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).