Leukemia is cancer of the white blood cells. Acute myeloid leukemia (AML) is a type of leukemia characterized by abnormal proliferation of myeloid precursors in the bone marrow, blood, and other tissues. This leads to reduced production of normal blood cells. AML is diagnosed based on examination of bone marrow aspirate and biopsy, which show over 20% myeloblasts. Specific subtypes are classified based on cell morphology and staining characteristics. Treatment of AML aims to induce remission by eliminating leukemia cells.

1. LEUKEMIA
Dr. Devdutta Nayak
BIRATNAGAR EYE HOSPITAL

2. BASICS
• Red blood corpuscles
• Platelets
• White blood corpuscles
Granulocytes
Neutrophils
Eosinophls
Basophils  Mast cells
Agranulocytes
Monocytes  Macrophages, Tissue Histiocytes
Lymphocytes
B cells  Plasma Cells- Immunoglobulins
T cells ( CD 4+ , CD 8+)
NK cells

3. HEMATOPOIESIS

4. Hematopoietic
stem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Lymphoid
progenitor
B-lymphocytes
T-lymphocytes
Plasma
cells
naïve
ALL
AML

5. • LYMPHOID ORGANS
Primary – Bone Marrow & Thymus
Secondary – Spleen, Lymph nodes, Mucosa
associated aggregates( e g payer‟s
patches, tonsils)
No Lymph nodes in Orbit
Mucosa associated lymphoid tissue present in
conjunctiva and in lacrimal gland

6. • Virchow (1845, 1863) first coined the terms LEUKEMIA and
LYMPHOSARCOMA
• 1st description of Hodgkin‟s Disease – Carswell in 1828.
• Term “Hodgkin‟s disease” by Wilks in 1865; later also came to
be known as Lymphadenoma.
• In 1860, Liebreich first described Leukemic Retinopathy
• Gall & Mallory in 1942 – gave the first modern classification of
Lymphomas(Non-Hodgkin‟s)
EVOLUTION OF TERMS & CONCEPTS in HEMATONCOLOGY

7. • Later classifications by Rappaport (1966), Lennert (1974),
Working Formulation (1982).
• REAL classification (1994) : clubbed Leukemias of Lymphoid
origin and Lymphomas (Hodgkin‟s & NHL) in one classification.
• FAB classification of Myeloid Neoplasms( leukemias)-1970s
• WHO classification of hematopoeitic and lymphoid neoplasms
2001 & 2008
(based on disease presentation, morphology,
immunophenotype and genetics)

8. • Lymphoid neoplasms include a diverse group of tumors of B-
cell, T-cell, and NK-cell origin (including Multiple Myeloma and
related disorders).
• Myeloid neoplasms arise from early hematopoietic progenitors
a) acute myeloid leukemias, in which immature progenitor
cells accumulate in the bone marrow
b) myelodysplastic syndromes, which are associated with
ineffective hematopoiesis and resultant peripheral blood
cytopenias
c) chronic myeloproliferative disorders, in which increased
production of one or more terminally differentiated myeloid
elements usually leads to elevated peripheral blood counts.
• The histiocytoses are uncommon proliferative lesions of
macrophages and dendritic cells in the connective tissues.

9. What is leukemia?
Leukemia is cancer of the white blood cells.
White blood cells help body fight infection. In
leukemia, however, the bone marrow produces
abnormal white blood cells. These cells crowd
out the healthy blood cells, making it hard for
blood to do its work.

10. Leukemias : Hematological neoplasms with widespread
involvement of Bone Marrow and Blood.
• According to clinical presentation
Acute leukemias – appearance of clinical features
early in the course with fatal outcome in couple of
years if left untreated
Chronic leukemias – insidous onset of symptoms
with relatively longer expected survival, terminating
in Blast Crisis

11. Signs and Symptoms
• Most of the signs and symptoms are due to:
1-Anemia.
2-Leukopenia.
3-Thrombocytopenia.
• Bicytopenia,Pancytopenia.
• All symptoms associated with leukemia can be attributed
to other diseases, consequently, leukemia is always
diagnosed by laboratory investigations.

