Residency · Residency · Pediatrics

Pediatric Oncology Emergencies and Cancer Overview

Introduction

Cancer is the leading cause of disease-related death in children aged 1-14 years in developed countries. Approximately 15,000 children under age 20 are diagnosed with cancer annually in the United States. Overall survival has improved dramatically to nearly 85% due to advances in multimodal therapy. However, pediatric cancers can present with life-threatening emergencies requiring rapid recognition and intervention. This lecture covers the most common pediatric malignancies, their presentations, and the critical oncologic emergencies.

Overview of Common Pediatric Cancers

Leukemia (30% of Childhood Cancers)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with a peak age of 2-5 years. It presents with pallor, fatigue, bruising, petechiae, bone pain, hepatosplenomegaly, and lymphadenopathy. Diagnosis is made when the CBC shows anemia and thrombocytopenia with or without leukocytosis, the peripheral smear reveals blasts, and bone marrow aspirate confirms greater than 25% blasts. Risk stratification is based on age, WBC count, cytogenetics (favorable: hyperdiploidy, ETV6-RUNX1; unfavorable: Philadelphia chromosome, MLL rearrangement, hypodiploidy), and minimal residual disease (MRD). Acute myeloid leukemia (AML) accounts for 15-20% of pediatric leukemias, with Auer rods on smear being pathognomonic. AML is associated with Down syndrome, particularly the AMKL subtype.

Brain Tumors (25% of Childhood Cancers)

Brain tumors are the most common solid tumors in children. Posterior fossa tumors predominate and include medulloblastoma (PNET), cerebellar astrocytoma (pilocytic), ependymoma, and brainstem glioma. Presenting features include headache (worse in the morning, waking the child from sleep), vomiting, papilledema, cranial nerve palsies, ataxia, personality changes, and macrocephaly in infants.

Lymphoma

Hodgkin lymphoma has a bimodal distribution with adolescents most commonly affected. It presents with painless cervical or supraclavicular lymphadenopathy and B symptoms (fever, night sweats, weight loss), with Reed-Sternberg cells on biopsy. Non-Hodgkin lymphoma is more common in younger children and includes Burkitt lymphoma (presenting as an abdominal mass or jaw mass in the African form), lymphoblastic lymphoma (presenting as a mediastinal mass), anaplastic large cell lymphoma (ALCL), and diffuse large B-cell lymphoma (DLBCL).

Neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in children, derived from neural crest cells, with a median age at diagnosis of 18 months. The adrenal gland is the most common primary site, followed by the paraspinal sympathetic chain. Presentations include an abdominal mass, proptosis with periorbital ecchymoses ("raccoon eyes"), opsoclonus-myoclonus syndrome, and skin nodules ("blueberry muffin" appearance in neonates). MYCN amplification portends a poor prognosis, while stage 4S disease in infants can spontaneously regress.

Wilms Tumor (Nephroblastoma)

Wilms tumor is the most common renal tumor in children, with a peak age of 3-4 years. It typically presents as a painless abdominal mass, often found incidentally by a parent. The abdomen should not be palpated aggressively due to the risk of rupture. Associated syndromes include WAGR (Wilms tumor, aniridia, GU anomalies, intellectual disability), Beckwith-Wiedemann, and Denys-Drash. Treatment consists of surgical resection, chemotherapy, and selective radiation, with favorable histology achieving greater than 90% survival.

Bone Tumors

Osteosarcoma is the most common primary bone malignancy, peaking in adolescence and typically affecting the metaphyses of long bones (distal femur, proximal tibia). It shows a "sunburst" pattern on X-ray. Ewing sarcoma peaks at age 10-15 years, is diaphyseal in location, and shows an "onion skin" periosteal reaction with the characteristic chromosomal translocation t(11;22) producing the EWS-FLI1 fusion.

<image>Visual overview of the most common pediatric cancers organized by frequency and age of peak incidence, showing leukemia (ALL peak 2-5 years), brain tumors, lymphoma, neuroblastoma (peak 18 months), Wilms tumor (peak 3-4 years), bone tumors (peak adolescence), and soft tissue sarcomas with key clinical features for each</image>

Oncologic Emergencies

Tumor Lysis Syndrome (TLS)

Tumor lysis syndrome is a metabolic emergency resulting from rapid tumor cell destruction releasing intracellular contents. It is most common with high tumor burden and rapidly proliferating malignancies such as Burkitt lymphoma, ALL with high WBC, and T-cell lymphoblastic lymphoma. The Cairo-Bishop criteria include hyperuricemia, hyperkalemia, hyperphosphatemia (with secondary hypocalcemia), elevated LDH, and acute kidney injury. Prevention involves aggressive IV hydration at 2-3 times maintenance with D5 1/4NS or 1/2NS without potassium, rasburicase (recombinant urate oxidase) for high-risk patients, and allopurinol for intermediate risk. Treatment includes urgent management of hyperkalemia (calcium gluconate, insulin/dextrose, kayexalate, dialysis if refractory), phosphate binders, avoidance of calcium supplementation unless symptomatic (as it drives calcium-phosphate precipitation), and renal replacement therapy for refractory cases.

