Paediatric lymphomas

Dr.P.Ramu.MD
Designated Professor
Paediatrics
 Paediatric Lymphomas
• Introduction
• Classification
• Epidemiology
• Clinical features
• Diagnosis
• Treatment
• Complications
• Prognosis.
 INTRODUCTION
• Lymphoma is an unctrolled malignant proliferation
of lymphoid cells(found in primary lymph organs
like bone marrow & Thymus and secondary lymph
organs like lymph node, spleen and mucosa
associated lymphoid tissue
• 3rd most common cancer in children
• Incidence- 15/million children
• 2 broad categories
• 1. Hodgkins disease
• 2. Non Hodgkins disease
 Hodgkins disease
• Malignant process of Lympho
reticular system
• 6% of childhood cancers
• 5% of cancers in < 14 yrs
• 15% between 15-19yrs
• Rare < 10 yrs
• Reed-Sternberg (RS) cell, a
pathognomonic feature of HL
 Epidemiology
• Bimodal incidence
• Early peal middle to late 20s, 2nd peak after 50 yrs
• Male: Female Ratio:-
• 4:1 for 3-7yrs
• 3:1 for 7-9yrs
• 1-3:1 for > 10 yrs
• 100 fold risk for unaffected monozygotic twin of affected
twin
• Associated with specific HLA antigen, HPV-6, CMV, EBV
& Immuno deficiency
 Rye Classification System
• 1. Lymphocyte predominant
• 2. Mixed cullularity
• 3. Nodular sclerosis
• 4. Lymphocyte depletion
 Rye Classification System
• Lymphocyte predominant:-
• 10-15%of patients
• More common in males
• Younger patients
• Localized disease
• Mixed cullularity:-
• 30% of patients
• <10yrs of age
• Advanced disease
• Extra nodal extention
 Rye Classification System
• Nodular sclerosis :-
• Rare in children
• Common with HIV
• Lymphocyte depletion:-
• Most common
• 40% of younger patients
• 70% of adolescents
 Real Classification(Revised European –
American classification of Lymphoid neoplasms)

• Nodular lymphocyte predominant

• Classical Hodgkin Lymphoma
• Lumphocyte rich
• Mixed cellularity
• Nodular sclerosis
• Lymphocyte depletion
• Anaplastic large cell lymphoma Hodgkin like
Lugano Classification for Hodgkin Lymphoma
 Clinical manifestations
• Lymphadenopathy-cervical/supra cavicular
• Painless, non tender, firm & rubbery
• Hepato splenomegaly
• Cough, dyspnoea, hypoxia
• Pleural or pericardial effusion
• Hepato cellular dysfunction
• B.M. Infiltration
• Anaemia,Neutropenia, thrombo cytopenia
• Disease below diaphragm is rare( only 3%)
 Systemic symptoms(B symptoms)
• Important in staging
• Unexpained fever >390C
• Weight loss > 10% in 3M
• Drenching night sweats
• Immune system abnormalities:
• Anergy to delayed hyper sensitivity skin test
• Abnormal cellular immune response
• Decreased CD4:CD8 ratio
• Reduced NK cell cytotoxicity
 Diagnosis
• Light microscopy • Bone marrow aspiration
• Immuno cytochemistry • Serum Copper &
• Molecular studies Ferritin
• Mediastinal mass in • Bome scan
chest X-Ray • Gallium 67 scan/FDG/
• CT Scan- Chest, PET
abdomen & Pelvis
• Blood CP & ESR
• LFT
Anterior mediastinal mass in a patient with Hodgkin
disease before therapy(A) & After 2 months of
chemotherapy(B)
CT Scan of an young individual with
Hodgkin lymphoma
PET/CT in the coronal plane-Hodgkin
lymphoma
 Ann Arbor staging classification for
Hodgikin Disease
• Stage I: Involvement of single lymph node(1) or single
extra lymphatic site or organ(1f)
• Stage II: Involvement of 2 or more lymph node regions on
the same side of the dia[hragm (II)
• Or localized involvement of an extra lymphatic site or
organ and one or more lymph node regions on the same
side of the diaphragm (IIf)
• Stage III: Involvement of lymph node regions on bothsides
of the diaphragm (III), which may be accompanied by the
involvement of spleen (IIIs), or localized involvement of an
extra lymphatic site or organ(IIIf) or both(IIIsf)
 Ann Arbor staging classification for
Hodgikin Disease

• Stage IV: Diffuse or disseminated involvement of one or

more extra lymphatic organs or tissues with or without
associated lymph node involvement.