13. Causes
• Leukemia,like other malignancies, results from somatic
mutations in the DNA.
• Certain mutations produce leukemia byactivating
oncogenes or deactivating tumor suppressor genes.
• These mutations may occur spontaneously or as a result
of exposure to radiation or carcinogenic substances and
likely to be influenced by genetic factors.

14. Causes-cont‟d.
• Ionizing radiation
• Viruses: Human T-lymphotropic virus (HTLV-1)
• Chemicals: Benzene,chemotherapy
• Smoking: slight increase in leukemia incidence
• Genetic predisposition toward developing
leukemia: Down syn.,Fanconi anemia

16. Classification
• Multiple classification systems.
• FAB classification:
French-American-British Classification.
• FAB Classification relies on morphologic,
cytochemical,and immunophenotyping criteria to define
8 major subtypes (M0-M7).

17. FAB vs WHO Classification
• French-American-British (FAB) Cx
• Cellular morphology and cytochemical stain
• Acute leukemia as > 30% bone marrow blasts
• Widely used
• World Health Organization Cx
• Cellular morphology and cytochemical stain
• Immunologic probes of cell markers, cytogenetics,
molecular abnormalities & clinical syndrome
• Acute leukemia as > 20% bone marrow blasts
• Standard for diagnosis

18. Acute myeloid leukemias (AML)
Classification - FAB
1. M0: minimally differentiated
2. M1: myeloblastic leukemia without maturation
3. M2: myeloblastic leukemia with maturation
4. M3: hypergranular promyelocytic leukemia
5. M4: myelomonocytic leukemia
6. M4Eo: variant, increase in marrow eosinophils
7. M5: monocytic leukemia
8. M6: erythroleukemia (DiGuglielmo's disease)
9. M7: megakaryoblastic leukemia

19. AML classification - WHO
AML not otherwise categorized
1. AML minimally differentiated
2. AML without maturation
3. AML with maturation
4. Acute myelomonocytic leukemia
5. Acute monocytic leukemia
6. Acute erythroid leukemia
7. Acute megakaryocytic leukemia
8. Acute basophilic leukemia
9. Acute panmyelosis with myelofibrosis

22. Acute vs Chronic Leukemia
Acute Chronic
Age Children & young
adults
Middle age and
elderly
Onset Sudden insidious
Duration weeks to months years
WBC count Variable High

23. Acute vs Chronic Leukemia
Acute Chronic
Platelets Low Early: Normal/ High
Late: Low
Anemia High (>90%) None/ mild
Predomi-
nant cells
Blast cells Mature cells
AML = myeloblast
ALL= lymphoblast
CML=granulocytes
CLL=lymphocytes

24. Acute vs Chronic Leukemia
Acute Chronic
Marrow
cellularity
>20% marrow
blasts (WHO)
> 30% marrow
blasts (FAB)
>70% marrow
cellularity
(hypercellular);
No dysplasia
Diagnosis PBS, BM exam,
cytochemical
stains, surface
markers,chromos
ome
PBS (peripheral
blood smear)

25. Acute Myeloid Leukemia

26. Definition
• Acute myeloid leukemia (AML): acute myelogenous
leukemia, acute non-lymphocytic leukemia.
• AML consists of a group of relatively well-defined
hematopoietic neoplasms, involving precursor cells
committed to the myeloid line(WBCs, RBCs, PLTs).

27. Chracteristics
• AML is characterized by a clonal proliferation of
myeloid precursors with a reduced capacity to
differentiate into mature cellular elements.
• Accumulation of leukemic blasts or other
immature forms in the BM, peripheral blood and
other tissues with a variable reduction in the
production of normal RBCs, platelets and
mature granulocytes.

28. Specific:
• M2 : Chloroma:- presents as a mass lesion, „tumor of
leukemic cells‟
• M3 : DIC
• M4/M5 : Infiltration of soft tissues,
gum infiltration, skin deposits, Meningeal involvement-
headache, vomiting, eye symptoms.

