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

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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.

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Data availability

All relevant data are available from the corresponding author upon reasonable request.

References

  1. Emile J-F, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, Requena-Caballero L, Jordan MB, Abdel-Wahab O, Allen CE, Charlotte F, Diamond EL, Egeler RM, Fischer A, Herrera JG, Henter JI, Janku F, Merad M, Picarsic J, Rodriguez-Galindo C, Rollins BJ, Tazi A, Vassallo R, Weiss LM, Histiocyte Society (2016) Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 127:2672–2681. https://doi.org/10.1182/blood-2016-01-690636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chan JKC, Lamant L, Algar E, Delsol G, Tsang WYW, Lee KC, Tiedemann K, Chow CW (2008) ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy. Blood 112:2965–2968. https://doi.org/10.1182/blood-2008-03-147017

    Article  CAS  PubMed  Google Scholar 

  3. Gupta GK, Xi L, Pack SD, Jones JB, Pittaluga S, Raffeld M, Jaffe ES (2019) ALK-positive histiocytosis with KIF5B-ALK fusion in an adult female. Haematologica 104:e534–e536. https://doi.org/10.3324/haematol.2019.230094

    Article  PubMed  PubMed Central  Google Scholar 

  4. Huang H, Gheorghe G, North PE, Suchi M (2018) Expanding the phenotype of ALK-positive histiocytosis: a report of 2 cases. Pediatr Dev Pathol 21:449–455. https://doi.org/10.1177/1093526617740784

    Article  PubMed  Google Scholar 

  5. Chang KTE, Tay AZE, Kuick CH, Chen H, Algar E, Taubenheim N, Campbell J, Mechinaud F, Campbell M, Super L, Chantranuwat C, Yuen ST, Chan JKC, Chow CW (2019) ALK-positive histiocytosis: an expanded clinicopathologic spectrum and frequent presence of KIF5B-ALK fusion. Mod Pathol 32:598–608. https://doi.org/10.1038/s41379-018-0168-6

    Article  PubMed  Google Scholar 

  6. Diamond EL, Durham BH, Haroche J, Yao Z, Ma J, Parikh SA, Wang Z, Choi J, Kim E, Cohen-Aubart F, Lee SCW, Gao Y, Micol JB, Campbell P, Walsh MP, Sylvester B, Dolgalev I, Aminova O, Heguy A, Zappile P, Nakitandwe J, Ganzel C, Dalton JD, Ellison DW, Estrada-Veras J, Lacouture M, Gahl WA, Stephens PJ, Miller VA, Ross JS, Ali SM, Briggs SR, Fasan O, Block J, Heritier S, Donadieu J, Solit DB, Hyman DM, Baselga J, Janku F, Taylor BS, Park CY, Amoura Z, Dogan A, Emile JF, Rosen N, Gruber TA, Abdel-Wahab O (2016) Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov 6:154–165. https://doi.org/10.1158/2159-8290.CD-15-0913

    Article  CAS  PubMed  Google Scholar 

  7. Estrada-Veras JI, O’Brien KJ, Boyd LC, Dave RH, Durham BH, Xi L, Malayeri AA, Chen MY, Gardner PJ, Alvarado Enriquez JR, Shah N, Abdel-Wahab O, Gochuico BR, Raffeld M, Jaffe ES, Gahl WA (2017) The clinical spectrum of Erdheim-Chester disease: an observational cohort study. Blood Adv 1:357–366. https://doi.org/10.1182/bloodadvances.2016001784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. West DS, Dogan A, Quint PS, Tricker-Klar ML, Porcher JC, Ketterling RP, Law ME, McPhail ED, Viswanatha DS, Kurtin PJ, Dao LN, Ritzer RD, Nowakowski GS, Feldman AL (2013) Clonally related follicular lymphomas and Langerhans cell neoplasms: expanding the spectrum of transdifferentiation. Am J Surg Pathol 37:978–986. https://doi.org/10.1097/PAS.0b013e318283099f

    Article  PubMed  Google Scholar 

  9. Péricart S, Waysse C, Siegfried A, Struski S, Delabesse E, Laurent C, Evrard S (2019) Subsequent development of histiocytic sarcoma and follicular lymphoma: cytogenetics and next-generation sequencing analyses provide evidence for transdifferentiation of early common lymphoid precursor-a case report and review of literature. Virchows Arch 476:609–614. https://doi.org/10.1007/s00428-019-02691-w

    Article  PubMed  Google Scholar 

  10. Shao H, Xi L, Raffeld M, Feldman AL, Ketterling RP, Knudson R, Rodriguez-Canales J, Hanson J, Pittaluga S, Jaffe ES (2011) Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases. Mod Pathol 24:1421–1432. https://doi.org/10.1038/modpathol.2011.102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li T, Deng Y, Shi Y, Tian R, Chen Y, Zou L, Kazi JU, Rönnstrand L, Feng B, Chan SO, Chan WY, Sun J, Zhao H (2018) Bruton’s tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma. Oncogene 37:6180–6194. https://doi.org/10.1038/s41388-018-0397-7

