Oncology
Dr. YOSRA SAMIR FADLE
Childhood leukemias
What is the normal hematopoiesis ?
What are the hematologic malignancies in children?
Hematologic Malignancies:
 Leukemias ( Acute and Chronic )
 Lymphomas (Hodgkin and Non- Hodgkin )
 Plasma cell disorders (Multiple myeloma ) “not common in children”
Leukemia
Malignancy of hematopoietic cells
Lymphoma
Malignancy of hematopoietic cells
Starts in bone marrow, can spread to
blood, nodes
Starts in lymph nodes, can spread to
blood, marrow
Myeloid or lymphoid
Lymphoid only
Acute or chronic
Hodgkin or non-Hodgkin
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Oncology
Dr. YOSRA SAMIR FADLE
Leukemia
Definition:Un-controlled proliferation of hematopoietic lymphoid or myeloid progenitor
cells.
Causes:
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Genetic causes.
Immune deficiency.
Chromosomal abnormality.
Exposure to ionizing radiation.
Unknown causes.
Pathophysiology of Acute Leukemia:
 Malignant proliferation of immature myeloid or lymphoid cells in the bone
marrow
 Caused by either
• Colonal expansion OR Maturation failure .
Badness
 Crowding out of normal cells.
 Inhibition of normal cell functions.
 Infiltration of other organs.
How is a diagnosis made?
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Clinical setting
Morphology
Immunophenotyping
Molecular studies
Cytogenetics
Oncology
Dr. YOSRA SAMIR FADLE
 Clinical setting ( Clinical presentation ) : Pallor, purpura, and fever.
 Hepatosplenomegaly.
 LymPhadenopathy.
 Bone pains and arthralgia due to periosteal infiltration.
 Fatigue and weight loss.
 Morphology: Bone marrow aspiration and biopsy:
 Lymphoblast or myeloblast in acute leukemia> 20%
 Different stages of myelocyte differentiation in chronic myeloid
leukemia
 Immunophenotyping : Markers of T or B lymphocytes .
 Markers of myeloblasts.
- T-lineage ALL means worse prognosis.
- B-lineage ALL means better prognosis.
 Molecular studies and Cytogenetics
 Phladilphia chromosome
 t(9;22) which is common in chronic
myeloid leukemia
Acute leukemia
Sudden onset
Can occur in either adults or children
Rapidly fatal without treatmen
Composed of immature cells (blasts)
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Chronic leukemia
Slow onset
Occurs only in adults
Longer course
Composed of mature cells
Oncology
Dr. YOSRA SAMIR FADLE
Auer rods in acute myeloid leukemia
Treatment and Prognosis of ALL
Treatment
 Chemo therapy± bone marrow transplantation.
 immunotherapy
Prognosis
 Immunophenotype (T is worse)
 Age (1-10 be er)
 WBC (>50,000 worse)
 Cytogenetics (hyperdiploidy better!)
 Initial response to treatment means (good prognosis)
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Oncology
Dr. YOSRA SAMIR FADLE
Pediatric Lymphomas
Definition
Clonal proliferation of lymphoid elements in LN with occasional BM
and tissue and rare blood spread.
Lymphoid neoplasms include a diverse group
of tumors of: B-cell,
 T-cell,
 and NK-cell origin.
I-HODGKIN’S
Classification of lymphoma
II- NON - HODGKIN’S
I--HODGKIN’S LYMPHOMA
 Introduction:
Hodgkin lymphoma (formerly called Hodgkin's disease) is a group of malignancies
characterized by:
Reed-Sternberg cells in an appropriate reactive cellular background consisting of
lymphocytes, histiocytes , neutrophils, plasma cells, and fibroblasts.
An important clinical feature is :
 its tendency to arise within lymph node areas.
 Spread in an orderly fashion to contiguous areas of lymph
nodes .
 Late in the course of the disease,
disease vascular invasion leads to
widespread haematogenous dissemination.
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Reed-Sternberg cell
Oncology
Dr. YOSRA SAMIR FADLE
 Hodgkin lymphoma has a bimodal age distribution with one peak in the 20s
and 30s, and a second peak over the age of 50.
Pathological classification of Hodgkin’s lymphoma( Rye Class.)
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Lymphocyte predominant
Nodular sclerosing
Mixed cellurarity ( neutrophils , eosinophils and plasma cells )- common
Lymphocte depleted
Lymphocyte rich
Symptoms of Hodgkin's lymphoma:
General symptoms:
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Fever
Weight loss
Loss of appetite
Night sweats
Pruritus
lethargy
Local symptoms:
 Enlarged, painless, non-tender, superficial lymph nodes
 Alcohol-induced pain ‫ــــ‬Rarely, patients with Hodgkin’s
lymphoma complain of severe pain following alcohol
ingestion. The pain typically occurs within a few
minutes after the ingestion of even a small amount of
alcohol in any area involved by the disease. “| The
mechanism is unknown.”
