Transcript 1 st admission

INTERHOSPITAL
CONFERENCE
17 NOVEMBER 2009
10 years old boy
Prolong fever, arthritis
PATIENT DATA
ผู้ป่วยเด็กชายไทย อายุ 10 ปี
ทีอ่ ยู่ อาเภอเมือง จังหวัดกาฬสิ นธุ์
Chief complaint
ไข้ สูง ปวดข้ อ 1
สั ปดาห์ ก่ อนมาโรงพยาบาล
PRESENT ILLNESS
1 เดือนก่ อน มาด้ วยไข้
7 วัน ปวดข้ อ ข้ อบวม
SEM at LUPSB, liver 4cm below RCM
 Lt wrist, Lt knee and ankle then Rt ankle arthritis
(migratory polyarthritis)
INVESTIGATION 1 เดือนก่อน
 CBC: Hct 28.6%, Hb 9 g/dl, corrected WBC 9,600, N 37%, L 43%,
M 18%, NRC 153/100 WBC, plt 117,000
MCV 72.9, MCH 22.9, MCHC 31.4, RDW 20.8
 ESR 82 mm/hr, ANA-, ASO positive 1:1, RF -, CRP + 1:64,
 Melioid titer 1:40, H/C no growth, PPD  CXR: mild cardiomegaly
 EKG: NSR, HR 120/min, QRS axis 750, PR 0.12 sec, QTc 0.38 sec,
borderline LVH
 Echocardiogram: EF 76.8%, mild LV enlargement, trivial MR
 Dx: acute rheumatic fever: 1 major (poly arthritis), 2 minor ( fever,
ESR, CRP), + evidence Strep infection (ASO+)
 Rx: cefotaxime x 8 d, amoxy+clavulanic acid x 6d,
ASA gr V (90mkd)
Severe joint pain, pain score= 10 : suspected malignancy/ JRA
Brufen, tramol, MST, morphine syrup prn
Prednisolone 2 MKD x 2 wk
LDH 2,476 U/L uric acid 6.3 mg/dl, ESR 135 mm/hr, CRP 1:16,
 Coomb’s test –, ANA-, RF-, UA normal
 eye exam: no uveitis

