Interesting Case

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Interesting Case

• Baby Ouseph
• 10 / 06 / 09

2
Introduction

• 54 year old male
• Known case of Coronary Artery Disease
• Single Vessel Disease

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History of Present illness

• Breathlessness
• Fatigue
• since 5 years
• Breathlessness noticed on climbing stairs or
  walking for long distances.
• h/o fatigue
• h/o decreased ability to concentrate

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• No h/o chestpain, palpitations, syncope,
  orthopnea or paroxysmal nocturnal dyspnea.
• No h/o fever
• No h/o suggestive of involvement of
  gastrointestinal, genitourinary or neurological
  involvement.

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Past History

• Diagnosed to have anemia on routine blood
  examination in the work place 8 months ago
• Iron supplementation 3 months
• Iron and Folic Acid supplementation 5 months
• No improvement in hemoglobin level

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Past History

• Coronary Angiogram 2 years back as a part of
  evaluation of breathlessness and fatigue
  diagnosed as SINGLE VESSEL DISEASE
• Not a known case of diabetic / hypertensive

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Personal History

• Smoker - 20 cigarettes per day for 30 years
• - stopped 15 years ago
• Occasionally consumes alcohol.

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On examination

• Pallor
• No icterus, cyanosis, clubbing, pedal edema
• Left axillary lymphadenopathy
• 2 x 3 cm lymph node
• - non tender
• - mobile
• - non matted
• No Thyroid swelling
• No sternal tenderness

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vitals

• Pulse 66 / min , regular
• BP 130 / 80 mm of Hg
• Temp 98.6 F
• RR 16 / min, regular

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• RS Bilateral normal vesicular breath sounds
• No added sounds
• CVS S1 , S2 , No murmurs
• P/A Soft
• No tenderness
• No hepatomegaly
• Splenomegaly
• ( 9 cm below left costal margin )
• Bowel sounds

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• NS HMF Normal
• No Sensory Motor Deficit
• No cerebellar signs of dysfunction
• DTR B/L
• Plantar B/L Flexor
• No Neck stiffness

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Provisional Diagnosis

• Anemia
• Splenomegaly
• Axillary Lymphadenopathy
• Under evaluation
• Chronic Myeloid Leukemia
• Lymphoma
• Myelodysplasia
• Hairy cell Leukemia
• Chronic Malaria
• Myelofibrosis

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Investigations

• CBC TC 10.4 K / u L
• DC N 74.3
• L 17.7
• E
• Hb 8.6 g/dl
• MCV 84.4 f L
• MCHC 32.8 g/dl
• Platelet 234 K / u L
• ESR 30 mm / hr

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• LFT within normal limits
• RFT Creatinine 1.3 mg / dl
• Blood Urea 48.1 mg / dl
• Serum Electrolytes within normal limits
• RBS 101.2 mg / dl
• CRP 1.74 mg / L

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• Urine R/E 2-3 pus cells / hpf
• ECG within normal limits
• CXR within normal limits
• USG Abdomen Pelvis Splenomegaly
• TSH 2.58 u IU /ml
• free T4 0.97 ng / dl

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• Serum LDH 766.4 U/L
• Reticulocyte count flow cytometer 2.24
• 
  ( 0.87-2.63)
• Absolute reticulocyte count 69 K/u L
• 
  (26-126)

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Peripheral Blood Smear 1

• RBCs Dimorphic picture, microcytes, macrocytes,
  
• polychromasia, teardrop cells,
• fragmented cells
• WBCs TC 14700 . 4 Atypical cells are larger
  in
• size with open chromatin
• Platelets Adequate
• Imp Dimorphic picture with polychromasia
• 4 atypical cells
• Tear drop cells

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Tear drop cells
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Normal Peripheral Blood Smear
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Peripheral Blood Smear 2

• Leucoerythroblastic picture

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• Serum Iron 95 ug/dl ( 60 180 )
• Serum Ferritin within normal limits
• Serum Cyanocobalamine gt 2000 pg/ml (189-883)
• Serum Folic Acid 18.43 ng/ml (3.1-17.5)
• Blood Lead level below detectable limits

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• Stool Occult Blood 3 samples Negative
• ANA Screen Negative ( 0.30 )
• Direct Indirect Coombs Test Negative
• Serum G6PD 194.5 mu / 10 9 er

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• Sucrose Lysis Test Negative
• Hams Test Negative
• Urine Hemosiderin Negative

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• Upper GI endoscopy Fundal Gastritis
• Echocardiogram within normal limits
• MDCT Chest Abdomen with Contrast
• No mediastinal or abdominal adenopathy
• Moderate Splenomegaly.
• No focal lesion.