29. A
B
C
Chloromas
NEJM 1998

30. Gum hypertrophy

31. Leukostasis
• accumulation of blasts in microcirculation with impaired
perfusion
• lungs: hypoxemia, pulmonary infiltrates
• CNS: stroke
• only seen with WBC >> 50 x 109/L

32. Pathological Features
• CBC and differential.
• Blood film (smear).
• Bone marrow examination: BM aspirate and trephine
biopsy.
1-Morphology.
2-Immunephenotyping.
3-Cytogenetics and molecular biology.

33. Jemshidi trephine & Salah
aspiration needle

35. Bone marrow in acute leukemia
• necessary for diagnosis
• useful for determining type
• useful for prognosis
• Acute leukemia are defined by the presence of > 20%
blasts in bone marrow (% of nucleated marrow cells).

36. • Bone marrow aspirate & trephine:
Hypercellular
• blast cells ( > 20%),
• presence of Auer rods - AML type
• Cytochemistry :
Special stains to differentiate AML from ALL ;
Positivity with Sudan black & Myeloperoxidase
(MPO) in AML.

37. WBC Count in AML
• WBC count in AML can be high, normal or low.
• Median WBC count in AML is 15 000/uL.
• 20% of patients have > 100 000/uL.
• 25-40% of patients have <5000/uL.
• 95% of patients have blast cells on blood
film.

38. Distinguishing AML from ALL
• light microscopy
• AML: Auer rods, cytoplasmic (azurophilic) granules
• ALL: no Auer rods or granules.
• flow cytometry
• special stains (cytochemistry)

39. Cytochemical Stains
• Since the early 20th century, cytochemical staining
of cells has been a useful tool in differentiating
hematopoietic diseases.
• Smears and imprints made from bone marrow,
lymph nodes, spleen, or peripheral blood are
preferred.
• In enzymatic techniques, fresh smears are used to
ensure optimal enzyme activity
• Certain elements may be inhibited during the
fixation of smears and imprints

41. Myeloperoxidase (MPX/MPO)
• The peroxidase enzyme reacts with H2O2 &
release O2, which oxidizes the indicator dye
and produce orange-brown granules in the
cells (3-amino-9-erythrocarbazol)
• Enzyme MPX is found in the 1o granules of
granulocytes, neutrophils and precursors (from
the promyelocyte stage on) & eosinophils
• Monocytes may be weakly pos
• Leukemic myeloblasts are usually pos and
Auer rods stain very strongly
• Used for differentiating AML (+) from ALL (-)

42. MPO (right) & Sudan black (left)
showing intense localised positivity
in blasts

43. Myeloperoxidase
(MPO)
p-Phenylene diamine + Catecol + H2O2
MPO > Brown black deposits

44. Chloracetate (Specific) Esterase
Myeloid Cell Line
Naphthol-ASD-chloracetate
CAE > Free naphthol compounds
+ Stable diazonium salt (eg, Fast Corinth
> Red deposit

45. Non-Specific Esterase (NSE)
• Nonspecific esterase liberates alpha-naphthyl
from the substrate alpha-naphthyl acetate.
Alpha-naphthyl couples with the dye molecule
to form dark reddish-brown granules
• Monocytes, monblasts, macrophages,
histiocytes, megakaryocytes and some
carcinomas are NSE pos.
• Abnormal erythroblasts are strongly pos.
• Lymphocytes are neg or may show dot
positivity.

46. Non-Specific Esterase
Monocytic Line
Naphthyl acetate
ANAE > Free naphthyl compounds
+Stable diazonium salt (eg, Fast blue RR
> Brown deposits

47. NSE (continued)
• Used for differentiating myelomonocytic and
monocytic leukemia (+) from granulocytic leukemia
(-)
• Monocyte NSE are fluoride sensitive.
http://www.healthsystem.virginia.edu/internet/hematology/hessedd/malignanthematologicdisorders/leukemias/aml-m4.cfm

48. Double Esterase in M4
NSE with Fl inhibition
Histiocyte

49. Periodic Acid Schiff (PAS)
• Periodic acid oxidizes glycogen, mucoproteins,
and other high-molecular weight carbohydrates
to aldehydes.
• Aldehydes react with colorless Schiff reagent,
staining them a bright red-pink.
• Megakaryocytes and platelets stain strongly
pos.
• Normoblasts will stain Pos.
• Lymphoblasts in ALL show course and granular
positivity.

