What is the typical presentation of leukemia in pediatric patients?

Clinical Presentation of Leukemia in Children

Leukemia in children typically presents with a constellation of hematologic manifestations (pallor, fever, bruising), organomegaly (hepatosplenomegaly, lymphadenopathy), and musculoskeletal complaints (bone/joint pain, particularly nocturnal), with over 50% of children exhibiting hepatomegaly, splenomegaly, pallor, fever, or bruising at diagnosis. 1, 2

Most Common Presenting Features (Present in >50% of Cases)

The five cardinal features present in more than half of children with leukemia include:

• Hepatomegaly (64%) - palpable liver enlargement on abdominal examination 1, 2
• Splenomegaly (61%) - palpable spleen below the costal margin 1, 2
• Pallor (54%) - resulting from anemia due to bone marrow infiltration 1, 2
• Fever (53%) - often related to infections from neutropenia or the disease itself 1, 2
• Bruising (52%) - caused by thrombocytopenia and platelet dysfunction 1, 2

Frequent Additional Manifestations (Present in 33-49% of Cases)

• Recurrent infections (49%) - due to neutropenia and leukocyte dysfunction 1, 2
• Fatigue or lethargy (46%) - resulting from anemia secondary to bone marrow failure 1, 2, 3
• Limb pain (43%) - particularly bone or joint pain, often worse at night 1, 2
• Hepatosplenomegaly (42%) - combined liver and spleen enlargement 2
• Lymphadenopathy (41%) - enlarged lymph nodes 2, 3
• Bleeding tendency (38%) - including easy bruising, petechiae, or other bleeding manifestations 1, 2
• Rash (35%) - various cutaneous manifestations 2

Critical Musculoskeletal Red Flags

Pain in the extremities or joints may be the only presenting symptom in some children with ALL. 4 These musculoskeletal presentations warrant particular attention:

• Nocturnal bone or joint pain - pain that is particularly worse at night is a significant red flag 1, 5
• Pain with walking or playing - bone or joint pain during normal activities should raise suspicion 1, 5
• Pain associated with systemic symptoms - when combined with fever and weight loss, this significantly increases suspicion for leukemia 1, 5

Important caveat: Musculoskeletal symptoms can initially be misdiagnosed as reactive arthritis, osteomyelitis, or juvenile idiopathic arthritis, potentially delaying appropriate diagnosis. 6 Radiological findings of leukemic bone involvement may appear before hematologic abnormalities but are not specific for the disease. 6

Constitutional Symptoms

• Weight loss (25%) - changes in appetite or unintentional weight loss 1, 3
• Night sweats - frequently present as constitutional symptoms 1
• Dyspnea and dizziness - related to anemia 1

Laboratory Abnormalities at Presentation

The characteristic laboratory constellation includes:

• Anemia (83%) - low hemoglobin levels are associated with early diagnosis 3
• Thrombocytopenia (80%) - low platelet counts 3
• Leukocytosis (46%) - elevated white blood cell count 3
• Blasts in peripheral blood smear - presence of immature cells 7
• Mono-, bi-, or trilinear pathology of the blood count 7

Critical point: Blood examinations can sometimes be subtle or within normal limits, representing a diagnostic difficulty. 6 However, 95% of patients present with the characteristic laboratory findings described above. 7

Clinical Presentation Variations by Leukemia Type

Acute Lymphoblastic Leukemia (ALL)

• Nonspecific presentation - fatigue, lethargy, constitutional symptoms (fevers, night sweats, weight loss), dyspnea, dizziness, infections, and easy bruising or bleeding 4
• Lymphadenopathy, splenomegaly, and/or hepatomegaly - found in approximately 20% of patients on physical examination 4
• Mature B-cell ALL - abdominal masses from gastrointestinal involvement or chin numbness from cranial nerve involvement are more suggestive of this subtype 4

Chronic Myeloid Leukemia (CML) in Children

• Fatigue (46%) - most common symptom at diagnosis 4
• Weight loss (25%) - frequently reported 4
• Fever and abdominal pain (23%) - common presenting features 4
• Spleen enlargement - determination of spleen size below the costal margin is required 4
• Extramedullary involvement - lymph nodes, skin, or soft tissue may be affected 4

Factors Associated with Delayed Diagnosis

Bone or joint pain, mucosal bleeding, and pallor are significantly associated with late diagnosis, while lymphadenopathy and bone tenderness facilitate earlier recognition. 3

• Late diagnosis markers: bone or joint pain (p<0.001), mucosal bleeding (p=0.013), pallor (p=0.005), elevated platelet count (p=0.028) 3
• Early diagnosis markers: lymphadenopathy (p=0.014), bone tenderness (p=0.024), low hemoglobin levels (p=0.023) 3

Asymptomatic Presentation

Approximately 5-6% of children are asymptomatic at diagnosis and are identified accidentally. 2, 7 This underscores the importance of routine physical examination and blood count evaluation in pediatric practice.

Essential Physical Examination Components

When evaluating a child with unexplained illness, the examination must include:

• Abdominal palpation - to assess for hepatomegaly and splenomegaly 2
• Palpation for lymphadenopathy - systematic examination of lymph node regions 2
• Careful scrutiny of the skin - looking for pallor, bruising, petechiae, and rash 2
• Assessment of spleen size - measuring distance below the costal margin 4

The occurrence of multiple symptoms and signs should alert clinicians to possible leukemia. 2 The majority of patients have a medical history spanning a few weeks, though in 11% of patients symptoms may persist for several months without impairing curability. 7