(A & B) A. Models depicting the biogenesis of systemic mastocytosis (SM) with an associated hematologic myeloid neoplasm (AHN) (I) 2 independent clones whereby SM and AHN coexist. II 1 common myeloid precursor and KIT variant is an early event. III 1 common myeloid precursor and KIT variant is a late event. IV 1 common myeloid precursor, KIT and FLT3-ITD are late-event drivers in 2 mutually exclusive AHN and SM clones. B. (ai) Bone marrow aspirate showing leukemic blasts admixed with atypical mast cells; original magnification ×100, May-Grünwald-Giemsa stain. bii Representative micrograph of the bone marrow biopsy; original magnification ×20 hematoxylin and eosin (H&E) stain shows paratrabecular formation of new bone. There is a paratrabecular and interstitial infiltration of atypical mast cells (arrow) and blasts (arrowhead) expressing CD34. The atypical mast cells are Tryptase (+), CD117 (+) and CD25 (+). In addition, there is a patchy increase in reticulin fibrosis around the atypical mast cells; original magnification ×10, reticulin stain.