50. PAS (continued)
• Myeloblasts are Neg.
• Aids in diagnosis of ALL, erythroleukemia, and
megakaryoblastic leukemia.
• Normal bone marrow smear used for control slides
http://www.pathologyoutlines.com/leukemia.html

51. Periodic Acid Schiff
Periodic acid + Glycogen
oxidation > Aldehyde + Schiff reagent
(para-rosaniline, Na metabisulfit
> Red deposit

52. AML

53. AML

54. Auer rods in AML

55. Auer Rods

56. P. Smear AML

57. MO: Minimally differentiated
• Undifferentiated Blasts
(No maturation)
• Myeloid phenotype -
CD13, CD33, CD34
• (-) SBB, MPO
• Negative: Auer rods,
Esterase

58. M1 AML without maturation
 > 30% myeloblasts
 Large cells, round nucleus
 Nucleoli (+)
 scanty cytoplasm
 >3% MPO, SBB (+)
 <20% NSE (+)
 CD 13, 33, 117

59. M2 AML with maturation
• Common type
• >30% myeloblasts
• >10% granulocyte
• Kidney shape nucleus
• Nucleoli (+)
• (+) Auer rods
• Eosinophilic granules
• >50% MPO, SBB (+)
• CD 13, 33

60. M3 (hypergranular promyelocytic)
• Promyelocyte-predominant
• Large, kidney shape (faggot
cells)
• (+) Auer rods
• basophilic, bi-lobed nuclei
• CD 13,33
• High incidence of DIC

61. Acute myeloid leukemia with very
abnormal cells (AML M3/ t15;17)

62. M4 Acute myelomonocytic
• >30% myeloblast (FAB)
• >20% granulocyte
• >20% promonocytes and
monocytes
• CD 11, 13, 33,14
• (+) Auer rods common
• High serum lysozyme level

63. M5: acute monocytic leukemia
1. M5a – without maturation
• Monoblasts , few promonocytes
2. M5b – with maturation
• Blast, Promonocytes (BM), Monocytes (Blood)

64. M5a
• Monoblasts ameboid with
round to oval nuclei,
• prominent nucleoli,
• <20%
promonocytes/monocytes
• Vacuolated cytoplasm

65. M5b
• > 20% promonocytes,
monocytes
• Promonocytes with
folded, convulated
nucleus
• Azurophilic granules

66. M6 - erythroleukemia
 Large, bizarre,
round-to-oval cells
 (+) nucleoli
 > 50% Erythroblasts
 > 30 % Myeloblasts
 CD 45,71 Glycophorin A
 CD 13, 15,33 myeloblast
 PAS (+)

67. M7 – acute megakaryoblastic
• >30% megakaryoblasts
• platelet like granules on
PAS stain
• NSE (+)
• Myeloid blasts may
show SBB or MPO (+)
• CD 41,42,61

68. Megakaryoblast

69. Acute Nonlymphocytic Leukemias

70. Acute lymphoblastic leukemia

71. • The most common malignancy in children, especially
affecting those aged 2-10 years.
• ALL is seen in only 20% of adult acute leukemias and
behaves more aggressively than the childhood type.
• FAB Classification of ALL :
 L1: Small homogeneous blasts; mostly in children
 L2: Large heterogeneous blasts; mostly in adults
 L3: “Burkitt” large basophilic B-cell blasts with vacuoles

72. WHO Classification of Lymphoproliferative
Syndromes
 Precursor B Lymphoblastic
Leukemia/Lymphoma (ALL/LBL) --
ALL in children (80-85% of childhood ALL);
LBL in young adults and rare; (FAB L1 or L2)
 Precursor T ALL/LBL --
15% of childhood ALL and 25% of adult ALL.
 Burkitt Leukemia/Lymphoma -- (FAB L3)

