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46y female WBC=62.000\ul Hb=16.1g% Normal indices Plat.=255000/ul Leokocytosis Neutrophilia Imm NE 1 Imm NE 2 Flags:

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Presentation on theme: "46y female WBC=62.000\ul Hb=16.1g% Normal indices Plat.=255000/ul Leokocytosis Neutrophilia Imm NE 1 Imm NE 2 Flags:"— Presentation transcript:

1 46y female WBC=62.000\ul Hb=16.1g% Normal indices Plat.=255000/ul Leokocytosis Neutrophilia Imm NE 1 Imm NE 2 Flags:

2 8 טסיות בשדה שיש בו מעל 100 תאים אדומים

3 תאי בלסט, גרנולציה ציטופלסמטית עדינה גרעינון גרנולציה Chediak-Higashi like granules

4 7 טסיות בשדה של כ -100 תאים אדומים סטייה שמאלה

5 Ring neut., dohle bodies Dysplastic myeloid cell Dysplastic changes

6 Manual differential: Blast 56% Myelocyte 3% Metamy 5% St 8% Neut 11% Eos 1% Bas 1% Plasma 1% Mon 1% Lymph 9% Prolymph 5% NRBC 1\100 Left shift Leukoerythroblastic changes תפיסת מח העצם + Dysplastic changes Cytoplasmic granulation AML with dysplasia

7 הממצאים הראויים לציון : בלסטים טרומבופניה שינויים דיספלסטיים נוכחות נורמובלסטים שינויים לויקואריתרובלסטיים

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11 Prognosis compared to average for AML Approximate % of adult AML patientsNameFAB Worse5%Undifferentiated acute myeloblastic leukemia M0 Average15%Acute myeloblastic leukemia with minimal maturation M1 Better25%Acute myeloblastic leukemia with maturation M2 Best10%Acute promyelocytic leukemiaM3 Average20%Acute myelomonocytic leukemiaM4 Better5%Acute myelomonocytic leukemia with eosinophilia M4 eos Average10%Monocytic leukemiaM5 Worse5%Acute erythroid leukemiaM6 Worse5%Acute megakaryoblastic leukemia M7

12 Prognosis compared to average for AML Approximate % of adult AML patientsNameFAB Worse5%Undifferentiated acute myeloblastic leukemia M0 Average15%Acute myeloblastic leukemia with minimal maturation M1 Better25%Acute myeloblastic leukemia with maturation M2 Best10%Acute promyelocytic leukemiaM3 Average20%Acute myelomonocytic leukemiaM4 Better5%Acute myelomonocytic leukemia with eosinophilia M4 eos Average10%Monocytic leukemiaM5 Worse5%Acute erythroid leukemiaM6 Worse5%Acute megakaryoblastic leukemia M7

13 Prognosis compared to average for AML Approximate % of adult AML patientsNameFAB Worse5%Undifferentiated acute myeloblastic leukemia M0 Average15%Acute myeloblastic leukemia with minimal maturation M1 Better25%Acute myeloblastic leukemia with maturation M2 Best10%Acute promyelocytic leukemiaM3 Average20%Acute myelomonocytic leukemiaM4 Better5%Acute myelomonocytic leukemia with eosinophilia M4 eos Average10%Monocytic leukemiaM5 Worse5%Acute erythroid leukemiaM6 Worse5%Acute megakaryoblastic leukemia M7

14 Acute Myeloid Leukemia With Characteristic Genetic Abnormalities Acute Myeloid Leukemia With an FLT3 Mutation Acute Myeloid Leukemia With Multilineage Dysplasia Acute Myeloid Leukemias and Myelodysplastic Syndromes, Therapy-Related Acute Myeloid Leukemia Not Otherwise Categorized Acute Leukemias of Ambiguous Lineage All categories of FAB AML with t(8;21)(q22;q22), (AML1/ETO) AML with inv(16)(p13q22) or t(16;16)(p13;q22(, )CBFb/MYH11) Acute promyelocytic leukemia (AML with t(15;17)(q22;q12(, )PML/RARa and variants(

15 tyrosine kinase receptor expressed in a variety of cells: myeloid and B-lymphoid lineage cells The expression of FLT3 is restricted to early bone marrow progenitor cells expressing CD34+ (fms-like tyrosine kinase receptor-3 (Flt3), fetal liver kinase-2 (Flk2) (CD135)

16 FLT3 contains a Juxtamembrane domain (JM) that functions to inhibit the kinase activity. Mutations in this domain, cause a helical conformation that distorts the small lobe of the kinase domain and blocks the JM domain from performing its "autoinhibitory" function. Internal tandem duplications (ITD) Or Activating loop mutation

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18 Mutations in the FLT3 receptor - in ~30% of patients with AML, This is the single most commonly mutated gene in AML - poor prognosis These mutations may play a role in the survival or proliferation of leukemic blasts. Although FLT3 mutations may play a role in the disease process, FLT3 is not sufficient to cause AML, Additional mutation required to present with full diseas Therapeutic impotrtance

19 Comparison of overall survival of significant disease groups in the World Health Organization classification. P <.001.