 BMA: inadequate
 BM biopsy: fragment of cartilage, no bone marrow tissue seen
 Film bone survey: multiloculated cystic lesion at distal
femur, no osteolytic lesion, suspected benign condition,
No malignancy condition
 Bone scan: ?
 Ultrasound abdomen: hepatomegaly
of Lt
PRESENT ILLNESS
1
สั ปดาห์ ก่อนมาโรงพยาบาล มีไข้ สูง ส่ วนใหญ่ เป็ นไข้ กลางคืน
ปวดเมื่อยต้ นขา 2 ข้ าง ปวดข้ อศอก ทั้ง 2 ข้ าง ข้ อมือ ข้ อนิว้ มือ ข้ อ
เข่ าขวา ไม่ ไอ ไม่ หอบ ปวดศีรษะเล็กน้ อย ปัสสาวะอุจจาระปกติ
ไม่ มีนา้ หนักลด รับประทานอาหารได้
 2 วัน ก่ อนมา ไข้ ตลอดวัน ปวดข้ อมากขึน
้ ปวดสะโพก 2 ข้ าง เดิน
ลาบาก
PAST HISTORY
 มีเลือดกาเดาไหลเป็ นๆหายๆ
(ตั้งแต่ อายุ 3-4 ปี ปี ละ 3-4 ครั้ง)
 7 เดือนก่ อน มาด้ วยไข้ 2 เดือน เบื่ออาหาร อ่ อนเพลีย ท้ องโตขึน
้ ซีดลง
นา้ หนักลดลง 2 กิโลกรัม ใน 1 เดือน
 ตรวจร่ างกาย พบซีด ม้ ามโต 10 cm below LCM,
 CBC: pancytopenia
 BMA: erythroid hyperplasia, no blast
 BM biopsy: bony tissue with paucity number of
hematopoietic cells without evidence of leukemia
 Lymph node biopsy at inguinal: reactive lymphoid hyperplasia
PAST HISTORY
 CT abdomen: diffuse splenomegaly
 Splenectomy:
diffuse sinusoidal hemangiomatosis with
extramedullary hemopoeisis
 EBV Ig M +, IgG+, CMV IgM-, IgG+
 Antibiotic
17 days
 Hb typing: Homozygous Hb E
PAST HISTORY
 จากนั้นมา follow up ทุก 1 เดือน
มีไข้ บางครั้ง เลือดกาเดาไหล
เล็กน้ อย admit 1 ครั้ง เมื่อ 4 เดือนก่อน x 2 วัน
Hct 29% WBC, platelet ปกติ
 ได้ รับ folic, MTV, zyrtec
Family history
มารดาเป็ นโรคหอบหืด
 มีญาติทางบิดาเป็ นโรคเลือด (ไม่ ทราบว่ าเป็ นโรคอะไร)
 ปฏิเสธประวัติมะเร็ งในครอบครั ว
PHYSICAL EXAMINATION
 Vital signs:
BT 39.70 C
BP 110/70 mmHg
PR 112/min RR 22/min
BW 23 kg (P3-10)
Ht 130 cm (P25)
 GA: A boy, fully consciousness, well co-operate
 HEENT: mild pale conjunctiva , anicteric sclera
pharynx and tonsils: not injected
Rt cervical lymph node 0.5 cm
PHYSICAL EXAMINATION
 Heart
: systolic ejection murmur gr II at LPSB
 Lungs : normal and equal breath sound, no adventitious sound
 Abdomen: soft, liver 3 cm below RCM
 Extremities: no edema
 Tender and swelling of bilateral elbow, wrist, 4th, 5th MCP, Lt 2nd,
5th MCP, Rt knee joint
PROBLEM LISTS
 Prolong fever
 Polyarthritis
 Anemia
 Hepatomegaly
 SEM gr II
 S/P splenectomy
 Homozygous HbE
DDX
 Infection:
TB, virus (EBV, CMV),
Bacteria, fungus
 Connective tissue disease: JRA, SLE
 Malignancy: acute leukemia,
lymphoma
 IAHS
 LCH
INVESTIGATION
INVESTIGATION
 CBC: Hb 10.2 g/dL, Hct 31%, WBC corrected 4,900
N 45%, L 36%, M 18%, E 8%,
NRC 91/100 WBC, Platelet 131,000
MCV 85.7 fl, MCH 28.2 pg, MCHC 32.9 g/dL
 BUN 5 mg/dL, Cr 0.4 mg/dL, Uric acid 3.4 mg/dL
 Na 139, K 3,8, Cl 97, CO2 29 mmol/L, Ca 8.9, Mg 2, P 4 mg/dL
 Albumin 2.4 g/dL, AST 54 U/L, ALT 37 U/L. ALP 520 U/L
 Hemoculture; no growth
 UA : pH 5.5 ,sp.gr. 1.025, wbc 1-2 , rbc 0-1
 ESR : 75 mm/hr
INVESTIGATION
 LDH 542 U/L
 Ferritin 3,840 ng/ ml
 B-HCG 1.11 mIU/ml, AFP 3.08 IU/ml
 ASO-, CRP-, Melioid 1:20
Bone marrow
aspiration
Multiple radiolucency lesions
Ultrasound whole abdomen
:diffuse hepatomegaly
BMA: inadequate, rare nucleated cell, no blast
Cytochemistry
: numerous cell debris and very rare blood cell
have been observed, no hematologic
malignancy cell
:Other cause of bone marrow destruction
should be ruled out
Flow cytometry: blast gate 2.63% of total event
No evidence of hematologic malignancy
1st admission
HISTOPATHOLOGY REPORT
1st admission
Splenic hemagiomatosis
(1st admission)
Splenic hemagiomatosis
(1st admission)
Bone marrow biopsy:
Bone marrow necrosis
No malignancy cell
Bone biopsy at Lt
humerous:
Bone marrow necrosis
No malignancy cell
BONE MARROW NECROSIS (BMN)
Necrosis of myeloid tissue and medullary
stroma in the large areas of hematopoietic bone
marrow
 On BM biopsy: disruption of the normal bone
marrow architecture with a considerable loss of
fat space

