Lymphoma

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 ReedStenberg 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

Clinical Picture

10Cm ≥ )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

≥ 0.33%

ratio

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 I

Description 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 Vincristine sulphate

I.V. I.V.

Procarbazine Prednisone

oral. 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 leucopenia and thrombocytopenia.

occur

→

anemia,

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.