Many faces of the same myeloid neoplasm: a case of leukaemia cutis with mixed histiocytic and Langerhans cell differentiation

Shanmugam, Vignesh; Morgan, Elizabeth A.; DeAngelo, Daniel J.; Kim, Annette S.

doi:10.1136/jclinpath-2018-205161

Cited by 4 publications

(1 citation statement)

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“…The exact mechanisms driving such histiocytic outgrowths in MN are unknown. However, in-depth studies showed that somatic mutations affecting MAPK-signaling detectable in the "histiocytoses" are also evident in the CD34 + compartment, in the mature blood cells, and in CHIP of a proportion of such patients [134][135][136]. This suggests that MAPK-pathway hyperactivation by initially present or acquired mutations of genes encoding for its compounds may drive neoplastic myeloid progenitor cells toward histiocytic differentiation.…”

Section: Progression In Myeloid Neoplasmsmentioning

confidence: 99%

Progression in Myeloid Neoplasms: Beyond the Myeloblast

Faria

Tzankov

2023

Pathobiology

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Disease progression in myelodysplastic syndromes (MDS), myelodysplastic-myeloproliferative neoplasms (MDS/MPN), and myeloproliferative neoplasms (MPN), altogether referred to as myeloid neoplasms (MN), is a major source of mortality. Apart from transformation to acute myeloid leukemia, the clinical progression of MN is mostly due to the overgrowth of pre-existing hematopoiesis by the MN without an additional transforming event. Still, MN may evolve along other recurrent yet less well-known scenarios: (1) acquisition of MPN features in MDS or (2) MDS features in MPN, (3) progressive myelofibrosis (MF), (4) acquisition of chronic myelomonocytic leukemia (CMML)-like characteristics in MPN or MDS, (5) development of myeloid sarcoma (MS), (6) lymphoblastic (LB) transformation, (7) histiocytic/dendritic outgrowths. These MN-transformation types exhibit a propensity for extramedullary sites (e.g., skin, lymph nodes, liver), highlighting the importance of lesional biopsies in diagnosis. Gain of distinct mutations/mutational patterns seems to be causative or at least accompanying several of the above-mentioned scenarios. MDS developing MPN features often acquire MPN driver mutations (usually JAK2), and MF. Conversely, MPN gaining MDS features develop, e.g., ASXL1, IDH1/2, SF3B1, and/or SRSF2 mutations. Mutations of RAS-genes are often detected in CMML-like MPN progression. MS ex MN is characterized by complex karyotypes, FLT3 and/or NPM1 mutations, and often monoblastic phenotype. MN with LB transformation is associated with secondary genetic events linked to lineage reprogramming leading to the deregulation of ETV6, IKZF1, PAX5, PU.1, and RUNX1. Finally, the acquisition of MAPK-pathway gene mutations may shape MN toward histiocytic differentiation. Awareness of all these less well-known MN-progression types is important to guide optimal individual patient management.

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Section: Progression In Myeloid Neoplasmsmentioning

confidence: 99%