Tumor biology

  • Malignant neoplasms of hematopoietic stem cells
  • Lesions usually involve marrow diffusely and replace native bone marrow with neoplastic cells
  • Leukemias considered either acute (characterized by presence of immature cells, or blasts) or chronic (characterized by well-differentiated cells, mature)
    • Further classified as myelogenous leukemia (a malignancy of myeloid cell line) or lymphocytic leukemia (malignancy of lymphocytic cell line)
      • Lymphocytic type more common in children, especially acute lymphoblastic leukemia (ALL).
  • Leukemias classified as acute myologenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelocytic leukemia (CML), chronic lymphatic leukemia (CLL), and hairy cell leukemia.
  • Leukemoid tissue that lies outside bone marrow often referred to as chloroma or granulocytic sarcoma


  • ALL: Disease of childhood
  • CLL: Disease of the aged
  • AML: Occurs at all ages
  • CML: Occurs in middle life


Sex differences are minimal except in CLL, where there is male predominance


  • Bone pain may be only presenting complaint in children
  • Adult patient often dies before bone symptoms emerge
  • Rule out ALL in children with fleeting, recurrent, unexplained bone pain
  • Patient may also have clinical signs that reveal diffuse marrow involvement (anemia and  lethargy, thrombocytopenia, prolonged bleeding time and bruising, leukopenia and recurrent infection)

Physical findings

  • Swelling and tenderness of involved site may be present
  • Hepatosplenomegaly and lymphadenopathy may be present
  • Lesions may arise around joints in children and mimic and present as arthritis

Blood work

  • Condition may mimic osteomyelitis, however blood cultures will be negative
  • Peripheral smear generally demonstrates neoplastic cells, if they have entered into blood from marrow
  • Complete blood count (CBC) often shows anemia and thrombocytopenia
  • Bone marrow aspirate is diagnostic
  • Molecular diagnostic techniques, karyotyping, and flow cytometry necessary for typing

Plain films

  • In adults, usual sites of involvement are skull, pelvis, proximal humerus, and femur
    • Bone changes more striking with CLL than CML
  • In children, lesions usually localized to rapidly growing regions of long bones, especially proximal tibia, distal femur, distal tibia and distal radius, and ulna

Extent variable

Tumor effect on bone
  • Generalized osteoporosis may be present in children and adults
  • Children may have:
    • Metaphyseal bands (lucent and sclerotic), secondary to interference with proper osteogenesis; usually 1-7 mm in size
    • Focal lytic lesions, due to leukemic deposits or bone infarction secondary to vascular occlusion by tumor (15-50% of cases in children have focal lesions)
    • Periosteal reaction, result of tumor cells that have penetrated cortex (especially in long bones)
Bone response to tumor
  • Sclerotic reaction rare
    • If present, be suspicious of pathologic fracture

Not produced


Cortical erosion may be evident

Soft tissue mass

Rarely present

Bone scan

May show multiple sites of increased uptake

Differential diagnosis

In children
  • Metastatic neuroblastoma
  • If sclerotic, consider normal fracture healing
  • Immobilization
  • Vitamin C deficiency
  • Vitamin D deficiency or osteomalacia
In adults
  • Lymphoma
  • Multiple myeloma
  • Metastasis
  • Paget’s disease
  • Osteomalacia
Lucent bands in pediatric bone
  • Lucent bands are subtle linear lucencies oriented perpendicularly to cortex
  • Lucencies are nonspecific and may be seen in:
    • Leukemia
    • Systemic childhood illnesses


  • Gross: Hemorrhagic soft tissue
  • Microscopic
    • Replacement of bone marrow by blast cells in acute leukemia, with decrease in normal hematopoietic cells.
    • Accumulation of and replacement of the marrow by mature and immature cells in chronic leukemia, the type of which relates to the type of leukemia.
  • Classification is based on the nature of the blast cells, which can be either myeloid or lymphoid in origin
  • In addition to routine histology, cytochemistry, flow cytometry, cytogenetics and/or molecular analysis are critical for diagnosis

Natural history

  • Involvement of bone does not appear to have prognostic significance
  • Routine skeletal survey in every leukemic patient not recommended

Diagnosis and treatment

  • CBC, peripheral smear, and bone marrow aspirate usually diagnostic
  • If negative, move to biopsy of lesion.
  • Patients managed by hematologist-oncologist