73. • Confirmation:
• Immunophenotyping
• Molecular genetics
• Cytogenetics: Chromosomal
abnormalities

74. ALL L1

75. L3L2

76. Burkits / ALL L3

77. Prognostic factors
• High WBC – relapse in testis /cns
• Infants <1 yr, children >10 yr poor outcome
• L1- good prognosis
• L2,3- bad prognosis

78. Prognosis
• The response to treatment and overall survival of
patients with ALL are heterogenous.
• Prognostic factors are related to patient and tumor
characteristics:
1- Age
2- Performance status
3- Karyotype

79. Chronic Myeloid Leukemia

80. • Characterized by an uncontrolled proliferation of
granulocytes.
• Accompanying proliferation of erythroid cells and
megakaryocytes usually present.
• Many patients are asymptomatic but may present with
splenomegaly, weight loss, malaise, bleeding, or
thrombosis.
• Ch 22 – 09 translocation (bcr – abl)
Philadelphia Chromosome.

81. 3 Phases:
•Chronic Phase (90%)
•Accelerated Phase (<10%)
•Blast Crisis (Rare)
Chronic Phase pts. usually asymptomatic.
Accelerated Phase implies worsening Dx. (Sokal Index/
WHO criteria)
Blast crisis behaves like an acute leukemia.

82. WHO criteria for diagnosis of Accelerated Phase:
• 10–19% myeloblasts in the blood or bone marrow
• >20% basophils in the blood or bone marrow
• Platelet count <100,000, unrelated to therapy
• Platelet count >1,000,000, unresponsive to therapy
• Cytogenetic evolution with new abnormalities in addition
to the Philadelphia chromosome
• Increasing splenomegaly or white blood cell count,
unresponsive to therapy

83. Blast Crisis:
final phase in the evolution of CML, with rapid progression
and short survival.
Blast crisis is diagnosed if any of the following are present
in a patient with CML –
• >20% myeloblasts or lymphoblasts in the blood or bone
marrow
• Large clusters of blasts in the bone marrow on biopsy
• Development of a chloroma (solid focus of leukemia
outside the bone marrow)

84. Prognosis:
• Before advent of tyrosine kinase inhibitors (e.g. –
Imatinib Mesylate,Dasatinib, Nilotinib) median survival
was 3-5 years.
• Current survival rate approaching 95.2% at end of 8
years akin to rate in general population.

85. Chronic Lymphocytic Leukemia

86. • Monoclonal expansion of lymphocytes.
• In 95% of cases, CLL is a predominantly malignant
clonal disorder of B lymphocytes. The remainder is
secondary to a T-cell clone.
• Primary involvement of the bone marrow and secondary
release into the peripheral blood.
• Asymptomatic at diagnosis. As the disease progresses,
lymphadenopathy, splenomegaly, and hepatomegaly
develop.
• Secondary hypogammaglobulinemia exists.

87. • Most (>75%) people newly diagnosed with CLL are
over the age of 50.
• More prevalent in Men.
• Asymptomatic in early stages, diagnosed incidentally.
• Swollen lymph nodes, spleen, and liver, and
eventually anemia and infections.
• CD5 & CD23 +
• Flow cytometry, FISH
• Smudge cells in PBS.

88. Prognosis:
• Depends on the subtype:
 IgVh Mutation – Worst Prognosis
 del 17p
 del 11q
 trisomy 12
 del13q -- Best Prognosis
• Some subtypes have a median survival of 6–8 years,
while others have a median survival of 22 years.
• Very slow progressing.
Unfavourable

89. PATHOGENESIS OF OPHTHALMIC
MANIFESTATIONS
• INFILTRATION OF BONE MARROW
ineffective hematopoieseis- anemia, thrombocytopenia,
thrombaesthenia, immunodeficiency, auto immunity
• INFILTRATION OF VESSEL WALLS – weakening &
endothelial damage
• INFILTRATION OF TISSUES
skin, occular adnexa, orbit, eye ball, optic nerve, visual
pathway, meninges

