Abstract
Histiocytic sarcoma in advanced clinical stages is typically an aggressive neoplasm, with poor response to conventional chemotherapy. An 18-year-old male with refractory histiocytic sarcoma that had transformed from Rosai–Dorfman disease was admitted to our hospital. A pathogenic variant of MAP2K1 was detected by next-generation sequencing of tumor specimens. Affected regions showed excellent responses to the MEK inhibitor trametinib. It has been reported that RAS/MEK/ERK pathway is activated in many cases of histiocytic sarcoma. MEK inhibition may represent a useful treatment option in histiocytic sarcoma.
Similar content being viewed by others
References
Foucar E, Rosai J, Dorfman R. Sinus histiocytosis with massive lymphadenopathy. An analysis of 14 deaths occurring in a patient registry. Cancer. 1984;54:1834–40.
Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease. Blood. 2018;131:2877–90.
Facchetti F, Pileri SA, Lorenzi L, Tabanelli V, Rimsza L, Pittaluga S, et al. Histiocytic and dendritic cell neoplasms: what have we learnt by studying 67 cases. Virchows Arch. 2017;471:467–89.
Go H, Jeon YK, Huh J, Choi SJ, Choi YD, Cha HJ, et al. Frequent detection of BRAF(V600E) mutations in histiocytic and dendritic cell neoplasms. Histopathology. 2014;65:261–72.
Liu Q, Tomaszewicz K, Hutchinson L, Hornick JL, Woda B, Yu H. Somatic mutations in histiocytic sarcoma identified by next generation sequencing. Virchows Arch. 2016;469:233–41.
Tian X, Xu J, Fletcher C, Hornick JL, Dorfman DM. Expression of enhancer of zeste homolog 2 (EZH2) protein in histiocytic and dendritic cell neoplasms with evidence for p-ERK1/2-related, but not MYC- or p-STAT3-related cell signaling. Mod Pathol. 2018;31:553–61.
Harris MH, DuBois SG, Glade Bender JL, Kim A, Crompton BD, Parker E, et al. Multicenter feasibility study of tumor molecular profiling to inform therapeutic decisions in advanced pediatric solid tumors: the individualized cancer therapy (iCat) study. JAMA Oncol. 2016;2:608–15.
Worst BC, van Tilburg CM, Balasubramanian GP, Fiesel P, Witt R, Freitag A, et al. Next-generation personalised medicine for high-risk paediatric cancer patients—the INFORM pilot study. Eur J Cancer. 2016;65:91–101.
Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S, Vats P, et al. Integrative clinical sequencing in the management of refractory or relapsed cancer in youth. JAMA. 2015;314:913–25.
Garces S, Medeiros LJ, Patel KP, Li S, Pina-Oviedo S, Li J, et al. Mutually exclusive recurrent KRAS and MAP2K1 mutations in Rosai-Dorfman disease. Mod Pathol. 2017;30:1367–77.
Gounder MM, Solit DB, Tap WD. Trametinib in histiocytic sarcoma with an activating MAP2K1 (MEK1) mutation. N Engl J Med. 2018;378:1945–7.
Arcila ME, Drilon A, Sylvester BE, Lovly CM, Borsu L, Reva B, et al. MAP2K1 (MEK1) mutations define a distinct subset of lung adenocarcinoma associated with smoking. Clin Cancer Res. 2015;21:1935–43.
Voruz S, Cairoli A, Naveiras O, de Leval L, Missiaglia E, Homicsko K, et al. Response to MEK inhibition with trametinib and tyrosine kinase inhibition with imatinib in multifocal histiocytic sarcoma. Haematologica. 2018;103:e39–41.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict of interests to disclose.
About this article
Cite this article
Kumamoto, T., Aoki, Y., Sonoda, T. et al. A case of recurrent histiocytic sarcoma with MAP2K1 pathogenic variant treated with the MEK inhibitor trametinib. Int J Hematol 109, 228–232 (2019). https://doi.org/10.1007/s12185-018-2553-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-018-2553-9