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21 17y female Fever, headache 2 weeks לפני חודש חזרה מטיול בארה " ב

22 WBC RBC HB Hct MCV8484 MCH MCHC RDW PLT222278

23 Neut.% ANC Lymph% ALC Mon% AMC Eos% AEC100 18( מכשיר =0) baso ABC 17( מכשיר =0) 3 ( מכשיר =0) תהליך שגרם להופעת מונוציטוזיס בשלב ראשון שחלפה ופנתה מקום להופעת נויטרופניה זיהום וירלי זיהום חיידקי מסוים

24 ESR90mm/h64mm/h CMVIgGחיובי CMVIgMשלילי EBV Ab. Past infection

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27 זיהום כזה חמור סביר מאד שיעורר את המערכת החיסונית

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29 Phagocytosis Dohle bodies apoptosis

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31 הממצאים הראויים לציון : בורליה אפופטוזיס פגוציטוזיס

32 13 מתוך 17 מעבדות ציינו נוכחות בורליה 23.5% הרבה

33 מחלה זיהומית נגרמת ע " י חיידק הבורליה חיידק מסוג ספירוכטה spirochete מועבר ע " י עקיצת קרציה מסוג Ixodes Borrelia burgdorferi

34 fluflu-like symptoms in its initial stage Musculoskeletal Arthritic Neurologic Psychiatric cardiac doxylin

35 88y female Hb=11.6g%, normal indices RDW=16 flag: anisocytosis WBC=67700/ul Mono 73.7% AMC=49900/ul Plat.=373000/ul ANC=7200/ul ALC=10300/ul

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38 Manual differential: Villous lymphocytes 87% Mon 1% neut 12%

39 מעבדות 101,112,114,129 ציינו נוכחות תאים שעירים

40 MZLHCL lymphocytosispancytopenia PB: Many villous lymphocytes PB: Monocytopenia, few hairy cells splenomegalysplenomegaly Replaced, hypercellu. BM BM dry tap Post germinal center B cells, unknown degree of differntiation Mature B cells CD5- CD25+, CD103+ Cyclin D1+ Cyclin D1-

41 Cyclin-dependent kinases (CDK) group of protein kinasesprotein kinases regulation of the cell cycle.cell cycle regulation of transcription and mRNA processing.transcriptionmRNA serine/threonine kinases.serine/threonine kinases t(11;14)(q13;q32t(11;14)(q13;q32)

42 הממצאים הראויים לציון : Villous lymphocytes

43 22y female Hb=10.9g% normal indices RDW=17.5 WBC=3700/ul ANC=1190/UL, ALC=2010/UL FLAG: IMMATURE GRANUKOCYTES PLAT.=147000\UL Esr=34/h

44 Prolymphocyte?

45 Tear drops

46 blasts

47 WBC=3700/ul Neut 23%(ANC=851) St 6% Myelo 3% Meta 1% Bas 2% Lymph 36% Prolymph 3% Mon 4% Atyp 2% Blast 20% Manual differential: No narrow Auer cytoplasm rods Left shift

48 ממצאים ראויים לציון : בלסטים סטיה שמאלה תאי דמעה קרוב לודאי ALL איפיון אימונולוגי – סקירה קצרה על ALL T cell?

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51 10/17

52 ALL is most common in childhood and young adulthood Peak incidence at 4-5 years of age, Another peak in old age. The overall cure rate in children is 85%,

53 Cytogenetic findingsPrognosis Hyperdiploidy > 50 ; t (12;21) Favorable Hyperdioloidy ; Normal(diploidy); del (6q); Rearrangements of 8q24 Intermediate Hypodiploidy-near haploidy; Near tetraploidy; del (17p); t (9;22); t (11q23) Unfavorable

54 Molecular genetic abnormalityCytogenetic translocation BCR-ABL fusion(P185t(9;22)(q34;q11) TEL-AML1fusiont(12;21)CRYPTIC E2A-PBX fusiont(1;19)(q23;p13 MLL-AF4 fusiont(4;11)(q21;q23 IGH-MYC fusiont(8;14)(q24;q32 TCR-RBTN2 fusiont(11;14)(p13;q11

55 The FAB classification : ALL-L1: small uniform cells ALL-L2: large varied cells ALL-L3: large varied cells with vacuoles(Burkitt like)vacuoles

56 WHO proposed classification of acute lymphoblastic leukemia s Igc IgB cellT cellTdtFAB ClassTypes --/++-+L1,L2Precursor B ---++L1,L2Precursor T +-+--L3B-cell

57 CD4/CD8surface CD3TdTALL Cells +/+ or -/--+ Early T-precursor ALL +/- or -/+++T-cell ALL

58 SIgCyIgCD10CD19TdTALL Cells ---++Early B-precursor ALL -++++Pre–B-cell ALL ++/- +-B-cell ALL

59 WHO proposed classification of acute lymphoblastic leukemia 1- Acute lymphoblastic leukemia/lymphoma Former Fab L1/L2 i. Precursor B acute lymphoblastic leukemia/lymphoma Cytogenetic subtypes: Hyperdiploidy > 50 t(12;21)(p12,q22) TEL/AML-1 t(1;19)(q23;p13) PBX/E2A t(9;22)(q34;q11) ABL/BCR T(V,11)(V;q23) V/MLL ii. Precursor T acute lymphoblastic leukemia/lymphoma 2- Burkitt's leukemia/lymphoma Former FAB L3 3- Biphenotypic acute leukemia


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