    Article  CAS  PubMed  Google Scholar 

  12. Boissard F, Fournié J-J, Quillet-Mary A, Ysebaert L, Poupot M (2015) Nurse-like cells mediate ibrutinib resistance in chronic lymphocytic leukemia patients. Blood Cancer J 5:e355. https://doi.org/10.1038/bcj.2015.74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Herman SEM, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ, Hamdy A, Johnson AJ, Byrd JC (2011) Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 117:6287–6296. https://doi.org/10.1182/blood-2011-01-328484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ponader S, Chen S-S, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA (2012) The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 119:1182–1189. https://doi.org/10.1182/blood-2011-10-386417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ross JS, Ali SM, Fasan O, Block J, Pal S, Elvin JA, Schrock AB, Suh J, Nozad S, Kim S, Jeong Lee H, Sheehan CE, Jones DM, Vergilio JA, Ramkissoon S, Severson E, Daniel S, Fabrizio D, Frampton G, Miller VA, Stephens PJ, Gay LM (2017) ALK fusions in a wide variety of tumor types respond to anti-ALK targeted therapy. Oncologist 22:1444–1450. https://doi.org/10.1634/theoncologist.2016-0488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank François-Xavier Frenois for the whole slide imaging (Imag’IN Platform, IUCT Toulouse, France) and the Cancer biobank of Toulouse University Cancer Institute (BB-0033-00014). We thank Isabelle Luquet and Frédéric Escudié for their help in analysing data. We also thank Juliet Raine and Ana Darquier for their advice during the writing process.

Funding

This study was funded by the Cancer Institute University of Toulouse (IUCT-Oncopole), France.

Author information

Authors and Affiliations

  1. Department of Pathology, Toulouse University Hospital Center, Cancer Institute University of Toulouse-Oncopole, 1 avenue Irène Joliot-Curie, 31059, Toulouse CEDEX 9, France

    Charlotte Syrykh, Sarah Péricart, Solène M. Evrard, Pierre Brousset & Camille Laurent

  2. INSERM UMR1037 Cancer Research Center of Toulouse (CRCT), ERL 5294 National Center for Scientific Research (CNRS), University of Toulouse III Paul-Sabatier, Toulouse, France

    Loïc Ysebaert, Solène M. Evrard, Fabienne Meggetto, Pierre Brousset & Camille Laurent

  3. Departement of Hematology, Toulouse University Hospital Center, Cancer Institute University of Toulouse-Oncopole, Toulouse, France

    Loïc Ysebaert

  4. Programme Hospitalo-Universitaire en Cancérologie CAPTOR, Toulouse, France

    Loïc Ysebaert & Camille Laurent

  5. Institut Carnot Lymphome CALYM, Laboratoire d’Excellence ‘TOUCAN’, Toulouse, France

    Loïc Ysebaert, Fabienne Meggetto, Pierre Brousset & Camille Laurent

  6. Department of Nuclear Medicine, Toulouse University Hospital Center, Cancer Institute University of Toulouse-Oncopole, Toulouse, France

    Salim Kanoun

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  1. Charlotte Syrykh
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  2. Loïc Ysebaert
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  3. Sarah Péricart
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  7. Pierre Brousset
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  8. Camille Laurent
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Contributions

C Syrykh, C Laurent and L Ysebaert collected samples and data. C Syrykh, C Laurent, S Péricart, S M. Evrard and P Brousset analysed data and drafted the paper. F Meggetto performed experiments and S Kanoun interpreted PET images. All authors read and approved the submitted manuscript.

Corresponding author

Correspondence to Camille Laurent.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

Tissue samples were collected at the CRB Cancer des Hôpitaux de Toulouse bio bank. According to French law, the collection has been declared to the Ministry of Higher Education and Research (DC 2009-989) and obtained a transfer agreement (DC-2008-820). The samples were processed following standard ethical procedures (Helsinki Declaration), and the study was approved by the local ethical committee Comité de Protection des Personnes Sud-Ouest et Outremer II. Clinical and biological samples annotations have been declared to the CNIL (Comité National Informatique et Liberté; i.e. Data Processing and Liberties National Committee).

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Syrykh, C., Ysebaert, L., Péricart, S. et al. ALK-positive histiocytosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a multitarget response under ibrutinib. Virchows Arch 478, 779–783 (2021). https://doi.org/10.1007/s00428-020-02937-y

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  • DOI: https://doi.org/10.1007/s00428-020-02937-y

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