Haematology- Patho

Dr. Pooja Niagde

Introduction
 WBC
Myeloid Lymphoid

WBC

Granulocyte Monocyte Lymphocyte

 HSC – CD 117(C-KIT); CD 34
Lymphoid Myeloid CD- 33
• T cell B cell
• CD-?

• Pan T - Pan B - *
*
• Normal count  ?

• N – 40 - 70%  Pyogenic infection, drugs(steroid)

• L – 20-40% 

• M – 2-10% 

• E – 2-4% 

• B – 0-1% 
Maturation of Myeloid & Lymphoid Series
When a condition k/a Leukemia/Lymphoma
Peripheral Smear
Lymphoblast Vs Myeloblast
• Nucleoli

• Cytoplasm

• Auer rods – M Characteristic

Auer Rods
 Specific Stains

Lymphoblast Vs Myeloblast
Block Positivity
 Leukemia & Lymphoma
• Myeloid • Hodgkin
• Acute
• Non- Hodgkin
• Chronic

• Lymphoid
• Acute
• Chronic
Leukemia

Acute Vs Chronic

Blast %

Proliferation

Differentiation
 AML

• Myeloblast infiltration in blood

• Age 
• Pathophysiology –
• Genetic / acquired  mutation  inhibition of maturation
 AML
1. Cytogenetics related
• t (8 : 21)  M2
• t (15: 17)  M3 (RAR gene)
• inv 16  M4

2. Therapy related - worst*

3. MDS related – Bad  Gene involved 5q , 7q

• Hallmark -?
• Auer rods  Myeloblast
AML – FAB Classification
• Most Common ?

• M3 Max. Auer Rods (M2, M3, M4)

• M4 & M5  NSE +ve

• M5 

• M7  ??
C/F – Bone Marrow infiltration

• RBC –

• WBC –
• Hypercellular bone marrow

• Plt-
Organ infiltration
• Bone –

• Lymph node

• Other organs- i.e. Liver, spleen

• Meningeal involvement
Multiple Auer Rods 
Immunophenotyping
• AML
• Myeloid – CD???

• M7 
T/T
• TOC  BM Transplant

• M3 (APML)  ATRA
Chronic Myeloproliferative D/o
1. CML
2. Polycythemia Vera (PV)
3. Essential Thrombasthenia (ET)
4. Primary Myelofibrosis (PM)
PV PMF ET

Mutation

Hb BM Fibrosis Plt > 6 lakh / mm3

Hct BM aspiration

EPO P.Sm. *

Splenomegaly  +nt ++ +/-

Myelodysplastic Syndrome
• Gene involved –
• Primary – Primary origin
• Secondary - Therapy related- MDS  Poor prognosis
Aplastic Anemia, PNH
 MDS
• RBC – Ovalocyte, Ringed sideroblastic
- Perinuclear hemosiderin pigment

• Megakaryocyte - Pawn ball appearance

CML
• Mutation –
• Immature Granulocyte
• Basophilia
• Splenomegaly

• Age > 50yr

ABL – BCR Hybrid gene
 3 Phases of CML
• Chronic Accelerated Blast

• < 10 % blast > 10-19 % blast > 20% blast in blood or BM

• > 20% Basophils Biphenotypic leukemia

• ↓ NAP score

• T/T – DOC - Imatinib

TOC - BMT
Garden Party Appearance
WBC
• Hypo-segmented neutrophils
ALL – MC  Overall & in Children

Prognosis Good Vs Bad

Age
Sex

Genetics(Hyper/ Hypodiploidy)

B/T cell

Involvement of
CNS, Testis, mediastinum
 Types
• Pre B-cell ALL • Pre T-cell ALL
• More common • Less common
• BM +++ • Thymus +++ (Thymoma)
• Max  3 years • Max  Puberty
• ↓ Cell lines • Retrosternal mass
• CD 10/19/20 (+) • CD 1/2/5/7 (+)
• Better prognosis • Poor prognosis
• B cell ALL  a/w PAX5 Mutation
• t (9: 22)
• Philadelphia +ve
• 190 kDa  Stronger Tyrosine Kinase activity

• CML 210 kDa

• Weaker Tyrosine Kinase activity
 FAB Classification

• L1 Lymbloblast  MC type ; Better prognosis Scanty cytoplasm &

inconspicuous nuclei

• L2  large , pleomorphic cells, abundant cytoplasm & prominent

nucleus

• L3 least common, similar to

Mature B cells
Symptoms ~ AML
• Lymphadenopathy more common ALL >> AML
• Tdt and PAS
C/F
• Enlargement of Superficial L.N.
• Usually symmetrical, discrete and Non-tender.
• Mild leucocytosis
Smudge or Basket cell
BM examination
• ↑ Lymphocyte count (25 – 95%)
• ↓ myeloid & erythroid precursors

• Markers
CD 5 & 23 may also present
T/T
• Symptomatic for Anemia & H’ge
• Chemotherapy – Cristine PAL

• Intracranial / meningeal ALL 

• TOC 
CLL- Chronic Lymphocytic Leukemia
• (CLL)  enters in L. N.  Small Lymphocytic lymphoma (SLL)
• CLL  Mature B cell tumor (95%)
• It involves BM & Blood (while SLL involves L.N.)
• Age- 50- 60 years (M : F  2:1)

