Page 13 - Haematologica April 2020

Editorials
Figure 1. Clinical, immunophenotypic, and molecular changes in histiocytic sarcoma and relation to other histiocytoses. LCH: Langerhans cell histiocytosis; HLH: hemophagocytic lymphohistiocytosis; RDD: Rosai Dorfman Disease; ECD: Erdheim-Chester disease.
mutations had a predilection for gastrointestinal tract involvement. This group was characterized by loss of gene sets related to cellular proliferation and the cell cycle. Further data suggest that a subset of these cases involve co-occurring NF1 and PTPN11 mutations, suggesting that activating mutations of PTPN11 may synergize with NF1 mutations to potentiate oncogenesis. None of these cases had abnormalities in genes associated with B-cell lym- phomas, besides SETD2, or had B-cell-related gene rearrangements.
In contrast, cases with wild-type NF1/PTP11 had RAS/MAPK pathway activating mutations, and were unrelated to site of presentation, and had activating muta- tions involving KRAS, NRAS, BRAF, and MAP2K1. This group alone demonstrated an association with immunoglobulin gene rearrangements and genes associat- ed with B-cell lymphomas, including BCL2 rearrange- ment. This molecular profile offers an intriguing insight into the relationship between histiocytic sarcoma and B- cell lymphoma. The ability to identify subsets of histio- cytic sarcoma according to their molecular profiles offers a
potential for improvement in the diagnosis and targeted therapy of these neoplasms that has so far foiled conven- tional pathological examination.
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