Acute leukemia is the most common malignancy in childhood and may present with a variety of symptoms including fever, fatigue, bleeding, adenopathy, or bone pain.
Most oncologic emergencies arise from metabolic, hematologic, structural, or toxic chemotherapy effects.
Findings associated with inflammation may be absent in the immunocompromised patient, with fever potentially the only sign of serious infection. However, immunocompromised patients may have serious infections without the presence of fever.
Infection may progress rapidly in the immunocompromised host; evaluation and initiation of antibiotic therapy must be done urgently.
Tumor lysis syndrome (TLS) results from the death of tumor cells and release of their intracellular contents leading to hyperuricemia, hyperphosphatemia, and hyperkalemia.
Mediastinal compression from tumor may result in superior vena cava syndrome (SVCS) or superior mediastinal syndrome (SMS), resulting in an airway emergency.
Approximately 10% of childhood deaths are related to cancer.1 Acute leukemia, central nervous system (CNS) tumors, and lymphomas account for more than one-half of all childhood malignancies. Advances in cancer treatment have led to improvement in survival rates. However, this progress has often come with increased intensity of treatment regimens, with concomitant increase in possible toxicity. It is important for the emergency physician to be aware of the common malignancies that occur in children and to be ready to treat the complications of cancer at presentation and during treatment.
Leukemia is a condition in which there is uncontrolled, clonal proliferation of an immature white blood cell (WBC) within the bone marrow, with subsequent suppression of normal hematopoiesis. Acute leukemia is the most common childhood malignancy, with an incidence of approximately 30 cases per million persons younger than 20 years of age.2 Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of pediatric leukemia, with acute myelogenous leukemia (AML) accounting for the other 25%. Chronic myelogenous leukemia (CML) accounts for less than 1% of all childhood cancers.
The peak incidence of ALL in children occurs between the ages of 3 and 5 years. Overall, greater than 80% of patients survive more than 5 years beyond diagnosis, with many patients considered cured of the disease.3 Unlike ALL, the incidence of AML is relatively constant throughout childhood and in general has a poorer prognosis, with approximately 60% of patients surviving at 5 years from diagnosis.4
The signs and symptoms of acute leukemia reflect replacement of bone marrow or result from extramedullary collections of leukemic blasts. Common presentations include pallor, fatigue, petechiae, purpura, and infection as a result of defective hematopoiesis from marrow replacement. Lymphadenopathy, hepatomegaly, splenomegaly, and mediastinal or testicular masses may represent extramedullary involvement. Bone pain may result from leukemic involvement of the periosteum and bone, causing patients to limp or even refuse to walk. Leukemia may be present in the CNS, leading to cranial nerve deficits, headache, or changes in vision. The leukocyte count at diagnosis varies greatly and may be high, low, or normal. Even in the absence of neutropenia at diagnosis, patients should be considered immunocompromised as the WBCs produced may not be functional. Many patients will be anemic and/or thrombocytopenic, though blood counts may be normal. The diagnosis of leukemia is confirmed by evaluation of the bone marrow. Further morphologic and cytogenetic characterization of the leukemic blasts determines the particular treatment regimen. Leukemia is treated with multi-agent chemotherapy regimens (with duration and intensity dependent on the type of leukemia) that frequently lead to severe myelosuppression. Exciting advancements in immunotherapy are leading to improved survival in patients with relapsed or refractory disease.5
Hodgkin lymphoma (HL) is a malignancy of the lymph nodes. The Reed–Sternberg cell is considered to be the malignant cell in classical HL.6 Approximately 5% of pediatric malignancies are HL, with a peak incidence in adolescents and young adults.1 The majority of pediatric patients have painless supraclavicular or cervical lymphadenopathy. Nodes are rubbery, matted, and unlike reactive nodes, do not decrease in size with time. The abdominal examination may reveal hepatomegaly or splenomegaly. Mediastinal involvement is common, and a chest radiograph should be obtained. Systemic or “B” symptoms may occur in one-third of the patients and include fever, weight loss, and night sweats. The differential diagnosis of HL includes other causes of lymphadenopathy, such as infectious mononucleosis, mycobacterial infections, or other metastatic malignancies. Abnormalities may be seen on complete blood count (CBC) secondary to metastatic disease in the bone marrow. Biopsy of an affected lymph node is required for diagnosis. Treatment regimens include multidrug chemotherapy and/or radiation, with 5-year survival rates of >90%.
