Lymphoma

Dr. Ahmed Mansour , Phd

Professor of Haematology
Mansoura University Pediatric Hospital
Mansoura Faculty of Medicine
 Lymphomas
Definitions:

Malignant disease of lymphatic tissues.

2nd most common malignant disease in
childhood in Egypt.
2 types:
- Hodgkin’s lymphoma.
- Non Hodgkin lymphoma (more Common
in Pediatrics).
 Hodgkin’s Disease

One of malignant lymphomas.

Affect males > females 3:1.
Age: 5-15Ys.
It is unicentric in origin.
 Etiology

Unknown But there are

theories. e.g Related
to Epstein-Barr Virus
(EBV) infection which
can cause infectious
mononucleosis.
Epstein-Barr Virus and Hodgkin
disease
•Both epidemiologic and
serologic evidence.

•By PCR EBV fragments

are found in 58% of Reed-
Stenberg cells

•EBV genome is stable ???

---At diagnosis
---In relapse
•Some countries have very high
prevalence of EBV positivity in HD

e.g. Iran, Greece, Kenya 92-94%

Nodal mass
10Cm ≥
Clinical Picture
)Bulky(
Most common presentation is “peripheral L.N
Enlargement”. (90% of cases).
Most common:
- Cervical 60-80%
- Axillary 20%
- Inguinal 5%.
Characters of L.N.:
- Consistancy → Rubbery.
- Painless.
- Not tender.
•Mediastinal syndrome → as it can be presented by
mediastinal L.N enlargement (60% of cases).
Bulky mediasinal
mass
Mass/thoracic

ratio≥ 0.33%
Bulky mediasinal mass
Mass/thoracic ratio≥ 0.33%

Internal transverse diameter of

a thorax between T5 and T6
--Maximum inspiration
--Upright position
 Clinical Picture
Splenomegaly → stage of ds is at least stage III.
Hepatomegaly & presence of Enlarged L.N at porta
hepatis → Obstructive jaundice.
Bone marrow involvement which may be presented
by:
Pallor → due to Anemia
Bleeding manif.→ due to thrombocytopenia.

Systemic symptoms: 30%


Intermittent fever (pel-Ebstine).
Anorexia, fatigue and weakness.

Night sweats.

Loss of weight >10% during last 6 months.

Clinical Picture
Splenic involvement

--Splenic index (CT)

(59% accuracy)

--FDG-PET= Flourodeoxyglucose
-positron emission tomography
(92% accuracy)
Clinical Picture
Itching

--15-25% of patients

--Severe ------- advanced stage

--B-symptoms

--Return -------- Relapse

Clinical Picture

Alcohol-induced pain???

May be:
--Oedema
--Vasodilatation
-- Histamine release
Clinical Picture
Pulmonary disease

17% of patients

--2/3 of cases have intrathoracic

-- Lung CT is essential
-- Common with nodular sclerosis
-- 4 forms of pulmonary
I involvement
Clinical Picture
4 forms of pulmonary involvement:

--Congenital lesion (LNS)

--Peribronchovascular
--Subpleural spread
--Intraparenchymal
D.D:
--Pulmonary T.B
--Fungal infection
Clinical Picture
CNS manifestation
Intra-cranial infiltration
Metabolic ↑ Ca, ↓ Na, ↓ glucose

Infection (Herpes, Meningitis, abscess)

Chemotherapy-related (oncovin-steroid)

Radiotherapy related.

Paraneoplasmic manifestations (autoimmunity)

Clinical Picture
Jaundice

--Hepatic involvement.
--Hemolytic anemia
--Hepatitis (viral-Toxic-Toxoplasma)
--Enlarged L.Ns in the porta hepatis
--Blood transfusion
Clinical Picture
Hematologic

--Immune hemolytic anemia:

--Immune thrombocytopenia
--Immune neutropenia

--Bone marrow suppression / infiltration

--Eosinophilia (15% of patients)

 Diagnosis
I- L.N Biopsy:
The most important diagnostic test.
Biopsy should be taken from the Biggest L.N Bec. it is the
pathologic one.
 Diagnosis
Presence of Reed-sternberg
giant cells surrounded by benign
inflammatory cells is diagnostic
for Hodgkin’s disease.
Accordingly the disease is
histopatholgically classified into
4 types (Rye classification):

Lymphocyte predominance: Best prognosis.

Lymphocyte depletion: Worst prognosis.

Mixed cellularity: Most common in children.

Nodular sclerosis: Most common in adults.

 Clinical staging of the disease:
Ann Arbor classification
Stage Description

I Single lymph node region

or
of a single extralymphatic organ or site (IE).
II Two or more lymph node regions on the same side of the diaphragm
or
localized involvement of an extralymphatic organ or site and of one
more lymph node regions on the same side of the diaphragm (IIE).

