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Leukemia

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

Age

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

Gender

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

Presentation

  • 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

Site
  • 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
Size

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
Matrix

Not produced

Cortex

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

Pathology

  • 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

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