• The absence or presence of fever > 38C for three

consecutive days , drenching night sweats , or unexplained
loss of > 10% body weight in the 6 months preceding
admission are to be denoted in all cases by the suffice
letters A & B respectively.
Ann Arbor staging classification for
Hodgikin Disease
 TREATMENT
• Treatment depends on:
• Stage of the disease
• Age at diagnosis
• Presence / absence of B symptoms
• Presence of hilar lymphadenopathy
• Presence of bulky nodal disease

• Current Treatment Regimen :

Combined chemotherapy with or without low dose
involved field radiation therapy
 Chemotherapy Regimens
• MOPP: (Mechlorethamine Vincristine , Procarbazine ,
Prednisolone)
• COPP :
(Cyclophosphamide , Vincristine , Procarbazine ,
Prednisolone)
• ABVD :
(Adriamycin , Bleomycin , Vinblastine , Dacarbazine)
• BEACOPP : ( For advanced stage disease )
(Bleomycin , Etoposide , Doxorubicin ,
Cyclophosphamide , Vincristine , Procarbazine ,
Prednisolone)
 TEP Evaluation After 2 Chemotherapy
Cycles Using Deauville Criteria 5-Point Scale
 Prognostic Factors
• Prognosis
• FAVORABLE:
• <10, F, favorable subtypes (LP and NS)
• Stage I non-bulky disease

• UNFAVORABLE:
• Persistently elevated ESR;
• LD histopathology;
• bulky disease--largest dimension >10cm;
• B symptoms;
 Long term complications
Secondary malignancy
- Acute Myelogenous Leukemia
- Non Hodgkin lymphoma
- Carcinomas of breast , lungs& thyroid

Short stature
Hypothyroidism
Sterility
Dental caries
Sub clinical pulmonary dysfunction
Ischemic heart disease
 Prognosis
• Early stage disease
• 5 year survival ….95%

• Advanced Stage Disease

• 5 year survival ….90%

• Relapses common within first 3 years from diagnosis

• Relapses treated with Autologous Stem Cell

Transplantation
NON-HODGKIN
LYMPHOMA
 EPIDEMIOLOGY
• 6% of childhood cancer 60% of all lymphomas in
children(M:F 2.5:1)
• 8-10% of all malignancies in children between 5- 19 yrs
of age
• Secondary causes of NHL include;
• Inherited / acquired immune deficiencies
• Viruses- HIV, EBV
• Post BMT, Post solid organ transplant
• Ataxia Telangiectasia
• Bloom syndrome
Incidence of non-Hodgkin lymphoma subtypes
A- In 0- to14-yr-old children
B- In 15- to 19-yr-old adolescents
 Pathological Sub types of NHL
Burkitt Lymphoma
-40% of NHL
-B Cell Origin
Lymphoblastic Lymphoma
-30% of NHL
-80% T Cell Origin & 20% B Cell Origin
Diffuse Large B Cell Lymphoma
-20% of NHL
-B Cell Origin
Anaplastic Large Cell Lymphoma
-10% of NHL
-70% T Cell Origin
Pathological Sub types of NHL
Germinal center–derived B-cell
lymphomagenesis
 Burkitt Lymphoma

• Small non-cleaved cell-(40-50%)

• -Mature B-cell phenotype
• -Burkitt's and non-Burkitt's
• -90% abdomen
• -Ascites and intusussception
• -Endemic in Africa (Burkitt's), with EBV 97%
 Lymphoblastic Lymphoma

