Histiocytic/dendritic cell tumors are rare in clinical practice. It is postulated that they originate from bone marrow stem cells. Accumulating evidence has established the existence of immunoglobulin gene and T-cell receptor gene rearrangements in these tumors. Cases of transdifferentiation across lineages from follicular lymphoma to histiocytic/dendritic cell tumors have also been reported. Herein, we report 2 adult males with histiocytic neoplasms coexisting with B-cell lymphoma. Laser capture microdissection and capillary electrophoresis polymerase chain reaction analysis revealed comparable immunoglobulin gene rearrangement in both patients. In one case, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Langerhans cell sarcoma, and histiocytic sarcoma coexisted in the lymph nodes. 11q22 deletion often present in CLL/SLL and expression of the BRAF V600E gene was detected in all the 3 components. In the other case, there diffuse large B-cell lymphoma and histiocytic sarcoma coexisted in the spleen. Forty-seven mutated genes commonly found in B-cell lymphoma were detected by next-generation sequencing. In the same line, DTX1, IRF8, KMT2D, MAP2K1, and TET2 genes were found to have similar mutation sites. The results of this study will contribute in providing new ideas for targeted treatment of these diseases.
SwerdlowSHCampoEHarrisNL, et al. eds. Histiocytic and Dendritic Cell Neoplasms. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC; 2017.
2.
PileriSAGroganTMHarrisNL, et al.Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002;41(1):1-29.
3.
CignettiABryantEAllioneBVitaleAFoaRCheeverMA. CD34(+) Acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood. 1999;94(6):2048-2055.
4.
HackerCKirschRDJuXS, et al.Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol. 2003;4(4):380-386.
5.
ChenWLauSKFongD, et al.High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/dendritic cell sarcomas. Am J Surg Pathol. 2009;33(6):863-873.
6.
HayesCMaYDelioukinaMAlkanSHuangQ. Bone marrow manifestation of plasmablastic transformation of chronic lymphocytic leukemia: a case report. J Hematop. 2014;7(4):189-193.
7.
StoeckerMMWangE. Histiocytic/dendritic cell transformation of B-cell neoplasms: pathologic evidence of lineage conversion in differentiated hematolymphoid malignancies. Arch Pathol Lab Med. 2013;137(6):865-870.
8.
ShaoHXiLRaffeldM, et al.Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases. Mod Pathol. 2011;24(11):1421-1432.
9.
SteussyBLekostajJQianQ, et al.Leukemic transdifferentiation of follicular lymphoma into an acute histiocytic leukemia in a 52-year-old caucasian woman. Lab Med. 2016;47(2):155-157.
10.
BuserLBihlMRufleA, et al.Unique composite hematolymphoid tumor consisting of a pro-T lymphoblastic lymphoma and an indeterminate dendritic cell tumor: evidence for divergent common progenitor cell differentiation. Pathobiology. 2014;81(4):199-205.
11.
HuangWQiuTZengLZhengBYingJFengX. High frequency of clonal IG and T-cell receptor gene rearrangements in histiocytic and dendritic cell neoplasms. Oncotarget. 2016;7(48):78355-78362.
12.
ChangNYWangJWenMCLeeFY. Langerhans cell sarcoma in a chronic myelogenous leukemia patient undergoing imatinib mesylate therapy: a case study and review of the literature. Int J Surg Pathol. 2014;22(5):456-463.
13.
YoonHSChoiYSParkTS. Chronic myelogenous leukemia after therapy for langerhans cell histiocytosis in an adolescent. J Pediatr Hematol Oncol. 2015;37(7):572-573.
14.
KöhlerTPlettigRWetzsteinW, et al.Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells. Stem Cells. 2000;18(2):139-147.
15.
DiamondELDurhamBHHarocheJ, et al.Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov. 2016;6(2):154-165.
16.
VaughnJLFreitagCEHemmingerJAJonesJA. BRAF V600e expression in histiocytic sarcoma associated with splenic marginal zone lymphoma: a case report. J Med Case Rep. 2017;11(1):92.
17.
ChenWJaffeRZhangL, et al.Langerhans cell sarcoma arising from chronic lymphocytic lymphoma/small lymphocytic leukemia: lineage analysis and BRAF V600E mutation study. N Am J Med Sci. 2013;5(6):386-391.
18.
O’MalleyDPAgrawalRGrimmKE, et al.Evidence of BRAF V600E in indeterminate cell tumor and interdigitating dendritic cell sarcoma. Ann Diagn Pathol. 2015;19(3):113-116.
19.
AnsariJNaqashARMunkerR, et al.Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment. Eur J Haematol. 2016;97(1):9-16.
20.
MerirantaLPasanenALouhimoR, et al.Deltex-1 mutations predict poor survival in diffuse large B-cell lymphoma. Haematologica. 2017;102(5):e195-e198.
21.
RossiDTrifonovVFangazioM, et al.The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012;209(9):1537-1551.
22.
KubukiYYamajiTHidakaT, et al.TET2 Mutation in diffuse large B-cell lymphoma. J Clin Exp Hematop. 2017;56(3):145-149.
23.
HambletonSSalemSBustamanteJ, et al.IRF8 Mutations and human dendritic-cell immunodeficiency. N Engl J Med. 2011;365(2):127-138.
24.
WangHJainSLiP, et al.Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses. Proc Natl Acad Sci USA. 2019;116(19):9511-9520.
25.
ShinDMLeeCHMorseHC3rd. IRF8 Governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. PLoS One. 2011;6(11):e27384.
26.
AngelovaEAMedeirosLJWangW, et al.Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience. Mod Pathol. 2018;31(11):1717-1732.
27.
WaterfallJJAronsEWalkerRL, et al.High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias. Nat Genet. 2014;46(1):8-10.
28.
SchmidtJRamis-ZaldivarJENadeuF, et al.Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation. Blood. 2017;130(3):323-327.
29.
GounderMMSolitDBTapWD. Trametinib in histiocytic sarcoma with an activating MAP2K1 (MEK1) mutation. N Engl J Med. 2018;378(20):1945-1947.
30.
ChakrabortyRHamptonOAShenX, et al.Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007-3015.
31.
ZhangJDominguez-SolaDHusseinS, et al.Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med. 2015;21(10):1190-1198.
32.
Ortega-MolinaABossIWCanelaA, et al.The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat Med. 2015;21(10):1199-1208.
33.
KorfiKAliSHewardJAFitzgibbonJ. Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations. Epigenetics. 2017;12(5):370-377.
34.
FerreroSRossiDRinaldiA, et al.KMT2D Mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020;105(6):1604-1612.
