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

Cervical adenopathy

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

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

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

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

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

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

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

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

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%

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

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

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

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,

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

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

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 60-80+%; high risk of tumor lysis and hyperuricemia Relapse: Re-induction, followed by BMT

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

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

Hodgkin’s disease with Reed Sternberg cell often CD20+

Incidence and Etiology Hodgkin’s 5% of childhood cancers Bimodal peaks, at 15-35 and >50; rare < 5 M:F ratio of 3:1; variation r/t geography and SES, and type Increased in immunologic disorders, HIV, EBV

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

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

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

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

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;

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