Pediatric Lymphomas
Dr.Hussein Alatabi MBChB,DCH,FICMS,CABPCervical adenopathy
Concerns in enlarged LNSize >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 weeksStaging 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 HDRadiology -CXR (PA & Lat) -CT scans neck, chest, abdomen -Gallium, bone scan -PET scan
Lymphoma Staging
Murphy Ann ArborI: 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 NHLPET or galliumLYMPHOMA
HODGKINSNON-HODGKINS
LYMPHOBLASTIC LYMPHOMA
BURKITT’SLYMPHOMA LARGE CELL LYMPHOMA
IMMUNOBLASTIC
ANAPLASTIC
(40%)
(60%)
(<15%)
(30-40%)
(40-50%)
(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 factorsTypes 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 intussusceptionSmall 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 issuesLarge-cell lymphoma (15-20%)Anaplastic (Ki-1) lymphoma – ALK fusion proteinDiffuse Large B-cell lymphoma (DLBCL)frequent Mediastinal involvementMore like Hodgkin lymphoma than other NHLs“Peripheral T-cell” lymphomaOften involves skin, CNS, lymph nodes, lung, testes, muscles, and GI tract
“low grade” lymphomas – rare in childrenFollicularmarginal zone/MALTprimary 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 lookRadiation Therapy: emergency airway obstruction or CNS complication – may be used for local control of residual massChemotherapy: Combination chemo is usual, with overall cure rates 60-80+%; high risk of tumor lysis and hyperuricemiaRelapse: Re-induction, followed by BMTNHL chemotherapy overview
Low-stage NHL’s are treated with CHOP (+/- rituximab – anti-CD20)Higher-stage lymphoblastic lymphomas are treated on leukemia protocolsHigher-stage non-lymphoblastic NHLs require extremely aggressive chemotherapy with significant infectious risks, but still have generally good remission ratesHigh-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 responseHodgkin’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 celloften CD20+
Incidence and EtiologyHodgkin’s 5% of childhood cancersBimodal peaks, at 15-35 and >50; rare < 5M:F ratio of 3:1; variation r/t geography and SES, and typeIncreased 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 lossMediastinal 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 biopsyHD and DLBCL tend to have areas of necrosis and therefore look more “bumpy” than T-ALLHodgkin’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