90. • MECHANICAL EFFECTS : tumor mass
• INCREASED INTRAVASCULAR CELL MASS
• HYPER VISCOSITY – paraproteinemia
• HYPERCOAGULABILITY

91. • ISCHEMIA & INFARCTION
• METABOLIC EFFECTS : Hypercalcemia, renal failure
• PARANEOPLASTIC SYNDROME : Cerebellar
degeneration in lymphoma
• EFFECT OF THERAPY

92. CHANGES DUE TO HEMATOLOGIC
ABNORMALITIES

93. ANEMIA
• Conjunctival pallor
• Ophthalmoscopic signs ( Hb < 50%)
Generalized pallor of fundus and optic disc
Dilatation of retinal arteries and veins- equal calibre and color
Retinal hemorrhage
Extra retinal hemorrhage – choroidal, pre-retinal/ sub-hyaloid
Retinal edema
Retinal exudates – hard exudates
Cotton wool spots

94. Multiple intraretinal and preretinal hemorrhages and Roth's
spots – case of severe anemia

95. • Ischemic optic neuropathy (NAAION)
• Pseudotumor cerebri

96. THROMBOCYTOPENIA AND THROMBOASTHENIA
• Lid ecchymosis
• Sub conjunctival hemorrhage – petechiae to ecchymosis
• Hematidrosis ( bloody tears)
• Hyphema
• Vitreous hemorrhage
• Retinal hemorrhages – variable colour
• Intracranial hemorrhage –
posterior visual pathway – homonymous hemianopia
cerebellum and brain stem – nystagmus & diplopia
• Bleeding tendency in leukemias contributed by the
perivascular infiltration.

97. • Rarely massive intra orbital bleed causes sudden proptosis,
compartment syndrome, compressive optic neuropathy.

98. THROMBOTIC TENDENCY : Virchow‟s Triad
endothelial damage (infiltration of the vessel wall)
altered blood flow – stasis or turbulence
hypercoagulable states – altered function of
platelets
HYPERVISCOSITY – Stasis of blood flow
paraproteinemia -Waldenstrom Macroglobulinemia > MM
(Rouleaux formation).
increased cell mass- polycythemia, thrombocythemia, and
leukocytosis.
STASIS also contributed by mechanical compression of vessels.
ISCHEMIA and INFARCTION

99. Polycythemia- increased RBCs
• Dilated tortuous arteries and veins
• Disc edema
• Multiple Retinal hemorrhages
• Venous thrombosis
• Ischemic optic neuropathy
• Carotid and vertebro-basilar insufficiency
• Cavernous Sinus Thrombosis
• Conjunctival congestion

100. • NAAION 
• CRVO 
• BRVO 
• STROKE

101. MECHANICAL EFFECTS

102. • Lids
Ptosis
Entropion
• Orbit
Occular deviation, restriction of movements
Proptosis – orbital and lacrimal gland involvement
Disc edema
• Vascular compression- arterial, venous
• Compressive Neuropathy
• Blockage of trabecular meshwork by neoplastic cells-
2ndary glaucoma

103. METABOLIC ABNORMALITIES

104. OCULAR HYPERCALCEMIA
• Hematologic malignant neoplasms (multiple myeloma,
leukemia, or lymphoma) can elevate calcium levels.
• Basement membranes and Epithelial cells - more likely
affected.
It is suggested that these sites are relatively alkaline,
favoring the deposition of calcium salts 
Calcification of corneal epithelium and Bowman‟s layer.

105. • In the conjunctival epithelium, white perilimbal deposits
occur.
• Band keratopathy.
• Scleral calcification can be seen by computed
tomography and may appear clinically as white flecks.
• Pigmented layers of the iris, ciliary body, and choroid
may also demonstrate calcium deposits.
DD
• Dystrophic calcification, granulomatous diseases such
as sarcoidosis, hyperthyroidism, vitamin A intoxication,
and renal failure.