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Bone Marrow Study

• Aspiration Cytology Diluted marrow with
• erythroid
  preponderance
• Biopsy section shows bony trabeculae separating
• marrow spaces which appear
  fibrotic
• areas and hypercellular in other
  areas.
• Imp Idiopathic Myelofibrosis

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Myelofibrosis Normal
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Axillary Lymph node Biopsy

• Extramedullary Hematopoesis

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Extramedullary hematopoesis
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• JAK2 Mutation Assay PCR Gel Electrophoresis
• NOT DETECTED

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Final Diagnosis

• Primary Myelofibrosis

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Primary Myelofibrosis

• Earlier known as Agnogenic Myeloid Metaplasia
• Clonal proliferation of myeloid cells with
  variable morphologic maturity and hematopoietic
  efficiency.

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• Primary Disease Process results in chronic
  myeloproliferation and atypical megakaryocytic
  hyperplasia.
• The secondary process of bone marrow fibrosis
  nonclonal fibroblastic proliferation and
  hyperactivity induced by growth factors
  abnormally shed from clonally expanded
  megakaryocytes
• BMF is the hallmark of PMF and contributes to the
  impaired hematopoiesis that leads to severe anemia

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Etiology

• Exposure to thorium dioxide, petroleum products (
  toulene, benzene ) and ionizing radiation
• Chromosomal abnormalities
• deletion in chromosome bearing Rb gene 13q,
  20q and partial trisomy 1q.
• Mutations of JAK2 (Janus kinase 2), a gene found
  on 9p - 50 patients with PMF.

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• Mutations of the thrombopoietin receptor (MPL)
  are also capable of activation of JAK/STAT
  signalling in patients with PMF
• Bone marrow fibrosis (BMF) in PMF results from
  the abnormal deposition of excess collagen
  derived from fibroblasts COLLAGEN III,IV,I
• Stimulated by TGF - Beta

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Clinical features

• 50 70 cases fatigue
• Low grade fever, night sweats
• 15 20 asymptomatic diagnosed when evaluated
  for splenomegaly / hepatomeglay.
• Pulmonary hypertension rarely

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• Splenomegaly THE HALLMARK.
• Spleen may be so large that its lower border
  is below the pelvic brim and its right border
  extends across the midline.
• Hepatomegaly Palpable hepatomegaly is present
  in 40 to 70 percent of patients

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• Extramedullary hematopoiesis
• splenomegaly, hepatomegaly, lymphadenopathy
• Skin involvement is rare
• erythematous plaques, nodules, erythema,
  ulcers or bullae
• Bone Joint involvement Osteosclerosis
• 
  Periosteitis
• 
  Secondary Gout
• 
  Cortical bone blood flow

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Lab

• Anemia lt 10 g / dl
• Leukocytosis Thrombocytosis 11 13
• Leukopenia Thrombocytopenia 8 26
• Median absolute number of circulating CD34
  hematopoietic precursor cells in 84 consecutive
  patients with PMF - 400 times that of healthy
  normal subjects
• (normal range 0.15 to 0.35 cells/microL)

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• Raised S.LDH
• Raised S.ALP
• Raised S.Uric acid
• Raised S.Leukocyte Alkaline phosphatase
• Raised S.Vit B12
• Bone Marrow Aspiration usually DRY TAP
• Bone Marrow Biopsy fibrotic changes

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SUSPECT WHEN

• Nucleated RBCs in the peripheral blood
• Teardrop RBCs in the peripheral blood smear
• Early WBC forms in the peripheral blood
• Palpable splenomegaly

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Proposed revised WHO criteria

• MAJOR CRITERIA
• Presence of megakaryocyte proliferation and
  atypia, usually accompanied by either reticulin
  and/or collagen fibrosis, or,
• in the absence of significant reticulin
  fibrosis, the megakaryocyte changes must be
  accompanied by an increased bone marrow
  cellularity characterized by granulocytic
  proliferation and often decreased erythropoiesis
• Not meeting WHO criteria for PV, CML, MDS, or
  other myeloid neoplasm
• Demonstration of JAK2 617VgtF or other clonal
  marker (eg, MPL 515WgtL/K), or in the absence of a
  clonal marker, no evidence of bone marrow
  fibrosis due to underlying inflammatory or other
  neoplastic diseases

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• MINOR CRITERIA
• Leukoerythroblastosis
• Increase in serum lactate dehydrogenase level
• Anemia
• Palpable splenomegaly
• TO MEET ALL 3 MAJOR 2 MINOR

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Treatment

• ALLOGENIC BONE MARROW TRANSPLANTATION
• HYDROXYUREA
• ANAGRELIDE
• SPLENECTOMY

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Thank You