Week 12: Myelodysplastic Syndrome

MyelodysplasiaMyelodysplasia DiserythropoiesisDiserythropoiesis DismyelopoiesisDismyelopoiesis DismegakaryopoiesisDismegakaryopoiesis FAB calssificationFAB calssification Ring SideroblastRing Sideroblast Type I and II blastsType I and II blasts WHO classificationWHO classification

Myelodysplastic Syndrome

Primary, neoplastic, pluripotential stem cell Primary, neoplastic, pluripotential stem cell disorderdisorder

Severe cytopenias and maturation Severe cytopenias and maturation abnormality (dysplasia) in one or more cell abnormality (dysplasia) in one or more cell lineslines

30 - 40% of RAEB develop AML, mostly 30 - 40% of RAEB develop AML, mostly elderlyelderly

Evidence of impaired colony formationEvidence of impaired colony formation

FAB Classification of MDS (1982)

Refractroy Anemia (RA)Refractroy Anemia (RA) RA with Ringed Sideroblasts (RARS)RA with Ringed Sideroblasts (RARS) RA with Excess Blasts (RAEB)RA with Excess Blasts (RAEB) Chronic Meylomonocytic Leukemia Chronic Meylomonocytic Leukemia

(CMML)(CMML) RAEB in Transformation (RAEB-t)RAEB in Transformation (RAEB-t)

WHO Classification of MDS (1997) RA becomesRA becomes

RARA Refractory cytopenia Refractory cytopenia

w/multilineage dysplasia w/multilineage dysplasia (RCMD) -- complex (RCMD) -- complex karyotypes (+8, -7, 7q-, karyotypes (+8, -7, 7q-, -5, 5q-, 20q-)-5, 5q-, 20q-)

RARS becomesRARS becomes RARSRARS RCMD w/ ringed RCMD w/ ringed

sideroblastssideroblasts

RAEB becomesRAEB becomes RAEB types I and IIRAEB types I and II 5q- Syndrome -- 5q- Syndrome --

middle age to elderly middle age to elderly females; deletion females; deletion between bands 31 and between bands 31 and 33; macrocytosis; good 33; macrocytosis; good prognosisprognosis

MDS, unclassifiableMDS, unclassifiable

WHO Classification of MDS/MPS

Chronic Myelomonocytic Leukemia (CMML) -- Chronic Myelomonocytic Leukemia (CMML) -- from old FAB MDSfrom old FAB MDS

Atypical CML (aCML) -- no Ph chromosomeAtypical CML (aCML) -- no Ph chromosome Juvenile Myelo/Myelomono Leukemia (JMML)Juvenile Myelo/Myelomono Leukemia (JMML)

Note: FAB RAEB-t is reclassified as “AML Note: FAB RAEB-t is reclassified as “AML w/multilineage dysplasia following MDS” because w/multilineage dysplasia following MDS” because definition of AML is 20% blasts with WHOdefinition of AML is 20% blasts with WHO

Dyserythropoiesis

AnemiaAnemia Normocytic or macro-ovalocytesNormocytic or macro-ovalocytes Low retic countLow retic count NRBCNRBC Megaloblastic changesMegaloblastic changes Ringed sideroblastRinged sideroblast Pappenheimer bodiesPappenheimer bodies Basophilic stipplingBasophilic stippling

Dyserythropoiesis

Ringed sideroblast

Dysmyelopoiesis

NeutropeniaNeutropenia MonocytosisMonocytosis Pseudo Pelger-HuetPseudo Pelger-Huet Hypogranular PMNHypogranular PMN <20% blasts in BM<20% blasts in BM Type I and type II blastsType I and type II blasts

Dysgranulopoiesis

Blasts in MDS

Type I blastsType I blasts No granulesNo granules Prominent nucleoliProminent nucleoli Central nucleusCentral nucleus

Type II and III blastsType II and III blasts Few 1Few 1oo granules granules Prominent nucleoliProminent nucleoli Central nucleusCentral nucleus Auer rodsAuer rods

PromyelocytePromyelocyte Many 1Many 1oo granules granules Less prominent Less prominent

nucleolinucleoli Eccentric nucleusEccentric nucleus

Type I Blast

Type III Blast

CMML and NSE

Dysmegakaryopoiesis

Low platelet countLow platelet count Giant PlateletGiant Platelet Dwarf (micro) megakaryocyteDwarf (micro) megakaryocyte

Abnormal platelets

Micromegakaryocyte