Leukaemias

In childhood acute lymphoblastic leukaemia (ALL) is by far the most frequently occurring leukaemia representing over 75% cases. (p. 308).

Presentation is usually with symptoms and signs of bone marrow infiltration and these can appear to occur quite rapidly, although are often preceded by several weeks of general malaise or recurrent infections and fevers. Usual features at the time of diagnosis are pallor, abnormal bruising or bleeding, bone pain (which may manifest as limping in young children) and on clinical examination lymphadenopathy and hepatomegaly in some children.

Diagnosis is suspected on the differential blood count but bone marrow examination is essential to confirm the diagnosis (p. 308), to perform immunocytochemical stains and cytogenetics which are of diagnostic and prognostic significance (Box 22.2).

Treatment of childhood and young adult ALL is performed according to risk stratification as in Box 22.2. In general treatment involves several phases which is similar to that of adult ALL (p. 308).

Relapsed ALL may still be curable with high-dose chemotherapy and stem cell transplantation, but the chances of long-term cure are much lower with the high-risk subgroups and if relapse is within a year of completing initial treatment.

In addition certain subgroups such as B-cell ALL are often treated on different regimens similar to those used for a Burkitt’s lymphoma (p. 305, Burkitt’s lymphoma). Both these malignancies are associated with a t(8;14) translocation so may be variations of the same malignancy.

Brain tumours

Brain tumours are the second most common malignancy in children and remain a significant cause of cancer into young adulthood. In children the majority of tumours occur infratentorially but this proportion changes with increasing age.

Presenting features include headaches, often worse in the morning and associated with morning vomiting, papilloedema (sometimes detected by an optician), ataxia, personality change, nerve palsies and nystagmus.

Common subtypes of brain tumour include astrocytoma, medulloblastoma, glioma, craniopharyngioma and ependymoma. In children, particularly in the very young, the emphasis of treatment is to delay, avoid or minimize the need for radiotherapy to avoid long-term side effects. These are covered in more detail on p. 264.

Wilms’ tumour

Wilms’ tumour or nephroblastoma occurs most frequently in children under 5 years of age and very rarely in older children or young adults. Most tumours are unilateral, but are bilateral in 5% of cases and in a further 5–10% will have more than one tumour in the same kidney. Risk factors include certain genetic syndromes such as Beckwith–Weidemann syndrome. They are often asymptomatic until they present as an abdominal mass, pain and/or anorexia.

Histologically they are divided into a favourable group with well-defined elements and the anaplastic (or unfavourable group) with poorly defined cellular morphology. Less than 25% have a mutation within the WT1 (Wilms’ tumour) gene.

Staging is undertaken with imaging and treatment is according to stage (Figure 22.2). Anaplastic tumours are treated with more aggressive chemotherapy except in stage I where their prognosis is similar to favourable histology tumours. Overall more than 80% are cured of their disease. Treatment for relapse is rarely curative.

Figure 22.2 Staging and management of Wilms’ tumour.

Neuroblastoma

Neuroblastoma is a neuroendocrine tumour which originates from any neural crest element of the sympathetic nervous system. It predominantly occurs in those under 3 years of age. The highest incidence is in the first 12 months of life with less than 10% of cases occurring in those over the age of 5 years.

Clinical presentation is varied depending on the location and extent of the tumour. Fatigue, fever and anorexia are the most common initial presenting features with more localizing features dependent on tumour site. Adrenal primaries are often extensive at presentation and may involve the IVC. Paravertebral tumours may lead to spinal cord compression. At least 50% of cases are metastatic at presentation. Elevated catecholamines are found in over 90%. Staging includes a CT, bone scintigram, bone marrow sampling and radiolabelled MIBG (meta-iodobenzylguanidine) scan. MIBG is taken up by 95% of neuroblastomas and acts as a tool for staging and monitoring disease response.

Poor prognostic features are advanced stage, age over 1 year, and over-expression of N-myc oncogene.

Treatment may be with surgery alone in early stage disease, but the majority require combination chemotherapy. Trials are examining the role of intensification of treatment in poor prognosis disease. The risk of relapse is high and the long-term survival for those with metastatic disease at presentation is less than 30%.

Lymphomas

Lymphomas occur in childhood and Hodgkin’s disease has a peak in incidence in young adulthood (p. 298). In general these tumours are treated similar to their adult counterparts except that radiotherapy is avoided, except in refractory disease, to reduce the risk of its effect on growth and the risk of second malignancy. Chemotherapy regimens are similar to adults but trials are ongoing to assess the role of rituximab in children. The most common subtypes of NHL in children are Burkitt-like lymphomas (p. 305) and diffuse large B-cell lymphomas (Table 22.2). Anaplastic large cell tumours are rare as are other adult subtypes such as cutaneous T-cell lymphoma and MALT lymphoma (p. 306). Prognostic factors are similar to adult tumours.