Aplastic anemia: only loss of myeloid tissue
and no destruction of reticular structure
 Aseptic necrosis: no destruction of the spicular
architecture


Hypoxemia after failure of microcirculation:
 Inflammatory damage or mechanical obstruction
: DIC, sickle cell disease or tumor cell plug
 Immune process
 Toxicity and the release of toxins, cytokines,
or vasoactive substances from damaged cells
: TNF
Major complication: pancytopenia, embolic processes
 Repopulation of the bone marrow cavity
can occur after BMN resolved

IDENTIFIED UNDERLYING MALIGNANCY
90%
Extensive search for neoplastic
disease is justified whenever BMN
is diagnosed
1st described by Wade and Stevenson, 1942
: Sickle cell disease, died of cerebral infarction


Nies et al. 1965: define BMN in acute leukemia
34/ 316 (10.75%) postmortem

Kiraly and Wheby.1976: 13/664 (2%) in BM
specimens during 12 –year period

Norgard, 1979. retrospectively reviewed 120/368
(32.5%), only 4 were diagnosed at initial
GRADING
Small necrotic lesions: <25% of the dimention of
the biopsy (39%)
 Intermediate BMN
< 50% (24%)
 Large BMN
>75% (12%)
 Extensive: throughout the dimension of the
specimen

Pennaforte et al. 1986: extensive 4/1149 (0.3%)
 Maisel etal. 1988: severe BMN > 50% of
dimension (3%)

BMN IN CHILDREN
Macfarlane and Tauro: 4/379 (1%) in ALL
 Pui et al: 7/1419 (0.5%) in cancer patients

BONE MARROW NECROSIS (BMN)
ANN M. JANSSENS ET AL. CANCER 2000
Clinicopathologic entity, rare condition
 Review 240 cases, 1980-1999
 Inclusion
1. BMN diagnosed during life
2. necrosis > 50% of the diameter of
biopsy specimen

UNDERLYING DISEASE ASSOCIATION
Malignancy 91%
 Hematologic malignancies 60%
 Acute leukemia 41%, lymphoma 15%
 ALL 18%, AML 13%
 Children 18/25 cases were ALL
 BMN developed before diagnosis: ALL 26/37
(AML 16/24)
 After induction chemotherapy 1/37
 At recurrence 10/37

UNDERLYING DISEASE ASSOCIATION
Solid tumors 30%
 Not found primary origin, even after extensive
search 12/43
 Non malignancy only 9%: sickle cell crisis,
infection, drug, HUS, antiphospholipid
syndrome, DIC, hyperparathyroidism, anorexia
nervosa, idiopathic etc.


16/22 documented infection: underlying
malignancy were found later (early - 1 yr)
Infection
 E.coli
 Streptococcus
 Staphylococcus
 Citrobacter freundii
 Salmonella
 Mucormycosis
 Q fever
 TB
 Parvovirus
 HIV
Drug
 Sulphasalazine
 Sulphathiazol
 Sulphanamide
 Interferon-alpha
 G-CSF
 ATRA
 Hydroxyurea
 Fludarabine
PRESENTATION
Bone pain
75%
 Fever
68.5%
 Anemia
91%
 Thrombocytopenia
78%
 Leukoerythroblastic picture
51%
 Elevated LDH, alkaline phosphatase 50%

