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By- Dr. Priya Jaswani
 Slide discussion of Leukemoid reaction and
Chronic Myeloid Leukemia .
A 39 yr male patient came with c/o
abdominal pain-2 week in duration
vague dragging pain
associated with fullness of abdom...
 h/o fatigue, fever ,increased sweating,early
satiety + ,
 h/o loss of appetite +
 No h/o loss of weight, no h/o bleedi...
 Hemoglobin: 8.5 g/dl
 RBC series : Moderate anisopoikilocytosis .
Predominantly normocytes are seen . Few
macrocytes an...
 WBC Series :
 Total Leucocyte count is
1.80 lakh cells / cumm.
Differential count :
Blasts:02%
Promyelocyte : 03%
Myelo...
Marked Leukocytosis
Predominantly neutrophils,
metamyelocytes, myelocytes
Myelocyte bulge.
Less 3% are Myeloblast
Eos...
 Absolute
basophilia is seen .
 Hypogranular
basophils were
also seen .
 Platelets showed
variation in size .
 Few platelets
lacked
granulation.with
targetoid
appearance.
 Disturbed platelet
...
 Cellularity :Markedly hypercellular
(95 %)
 M:E ratio : 12:1
 Erythroid series : Dimorphic .
 Myeloid series : Blasts 02% ,
Promyelocyte 02% ,
Myelocytes 25% ,
Metamyelocytes 21%
Neutrophils including band cells 29...
 Megakaryocytes are
increased in number
with focal clustering .
 Megakaryocytes are
smaller and
hypolobated : ‘Dwarf
for...
 A 38 year old female was admitted in medical ward with
the complain of Fever since one month . It was of
moderate grade ...
 Hb: 7.4 g/dl
 RBC series : Mild anisopoikilocytosis
moderate hypochromia
.Predominantly microcytic
hypochromic cells se...
 WBC Series : Total Leucocyte count is
56,000 cells / cumm.
Differential count : Blasts:00
Promyelocyte : 01%
Myelocyte :...
 Toxic granulation
in Neutrophils.
 Leukocytosis, defined as an increase in white
blood cell (WBC) count, is a common finding
with a broad differential diag...
 Further if increased blasts are seen then it
should prompt a workup for acute leukemia.
 For confirmation of reactive l...
1.Brief introduction of
Myeloid Leukemoid reaction
Chronic Myeloid Leukemia
Chronic Neutrophilic leukemia
2.Differentiatio...
 Leukemoid reaction — a secondary
reversible significant increase in the number
of leukocytes in response to a stimulus,
...
 As reactive changes in blood are similar to
hematological malignancies, it is important
to differentiate them from leuke...
 The diagnosis of Myeloid Leukemoid
Reaction is based on the exclusion of chronic
myelogenous leukemia (CML) and
chronic ...
 Chronic Neutrophilic Leukemia is a rare,
distinct myeloproliferative syndrome with a
poor prognosis.
 The differential ...
MYELOID TYPE LEUKEMOID REACTION :
Leukemoid reactions of myeloid type develop in
various infectious and noninfectious proc...
ACUTE STRESS STATES :
 Post surgery
 Post hemorrhage
 Myocardial Infarction
MISCELLANEOUS :
 Steroid therapy
 Gout
 ...
LEUKEMOID REACTION CML CNL
Any age Middle age (40-65
years)
Elderly (54-85 years)
In leukemoid reaction the clinical course is related to cause .
In CML clinical course is :Progressive .
The progression o...
LEUKEMOID
REACTION
CML CNL
Features of
underlying
cause
• Fatigue, lethargy, weight loss,
sweats
• Splenomegaly in >75 per...
Leukemoid Reaction CML CNL
TLC is > 50,000
cells/cumm .
TLC ranges from
30,000 cells/cumm to
10 lakh cells /cumm.
TLC > 25...
LEUKEMOID REACTION CML CNL
Leucocytes consist mostly of
mature neutrophils.
The differential count discloses a
marked left...
Band
forms
promyelo
cyte
myelocyte
meta
myelo
cyte
CML PERIPHERAL SMEAR CHRONIC PHASE
Leukemoid
reactiom
CML( Chronic
phase )
CNL
Increased
cellularity with
myeloid
hyperplasia .
But NO marrow
fibrosis
Marked...
 Increased
cellularity with
myeloid
hyperplasia is the
principle picture
of an Leukemoid
Reaction.