III Lymph node regions on both sides of the diaphragm

or
spleen, splenic hilar node, celiac node, porta hepatis node (IIIS).

IV Diffuse or disseminated involvement of one or more extralymphatic

organs or tissues with or without associated lymph node
enlargement.
Each stage is further subdivided into A or B according to absence (A) or
presence (B) of systemic symptoms.
Clinical staging of the disease:
Ann Arbor classification
 Diagnosis
II- Radiologic studies:
Plain X-ray chest: to detect mediastinal L.N or lung
disease.
Abdominal ultrasound.
C.T scan: neck, chest, abdomen, pelvis.
MRI.
 Diagnosis
III- Hematologic studies:
Complete blood picture: anaemia and leucopenia.
Bone marrow exam: for B.M infiltration.
IV- Biochemical studies:
↑ ESR
↑ Serum Copper level.
↑ Serum ferritin.
↑ Fibrinogen and haptoglobin level.
↑ Serum lactic dehydrogenase and alkaline phosphatase
levels.
These biochemical changes are indicative of active
disease.
 Indices of activity
↑ serum copper
↑ serum ferritin
↑ ESR
↑ fibrinogen
↑ haptoglobin
↑ serum alkaline phosphatase
↑ serum soluble IL-2 receptors
↑ serum β2-macroglobulin
 Prognosis
Good prognosis is suspected with:
Young age.
Stages I or II.
Females.
Lymphocytic predominance
type.
Absence of systemic
symptoms.
 Treatment
Radiotherapy: for early stages of the disease I, II, III A.

3600-4000 cGy.
Chemotherapy: for advanced stages.
MOPP protocal:
Mustine hydrochloride I.V.
Vincristine sulphate I.V.
Procarbazine oral.
Prednisone oral.
These drugs are given in cycles (14 days) for 6-8 cycles.
Bone marrow transplantation: for recurrent and resistant
disease.
 Now used Protocol

COPP - ABVD

Cyclophosphamide Adriamycin
Oncovein ( Vincrisine). Bleomycin

Procarbazine vinblastine
Prednisone Dacarbazine
Now used Protocol
6 – 8 cycles, each cycle = 1 month

1st month Next month

COPP ABVD

Alternatively
For 14 days For 14 days
Then 14 days rest Then 14 days rest
Non Hodgkin lymphoma (NHL(

Accounts for 60% of all childhood

lymphomas.
Affects males > females. 2.5:1.
Multicentric in origin.
 Clinical Picture
Abdominal mass (Burkitt lymphoma) is the most common
clinical presentation in our country.
Peripheral L.N enlargement: cervical, axillary, inguinal…
etc. The glands are usually hard (not rubbery), painless and
not tender.
Mediastinal L.N enlargement → mediastinal syndrome.
Hepatosplenomegaly may occur.
Bone marrow infiltration may occur → anemia,
leucopenia and thrombocytopenia.
 Diagnosis

Lymph node biopsy.

Bone marrow examination to differentiate
NHL from leukemia.
Peripheral blood exam.
Radiologic studies as for Hodgkin’s
disease.
 Clinical Staging

As for Hodgkin’s disease but it is

not sub classified to A or B. (because
the disease is more aggressive than
Hodgkin’s disease).
 Treatment
Surgery: for localised and abdominal cases.
Radiotherapy: has a limited role as the disease is
progressive in children.
Chemotherapy:
The most important line of treatment.
Continuous treatment (not cyclic) for 1.5 years.

Durgs used:
Cyclophosphamide.
Vincristine.

Methotrexate.

Adriamycin.

Bone marrow transplantation: for recurrent and resistant

diseases.
 T
H
A
N
K
You
Evidence of Relation to EBV?
- Occur in more than one member of the family.
-Increased in twins.
-Characteristic cells of Hodgkin’s lymphoma
contain EBV.
Value of CNS Examination?
-CNS infiltration
-Intracranial haemorrhage: thrombocytopenia
-Effect of chemotherapy
-Menigitis & meningeo-encephalitis
-Corticosteroid therapy
-Malignancy associated psychosis
A child with Hodgkin’s presented
with jaundice, What’s DD?
-L.N in porta-hepatis Obstructive jaundice.
-Associated Hepatitis: * Blood transfusion
* EBV
-Auto-immune haemolytic anaemia Jaundice
with =ve coomb’s test.
-Toxic hepatitis due to chemotherapy.
-Incompatible blood transfusion.
A child with Hodgkin’s presented
with jaundice, What’s DD?
-Bone marrow involvement Aneamia.
-Auto-immune haemolytic anaemia.
-Fe deficiency anaemia : failure of fe
incorporation in haem molecule.
-Effect of chemotherapy.