1. Dr.Hussein Alatabi MBChB,DCH,FICMS,CABP
Pediatric Lymphomas
Dr.Hussein Alatabi
MBChB,DCH,FICMS,CABP

2. Cervical
adenopathy

4. Concerns in enlarged LN
Size >1-2 cm
Increasing size over 2-4 weeks
Matted or fixed
Supraclavicular LN
Fevers >38.5 for 2-4 weeks
Constitutional symptoms
HSM

5. When to biopsy Supraclavicular node Increasing size over 2-4 weeks
Constitutional symptoms
Asymptomatic enlarged node-not decreasing in size over 6 weeks or not normal after 8-12 weeks

6. Staging Evaluation Laboratory -CBC with smear -Chem profile
LHD, uric acid
Disease specific
-ESR, IL2R for HD
-LP if head/neck NHL
-BMA/Bx for all NHL, only IIB or higher HD
Radiology
-CXR (PA & Lat)
-CT scans neck, chest, abdomen
-Gallium, bone scan
-PET scan

7. Lymphoma Staging Murphy  Ann Arbor
I: tumor at one site (nodal or extranodal -- “E”)
II: two or more sites; same side of body (or resectable GI primary)
III: both sides of body but not IV (& unresec. GI & mediastinal for NHL)
IV: CNS or marrow involvement (Murphy); lung, liver, marrow, or bone for Ann Arbor (< 25% marrow)
“B” sxs are defined for HD, as is “bulky disease”
Head and neck (possibility of CNS involvement) is a further consideration for NHL
PET or gallium

8. LYMPHOMA HODGKINS NON-HODGKINS LYMPHOBLASTIC BURKITT’S LARGE CELL
IMMUNOBLASTIC
ANAPLASTIC
(40%)
(60%)
(<15%)
(30-40%)
(40-50%)
(50%)

9. Non-Hodgkin’s Lymphoma
Malignant solid tumor of immune system
Undifferentiated lymphoid cells
Spread: aggressive, diffuse, unpredictable
Lymphoid tissue; BM and CNS infiltration
High growth fraction and doubling time
Dx and Rx ASAP
Rapid CTX response; tumor lysis concern

10. Incidence/Etiology - NHL
6% childhood cancer 60% of childhood lymphomas
Peak age of 5-15; M:F ratio of 2.5:1
Increased with
SCIDS, HIV, EBV
post t-cell depleted BMT
post solid organ transplant
Geographic, viral, genetic & immunologic factors

11. Types of NHL 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

12. 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%

13. Burkitt Facts
100 new cases/year in US, 2-3:1 male:female; mean age 11 years (in non-endemic form)
small, noncleaved cell; mature B phenotype; intraabdominal (sporadic) or jaw (endemic) most common primary site
90% have t(8;14)
(8 ~ c-myc; 14 ~ heavy chains)
others are 8;2 or 8;22
(2, 22 ~ light chains)
Extremely rapidly-growing; tumor lysis issues

14. Large-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

15. “low grade” lymphomas – rare in children
Follicular
marginal zone/MALT
primary CNS (often seen with HIV infection)
peripheral cutaneous (mycosis fungoides)

16. Clinical Presentations
Abdomen: (35%): pain, distention, jaundice, GI problems, mass
Head/neck (13%): lymphadenopathy, jaw swelling, single enlarged tonsil, nasal obstruction, rhinorrhea, cranial nerve palsies
Mediastinum (26%): SVC syndrome
CNS (rare): HA, V, irritability, papilledema
+Fever, malaise, night sweats, wt. loss,

17. Staging of NHL I Single tumor /node NOT in mediastinum or abdomen
II 1-2 nodes same side of diaphragm or resectable GI primary
III 2+ nodes both sides of diaphragm; intrathoracic or extensive intra-abd
IV Any of above with CNS and/or BM

18. Prognosis affected by…
Incomplete remission in first 2 mos. Rx
Large tumor burden (LDH >1000)
Stages III and IV: CNS or BM involvement
Delay in treatment
Relapse
**More favorable: Stage I or II, head/neck, peripheral nodes, GI tract

19. NHL Treatment Surgery for diagnostic bx or second look
Radiation Therapy: emergency airway obstruction or CNS complication – may be used for local control of residual mass
Chemotherapy: Combination chemo is usual, with overall cure rates %; high risk of tumor lysis and hyperuricemia
Relapse: Re-induction, followed by BMT

20. NHL chemotherapy overview
Low-stage NHL’s are treated with CHOP (+/- rituximab – anti-CD20)
Higher-stage lymphoblastic lymphomas are treated on leukemia protocols
Higher-stage non-lymphoblastic NHLs require extremely aggressive chemotherapy with significant infectious risks, but still have generally good remission rates
High-dose chemotherapy with stem cell rescue is considered an option for relapse, though without the success rates of HD; T cell disease probably requires an allogeneic response

21. Hodgkin’s Disease
Immune system malignancy, involving B or T lymphocytes
Reed-Sternberg cells
Spread: slow, predictable, with extension to contiguous lymph nodes
Infiltration to non-lymphoid organs is rare

22. Hodgkin’s disease with Reed Sternberg cell often CD20+

23. Incidence and Etiology
Hodgkin’s 5% of childhood cancers
Bimodal peaks, at and >50; rare < 5
M:F ratio of 3:1; variation r/t geography and SES, and type
Increased in immunologic disorders, HIV, EBV

24. Types of Hodgkin’s Lymphoma
Nodular sclerosing (NS), 40-60%, lower cervical, supraclavicular, mediastinal nodes
Mixed cellularity (MC), 15-30%; advanced disease with extranodal involvement
Lymphocyte predominance (LP), 5-15%, presents as localized disease
Lymphocyte depletion (LD) (<5%); widespread disease

25. Clinical Presentation
Painless lymph node swelling (90%) that persists despite antibiotic therapy
Palpable non-tender, firm, mobile, rubbery nodes; Mediastinal adenopathy (60%); SVC
Bulky: when mass is > 1/3 thorax diameter
B symptoms: Fever of >38C for 3 days, drenching night sweats, 10% weight loss

26. Mediastinal masses
Risk for anesthesia (esp. if tracheal compression > 50% by CT)
Least invasive diagnostic procedure therefore indicated (incl. thoracentesis)
Emergent steroids or RT generally acceptable prior to biopsy
HD and DLBCL tend to have areas of necrosis and therefore look more “bumpy” than T-ALL

27. Hodgkin’s Ann Arbor Staging
I Single lymph node region
II Two+ node regions on same side of diaphragm
III Nodes on both sides of diaphragm, or localized extralymphatic spread
IV Diffuse or disseminated involvement of one+ extralymphatic organs or tissues

28. Prognosis
FAVORABLE:
<10, F, favorable subtypes (LP and NS) and Stage I non-bulky disease
UNFAVORABLE:
Persistently elevated ESR; LD histopathology; bulky disease--largest dimension >10cm;
B symptoms;

29. Treatment and Prognosis
Dependent on age, stage, and tumor burden
RT alone, CTX alone
RT: varies from involved field for localized disease to extended field to total nodal irradiation, inverted Y plus mantle
most often multimodal therapy, with low-dose involved field RT and multi-agent CTX
Combined modality 70-90% LT cure