Pediatric Lymphomas

Resident Education Lecture Series

Cervicaladenopathy

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 LYMPHOMA

BURKITT’SLYMPHOMA

LARGE CELLLYMPHOMA

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 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

Burkitt Prognosis

Adult Data:Stage:EFS OSI-II 91%

78%IV 25%25%but in patients < 40 yo

70% 60%

Pediatric Data:Localized > 90%Disseminated (but not B- ALL) 80-90% on newer protocols

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,

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

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 celloften 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

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

Hodgkin Px and Rx

Splenectomy generally no longer used

Exact type and ratio of combined modality therapy changes… due to differences in success rates for salvage therapy and concerns for late effects of therapy Second malignancy risks Sterility risks

From ABP Certifying Exam Content Outline

Know how to evaluate a child with an acute cervical lymphadenopathy

Know the differential diagnosis of neck masses: lymphoma, cystic hygroma, thyroglossal duct cyst branchial cleft abnormalities

From ABP Certifying Exam Content Outline, continued

Recognize the need for evaluation of supraclavicular lymph node enlargement

Identify the chest x-ray as an important part of the initial evaluation of the patient with an unexplained lymphadenopathy

Know that overwhelming sepsis is a serious complication in patients with Hodgkin disease who have undergone splenectomy,

and know that such patients should be evaluated thoroughly if fever develops

Credits

Meghen Browning MDAnne Warwick MD MPH