LYMPHOMA

DR(MRS) MILDRED OLUCHI IZUKA (MBBCh, FWACP, FMCPaed)

CONSULTANT PAEDIATRICIAN / Dep.HOD
DEPARTMENT OF PAEDIATRICS
FEDERAL MEDICAL CENTRE UMUAHIA / COLLEGE OF HEALTH SCIENCES GREGORY
UNIVERSITY UTURU
 OUTLINE
• Introduction
• Epidemiology
• Pathophysiology
• Clinical features
• Staging
• Diagnosis
• Differential diagnosis
• Treatment
• Complications
• Prognosis
• Conclusion
 DEFINITION
• These are a heterogeneous group of malignant tumors
that originate from the lymphoreticular system.
• As a group they constitute the commonest cancer
among children in the tropics and the 3rd commonest
in USA.
• They are broadly divided into Hodgkin dx (HD) and
Non-Hodgkin Lymphoma (NHL).
 NON –HODGKIN
LYMPHOMA(NHL)
• Accounts for about 60% of all malignancies in children
and adolescents.
• Represents 8-10% of all malignancies in children b/w
5-19yrs of age.
• Annual incidence in USA is 750-800 cases/year in
children <19yrs.
• >70% of patients present with advanced dx.
 EPIDEMIOLOGY

• Sex: Male: female is 2-3:1.

• Age: Median age of presentation is 10 years. It is rare to have
cases under 3 years of age.
• Risk factors: Inherited or acquired risk factors have been
identified, including those listed next.
 AETIOLOGY
• Most patients present with de novo dx.
• NHL may develop as a second malignancy after
chemotherapy and/or radiation therapy (RT) or in the setting
of congenital or acquired immunodeficiency.
• Genetics: Immunological defects (Bruton type of sex-linked
agammaglobulinemia, common variable
agammaglobulinemia, severe combined immunodeficiency
ataxia-telangiectasia, Bloom syndrome, WiskottAldrich
syndrome, and autoimmune lymphoproliferative syndrome).
• Viral causes e.g. HIV, EBV, HTLV-1, etc.
 AETIOLOGY
• Posttransplant immunosuppression: Post bone marrow
transplantation (especially with the use of T-cell-depleted
marrow), post solid organ transplantation.
• Lymphomatoid papulosis in children may evolve into or
coexist with anaplastic large-cell lymphoma (ALCL).
• Drugs: Infliximab and other immunosuppressive agents used
in inflammatory bowel disease and autoimmune disease.
NEW WHO CLASSIFICATION
SYSTEM
 NEW WHO CLASSIFICATION
SYSTEM
• The World Health Organization (WHO) classification for
lymphoid neoplasms from the International Lymphoma
Study Group was revised in 2016 and incorporates histology
as well as immunohistochemistry, gene expression profiling,
cytogenetic, and molecular and clinical features
• Differences in pediatric and adult disease become apparent
with the recognition of new subtypes of lymphoma.
• Pediatric NHL is mostly (more than 95%) of high grade and
Includes the following four major subtypes:
 PATHOGENESIS
4 major pathological subtypes of NHL
exist:
• Burkitt lymphoma (BL); 40%
• Lymphoblastic lymphoma LL; 30%
• Diffuse large B-cell Lymphoma (DLBCL);
20%
• Anaplastic Large Cell Lymphoma (ALCL);
10%
 PATHOGENESIS
Almost all forms of BL and DLBCL are of B-cell origin.
LL are 80% T-cells, 20% B-cells.
ALCL are 70% T-cells, 20% null cells and 10%B-cells.
There are cytogenetic aberrations in some subtypes:
• ALCL commonly have a t(2;5) translocation(>5%)
• BL commonly have a t(8;14) translocation in 90% of
cases and a t(2;8) or t(8;22) in 10% of cases.
 PATHOGENESIS
• Many of these high-grade lymphomas disseminate
noncontiguously, evolve into a leukemic phase, and involve
the CNS.
 CLINICAL FEATURES
• Depends primarily on the pathological subtype and primary
and secondary sites of involvement.
• Sites of involvement could be lymphatic tissues e.g. L/Ns,
spleen, liver, Peyer patches or extra lymphatic tissues e.g.
CNS, BM, bone, skin.
• Site specific manifestations include painless rapid L/N
enlargement, cough, superior vena cava syndrome, dyspnea,
abdominal mass, intestinal obstruction, intussusception-like
symptoms, ascites, tonsil enlargement, paraplegias, tumor
lysis syndrome
Stage I Single tumor (extranodal).
CLINICAL
Single anatomic area STAGING
(nodal).
Stage IIAnn ArborSingle
systemtumor and
(extranodal) with regional nodestaging
St. Jude/Murphy involvement.
Two or more nodal areas on the same side of the diaphragm.
Two single (extranodal) tumors with or without regional node involvement
on the same side of the diaphragm.
Primary gastrointestinal tumor, usually in the ileocecal area, with or without
the involvement of associated mesenteric nodes only.
Stage IIR Completely resected intra-abdominal disease.