106. • Disease process
• Altered functions of neutrophils, macrophages and
lymphocytes – both innate and adaptive immune
system affected
• Effect of the therapy
IMMUNODEFICIENCY

107. • Opportunistic
infections
• CMV Retinitis 
• Herpes virus
• Toxoplasmosis
• Fungal infections

108. Sub retinal abscess
• most cases of subretinal
abscess are due to
Nocardia, branching gram-
positive filamentous bacteria
• Other causes
Pseudomonas, Klebsiella,
and viridans streptococci
• Mostly in chronic myeloid
leukemia and bone marrow
transplant pts..
Sub retinal abscess with
exudative RD

109. • Rhino-cerebral
mucormycosis

110. MANIFESTATIONS
vis a vis
TISSUES

111. RETINA
Retinal veins become distended and tortuous- first change
(most often because of anemia).
Retinal edema – maximal over optic disc.
As disease progresses, retinal arteries become distended
and venous column becomes broken by AV crossings
into turgid sausage like segments.

112. • Retinal infiltrates take the form of grayish white nodules
associated with local hemorrhage
• Sheathing of retinal vessels and intravascular
margination.
• Perivascular infiltrates, widest along convexities of veins
• Hard exudates and cotton wool spots may be seen; the
cotton wool spots may result from actual leukemic
infiltration of the retina or from nerve fiber layer
infarction.

113. • AML – extensive retinal
hemorrhages- sub hyaloid
extending to macula, flame shaped,
subhyaloid, Roth spots 
• Leukemic infiltration

114. • Roth Spots - leukemic
infiltrates surrounded by
hemorrhages.
• DD
Endocarditis
Anemia
Retinopathy in HIV
Hypertensive or Diabetic
retinopathy

115. • COTTON-WOOL SPOTS: consist of accumulations of
cytoid bodies in the axons of the nerve fiber layer. The
accumulation of material is thought to be related to
disruption of axoplasmic transport by focal ischemia.
• These spots occur in
diabetes mellitus,
hypertension,
collagen vascular diseases,
anemia.

116. • In chronic leukemias & paraproteinemia ( hyperviscosity)
Microaneurysms in the retinal periphery adjacent to
areas of ischemia and nonperffusion.
rarely progress to frank neovascularization in a sea-fan
pattern.
DD – Sickle cell anemia
Central and branch retinal vein occlusions

117. VITREOUS
Infiltration of the vitreous is rare but hematological malignancies
account for most no of cases of tumors involving vitreous.
• Vitreous involvement may be the only ocular sign of an
intraocular malignancy
• The most common primary intraocular malignancy to involve
the vitreous is primary intraocular lymphoma
• Vitreous involvement may be purely inflammatory.
• Clinically, the tumor cells in the vitreous
often adhere to create opacities that are larger than the
vitreous cells typically seen in
inflammatory vitritis.

118. UVEA
The acute leukemias are more
commonly associated with
choroidal involvement .
Overlying retinal pigment epithelial
degeneration and clumping leads
to ‘leopard spot’ pattern which is
thought to be due to invasion or
compression of the choriocapillaris
by leukemia cells.
DD - chronic subretinal fluid collection e g
Uveal effusion syndrome, CSCR.
Leukemic nodular choroidal infiltrates
with overlying vitritis in a patient with
leukemia. 

119. • Choroidal masses with exudative RD
• Cases with choroidal vessel infiltration – peculiar colour
of fundus yellow to light pink
• POSTERIOR CILIARY BODY CYSTS
Multiple myeloma &
Waldenstrom macroglobulinemia
(plasmacytoma)
• IRIS INFILTRATE
T Cell Lymphoma 

120. • ANTERIOR AND POSTERIOR UVEITIS
(MASQUERADE SYNDROMES)
PSEUDOHYPOPYON 
• SECONDARY GLAUCOMA

121. OPTIC NERVE
• Prelaminar fluffy, white infiltrate
superficial to the lamina cribrosa
on the optic nerve head.
• Retrolaminar infiltrate visible on
neuroimaging.
• An important distinction between
direct infiltration by leukemia cells
and disk edema from elevated
intracranial pressure due to
leukemic meningitis must be made
as Orbital radiation can benefit in
infiltrative disease.