• CLL / SLL (Low grade)

• DLBCL ( High grade)

Genetics
• 11 q
• 12 q  *

• 13 q*
• 17 p
• NOTCH Mutation (Gain of function)  T cell
• Not a/w with radiation
• Abnormal B cell  Autoimmune Ig 
• AIHA + CLL 
• C/F
• Usually asymptomatic
• Lymphadenopathy may present

• HPE 

• IOC – Flow cytometry  CD 5 & 23 +ve

T/T

• Palliative & symptomatic

• Avoid BMT
• DOC Fludarabine
 Lymphoma
Hodgkin Non-Hodgkin
• More symptoms • Less symptoms
• Early Dx • Late Dx
• Good Prognosis • Bad prognosis
• ? • Absent
• Also seen in CMV
• L.N involvement - Continuous • Non-Continuous L.N involvement
• Rarely extra-nodal • Extra-nodal involved
• B cell type & T cell type
Hodgkin Lymphoma
• MC L.N. involved – ?
• Reed Sternberg cell
• Owl eye appearance
• CD ??

• Classical form –
• a/w EBV
• Types of Hodgkin lymphoma
1. Nodular sclerosis
2. Mixed cellularity

3. Lymphocytic Rich
4. Lymphocytic Depleted
5. Lymphocytic predominant (Atypical CD 20, 45)
 Type Cell Remark

Nodular sclerosis Mediastinal invol. Fibrosis F > M

MC Worldwide CD 15,30 +ve
Mixed cellularity Classical RS + Bimodal Peak
MC in India Lymphocyte 5-15yr >40 yrs
Classical RS
Lymphocytic Rich
Lymphocyte ++
Lymphocytic Least common
Depleted Worst - a/w HIV
Lymphocytic CD 20 +ve Best Prog M >> F
predominant Popcorn Cell BCL 2 +ve
Germinal centre Mantle  Marginal zone
 Non-Hodgkin Lymphoma
• B cell Lymphoma T Cell Lymphoma
Follicular L.
Germinal • Mycosis Fungoides
Burkitt’s L.
Centre • ALCL
Diffuse large B cell L.
Mantle cell L.
Marginal zone
Hairy cell Leukemia
 Follicular Lymphoma

• Gene t (14: 18)

• ↑↑ BCL 2
• Indolent course  good prognosis

• HPE 

Markers-
Diffuse large B cell Lymphoma
MC Lymphoma worldwide
Types -3
1. Idiopathic (50%)
2. ↑↑ BCL 6
3. Follicular L. transformation DLBCL
• Infectious agents  EBV, HHV-8
• Aggressive tumor – Worst prog.
• HPE –
• Markers 
Can You Guess?
 Burkitt’s L.

• Most aggressive Lymphoma

Types
• Endemic (Africa) –
- 100% a/w EBV
• Non- endemic – Abdominal Mass (Adults)
25% a/w EBV
• a/w HIV
• Gene –t(8: 14) MC 8 Chromosome- overexpression C myc oncogene
t (2: 8)
t (8: 22)

HPE –
tumor cells + macrophage

CD 19, 20 ** Ki 67 (100%)
Mantle Cell Lymphoma

• Gene

• Markers 


Marginal Zone Lymphoma

1. MALT  MALToma

• MC Site of MALT 

• MC Site of MALToma

2. Extranodal  Orbit
• Etiology MALToma

• Repeated stimulation of lymphoid tissue

• E.g. H. Pylori, RA, Sjogren syndrome Hashimoto's thyroiditis

• H.Pylori stomach Maltoma

• T/t 


Hairy cell leukemia
• MC 
• Cells have Hair like projections  best seen on Phase contrast
Microscopy

• Cell  Pancytopenia
• Elderly
• Leukemic reticulo-endotheliosis
• BM examination
• Aspiration  Dry tap
• Biopsy 

CD 11, 25, 103 +ve ; (best markers)-?

Stain 
Massive splenomegaly  involve red pulp
T/T – Cladribine
T cell Lymphoma
• Mycosis Fungoides
• Cutaneous T cell lymphoma (Skin)  collection 

• If involves Blood 

• CD 4 T cells
Pautrier’s Microabscess
Anaplastic Large Cell Lymphoma
• Alk gene mutation on Chr. 2p
• HPE 

CD 30 +VE
Hallmark Cell & Doughnut Cell
Lymphoma
1. C/F  Fatigue, Weakness , Wt. Loss

 fever, Night sweat, Myalgia

Pel Ebstein fever – Cyclic pattern of fever

 Symptoms will worsen with Alcohol

• REAL Classification for Lymphoma

• Staging  Ann Arbor Staging Method

T/T
•
 Langerhans Cell Histiocytosis
• K/a
• C/F  Skin rash, Bone pain d/t Bone #, dislocation
• 4 types
1. – Benign Mostly in children
2. Letterer–Siwe disease – Infants < 2 yr.
3. Hand Schuller Christian Ds. – Children (3-10 yr)
4. Pulmonary Histiocytosis a/w Smoking
 RBC  Blood transfusion
• Blood group system  ABO
• Rarest Blood group -??

• Inheritance  Co-dominance
• Cross matchings - Donor Recipient

• Major

• Minor
 Agglutinogen = Ag
Agglutinin = Ab

Universal Donor

Universal recipient