Leukoerythroblastic picture
primitive red cells (nucleated rbc or erythroblasts)
primitive white blood cells (myelocytes)
Cytology
 Bone marrow aspiration can be unsuccessful
 Multiple aspirates from different sites
(sternal, posterior iliac crest, etc.)
 Serosanguineous, watery dark red or clear fluid
Histology
 Combination of gelatinous transformation and
necrosis of the myeloid tissue
 Background of gelatinous transformation
surrounds cellular debris with indistinct cellular
margins, pyknotic nuclei, and abnormal
eosinophilic staining cytoplasm
 The hallmark of bone necrosis: loss of
osteocytes, osteoblasts, and osteoclasts
background of amorphous extracellular eosinophilic
material that surrounds cells that disintegrate.
shows cells that lose their normal staining characteristics.
irregular or indistinct margins; the cytoplasm can shrink or
vacuolate, and the nucleus shows pyknosis, karyorrhexis, and
karyolysis
Bone Marrow Scanning
 Technetium 99m sulfur colloid and indium
chloride localize selectively to the
reticuloendothelial elements of the marrow
 Dx BMN, residual BM activity, guided biopsy,
recovery
MRI: changes in bone marrow signal intensities

Life-threatening complication:
embolization of fat and necrotic bone marrow
to pulmonary arteries
PROGNOSIS
Median survival of the hematologic
malignancies :1 - 4 months, 69% died
 Childhood ALL: 13/18 alive
Survival: 4 months- 6 years
 Solid tumor and BMN: widespread
metastasis, short survival

PROGRESSION OF THE PATIENT
High grade fever
 Petechiae hemorrhage at face, periorbital
 Increased hepatomegaly
 Blood component therapy, antibiotic, pain
management

Consult for liver biopsy
 Repeat BMA and biopsy
 Plan MRI liver and bone
 Steroid

Hepatomegaly
CBC Hb Hct cWBC NRC N L M E other
D1 5.1 15.9 8.8 130 50 35 10 5
D3 6.7 21 3.3 200 32 41 13 4band2, meta2,myelo1, atyp L5
D10 6.1 19.5 11.7 80 36 44 16 4
D15 6.9 21.3 4.1 21 60 30 5 2band2 atypl1
D16 5.7 17.4 3.9 19 41 55 2 atyp3
D17 8.2 24.3 4.9 44 42 52 3 band 2, atyp1
D24 7.4 21.6 10.8 31 42 38 9 band6, atyp 5
D25 9 26.8 7.8 48 38 40 10 band2, meta3, myelo1, atyp 4, blast2
D30 7.4 22 3.2 50 49 32 9 blast10
D31 6.8 20.2 9.2 52 41 47 10 atyp2
D35 5.6 17 15.1 42 38 10
blast8,atyp2
Plt
172
144
27
7
74
21
40
30
49
34
13
Developed massive GI bleeding
treatment: LPB, Platelet, FFP, antibiotic
Cardiac arrest: CPR x 30 min
ABG
pH PCO2 PO2 HCO3 ABE O2 sat
7.07 19.2 444 5.7 -22 100
PT INR PTT D-dimer
31.2 2.67 34.4 0.6 mg/L
Bone marrow aspiration at
sternum
BM biopsy from
1. right ASIS:
Abnormal blast cells infiltrate with focal
necrosis and crush artifact
2. A small amount of marrow tissue from Lt
ASIS: abnormal blast cells
3. Sternum: numerous blast cell infiltrate
: precursor T lymphoblastic leukemia/
lymphoblastic lymphoma

CD3+, CD20-, CD79a-, CD34-, MPO-, TdT+
Liver biopsy
: precursor T lymphoblastic leukemia/
lymphoblastic lymphoma

CD3+, CD20-, CD79a-, CD34-, MPO-, TdT+
THANK YOU
Extensive search for neoplastic disease
Multiple aspirates from different sites
: biopsy site in which viable hematopoietic
bone marrow