98 Leukemia

Clinical Presentation

A lethargic 7-year-old boy presents with painful knees/shins.

Figure 98A

Figure 98B

Radiologic Findings

Coned-down frontal views centered on the knee and ankle demonstrates subphyseal metaphyseal lucent bands involving distal femur as well as proximal and distal tibia (Figs. 98A and 98B). The bone configuration/modeling appears normal.

Diagnosis

Acute lymphoblastic leukemia (ALL)

Differential Diagnosis

The differential diagnosis of lucent metaphyseal bands are:

Infection (congenital)
Neuroblastoma
Rickets, hypophosphatasia
Scurvy, nutritional deficiency
Juvenile idiopathic arthritis

Discussion

Background

Of all pediatric malignancies, leukemia is the most common, accounting for 30 to 40% of all childhood cancers. ALL is the most common form, comprising up to 85% of patients. The disease is most frequent in children 2 to 5 years of age. Skeletal manifestations may be the initial presentation in up to 20% of cases. Between 70 and 90% of children with leukemia will manifest skeletal radiographic changes during their course of illness and treatment. Long bones (usually lower limbs) are more often affected than axial bones.

Etiology

Radiation exposure has been linked with the development of ALL; patients with ataxia telangiectasia, Down syndrome, and Fanconi’s anemia are also predisposed.

Oncogenic mechanisms include enhanced expression of protooncogenes (MYC, TAL-1, LYL-1, HOX-11), the expression of translocation-generated fusion oncogenes (BCR-ABL, TEL-AML-1, E2A-PBX-1, and MLL fusions), and alterations in chromosomal number (decrease or increase). The majority of these mechanisms are insufficient on their own to generate a full leukemic phenotype. The nature and number of mutations needed to induce leukemia appear to vary, depending on unknown initiation lesions, some of which may be acquired in utero.

Clinical Findings

Fever, lethargy, irritability, pallor, loss of appetite, petechiae, bleeding
Testicular enlargement
Headaches and cranial nerve palsies if central nervous system (CNS) involvement
Inability or reluctance to walk/move limb, pain (27 to 50%), tenderness, swelling
Lymphadenopathy, hepatosplenomegaly

Complications

Infiltration of marrow results in thrombocytopenia and anemia.
Osteopenia predisposes to pathologic fractures (~2% of patients have vertebral body compression).
Rarely, see bone marrow necrosis prior to treatment
Pulmonary complications include infection, edema, hemorrhage, cryptogenic organizing pneumonia, and malignant infiltration.
Subsequent learning difficulties and decreased cognitive function described on some long-term follow-up studies.