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignancies of the lymphatic tissue. Unlike HL, there is no peak age incidence, but cases increase steadily with age. Compared to the indolent nature of many adult lymphomas, childhood NHLs are often rapidly proliferating. The most common types of NHL seen in children are Burkitt, Burkitt-like, and large B cell lymphoma (all of mature B cell origin), lymphoblastic lymphoma (predominately of precursor T cell origin), and anaplastic large cell lymphoma (ALCL). Clinically, children with NHL present with clinical symptoms that correlate with the histologic subtype. Lymphoblastic lymphomas often present with a mediastinal mass or supraclavicular adenopathy leading to cough, wheeze, chest pain, airway obstruction, or signs and symptoms of superior vena cava obstruction. Burkitt lymphomas most often present with abdominal involvement causing pain, nausea, vomiting, distension, ascites, or bowel obstruction. Right lower quadrant pain reflects distal ileal, appendiceal, or cecal involvement and may mimic appendicitis. Abdominal lymphoma may be a lead point for an intussusception. Bone, bone marrow, and the CNS are common sites of metastasis. ALCLs have a broad spectrum of clinical presentations including lymphadenopathy and skin and bone involvement. Patients presenting with NHL often require emergency management owing to the rapid doubling time and growth rate of the tumor (Burkitt lymphoma) or owing to tumor mass encroachment on vital structures (lymphoblastic lymphoma). Initial laboratory studies include a CBC to assess for marrow involvement, as well as electrolytes, creatinine, calcium, phosphorous, and uric acid to evaluate for TLS (discussed later). A chest radiograph may reveal a mediastinal mass (Fig. 108-1). Patients with an abdominal mass are evaluated with abdominal ultrasound or computed tomography (CT) scan. Multi-agent chemotherapy with/without radiation is the mainstay of treatment, with up to 80% or higher long-term, disease-free survival, depending on histologic type.
Tumors of the CNS represent the second most common malignancy in childhood.7 Factors increasing the risk of developing a CNS malignancy include various genetic disorders, such as neurofibromatosis or tuberous sclerosis, and exposure to ionizing radiation. Classification of CNS tumors is generally based on histologic type. Tumors arising in the supratentorial region include cerebral astrocytoma, optic glioma, and craniopharyngioma. These occur more commonly in neonates and infants. Infratentorial tumors such as cerebellar astrocytoma, medulloblastoma, ependymoma, and brain stem glioma are more commonly seen after 2 years of age.
Supratentorial tumors may cause headache, seizures, or visual impairment. However, compared to adults, seizure is rarely the initial presenting sign of a CNS tumor in children. Truncal ataxia or incoordination is typical of infratentorial tumors. Impingement of the brain stem may lead to cranial nerve palsies or Horner syndrome. Raised intracranial pressure (ICP) in infants and toddlers may manifest as vomiting, anorexia, irritability, developmental regression, or impaired upward gaze (“sunsetting” sign). There may be excessive enlargement of the head circumference and persistently palpable cranial sutures. Parents may note a change in behavior or personality in their child. Older children may complain of headache, fatigue, or vomiting. Headaches that are recurrent, intense, associated with vomiting, or that awaken the child from sleep should raise the suspicion of a malignancy. In addition, patients may have back pain, bladder or bowel dysfunction, or focal neurologic deficits that suggest spinal cord or cauda equina involvement.
Tumors of the CNS may be diagnosed by CT; however, magnetic resonance imaging (MRI) is more sensitive. Treatment of CNS tumors is dependent on histology and location, and may include multi-agent chemotherapy, radiation therapy, and/or surgery.
Wilms tumor (nephroblastoma) arises from embryonal renal cells. The peak age of diagnosis is 2 to 3 years, with most cases diagnosed before 5 years of age. Most children appear well at diagnosis, with a nontender abdominal mass. Systemic symptoms are rare. Hematuria is uncommon with Wilms tumor, and if present is usually microscopic. Other uncommon features at diagnosis include pain, hypertension, polycythemia, or an acquired von Willebrand disease. Rarely, cases are associated with an underlying genetic predisposition syndrome such as Beckwith–Wiedemann, Denys–Drash, or Wilms tumor, aniridia, genitourinary anomalies, mental retardation (WAGR) syndrome.8 Tumor may be present in both kidneys at diagnosis in 5% to 10% of cases. Initial workup includes a CBC, urinalysis, and imaging of the chest and abdomen. Ultrasound or CT will often reveal a large, encapsulated mass arising from the kidney (Fig. 108-2). Patients suspected of having a Wilms tumor are referred for further evaluation and management, which includes surgical resection and chemotherapy +/– radiation therapy. Nephrectomy or biopsy should only be performed by a surgeon experienced with Wilms tumor in order to avoid rupture and possible upstaging of the tumor.
