Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia

Shintaro Kazama; Kazuaki Yokoyama; Toshimitsu Ueki; Hiroko Kazumoto; Hidetoshi Satomi; Masahiko Sumi; Ichiro Ito; Nozomi Yusa; Rika Kasajima; Eigo Shimizu; Rui Yamaguchi; Seiya Imoto; Satoru Miyano; Yukihisa Tanaka; Tamami Denda; Yasunori Ota; Arinobu Tojo; Hikaru Kobayashi

doi:10.3389/fonc.2022.974307

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia

Front Oncol. 2022 Sep 16:12:974307. doi: 10.3389/fonc.2022.974307. eCollection 2022.

Authors

Shintaro Kazama¹, Kazuaki Yokoyama², Toshimitsu Ueki¹, Hiroko Kazumoto¹, Hidetoshi Satomi³, Masahiko Sumi¹, Ichiro Ito⁴, Nozomi Yusa⁵, Rika Kasajima⁶, Eigo Shimizu⁷, Rui Yamaguchi⁸, Seiya Imoto⁷, Satoru Miyano⁹, Yukihisa Tanaka¹⁰, Tamami Denda¹⁰, Yasunori Ota¹⁰, Arinobu Tojo¹¹, Hikaru Kobayashi¹

Affiliations

¹ Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan.
² Division of Molecular Therapy, Institute of Medical Science, Advanced Clinical Research Center, The University of Tokyo, Tokyo, Japan.
³ Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan.
⁴ Department of Pathology, Nagano Red Cross Hospital, Nagano, Japan.
⁵ Department of Applied Genomics, Research Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁶ Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
⁷ Division of Health Medical Data Science, Health Intelligence Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁸ Division of Cancer Systems Biology, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁹ Department of Integrated Data Science, Medical and Dental Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan.
¹⁰ Department of Diagnostic Pathology, IMSUT Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹¹ Department of Data Science and Faculty Affairs, Tokyo Medical and Dental University, Tokyo, Japan.

Abstract

Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are distinct entities of blood neoplasms, and the exact developmental origin of both neoplasms are considered be heterogenous among patients. However, reports of concurrent LCH and AML are rare. Herein we report a novel case of concurrent LCH and AML which shared same the driver mutations, strongly suggesting a common clonal origin.An 84-year-old female presented with cervical lymphadenopathy and pruritic skin rash on the face and scalp. Laboratory tests revealed pancytopenia with 13% of blasts, elevated LDH and liver enzymes, in addition to generalised lymphadenopathy and splenomegaly by computed tomography. Bone marrow specimens showed massive infiltration of MPO-positive myeloblasts, whereas S-100 and CD1a positive atypical dendritic cell-like cells accounted for 10% of the atypical cells on bone marrow pathology, suggesting a mixture of LCH and AML. A biopsy specimen from a cervical lymph node and the skin demonstrated the accumulation of atypical cells which were positive for S-100 and CD1a. LCH was found in lymph nodes, skin and bone marrow; AML was found in peripheral blood and bone marrow (AML was predominant compared with LCH in the bone marrow). Next generation sequencing revealed four somatic driver mutations (NRAS-G13D, IDH2-R140Q, and DNMT3A-F640fs/-I715fs), equally shared by both the lymph node and bone marrow, suggesting a common clonal origin for the concurrent LCH and AML. Prednisolone and vinblastine were initially given with partial response in LCH; peripheral blood blasts also disappeared for 3 months. Salvage chemotherapy with low dose cytarabine and aclarubicin were given for relapse, with partial response in both LCH and AML. She died from pneumonia and septicemia on day 384. Our case demonstrates a common cell of origin for LCH and AML with a common genetic mutation, providing evidence to support the proposal to classify histiocytosis, including LCH, as a myeloid/myeloproliferative malignancy.

Keywords: BRAF V600E; MAPK pathway; NRAS; acute myeloid leukemia; dendritic cells; histiocytic disorders; inflammatory myeloid neoplasm; langerhans cell histiocytosis.

Publication types

Case Reports