Symptoms related to the mass:
1. Mediastinal mass:
retrosternal chest pain, cough, or shortness of breath.
2. Retroperitoneal lymphadenopathy
discomfort and pain in the paravertebral or loin regions, particularly in the
supine position.
Signs of HL:
1. Lymph node enlargement
2. Cachexia
3. Anemia
4. Splenomegaly
5. Hepatomegaly
6. Jaundice. (Rare)
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Oncology
Dr. YOSRA SAMIR FADLE
Staging :
I.
II.
III.
IV.
Confined to single lymph node region
Involvement of two or more nodal areas on the same side of the diaphragm
Involvement of nodes on both sides of diaphragm.
Spread beyond the lymph nodes e.g. liver or bone marrow.
N.B. Each stage is subdivided
ed into A and B
Ann Arbor Staging System for Hodgkin's and Non
Non-Hodgkin's Lymphoma
Diagnosis :
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BLOOD: (FBC, Film, ESR, LFT, LDH, Urate , Ca.)
Lymph node excisioal biopsy , image guided needle biopsy.
Imaging:-Chest X-ray,
ray, CT of thorax, abdominal, pelvis
Bone marrow biopsy.
 Management :
Radiotherapy & short course of chemotherapy.
 prognosis
Prognosis of HL Depends on the stage :
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Oncology
Dr. YOSRA SAMIR FADLE
II- NON HODGKIN’S LYMPHOMA
 This is lymphoma without Reed-Sternberg cell.
 B lymphocyte more than T lymphocyte.
 The clinical presentation and natural history are more variable than in
Hodgkin’s lymphoma.
 The extra-nodal involvement and leukemic manifestations are common,
more than Hodgkin’s lymphoma.
Etiology
 Chromosomal translocations
 Immunodeficiency either inherited or acquired
 Infections:
- HTLV-1 :(adult T cell lymphoma)
- EBV: (Burkitt Lymphoma endemic type, post-transplant lymphoproliferative
disease)
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(in HIV): B-Cell Lymphomas (unusual site e.g. CNS lymphomas)
Hepatitis C infection.
Malaria :Burkitt Lymphoma endemic type
H. Pylori :(gastric B-Cell lymphomas)(MALT)
 Celiac disease (gluten sensitive enteropathy ( (T-Cell lymphomas)
Classification
• There are many classification system for NHL, more recent is the Revised
European American Lymphoma Classification ( REAL).
• All systems attempt to correlate clinical behavior with histopathology.
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Oncology
Dr. YOSRA SAMIR FADLE
Lymphomas may be grouped by how quickly they are likely to grow:
 Indolent :- (low-grade) lymphomas WHICH grow slowly& cause few
symptoms.
 Aggressive :- (intermediate-grade and high-grade) lymphomas WHICH grow
and spread more quickly& cause severe symptoms.
N.B : Over time, many indolent lymphomas become aggressive lymphomas.
Low grade non Hodgkin's lymphomas
 Small cell lymphoma.
 Follicular (it is the most common
type of lymphoma).
 Mantle cell lymphoma.
 Splenic marginal zone lymphoma.
 MALT lymphoma.
 Lymphoplasmacytic NHL.
High grade non Hodgkin's lymphomas
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Diffuse large B cell lymphoma(DLBCL).
Diffuse mixed cell lymphoma.
Burkitt's lymphoma.
Anaplastic large cell lymphoma .
Pathogenesis :
Clinically:
 Maturation arrest and proliferation.
 Due to genetic mutations
 Either B or T cell
 Any age, M=F
 Random LN
 More tissue infiltration (CNS, GIT,
testes,...)
General symptoms:
◊ Fever
◊ BLEEDING
◊ Weight loss
◊ Bone pain
◊ Loss of appetite
◊ Adenopathy
◊ Night sweats
◊ Hepatosplenomegally
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◊ CNS: headaches,
vomiting, nerve
palsies
Oncology
Dr. YOSRA SAMIR FADLE
Pathology of NHL
 More regular LNs.
 Diffuse or follicular loss of L.N histology
 No R.S cells
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Burkitt's lymphoma
Is a type of NHL.
Common in Africa (EBV infection )..
Pathologically:
Starry sky appearance
Clinically:
children with massive L.N in the jaw.
treated with chemotherapy( as B-cell lymphoma)
Burkitt's lymphoma
Investigations for lymphoma
Starry sky appearance
 Routine CBC, Chemical
 LN biopsy
 Cytogenetic studies.
o Routine stain.
o Immunohistochemistry
o FNAC for LN.
 Molecular biology techniques.
Diagnosis :
1.
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4.
Clinical manifestations .
Lymph node excision biopsy , image guided needle biopsy
Blood tests.
Imaging:-Chest X-ray, CT of thorax, abdominal, pelvis.
5. Bone marrow biopsy.
Prognosis:
Poor prognostic signs :-
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 Increased age, advanced stage, concomitant
disease .
 T cell lymphoma 5-years survival for treated
patients:
- 50% for low grade
- 30% for high grade