Superior Vena Cava (SVC) / Superior Mediastinal Syndrome

This emergency results from compression of the SVC and/or trachea by an anterior mediastinal mass. The most common causes are T-cell ALL/lymphoblastic lymphoma, Hodgkin lymphoma, and germ cell tumors. Patients present with facial and upper extremity edema, plethora, dyspnea, orthopnea, stridor, and syncope. Symptoms may worsen dramatically with sedation or supine positioning. It is critical to avoid sedation, general anesthesia, and supine positioning until the airway is secured, as anesthesia can precipitate complete airway collapse. Diagnosis is made by chest CT, and tissue should be obtained via the least invasive means (peripheral blood or bone marrow if leukemic involvement is suspected, pleural fluid, or percutaneous biopsy under local anesthesia). Emergency treatment with empiric corticosteroids (for lymphoid malignancies) and/or radiation is indicated if airway compromise is imminent.

Febrile Neutropenia

Febrile neutropenia is defined as a temperature of 38.3C or higher (once) or 38.0C or higher sustained over 1 hour in a patient with an ANC less than 500 (or expected to fall below 500). It is a medical emergency because of the risk of rapid progression to sepsis and death. Blood cultures should be obtained from both the central line and a peripheral site before antibiotics, but antibiotics must not be delayed. Empiric broad-spectrum antibiotics should be administered within 60 minutes and include cefepime, piperacillin-tazobactam, or meropenem. Vancomycin is added if there is hemodynamic instability, mucositis, suspected catheter-related infection, or skin/soft tissue infection. Antifungal coverage with caspofungin or voriconazole is added if fever persists beyond 4-7 days despite antibiotics.

Spinal Cord Compression

Spinal cord compression is caused by epidural tumor extension or vertebral body collapse and presents with back pain, weakness, gait changes, a sensory level, and bowel/bladder dysfunction. Emergency MRI of the entire spine should be obtained, dexamethasone 1-2 mg/kg IV bolus administered, and urgent radiation, chemotherapy, or surgical decompression pursued depending on tumor type.

Hyperleukocytosis and Leukostasis

Hyperleukocytosis is defined as a WBC greater than 100,000/mcL and is most dangerous in AML due to larger, stickier blasts. Leukostasis presents with respiratory distress, altered mental status, and retinal hemorrhages from microvascular sludging. Treatment includes aggressive hydration, hydroxyurea to reduce WBC, and leukapheresis for symptomatic leukostasis. RBC transfusion should be avoided until the WBC is reduced, as it increases viscosity.

<image>Infographic depicting the four major pediatric oncologic emergencies: tumor lysis syndrome (metabolic derangements), febrile neutropenia (infection protocol), superior mediastinal syndrome (airway management), and spinal cord compression (neurologic emergency), with key diagnostic findings and immediate management steps for each</image>

Red Flags Suggesting Malignancy in Children

Warning signs include unexplained persistent lymphadenopathy (greater than 2 cm, supraclavicular, non-tender, fixed), persistent unexplained fever with weight loss and night sweats, bone pain waking a child from sleep, easy bruising with petechiae and pallor, morning headaches with vomiting, an abdominal mass, leukocoria (white pupillary reflex suggesting retinoblastoma), and proptosis or periorbital ecchymoses.

<image>Clinical "red flag" warning signs illustration showing a child's body with labeled indicators of possible malignancy: leukocoria, proptosis, cervical lymphadenopathy, mediastinal mass on chest X-ray, hepatosplenomegaly, abdominal mass, bone pain locations, and petechiae/bruising distribution</image>

Clinical Pearls

A child with pancytopenia and bone pain has leukemia until proven otherwise, and an urgent peripheral smear and pediatric oncology consultation should be obtained. A child with an anterior mediastinal mass should never be sedated or laid flat without a secured airway plan, as fatal airway collapse can occur. Febrile neutropenia requires empiric antibiotics within 60 minutes, as delays increase mortality. Tumor lysis syndrome can occur before chemotherapy starts (spontaneous TLS), so labs should be checked at presentation in any child with suspected high-burden malignancy. All children completing cancer therapy require long-term survivorship follow-up for late effects including secondary malignancies, cardiotoxicity, endocrine dysfunction, neurocognitive impairment, and infertility.

References

1. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015;373(16):1541-1552.
2. Cairo MS, Bishop M. Tumour Lysis Syndrome: New Therapeutic Strategies and Classification. Br J Haematol. 2004;127(1):3-11.
3. Lehrnbecher T, Robinson P, Fisher B, et al. Guideline for the Management of Fever and Neutropenia in Children with Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update. J Clin Oncol. 2017;35(18):2082-2094.
4. Ward E, DeSantis C, Robbins A, et al. Childhood and Adolescent Cancer Statistics, 2014. CA Cancer J Clin. 2014;64(2):83-103.

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