ALK-positive histiocytosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a multitarget response under ibrutinib

Virchows Arch. 2021 Apr;478(4):779-783. doi: 10.1007/s00428-020-02937-y. Epub 2020 Oct 3.

Abstract

ALK-positive histiocytosis is a recently described entity with few reported cases in literature. Herein, we report an unusual case of ALK-positive histiocytosis showing an Erdheim-Chester disease (ECD)-like presentation, occurring in a 37-year-old woman with a 2-year history of chronic lymphocytic leukaemia (CLL). Our CLL patient relapsed 6 months after the end of fludarabine, cyclophosphamide and rituximab frontline therapy and complained of lower limb pains. A bone marrow biopsy was performed and showed concomitant CLL/small lymphocytic lymphoma and ALK-positive histiocytosis with an identical immunoglobulin heavy-chain gene rearrangement in both neoplasms, suggesting clonal relationship. After 4 years under ibrutinib therapy, our patient remains free of both diseases. This report extends the spectrum of composite hematolymphoid neoplasms and shows that ALK rearrangement should be considered in all histiocytosis subtypes. Moreover, both tumours eradication under ibrutinib suggests that BTK inhibitors may also be effective in histiocytic neoplasms.

Keywords: ALK; ALK-positive histiocytosis; Chronic lymphocytic leukaemia; Erdheim-Chester disease; Ibrutinib.

Publication types

  • Case Reports

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anaplastic Lymphoma Kinase / metabolism*
  • Biomarkers / metabolism
  • Female
  • Histiocytosis / diagnosis*
  • Histiocytosis / drug therapy
  • Histiocytosis / etiology*
  • Histiocytosis / metabolism
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications*
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Biomarkers
  • Piperidines
  • Protein Kinase Inhibitors
  • ibrutinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Adenine