 No fibrosis is
prese...
 Marrow is
hypercellular with
granulocytic
predominance.
 Megakaryocytes are
increased in number
with abnormal
morpholog...
 Scattered amongst
marrow cells are
macrophages with
linear striations or
granular cytoplasm
(Pseudo-Gaucher
cells ) , so...
 Two types of CML
 Granulocytic CML
 Granulocytic –
megakaryocytic
CML.
Leukemoid
reaction
CML CNL
Stimulated
neutrophils of
an LR have
increased LAP
scores
LAP Score is
markedly
diminished to 0...
 .Leukemoid
reaction
CML CNL
Normal Elevated Elevated
 In CML there is increase in
 uric acid level
 lactate dehydrogenase.
 Increase in the level of angiogenic factors
 Entire chromosomal complement is
evaluated to identify philadelphia
chromosome and other abnormalities.
 Can be done on...
 The presence of
the Philadelphia
chromosome –
shortened
chromosome 22.
 t(9,22)( q34,q11)
Nearly 95 % patients demonstrate Ph chromosome .
For CML patients who are cytogenetically
Ph-chromosome–negative (Ph-) the...
Normal in
Leukemoid reaction
Detect the BCR-ABL fusion gene
on chromosome 22
Qualitative in CML.
 Detects different length products
corresponding to chimeric BCR-ABL proteins
of 190,210 and 230 kda.
 So helps in disti...
 Immunophenoty
ping is
necessary for
assigning
specific lineage
to CML Blast
crisis cells.
Leukemoid
reaction
CML CNL
Peripheral
blood
Mature
neutrophils,
marked “left shift”
Immature cells,
basophils, and
eosinop...
LEUKEMOID
REACTION
CML CNL
Cytogenetic
analysis
No cytogenetic
abnormality .
Bcr-abl fusion .
T (9,22) q11 , q34.
Ph + chr...
LEUKEMOID
REACTION
CML CNL
Clonality
studies
Polyclonal Monoclonal Monoclonal
ACUTE INFECTIONS:
 Infectious
mononucleosis,
 Chicken pox,
 Scarlet fever,
 Mumps
 Measles
 Rubella.
 CHRONIC
INFEC...
DIFFERNTIATING
FEATURES .
LYMPHOID
LEUKEMOID
REACTION .
CLL / SLL
AGE Any age. > 60 years of age .
SYMPTOMS/SIGN Malaise ,...
Lymphoid leukemoid
reaction .
CLL/SLL
CBC Lymphocytosis . Lymphocytosis .
PERIPHERAL
SMEAR
Atypical
lymphocytes .
Small
ly...
Lymphoid
leukemoid
reaction
CLL /SLL
CLINICAL
COURSE
Self- limiting Progressive .
Flow cytometry Normal . Abnormal .
 -Left: Atypical
lymphocytes-> viruses
irritate the lymphocytes
caused them to become
bigger and nucleus
changes shape->
...
ALLERGIC STATES:
Asthma
Urticaria
Hay fever
Drug dermatitis
MISCLLANEOUS :
Tropical eosinophila
Eosinophilic Pneumonia
Eos...
 Chronic
eosinophilic
leukemia (CEL) is
a
myeloproliferative
disorder
characterized by
clonal
proliferation of
eosinophil...
 Persistent eosinophilia >1500/cumm.
 Myeloblasts <20% in blood and bone marrow .
 There is multilobation,vacuolation a...
 INFECTIONS:
 Tuberculosis
 Kala azar
 Malaria
 Trypanosomiasis
 Bacterial
endocarditis
 Needs to be
differentiated...
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
leukemoid reaction and leukemia
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leukemoid reaction and leukemia

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Differentiation of leukemoid reaction and Leukemia.

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leukemoid reaction and leukemia

  1. 1. By- Dr. Priya Jaswani
  2. 2.  Slide discussion of Leukemoid reaction and Chronic Myeloid Leukemia .
  3. 3. A 39 yr male patient came with c/o abdominal pain-2 week in duration vague dragging pain associated with fullness of abdomen no aggravating or relieving factors
  4. 4.  h/o fatigue, fever ,increased sweating,early satiety + ,  h/o loss of appetite +  No h/o loss of weight, no h/o bleeding tendency  PAST h/o -> No h/o Tb/HTN/DM  PERSONAL h/o -> consumes alcohol occasionally  P/A –mild distention of abdomen+ moderate splenomegaly(+) mild hepatomegaly Sternal tenderness was present . No lymphadenopathy .
