INTERHOSPITAL CONFERENCE

รพ.ขอนแก่น 17/6/2554

ผู้ป่วยหญิงไทยคู ่อายุ 33 ปี อาชีพ รับจ้างทั่วไป

ที่อยู่ อ.บ้านฝาง จ.ขอนแก่น

CC: ไข้ หอบเหนื่อยมากขึ้นมา 5 วัน PTA PI: 5 วัน PTA มีอาการไข้สูงหนาวสั่น เจ็บคอ ไอแห้ง ไม่มีเสมหะ ไม่มีน้ํามูก ปัสสาวะปกติ ไม่แสบขัด ถ่ายเหลว 8 ครั้ง ต่อวัน ถ่ายเหลวเป็นน้ํามากกว่าเนื้อ ไม่มีมูกเลือดปน ไป Admit รพ.เวชประสิทธิa์dmit 3วัน ได ้Augmentin,Ceftazidime iv + Pred 2*3 + Bactrim 2*2, Metronidazole 2*3 , CQ 1* hs อาการไม่ดีขึ้น จึงส่งตัวมารพ .ขอนแก่น

•  PH: –  เคยผ่าตัดต่อมไทรอยด์ที ่รพ.ศรีนครินทร์ เมื่อ 5 ปีก่อน บอกว่าไทรอยด์เป็นพิษ

– 3 เดือน PTA Dx:Possible SLE (ANA positive(nucleolar),polyarthritis, Pancytopenia ) with Lupus hepatitis (เคยมี transaminitis AST 107 ALT 108)

– CBC WBC 2200 N36% L47% M2%Band10% Hct 23.9 MCV90 MCHC33 Plt 99000

– F/U WBC 2200 -> 7000 -> 50000 with Lt. shift – BMA: peripheral destruction,stool occult blood

+ve เคย on pred 8*1tapering off มา 3 เดือน

•  PH: – u/s abdomen ,True hyperechoic mass 7.5*8.9

mm, 8.6*6.5 mm Rt lobe liver likely Hemangioma ปฏิเสธ liver biopsy

– anti dsDNA neg ,AMA neg, anti smooth m Ab neg, anti HIV neg ,HbsAg neg, antiHCV neg

– SPEP: polyclonal gammopathy – Hb typing EA Bart

•  Family history : Healthy

Physical examination

•  A middle age woman,fully conscious ,well co-operate,looked fatigue.

•  BT 38.2 0C PR 102/min RR 22/min BP 120/70 mmHg

•  HEENT : mild pale, anicteric sclera, pharynx and tonsil not injected,no malar rash, no discoid rash, no oral ulcer,old surgical scar at neck,CLN impalpable,no dry lip,tongue

•  HEART: PMI 5 th ICS and midclavicular line , no heaving , no thrill ,normal S1,S2, no murmur

•  Lung : trachea midline, fine crepitation at Lt.lower lung

•  Abdomen : soft,not tender,liver and spleen impalpable, active bowel sound

•  Extremities : no petechiae,no rash, no edema

LAB

CBC Hb 9.4, Hct 28 WBC 42000 PMN 34, Lym 7, Band 14 Metamyelo 27, myelo 17 Promyelo 2 Platelet 28000 MCV 85.6 Retuculocyte 0.30

•  PBS: – NCNC, few shistocyte – PMN predominate with left shift, no blast – Plt. decrease

• BUN 5 Cr 0.5 • Na 134 K 3.2 Cl 104 HCO3

23.3 Mg 2. Ca 7.8 • Uric acid 4.0 • UA sp.gr. 1.015 pH 6.0 ,Pro

trace ,Rbc 3-5,Wbc1-2

PT 12.4

INR 1.02

PTT 35.8

•  LFT – TP 5.9 Alb 2.0

– Glo 3.9

Chol 138 – TB 0.4 DB 0.1

– AST 37 ALT

53 – ALP 159

LDH 167

D-dimer=negative

CXR

3 เดือน PTA ขณะ admit

•  H/C : NG •  G/S ,AFB,mAFB: no organism •  Rectal S/C : NG •  Stool exam : normal •  Sputum C/S