Stage III Lymphoma involving sites on opposite sides of the diaphragm.

All primary intrathoracic tumors.
All paraspinal or epidural tumors.
Extensive intra-abdominal disease.
Stage IV Any of the above, with central nervous system (CNS) or bone marrow
involvement (< 25%) at presentation
Ann Arbor system and St.
Jude/Murphy staging
 LABORATORY INVESTIGATIONS
• Tissue biopsy, FNAC, Core biopsy depending on type
• flow cytometry for immunophenotype as well as cytogenetics and molecular assays.

• FBC, S/E/U/Cr, serum uric acid, Ca, phosphate, LDH, Viral

Panel.
• Others are LFT, serum bilirubin, bilateral BM aspiration and
biopsy, CSF cytology, cell count and protein,
Pleural/paracentesis fluid cytology, cell count, and protein.
 LABORATORY INVESTIGATIONS
• Radiological studies include CXR, PET scan, neck,
chest, abdominal and pelvic CT scan.
• Tests for genetic translocations include FISH,
Quantitative RT-PCR.
 TREATMENT
• Primary modality of treatment is multiagent systemic chemotherapy and
intrathecal chemotherapy.
• Targeted therapy is highly recommended
• Common regimens available include:
• FAB/LMB 96 which employs COPAD,
• Modified Ziegler’s regimen which employs COM(or Cy)P.
• BFM NHL 90 regimen which uses therapeutic approaches that include
induction cycle, consolidation phase, interim maintenance phase,
reinduction phase (for advanced dx only) and 1yr maintenance therapy
with 6-mercaptopurine and methotrexate
• At least 6 cycles of chemotherapy should be given over 6wks-6months but
 TREATMENT
• Rituximab in CD20-positive mature B-cell disease.
• In ALCL CD30 targeted treatment, such as
brentuximab, vedotin, and ALK inhibition in ALK1
disease.
 TREATMENT
• Supportive treatment include:
• Aggressive rehydration, Allopurinol (or Rasburicase).
• G-CSF prophylaxis to prevent neutropenia
• Prophylactic antibiotics to prevent infection
• Parenteral nutrition to prevent weight loss and nutritional
debilitation
• Indwelling central venous catheters to facilitate frequent blood
draws, chemotherapy and transfusion
• Radiation therapy is rarely if ever used except in CNS
involvement in LL, BL, acute SVC syndrome and acute
paraplegias.
 PROGNOSIS
• Patients with localized dx have a 90-100% chance of
survival.
• Patients with advanced dx have 60-95%chance of
survival.
• The variation in survival depends on the pathological
subtype, tumor burden at diagnosis as reflected in
serum LDH level, presence or absence of CNS dx and
specific sites of metastatic spread.
 CONCLUSION
• Childhood non-Hodgkin lymphoma (NHL) is distinguished from adult NHL
by differing frequencies of histopathologic types and by the greater
frequency of extranodal presentations. With current combination
chemotherapy regimens, survival is generally excellent (85 to over 90%)
for all patients, including those with disseminated disease, bone marrow
involvement, central nervous system (CNS) involvement, and high serum
lactate dehydrogenase (LDH).
• With improved survival in all subtypes and stages, recent efforts have
focused on maintaining excellent event-free survival (EFS) with reduced
late toxicity by incorporating more specific targeted therapies for patients
with less favorable subgroups of NHL and identifying new prognostic
factors.
 HODGKIN DISEASE
• Hodgkin lymphoma (HL) is characterized by progressive
enlargement of lymph nodes. It is considered unicentric in
origin and has a predictable pattern of spread by
extension to contiguous nodes.
• Occur rarely before 5yrs and in Nigeria 13-43% of all cases
occur in the paediatric age grp.
Has bimodal age incidence in industrialized countries,
early peak in the middle to late 20’s with a 2 nd peak after
50yrs.
AETIOLOGY AND EPIDEMIOLOGY
• Specific aetiology is unknown.
• Overall there is a slight female predominance when
considering all children less than 20 years (M:F 0.9).
• The Caucasian: African-American ratio is 1.3:1.
• Comprises 6.4% of all childhood cancers under the age of 20,
but 13.2% of cancers in adolescents between the ages of 15
and 19 years.
• Incidence increases to 32 per million for adolescents 15-19
years.
AETIOLOGY AND EPIDEMIOLOGY
• Bimodal age—incidence curve with one peak at 15-35 years
of age and the other above 50 years of age (incidence is
highest among 20- to 24-year olds).
• Association with Epstein-Barr virus (EBV) is known.
• Association with lower socioeconomic class
• Incidence increased among consanguineous family members
and among siblings of patients with HL.
 AETIOLOGY
A genetic predisposition has been suggested with a 100-fold risk for an
unaffected monozygotic twin of an affected twin; there is no increased risk for
dizygotic twins.
Studies of families suggest an increased association with specific HLA antigens-
HLAB27 and DR5.
Infectious agents have been shown to be involved e.g. Human herpes virus 6,
CMV, EBV.
Pre-existing immunodeficiency either congenital such as ataxia telangiectasia or
acquired such as HIV increases the risk of HD.
 PATHOLOGY
• The Reed-Sternberg(RS) cell, 15-45um in diameter with multiple or
multilobulated nuclei is considered the hallmark of HD.
• HD is xterized by a variable no of RS cells surrounded by an
inflammatory infiltrate of lymphocytes plasma cells and eosinophils in
different proportions depending on the histologic subtype.
• RS cell can also be found in infectious mononucleosis NHL etc.
REED STERNBERG CELL
 CLASSIFICATION
Rye system of classification.
• Lymphocyte predominance (LP)
• Mixed cellularity (MC)
• Nodular sclerosis (NS)
• Lymphocyte depletion (LD)
 LP affects 10-15% of younger patients and usually presents as localized dx.
 MC is seen in 30% of patientss <10yrs and often presents as advanced dx
with extranodal extension.
 LD is rare in children but common in patients with HIV.
 NS is the commonest subtype affecting 40% of younger patients and 70% of
adolescents.
 NEW WHO/*REAL
CLASSIFICATION
• Nodular lymphocyte predominance(NLPHL)
• Classical Hodgkin lymphoma (CHL)
• Lymphocyte rich (LR)
• Mixed cellularity (MC)
• Nodular sclerosis (NS)
• Lymphocyte depletion (LD)
• Anaplastic large cell lymphoma Hodgkin-like (ALCL)

