Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms

Abstract

Aims: The discovery of somatic genetic alterationsestablished many histiocytic disorders as haematolo-gic neoplasms. We aimed to investigate the demo-graphic characteristics and additional haematologiccancers of patients diagnosed with histiocytic disor-ders in The Netherlands.Methods and results: We retrieved data on histiocyto-sis patients from the Dutch Nationwide PathologyDatabank (Palga). During 1993 to 2022, more than4000 patients with a pathologist-assigned diagnosisof a histiocytic disorder were registered in Palga.Xanthogranulomas were the most common subtype,challenging the prevailing assumption that Langer-hans cell histiocytosis (LCH) is the most common his-tiocytic disorder. LCH and juvenile xanthogranuloma(JXG) had a peak incidence in the first years of life;males were overrepresented among all histiocytosissubgroups. 118 patients had a histiocytic disorderand an additional haematologic malignancy, includ-ing 107 (91%) adults at the time of histiocytosisdiagnosis. In 16/118 patients, both entities had beenanalysed for the same genetic alteration(s). In 11 ofthese 16 patients, identical genetic alterations hadbeen detected in both haematologic neoplasms. Thisincluded two patients with PAX5 p.P80R mutated Bcell acute lymphoblastic leukaemia and secondaryhistiocytic sarcoma, further supporting that PAX5alterations may predispose (precursor) B cells to dif-ferentiate into the myeloid lineage. All 4/11 patientswith myeloid neoplasms as their additional haemato-logic malignancy had shared N/KRAS mutations.Conclusions: This population-based study highlightsthe frequency of xanthogranulomas. Furthermore,our data add to the growing evidence supportingclonal relationships between histiocytic/dendritic cellneoplasms and additional myeloid or lymphoid malig-nancies. Particularly adult histiocytosis patientsshould be carefully evaluated for the development ofthese associated haematologic cancers.