, MA;

58. Department of Pediatric Oncology, Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA;

59. Department of Hematology and Medical Oncology, Maimonides Medical Center, Brooklyn, NY;

60. Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY;

61. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH;

62. Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH;

63. Center for Cancer and Blood Disorders, Phoenix Children’s Hospital, Phoenix, AZ;

64. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands; and

65. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

https://ashpublications.org/blood/article-pdf/139/2/256/1863353/bloodbld2021013338.pdf

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