FIGURE LEGENDS
Figure 1: During consolidation patient developed generalized hyperpigmented cutaneous nodules with central ulceration (A). CT imaging prior to treatment with trametinib demonstrating hepatosplenomegaly with multiple hypodensities, possibly JXG infiltrates (B). Patient after treatment with trametinib showing improvement in cutaneous JXGs (C).
Figure 2: Pre-B ALL at diagnosis, showing lymphoblasts in the peripheral blood (A; Wright stain x 1000), with CRLF2::IGHrearrangement (insert: CRLF2(Xp22/Yp11)(proximal 5’=green/distal 3’=red), FISH). During consolidation chemotherapy, the BM biopsy showed residual B-ALL (B; hematoxylin and eosin x100; insert PAX5 immunohistochemical stain x100), and no significant histiocytic proliferation seen. At this time, the patient started to present multiple skin lesions with the biopsy showing diffuse histiocytic proliferation with absence of cytological atypia; mitoses are rare (C; hematoxylin and eosin x100). CD68 and Factor XIIIa immunohistochemical stains show strong reactivity in histiocytic cells (D and E; brown reaction product, x 100). PCR showed clonal banding patterns in JXG, by both immunoglobulin and T-cell receptor gene rearrangement studies (not shown). A few weeks later, the repeated bone marrow biopsy revealed replacement by JXG (F; hematoxylin and eosin, x 200), diffusely positive for Factor XIIIa (G; brown reaction product, x200). PAX5 immunostaining was negative and flow MRD was negative for residual lymphoblasts (not shown). The results of molecular MRD follow up by using clono-SEQ assay (H). The flow cytometry MRD and immunostaining of PAX5 on core biopsy remained negative (data not shown).