  5. 5.  Hemoglobin: 8.5 g/dl  RBC series : Moderate anisopoikilocytosis . Predominantly normocytes are seen . Few macrocytes and tear drop cells seen . Polychromasia also seen .
  6. 6.  WBC Series :  Total Leucocyte count is 1.80 lakh cells / cumm. Differential count : Blasts:02% Promyelocyte : 03% Myelocyte :25 % Metamyelocyte : 17% Neutrophils (including band cells):39% Lymphocytes :01% Eosinophils;04% Monocytes :02% Basophils :07% Shift to left seen . Platelets :1.8 lakh /cumm No hemoparasite seen . Impression : Peripheral smear suggestive of Chronic Myeloid leukemia .
  7. 7. Marked Leukocytosis Predominantly neutrophils, metamyelocytes, myelocytes Myelocyte bulge. Less 3% are Myeloblast Eosinophilia & Basophilia
  8. 8.  Absolute basophilia is seen .  Hypogranular basophils were also seen .
  9. 9.  Platelets showed variation in size .  Few platelets lacked granulation.with targetoid appearance.  Disturbed platelet function.
  10. 10.  Cellularity :Markedly hypercellular (95 %)  M:E ratio : 12:1  Erythroid series : Dimorphic .
  11. 11.  Myeloid series : Blasts 02% , Promyelocyte 02% , Myelocytes 25% , Metamyelocytes 21% Neutrophils including band cells 29% . Eosinophils 06% Basophils 13 % lymphocyte 02% .  Megakaryocytes :Slighty Increased in number  Plasma cells :within normal limits.
  12. 12.  Megakaryocytes are increased in number with focal clustering .  Megakaryocytes are smaller and hypolobated : ‘Dwarf forms ’.  Evidence of dysmegakaryopoiesis is seen.
  13. 13.  A 38 year old female was admitted in medical ward with the complain of Fever since one month . It was of moderate grade not associated with chills or rigor .  She had cough along with expectoration since one month .  Also she complained of increased frequency of micturition.  Urine Culture :Positive for E.coli.  P/A: No hepatomegaly, no splenomegaly
  14. 14.  Hb: 7.4 g/dl  RBC series : Mild anisopoikilocytosis moderate hypochromia .Predominantly microcytic hypochromic cells seen.Few pencil cells , tear drop cells seen . .
  15. 15.  WBC Series : Total Leucocyte count is 56,000 cells / cumm. Differential count : Blasts:00 Promyelocyte : 01% Myelocyte :06% Metamyelocyte :19% Neutrophils (including band cells):56 % Lymphocytes :09% Eosinophils;03% Monocytes :04% Basophils :02% Shift to left seen. Platelets :1.8 lakh /cumm No hemoparasite seen .
  16. 16.  Toxic granulation in Neutrophils.
  17. 17.  Leukocytosis, defined as an increase in white blood cell (WBC) count, is a common finding with a broad differential diagnosis, encompassing both benign and malignant entities.  Classification and diagnosis of leukocytosis require confirmation of automated differential counts and examination of the peripheral blood smear.
  18. 18.  Further if increased blasts are seen then it should prompt a workup for acute leukemia.  For confirmation of reactive leucocytosis and chronic leukemias we require flow cytometric test, immunophenotyping and bone marrow examination with cytogenetic and molecular genetic tests.
  19. 19. 1.Brief introduction of Myeloid Leukemoid reaction Chronic Myeloid Leukemia Chronic Neutrophilic leukemia 2.Differentiation between above three on the basis of Peripheral smear, Bone marrow aspirate picture Bone marrow biopsy picture LAP score Cytogenetics Immunophenotyping 3.Brief discussion of Lymphoid leukemoid reaction and eosinophilic leukemoid reaction .
  20. 20.  Leukemoid reaction — a secondary reversible significant increase in the number of leukocytes in response to a stimulus, accompanied by the appearance in the blood of immature forms of leukocytes.  It is defined by a leukocyte count greater than 50,000 cells/μL, caused by reactive causes outside the bone marrow
  21. 21.  As reactive changes in blood are similar to hematological malignancies, it is important to differentiate them from leukemia.  Careful history, good physical examination, and limited imaging studies may assist in revealing the underlying cause of leukemoid reaction .