Neuroblastoma is a malignancy arising from neural crest cells, originating anywhere along the sympathetic chain or the adrenal medulla. It is the most common extracranial solid tumor in childhood, with almost all cases diagnosed before 5 years of age.8 Presenting signs and symptoms are most often related to the local effects of the primary or metastatic tumor. Two-thirds of neuroblastomas arise in the abdomen and pelvis, and may present as an abdominal mass. Cervical or thoracic primary tumors are more often seen in infants. Horner syndrome, with unilateral ptosis, miosis, and anhidrosis, may occur with cervical or high thoracic involvement. Tumors of the paraspinal ganglia may grow around and through the intervertebral foramina, causing spinal cord or nerve root compression. Metastatic disease may be present at diagnosis in up to half of the cases, most often in bone, bone marrow, liver, or skin. Lung or brain involvement is rare and usually represents end-stage or relapsing disease. Retrobulbar involvement can cause proptosis or periorbital ecchymosis. Bone pain and limping may be related to bone and bone marrow disease. Massive hepatomegaly due to liver involvement, more common in infants, can cause respiratory compromise or liver failure. Skin manifestations appear as bluish, nontender, subcutaneous nodules. Opsoclonus–myoclonus is a paraneoplastic syndrome characterized by myoclonic jerking and random eye movements seen in a small percentage of neuroblastoma patients at diagnosis. A CBC may reveal cytopenias due to marrow involvement. Abdominal ultrasound or CT scan may reveal a suprarenal mass, often with calcifications (Fig. 108-3). Lytic lesions and periosteal reaction may be seen on radiographs of painful areas of bone. The catecholamine metabolites homovanillic acid and vanillylmandelic acid are elevated and detectable in the urine in greater than 90% of patients. Treatment and prognosis of neuroblastoma is dependent on stage and histology, but usually consists of a combination of surgery and chemotherapy +/– radiation therapy.
FIGURE 108-3.
CT scan of a 2-year-old boy who presented with 2 weeks of bruising, pallor, and abdominal distension. Compared to the Wilms tumor shown in Figure 108-2, this mass is not encapsulated, and displaces normal structures (note the position of the abdominal aorta). Biopsy confirmed the diagnosis of neuroblastoma.
Common musculoskeletal tumors in children include osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma.9 Rhabdomyosarcoma is a malignant solid tumor from mesenchymal tissue that normally forms striated muscle, and may arise anywhere. Osteosarcoma is the most common primary malignancy of bone, with a predilection for the metaphysis of long bones, particularly the distal femur and proximal tibia. Ewing sarcoma occurs equally between long bones and flat bones; it may also present as a soft tissue mass without bone involvement. Rhabdomyosarcoma most often presents as a painless mass, and signs and symptoms are location dependent. Genitourinary tract involvement may manifest with hematuria or urinary obstruction. Vaginal tumors may present with hemorrhagic discharge and may mimic a foreign body. The most common presenting symptom of osteosarcoma and Ewing sarcoma is pain in a bone or joint, often after an injury. Other presentations include a palpable mass or pathologic fracture. Initial imaging of a soft tissue mass suspected to be rhabdomyosarcoma is dependent on location. Plain radiographs should be the first step in the initial evaluation of a suspected bone tumor. In osteosarcoma, the tumor may extend through the periosteum, causing new malignant bone deposition resulting in the characteristic radiographic “sunburst” pattern. Ewing sarcoma may cause a multilaminar periosteal reaction resulting in an “onionskin” appearance on plain film. Each of these tumors may metastasize to the lung, and in the case of rhabdomyosarcoma and Ewing sarcoma, to the bone marrow. Treatment of sarcoma consists of chemotherapy and local control with surgery and/or radiation therapy.
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