Chronic myelomonocytic leukemia transdifferentiation landscape: From histiocytosis to blastic plasmacytoid dendritic cell neoplasm

A 70-year-old man presented with splenomegaly, weight loss, and cytopenias. Marrow assessment led to the diagnosis of chronic myelomonocytic leukemia (CMML) (Image 1A, next-generation sequencing Illumina was performed on non-sorted/bulk cell population from bone marrow), mainly myelodysplastic form (leukocytosis <13G/L), and flow cytometry (FCM) found 0.2%–0.3% of physiological plasmacytoid dendritic cells. Cutaneous and nasal infiltrative lesions were associated (Image 1, panel H), which were revealed to be composed of atypical histiocytic cells (Image 1, panel B) expressing PS100 and CD68 (Image 1, panel C/D), leading to the diagnosis of histiocytosis of the L group (Associated with another myeloproliferative/myelodysplastic disorder); lysozyme staining was positive in a few cells; CD56 and BDCA2 staining were both negative. There was no argument for myeloid sarcoma. Ruxolitinib (JAK inhibitor) combined to cobimetinib (MEK inhibitor) was initiated and led to partial metabolic response and cytopenias improvement after 1 month (Image 1, panel I, PET). The patient progressed for 3 months thereafter with recurring skin lesions. Ruxolitinib was switched to azacitidine in association with cobimetinib. After 2 cycles, patient reached complete metabolic response (Image 1, panel J). One year later, he relapsed with various skin lesions. Biopsied revealed a dense dermal infiltration by medium- to large-sized cells with irregular nucleus (Image 1, panel E) expressing CD56/BDCA2, but not PS100/CD68/Lysozyme (Image 1, panel F/G), leading to the diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) with clonal evolution (Image 1, panel A). Blood FCM found 0.1% of circulating abnormal BPDCN cells, marrow examination was not done. This case not only illustrates the plasticity between CMML, BPDCN,1 and histiocytosis2, 3 but also potential therapeutic value of MEK inhibitors in combination with azacitidine in RAS-mutated CMML, especially in case of extra-medullar involvement.4 The authors declare no conflicts of interest. Data available on request due to privacy/ethical restrictions