  22. 22.  The diagnosis of Myeloid Leukemoid Reaction is based on the exclusion of chronic myelogenous leukemia (CML) and chronic neutrophilic leukemia (CNL).
  23. 23.  Chronic Neutrophilic Leukemia is a rare, distinct myeloproliferative syndrome with a poor prognosis.  The differential diagnosis between Leukemoid Reaction and Chronic Neutrophilic Leukemia may be difficult or even impossible because both conditions share identical morphological features, including a raised LAP score and the absence of the bcr/abl translocation .
  24. 24. MYELOID TYPE LEUKEMOID REACTION : Leukemoid reactions of myeloid type develop in various infectious and noninfectious processes. ACUTE BACTERIAL INFECTIONS: Pneumonia, Pyogenic meningitis Cellulitis Infected burns Diphtheria
  25. 25. ACUTE STRESS STATES :  Post surgery  Post hemorrhage  Myocardial Infarction MISCELLANEOUS :  Steroid therapy  Gout  Rheumatoid arthritis
  26. 26. LEUKEMOID REACTION CML CNL Any age Middle age (40-65 years) Elderly (54-85 years)
  27. 27. In leukemoid reaction the clinical course is related to cause . In CML clinical course is :Progressive . The progression of Ph+ CML that occurs when the condition is left untreated is described in three phases: Chronic Accelerated Blast
  28. 28. LEUKEMOID REACTION CML CNL Features of underlying cause • Fatigue, lethargy, weight loss, sweats • Splenomegaly in >75 percent; may cause (L) hypochondrial pain, satiety and sensation of abdominal Fullness. • Gout, bruising/bleeding, and occasionally priapism • Signs include moderate to large splenomegaly (40% >10 cm), hepatomegaly (2%), Fatigue, lethargy, weight loss . Hepato- spenomegaly present.
  29. 29. Leukemoid Reaction CML CNL TLC is > 50,000 cells/cumm . TLC ranges from 30,000 cells/cumm to 10 lakh cells /cumm. TLC > 25,000 cells /cumm .
  30. 30. LEUKEMOID REACTION CML CNL Leucocytes consist mostly of mature neutrophils. The differential count discloses a marked left shift, as evidenced by the presence of myelocytes and metamyeocytes . In addition PS discloses toxic granulation, Doëhle bodies, and cytoplasmic vacuoles in the neutrophils of patients with an LR attributed to an infection. In CML, there are more immature cells, absolute basophilia , and Eosinophils. Marked neutrophilia with fewer metamyelocytes and myelocytes (<5%). Immature granulocytes: promyelocytes, myelocytes, metamyelocytes are <10 % . Blasts <1% .
  31. 31. Band forms promyelo cyte myelocyte meta myelo cyte CML PERIPHERAL SMEAR CHRONIC PHASE
  32. 32. Leukemoid reactiom CML( Chronic phase ) CNL Increased cellularity with myeloid hyperplasia . But NO marrow fibrosis Markedly hypercellular. M:E ratio 15:1 to 32: 1. Myeloblast <5 %. Megakaryocytes show clustering and Dwarf forms. Pseudogaucher cells may be seen Hypercellular , majority are neutrophils , M;E ratio > 20:1 , Megakaryocytes are normal in number .
  33. 33.  Increased cellularity with myeloid hyperplasia is the principle picture of an Leukemoid Reaction.  No fibrosis is present.
  34. 34.  Marrow is hypercellular with granulocytic predominance.  Megakaryocytes are increased in number with abnormal morphology.  Increase in reticulin fibrosis.  Blasts less than 5%.
  35. 35.  Scattered amongst marrow cells are macrophages with linear striations or granular cytoplasm (Pseudo-Gaucher cells ) , some with sea blue colored granules resembling Sea-blue histiocytes .
  36. 36.  Two types of CML  Granulocytic CML  Granulocytic – megakaryocytic CML.
  37. 37. Leukemoid reaction CML CNL Stimulated neutrophils of an LR have increased LAP scores LAP Score is markedly diminished to 0- 20 and is characteristic finding . LAP Score is high .
  38. 38.  .Leukemoid reaction CML CNL Normal Elevated Elevated
  39. 39.  In CML there is increase in  uric acid level  lactate dehydrogenase.  Increase in the level of angiogenic factors
  40. 40.  Entire chromosomal complement is evaluated to identify philadelphia chromosome and other abnormalities.  Can be done on both peripheral blood and bone marrow .  Cytogenetics cannot identify complex translocations.