•  Numerous Kieb. Pneumoniae (ESBL) •  Numerous Coagulase Negative Staphylococci

•  Sent : Tazocin, Meropenem,Colistin

Abnormal granule

Flow cytometry

Flow cytometry •  CD7=0.7%,CD10=2.3%, •  CD11b=30.3%, CD13=99.6%, •  CD15=5.1%,CD19=2.1%,

CD33=97.4%CD34=0.8%, •  CD56=80.9%, CD64=1.2%, •  CD117=7.4%,HLADR=1.6%, •  MPO=97.1%,TdT=2.9%

Flow cytometry •  CD7=0.7%,CD10=2.3%, •  CD11b=30.3%, CD13=99.6%, •  CD15=5.1%,CD19=2.1%,

CD33=97.4%CD34=0.8%, •  CD56=80.9%, CD64=1.2%, •  CD117=7.4%,HLADR=1.6%, •  MPO=97.1%,TdT=2.9%

Suggestive of Acute Promyelocytic Leukemia(AML-M3)

Chromosome study

•  46,XX,t(15;17)(q22;q21)

Molecular study

•  PML-RARA gene in APL: positive (bcr 1)

Progress case

•  Am J Hematol. 1980;9(4):413-20.

•  Unusual intracytoplasmic inclusions in acute myeloblastic leukemia.

•  Wolf DJ, Fialk MA, Mouradian J, Gottfried EL, Pasmantier MW. Abstract

•  Unusual intracytoplasmic inclusions within early granulocyte precursor cells from a patient with acute myeloblastic leukemia (AML) are described. Based upon their staining characteristics and electron- and light-microscopic appearance, the inclusions are distinctly different from any previously described. The inclusions display a variety of shapes, including rectangles, squares, circles, ovals, and irregular, globular forms. Most of the inclusions are refractile and crystal-like. The possible composition of these inclusions is discussed. They are compared with inclusions previously described within leukemic and granulocytic cells.

•  PMID: 6163354 [PubMed - indexed for MEDLINE]

The bone marrow aspirate shows numerous abnormal promyelocytes with prominent cytoplasmic granules, characteristic of hypergranular acute promyelocytic leukemia.

Tallman M S , Altman J K Blood 2009;114:5126-5135

©2009 by American Society of Hematology

•  Microgranular Variant: In the microgranular variant, M3v, the leukemic cells have a monocytic appearance with clefted angel-wing nuclei and abundant cytoplasm having at best indistinct cytoplasmic granulation.

Acute promyelocytic leukemia (M3) Bone marrow aspirate from a patient with the hypergranular promyelocytic variant of AML (FAB classification M3). (Wright-Giemsa stain). The cell in the top center and far left are "faggot" cells, with numerous intertwining Auer rods (arrows).

Acute promyelocytic leukemia (M3V) Blood smear from a patient with the microgranular promyelocytic variant of AML (FAB classification M3V). (Wright-Giemsa stain). The promyelocytes vary in size and degree of cytoplasmic basophilia. The cytoplasm contains abundant, fine, azurophilic granules; nuclei are markedly lobulated and invaginated.

Myeloblasts with Auer rods

Acute promyelocytic leukemia (M3)

Hypergranular variant APL with DIC

APL, microgranular variant

Auer rod morphology in APL

•  APL represents a medical emergency with a high rate of early mortality, often due to hemorrhage from a characteristic coagulopathy

APL

•  Bone marrow failure syndrome •  DIC •  80% leukopenia --à hypergranular •  20% leukocytosis--à microgranular

Flow cytometry

•  CD 13 ,33 MPO -à positive •  CD11b CD 117 HLA-DR ->negative

Risk stratification

•  Low risk ---WBC < 10000, plt >40000

•  Intermediate risk --- WBC <10000,plt<40000

•  High risk ---WBC>10000

•  Without treatment, APL is the most malignant form of AML with a median survival of less than one month

•  treatment of APL is distinct from that of other types of AML and is comprised of several stages

• Remission induction • Consolidation • Maintenance