123. ORBIT
Insiduous painless, proptosis, edema
Mild restriction of occular movements, inability to close the lids.
Bilateral orbital deposits in few cases.
If pain + , pseudotumor is an important differential (30-40 yrs)
LYMPHOMA – ( old age)
GRANULOCYTIC SARCOMA myeloid infiltrates in child (<10y)

124. • LACRIMAL GLAND
Painless, rubbery mass fixed to the
orbital rim.
Downward and medial deviation
of the eyeball. Non-axial Proptosis.
CT scans usually show a homogeneous consistency with
indistinct borders characteristic of the infiltrative nature of
this lesion
• MICKULICZ syndrome 
• LACRIMAL SAC LYMPHOMA : 2nd most common
neoplastic cause of ephiphora

125. • Conjunctival leukemic infiltrate- Soft, hyperemic
SALMON PATCH

126. • LIDS
Mycosis Fungoides : ill defined spongy tumors of the lids.
This is a form of T-cell lymphoma.
elevated tumor with central
erosion

127. NEUROLOGY
Elevated Intracranial Pressure
Leukemic infiltration
Pseudotumor cerebri
Papilloedema
Cranial Nerve palsies – 3rd , 4th , 6th and 7th

128. • Strokes
involving visual pathway
cerebellum : nystagmus

129. OCCULAR ADVERSE EFFECTS OF
TREATMENT
• Pseudotumor cerebri: due to therapy for acute
promyelocytic leukemia with all-trans retinoic acid (a
vitamin A derivative) and with arsenic Trioxide
• Steroid induced cataract
• Bone Marrow transplant : Graft versus Host Disease
Conjunctival hyperemia, conjunctival chemosis,
pseudomembranous conjunctivitis, corneal sloughing
KCS, filamentary keratitis, immune mediated optic
neuritis

130. • Radiotherapy
Optic atrophy and
peripapillary RPE changes
Radiation retinopathy
Radiation cataract

131. Treatment
• Most treatment protocols use systemic chemotherapy
with or without radiotherapy.
• The basic strategy is to eliminate all detectable disease
by using cytotoxic agents.
• To attain this goal, 3 phases are typically used, as
follows:
 remission induction phase
 consolidation phase
 maintenance therapy phase.

132. • The initial treatment of ALL uses various combinations of
vincristine, prednisone, and L-asparaginase until a
complete remission is obtained.
• Maintenance therapy with mercaptopurine is continued
for 2-3 years following remission.
• Use of intrathecal methotrexate with or without cranial
irradiation to cover the CNS.
• Daunorubicin, cytarabine, and thioguanine currently are
used to obtain induction and remission of AML.
• Maintenance therapy for 8 months may lengthen
remission. Once relapse has occurred, AML generally is
curable only by bone marrow transplantation.

133. • Presently, treatment of CLL is palliative.
• CML is characterized by a leukocytosis greater than
100,000 cells. Emergent treatment with leukopheresis.
Otherwise, busulfan or hydroxyurea may control WBC
counts. During the chronic phase, treatment is palliative.
• CML blastic phase treatment with vincristine and
prednisone.
• Newer drugs for CML – Imatinib Mesylate, Dasatinib,
Nilotinib (for maintainance).
• Allogenic bone marrow transplant is the only curative
therapy for CML. High early mortality rate.

134. • Leukemic retinopathy usually not treated directly.
• As the hematological parameters normalize with systemic
treatment, many of the ophthalmic signs resolve.
• Leukopheresis for hyperviscosity also may alleviate
intraocular manifestations.
• When definite intraocular leukemic infiltrates fail to respond
to systemic chemotherapy, direct radiation therapy is
recommended.

135. • Relapse, manifested by anterior segment involvement,
should be treated by radiation.
• In certain cases, subconjunctival chemotherapeutic
agents have been injected.
• Optic nerve head infiltration in patients with ALL is an
emergency and requires prompt radiation therapy to try
to salvage some vision.

136. THANK YOU