Childhood lymphomas

Lymphomas account for around 8-10% of all childhood cancers (this equates to around 1 per 100,000 children per year). Around 30-35% are Hodgkin's disease, the rest non-Hodgkin lymphomas.

Hodgkin's disease

Clinical features

Uncommon <5 years; incidence increases during the early teenage years. The disease is biologically the same as that of adults and the histological classification is identical (for more details ffl p208), though mixed cellu-larity disease may be more common in the young. Staging is also similar to adults (ffl p210), but overall children and adolescents have a greater proportion of low-stage disease (I and II). Stage IV accounts for <10% of childhood cases.

Treatment and outcome

Treatment is so successful that most efforts are currently directed at reducing toxicity and late effects. Radiotherapy for stage I disease is being attenuated, and some therapists have abandoned it as first line treatment and rely on chemotherapy alone. Chemotherapy regimens in turn are evolving (to avoid or minimise alkylating agents and their effect on fertility and anthracyclines with their potential for cardiotoxicity), but at present the traditional drugs are still being used with or without involved field radiotherapy, particularly in stage III or IV disease.

The outlook for even stage IV disease is good, given the best current regimen of chemotherapy and involved field radiotherapy, and over 80% 478 should achieve long term EFS.

Non-Hodgkin's lymphoma

Childhood non-Hodgkin's lymphomas are a heterogeneous group of tumours quite different from those seen in adults. Virtually all are disseminated, high-grade diffuse malignancies of immature B or T lymphocytes, and many are closely related to subtypes of ALL that occur in this age group.

Classification of NHL has always been confusing, but the Revised European American Lymphoma system is currently preferred. This maps disease in children into 6 categories:

1. Burkitt's lymphoma, Burkitt-like lymphoma, high grade B-cell disease.

Different manifestations of biologically very closely related diseases and pathologically indistinguishable from B-ALL. ~45% of the total. Characteristic 'starry sk/ histological pattern and deeply basophilic blasts on Romanowsky stains with prominent vacuoles (FAB L3 features). Associated with chromosomal translocation involving MYC locus on chromosome 8 and Ig heavy chain gene on 14 (or less commonly with a k or l light chain gene on 2 or 22) with resultant dysreg-ulation of MYC gene transcription; the MYC product functions as a transcription factor.

2. Precursor B lymphoblastic lymphoma. Indistinguishable pathologically from common ALL. ~5% of the total. Commonly presents as a solitary subcutaneous swelling, typically on the scalp.

3. Precursor T lymphoblastic lymphoma. Indistinguishable pathologically from T-ALL. ~20% of the total. 66% have mediastinal involvement. Marrow involvement common in advanced disease; so may be classified as T-ALL rather than stage IV NHL.

4. Diffuse large B-cell lymphoma, including primary sclerosing mediastinal form; no leukaemic counterpart, accounts for ~3-4% of the total. Chiefly abdominal. Occasionally mediastinal. Has some features of Burkitt's but no MYC gene mutation.

5. Peripheral T-cell lymphoma unspecified; no leukaemic counterpart. Skin involvement. Retrospective review shows most so classified to be type 6 (large cell anaplastic, see below). Poorly defined entity hardly ever seen in children.

6. Large cell anaplastic, T or null cell type. No leukaemic counterpart. More frequently recognised, and complex biological features gradually becoming better understood. ~15% of the total. Used to be diagnosed as peripheral T-cell lymphomas or 'malignant histiocytosis'. Biological hallmarks are Ki-1 (CD30)+, also t(2;5).

Around 9 % childhood NHLs defy classification and <1% adult type follicular lymphomas will occasionally arise in older children.

St Jude staging system for childhood NHL

A staging system for childhood NHL has been developed, though therapy is increasingly being directed more by the biology of the disease rather than its anatomical distribution or extent. Staging affects prognosis only ^yg within given tumour type.

St Jude staging system for childhood NHL

Stage I Single tumour (extranodal or single nodal anatomic area), excluding mediastinum or abdomen

Stage II Single extranodal tumour with regional node involvement = 2 nodal areas on the same side of the diaphragm 2 single extranodal tumours ± regional node involvement on same side of the diaphragm

Primary GIT tumour, usually ileocaecal, ± involvement of associated mesenteric nodes

Stage III 2 extranodal tumours on opposite sides of the diaphragm = 2 nodal areas above and below the diaphragm Presence of 1° intrathoracic tumour (mediastinal, pleural or thymic)

Presence of extensive primary intra-abdominal disease Presence of paraspinal or epidural tumours, regardless of other sites

Stage IV Any of the above with initial CNS and/or bone marrow involvement

Treatment

Burkitt's lymphoma/B-ALL: Short 6 month course of pulsed intensive high dose therapy (vincristine, steroids, methotrexate, cyclophosphamide, anthracyclines and etoposide) including CNS treatment. No maintenance treatment needed.

B precursor lymphoblastic: If isolated to one site, 6 month program of ALL-type therapy may suffice, else treat as common ALL with extended maintenance (ffl lymphoblastic leukaemia p475).

T precursor lymphoblastic: Treated as T-ALL (ffl p161).

Diffuse large B-cell lymphoma: Treated as Burkitt's lymphoma.

Large cell anaplastic Ki-1+: Skin, CNS and mediastinal involvement and splenomegaly are adverse features. Best therapy undefined but usually treated with short intensive Burkitt-like regimens. EFS is around ~75% (high risk cases ~60%).

General points on therapy/outlook

• Surgery usually indicated for the complete resection of a localised abdominal primary tumour when possible.

• Low-dose involved field radiotherapy indicated for airway or spinal cord compression. Mediastinal irradiation for persistent local disease.

• Given best current therapy, the outlook for most patients is good with around 80% EFS for childhood lymphomas overall.

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