• *Revised European American Classification of Lymphoid Neoplasms.

NEW WHO/*REAL
CLASSIFICATION (REVISED)
 PATHOGENESIS
• HD appears to arise in lymphoid tissue and spread to
adjacent lymph node areas in a relatively orderly manner.
• Haematogeneous spread occurs to involve the liver, spleen,
bone marrow, bone, brain.
• Cytokines are elaborated that are responsible for some of
the systemic symptoms and include IL-1,2, TNF, TGF-
B(influence proliferation of RS cells and induce immune
suppression).
 CLINICAL FEATURES
• Painless non tender firm discrete cervical or supraclavicular lymphadenopathy.
• Features of airway obstruction (dyspnea, cough)
• Pleural or pericardial effusion.
• Bone marrow infiltration-anaemia, neutropenia thrombocytopenia.
• B-symptoms-unexplained fever>38 for 3 consecutive days, weight loss >10% total body
weight over 6 months, drenching night sweat.
• Others include pruritus, lethargy, anorexia, disulfiram-like effect.
 DIAGNOSIS
• Excision biopsy of lymph node and histological analysis
• Other investigations include CXR, CT scan of chest, abdomen
and pelvis
• Gallium-67 scan, PET scan FBC, ESR, LFT, BM aspiration and
biopsy, bone scan
• Serum copper and ferritin level is of prognostic importance
 TREATMENT
• Tx is determined largely by dx stage, age of pxt at presentation, A or B
symptoms, presence of hilar lymphadenopathy or bulky tumor
• Agents commonly used include Cyclophosphamide(C) Vincristin(O),
Prednisolone(P), Procarbazine(P), Adriamycin(A),
Bleomycin(B),Darcabazine(D), Etoposide(E), Methotrexate(M),
Cytosine Arabinoside(Cy)
• Different combinations that can be used include, MOPP, COPP, ABVD,
BEACOPP, COPP/ABV, etc.
• Combined chemotherapy with or without low dose involved field
radiation therapy is the current practice.
• A total of 6 cycles over 6 months is given.
 RELAPSE
• Most occur within the 1st 3yrs from diagnosis
• Poor prognostic features for relapse are tumor bulk,
stage at diagnosis and presence of B symptoms.
• Pxts who never achieve remission or relapse <12
months after initiation of therapy are candidates for
myeloablative chemotherapy and autologous stem cell
transplant with or without radiation therapy.
 COMPLICATIONS
• Long term complications are related to radiation and chemotherapy
and include
• Secondary malignancy(e.g. AML, breast, lung and thyroid cancers,
NHL)
• Sepsis
• Sterility
• Short stature
• Hypothyroidism
• Subclinical pulmonary dysfunction
• Ischemic heart dx and dental carries.
 PROGNOSIS
• Using current therapeutic regimens, pxts with
• Favorable prognostic factors and early stage dx have an event
free survival(EFS) of 85-90% and an overall survival(OS) at
5yrs of 95%.
• Advanced dx have an EFS of 80-85% and OS at 5 yrs of 90%.
• Prognosis after relapse depends on the time from
completion of tx to recurrence, site of relapse i.e nodal vs
extranodal and presence of B symptoms at relapse.
THANK YOU!!!
 SUGGESTED READINGS
Nelson textbook of Paediatrics, 19TH & 20TH edition.
Paediatrics and child health in a tropical region, 3rd edition
Paediatric Heamatology and Oncology (Oxford Specialist Handbooks
in Paediatrics)
https://emedicine.medscape.com/
Q&A