• Lymphoblastic (30-35%)
• 90% immature T cells (very similar to T-ALL)
• Remainder pre-B phenotype (as in ALL)
• 50-70% anterior mediastinum neck, supraclavicular,
axillary adenopathy
• Classic: older child with intussusception
 Diffuse Large B Cell Lymphoma(15-20%)
• Anaplastic (Ki-1) lymphoma – ALK fusion
protein
• - Diffuse Large B-cell lymphoma (DLBCL)
• - frequent Mediastinal involvement
• - More like Hodgkin lymphoma than other NHLs
• - “Peripheral T-cell” lymphoma
• - Often involves skin, CNS, lymph nodes, lung,
testes, muscles, and GI tract
 Clinical Manifestations
• Burkitt Lymphoma:-
• Abdominal Tumor
• Head & Neck Disease
• Involvement of bone marrow & CNS
• Lymphoblastic Lymphoma:-
• Intrathoracic / mediastinal supradiaphragmatic mass
Involvement of bone marrow & CNS
• Diffuse Large B Cell Lymphoma :-
• Abdominal Mass/ Mediastinal Mass
• Anaplastic Large Cell Lymphoma :-
• Primary cutaneous manifestation
• Systemic disease ( fever , weight loss)
• Dissemination to liver , spleen , lung , mediastinum & skin
 Clinical Manifestations
• Lymphadenopathy
• Superior vena cava syndrome
• Dyspnea
• Abdominal Mass
• Intestinal obstruction / intussusception
• Ascites
• Nasal Stuffiness
• Earache
• Tonsil enlargement
• Localised bone involvement
• Acute paraplegia secondary to CNS / spinal cord
compression
• Tumor Lysis Syndrome
Clinical Manifestations
 Staging system for childhood Non-
Hodgkin lymphoma
• Stage Description
• I A single tumor (extranodal) or single anatomic area
(nodal) with the exclusion of mediastinum or abdomen
• II A single tumor (extranodal) with regional node
Involvement two or more nodes areas on the same side of
diaphragm
• Two single (extranodal) tumors with or without the
regional node involvement on same side of diaphragm
• A primary gastrointestinal tract tumor usually in the
ileocecal area, with or without involvement of associated
mesenteric nodes, which may must be grossly ( > 90%)
resected
 Staging system for childhood Non-
Hodgkin lymphoma
• Stage III :
• Two single tumors (extranodal) on opposite side of the
diaphragm
• Two more nodal areas above and below the diaphragm
• Any primary intarthoracic tumor (mediastinal, pleural, or
thymic)
• Any extensive primary intra – abdominal disease
• Stage IV:
• Any of the above, with initial involvement of central
nervous system or bone marrow t time of diagnosis
Coronal postcontrast CT images demonstrate extensive
cervical (A) and mediastinal (B) lymphadenopathy
Sonographic image demonstrates PET scan demonstrates metabolically
two enlarged lymph nodes with active conglomeration of right-sided
abnormal internal morphology cervical lymph nodes
 Differential Diagnosis

• HodgkinDisease
• Leukemia
• Germ Cell Tumor
• Wilms Tumor
• Neuroblastoma
• Rhabdomyosarcoma
• Reactive lymphadenitis
 Laboratory findings
• Tissue Biopsy for;
-Flow cytometry
-Karyotyping
• Complete Blood Count
• Serum Electrolytes, Calcium , Phosphorus , Uric acid
• LFT’s& RFT’s
• Bone Marrow Aspiration & biopsy
• CSF Examination
• Chest X Ray
• CT Scan- Head & Neck , Chest , Abdomen & Pelvis
• PET Scan & Bone Scan
 Treatment

• Systemic Chemotherapy
• Intrathecal chemotherapy
• Radiotherapy indicated in ;
- CNS Disease
- SVC Syndrome
- Paraplegia
 Chemotherapy Regimens

• COPAD (Cyclophosphamide,Vincristine ,
Prednisolone , Doxorubicin)

• COMP (Cyclophosphamide , Vincristine ,

Methotrexate , 6 Mercaptopurine ,
Prednisolone)
 Duration of Treatment

• Burkitt Lymphoma & Diffuse Large B Cell

Lymphoma ………. 6 weeks to 6 months
• Lymphoblastic Lymphoma …..24 months
 Supportive Treatment

• G-CSF prophylaxis for fever & neutropenia

• Antibiotic prophylaxis
• Blood & platelet transfusions
• Allopurinol
• Parenteral nutrition
 Complications

• Infections
• Mucositis
• Pancytopenia
• Electrolyte imbalance
• Poor nutrition
• Growth retardation
• Cardiac Toxicity
• Gonadal Toxicity with Infertility
• Secondary malignancies
 Prognosis
• Localized disease
- 90-100% survival
• Advanced Disease
- 60-95% survival
 References
• Nelson text book of Paediatrics 22nd edition.
• Piyush Guptha PG text book.
THANK YOU