  41. 41.  The presence of the Philadelphia chromosome – shortened chromosome 22.  t(9,22)( q34,q11)
  42. 42. Nearly 95 % patients demonstrate Ph chromosome . For CML patients who are cytogenetically Ph-chromosome–negative (Ph-) the following special techniques can be used to detect BCR-ABL Fusion: • Fluorescence in situ hybridization (FISH) • Reverse transcriptase polymerase chain reaction (RT-PCR) %
  43. 43. Normal in Leukemoid reaction Detect the BCR-ABL fusion gene on chromosome 22 Qualitative in CML.
  44. 44.  Detects different length products corresponding to chimeric BCR-ABL proteins of 190,210 and 230 kda.  So helps in distinguishing CML from ALL and CNL.
  45. 45.  Immunophenoty ping is necessary for assigning specific lineage to CML Blast crisis cells.
  46. 46. Leukemoid reaction CML CNL Peripheral blood Mature neutrophils, marked “left shift” Immature cells, basophils, and eosinophils Marked neutrophilia, no immature cells Bone marrow Myeloid hyperplasia, orderly maturation, normal morphology Basophilia, eosinophilia, monocytosis, slight increase in blasts and reticulin fibrosis. Similar morphology with LR, packed bone marrow, slight increase in reticulin . LAP score High Low High
  47. 47. LEUKEMOID REACTION CML CNL Cytogenetic analysis No cytogenetic abnormality . Bcr-abl fusion . T (9,22) q11 , q34. Ph + chromosome in 95 % patients . Cytogenetic abnormalities in 37% of cases Immunopheno- typing CD13 (+++), CD15 (+++), CD34 (−) HLA-DR (−) CD13 (+++), CD15 (+++), CD34(−) HLA-DR (+) CD13 (+++) CD15(+++), CD34 (−) HLA-DR (+) Serum G-CSF High Low Low
  48. 48. LEUKEMOID REACTION CML CNL Clonality studies Polyclonal Monoclonal Monoclonal
  49. 49. ACUTE INFECTIONS:  Infectious mononucleosis,  Chicken pox,  Scarlet fever,  Mumps  Measles  Rubella.  CHRONIC INFECTIONS:  Tuberculosis  Brucellosis  Syphilis
  50. 50. DIFFERNTIATING FEATURES . LYMPHOID LEUKEMOID REACTION . CLL / SLL AGE Any age. > 60 years of age . SYMPTOMS/SIGN Malaise , Fever , pharyngitis , etc . Asymptomatic . ONSET Acute . (Enlargement of lymph node / spleen) . Indolent (Enlargement of lymph nodes / spleen)
  51. 51. Lymphoid leukemoid reaction . CLL/SLL CBC Lymphocytosis . Lymphocytosis . PERIPHERAL SMEAR Atypical lymphocytes . Small lymphocytes .
  52. 52. Lymphoid leukemoid reaction CLL /SLL CLINICAL COURSE Self- limiting Progressive . Flow cytometry Normal . Abnormal .
  53. 53.  -Left: Atypical lymphocytes-> viruses irritate the lymphocytes caused them to become bigger and nucleus changes shape-> cytoplasm gives shape of "ballerina skirt cells" -Right: Small lymphocytes-> Normal, small, rounded, slightly bigger than RBC, scant cytoplasm, round mature nuclei
  54. 54. ALLERGIC STATES: Asthma Urticaria Hay fever Drug dermatitis MISCLLANEOUS : Tropical eosinophila Eosinophilic Pneumonia Eosinophilic granuloma. PARASITIC DISEASES: Roundworm infestation Hookworm infestation. Filariasis . Trichinosis .
  55. 55.  Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder characterized by clonal proliferation of eosinophilic precursors .
  56. 56.  Persistent eosinophilia >1500/cumm.  Myeloblasts <20% in blood and bone marrow .  There is multilobation,vacuolation and degranulation of eosinophils .
  57. 57.  INFECTIONS:  Tuberculosis  Kala azar  Malaria  Trypanosomiasis  Bacterial endocarditis  Needs to be differentiated from :  Chronic Myelo- monocytic Leukemia  AML M4 and M5  Hodgkin’s disease

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