Mastocytosis Proliferation of mast cells accumulation in organs Heterogen. manifestations (spontan. regression x aggresive) Cutaneous Systemic

Mastocytosis 80%: cutaneous - children several clinicopathological categories no sex predilection no codon 816 mutation good prognosis, spontaneous regression adults: over 30 years, mostly: assoc. SM 20%: systemic - adults

Systemic mastocytosis (SM) Indolent SM Aggressive SM SM + assoc. clonal haematol. disease (AHNMD) Very rare: Mast cell leukemia Mast cell sarcoma Extracutaneous mastocytoma

Systemic mastocytosis Organ involvement Bone marrow – almost always (PB rarely) Spleen, lymph nodes, liver, GIT Skin : over 50% (if +, indolent course) Symptoms: 1.Constitutional 2.Skin 3.Mediator 4.Bone

Systemic mastocytosis diagnostic criteria (1 + 1 or 3 minor) Major Multifocal, dense aggregates of mast cells Minor Atypical mast cells (BM, elsewhere) KIT point mutation – codon 816 Co-expression of CD117, CD2 and/or CD25 Serum total tryptase over 20 ng/ml

Systemic mastocytosis – dif. dg. Reactive hyperplasia of mast cells Myeloid and lymphoid tumor (LPL) Interstitial dispersion of mast cells Langerhans cell histiocytosis Dendritic cell sarcoma AML

Systemic mastocytosis – genetics treatment Somatic point mutations of KIT Tyrosine kinase receptor for stem cell factor (mast cell growth factor) Asp816Val spont. activation of kit protein (indolent, aggressive SM) – interferon  cladribine; resistance to imatinib; Phe522Cys;Val560Gly FIP I like- I- PDGFR  q  SM with assoc. PB eosinophilia – imatinib mesylate