Table 22.2 Major histopathological categories of non-Hodgkin lymphoma in children and adolescents

Sarcomas

Both bone and soft tissue sarcomas occur in children and young adults. These are covered in detail in Chapter 15. Some sarcomas, however, peak in this age group. Osteosarcomas peak in early adolescence with Ewing’s sarcomas having their peak incidence in older adolescence. Rhabdomyosarcoma (RMS), a tumour of striated muscle, is the only soft tissue sarcoma to peak in children and adolescents. It is divided into two main histological subgroups, embryonal and alveolar. Alveolar rhabdomyosarcoma (ARMS) is characterized by one of two specific translocations, either t(2;13)(q35;q14) resulting in fusion of PAX3-FOXO1 in 60% ARMS or t(1;13)(q36;q14) resulting in PAX7-FOXO1 in 20% ARMS. Embryonal RMS is not associated with a specific translocation, but loss in chromosome 11. Common tumour sites include the head and neck, paratesticular and limb (Figure 22.3). It frequently presents with advanced disease. If localized it can present with a mass or proptosis if retro-orbital. It can give rise to nodal metastases and regional lymph nodes should be examined. Staging involves local MRI, CT of chest (and regional), bone scan, and bone marrow biopsy. Localized disease is treated with surgery, but due to the aggressive nature of these tumours, combination chemotherapy with e.g. IVADo (ifosfamide, vincristine, actinomycin and doxorubicin), is given. Radiotherapy is often given if margins are positive or there has been tumour regrowth after initial surgery. An Italian pilot study suggested that maintenance therapy with cyclophosphamide and vinorelbine may prolong progression free survival. In advanced disease combination chemotherapy is used but the outlook is poor. Poor prognostic factors include increasing age, particularly over age 16, advanced stage and alveolar subtype.

Figure 22.3 MRI of sagittal section through the foot showing a mass deep to the plantar fascia. Histology showed an embryonal rhabdomyosarcoma.

Germ cell tumours

Germ cell tumours of the ovary and testes peak in young adulthood and are described in more detail in Chapters 12 and 13. Similar treatment modalities are used in children and young adults, but there has been a move to reduce long-term side effects from chemotherapy and to try to maintain fertility in ovarian germ cell tumours. Trials are underway to examine the role of carboplatin rather than cisplatin and to reduce the dose of bleomycin in adolescent germ cell tumours to reduce late effects. Fertility sparing surgery is preferred if possible for ovarian germ cell tumours and many women retain their fertility with this type of surgery and BEP chemotherapy (p. 220).

Langerhans cell histiocytosis (LCH)

LCH is a proliferative disorder of histiocytes. Although not strictly a malignancy it may exhibit aggressive behaviour and require combination chemotherapy. Multiple bony lesions can occur at any site, but can occur within the skull leading to hypothalamic infiltration and diabetes insipidus. Systemic LCH tends to present in infancy as a widespread rash with bone marrow and soft tissue involvement. Organ dysfunction is a better indication of poor prognosis than the number of involved sites. Treatment of advanced disease is with chemotherapy.

Hepatoblastomas

Hepatoblastomas are rare but are most common malignancy of liver in children. There is an association with FAP. Hepatocellular carcinoma can also occur rarely but in older age groups. Clinical presentation is usually with a mass or abdominal distension. Jaundice is rare. Alpha-foetoprotein (AFP) is elevated in most cases. Unlike adult liver tumours, most hepatoblastomas respond to combination chemotherapy (cisplatin and doxorubicin) with good long-term survival.

Retinoblastoma

Retinoblastomas are very rare childhood tumours. All bilateral tumours and 20% of unilateral tumours are thought to be hereditary. The retinoblastoma tumour suppressor gene is on chromosome 13 with the pattern of inheritance being autosomal dominant with incomplete penetrance (Chapter 5, p. 55). Most cases present before age 3. In children not known to be in a retinoblastoma family presentation is with a squint or white papillary reflex. Those related to retinoblastoma families should be part of a screening programme. Surgery may be necessary for some but most cases are treated with radiotherapy. Long-term survival is over 95%, but second malignancy is common (osteosarcomas in radiotherapy field) and in those with hereditary retinoblastoma other malignancies, especially sarcomas can occur elsewhere in the body in young adulthood up to middle age.