lead to life-threatening airway compromise and/or superior vena cava (SVC)
syndrome. The approach to the presentation and management of AMM is discussed
in more detail in the section on thoracic tumors (see “Tumors of the Thorax”
section). Chloroma, a mass of leukemic blasts in the soft tissue, can occur in any
body part and is much more common with AML compared to ALL. When this mass
develops and rapidly expands near the spinal cord, compression of the cord can
result (see “Tumors in and Around the Spinal Cord” section). Leukemic
involvement in the spinal fluid can cause meningeal symptoms, cranial nerve palsy,
headache, seizure, increased intracranial pressure (ICP), or visual disturbances (from
retinal infiltrates). Boys can present with testicular enlargement. There may also be
skin lesions due to leukemia cutis (more common in monocytic leukemias and infant
leukemia) and gingival hypertrophy (with AML) due to leukemic infiltration.
It is not uncommon for patients with leukemia to be febrile at presentation.
Although the fever may be an inflammatory reaction driven by the leukemia itself,
serious infection must be explored. It is essential to determine if the febrile patient is
neutropenic. If the absolute neutrophil count (ANC) is less than 500/μL, broadspectrum antibiotics covering gram-positive and gram-negative bacteria (including
pseudomonas) should be administered in the ED. If localizing signs of a bacterial
infection are evident, or if high fevers are present (>39°C), empiric therapy should
be initiated even if the patient is not neutropenic. Management is summarized in
Table 98.3 . Patients may present with sepsis at the time of diagnosis or relapse. The
increased risk of sepsis may be because of neutropenia and/or immune dysfunction
caused by the underlying malignancy. Management of sepsis in the setting of
leukemia is not unique and the principles are similar to those described more
thoroughly in the Children’s Hospital of Philadelphia Severe Sepsis Clinical
Pathway 1 and Chapter 94 Infectious Disease Emergencies .
Pain. For some patients, limp or a refusal to walk or bear weight is one of the first
signs of leukemia. In fact, it is not uncommon for a patient to be treated for
diagnoses such as osteomyelitis or septic hip before the diagnosis of leukemia is
uncovered. It is essential for the emergency clinician to ensure that a refusal to walk
is not because of cord compression from chloroma as discussed above. Bone pain is
usually due to replacement of the bone marrow with rapidly proliferating leukemic

cells causing strain on the marrow spaces. Pathologic fractures may develop as the
expanding marrow compartments put strain on and weaken the bony cortex.

HISTIOCYTIC DISEASES
Goal of Treatment


Timely recognition of histiocytic diseases can be lifesaving. The most common
histiocytic disease, Langerhans cell histiocytosis (LCH), rarely requires emergency
care, whereas hemophagocytic lymphohistiocytosis (HLH) is a life-threatening
illness that can be rapidly fatal without appropriate intervention.
CLINICAL PEARL AND PITFALLS
Consider HLH in the acutely ill infant or young child as these patients can
deteriorate quickly and require urgent oncologic consultation and critical
care support.

Current Evidence
Histiocytic diseases are a complex and sometimes confusing group of disorders for
two reasons. First, several different disease entities make up this group, although
efforts have been made to simplify the terminology. Second, significant clinical
heterogeneity exists between the major disease entities. Histiocyte is a term referring
to several different cells that are thought to derive from a common CD34+
progenitor in the bone marrow. Depending on the cytokines to which the progenitors
become exposed, the differentiation can yield tissue macrophages, dermal/interstitial
dendritic cells, or Langerhans cells. In general, histiocytic diseases are rare; of the
group, the most common is LCH, which has an incidence of three to five cases per
million children.

Clinical Considerations
Clinical Recognition

LCH has clinical heterogeneity and the locations involved have implications for
therapy and prognosis. Low-risk LCH may present at any age and systemic
symptoms are rare. Skin, bone, lymph nodes, or a combination of these are most
commonly involved. Skin involvement can present as a red papular rash, resembling
a candidal diaper rash, which may appear on the groin, abdomen, back, or chest.
There may also be seborrheic flaking of the scalp, often misdiagnosed as “cradle
cap” in infants, draining otitis externa, or ulcerative lesions behind the ears, on the
scalp, or in the genital region. Bony involvement may be asymptomatic or painful.
A lytic lesion of the skull causing a tender mass is the most common but any bone
may be involved. Loose teeth from involvement of the jaw may occur. Certain sites
of disease have become known as “risk” organs because their involvement implies
more aggressive disease. These patients are often very young with disease that
involves the lung, liver, spleen, and/or bone marrow. Lung involvement is rare but
worrisome and usually manifests first as hypoxia. Liver and spleen involvement is


usually accompanied by enlargement of those organs, although hepatic dysfunction
may also be present. Bone marrow involvement is rare, but usually presents with
cytopenias, which should prompt a bone marrow aspirate and biopsy. Diabetes
insipidus (DI) due to involvement of the posterior pituitary is the most frequent
endocrine abnormality in LCH; some patients may present with an apparent
“idiopathic” presentation of DI before other lesions are identified. A few patients
may present with diarrhea or malabsorption as colitis related to LCH has been
described.
HLH is a very rare but severe and life-threatening systemic disease with rapid
progression from presentation to death without appropriate intervention. Thus,
consideration of this diagnosis in the ED can be critical to outcome. For these
reasons, it is essential for the emergency clinician to have some familiarity with this
disorder. Congenital HLH usually presents in infants and very young children. Other
forms of HLH develop secondary to Epstein–Barr virus (EBV) infection,

malignancy, or severe rheumatologic disorders or without a specific trigger.
Regardless of etiology, HLH presents with fever, hepatosplenomegaly, adenopathy,
and rash.
Clinical Assessment
All patients with suspected histiocytic disorders need a thorough history and
physical examination as well as a rapid assessment of severity of illness. Patients
with HLH may have significant systemic illness with organ dysfunction and vital
sign instability and will often require management in a critical care setting. At the
other extreme, patients with suspected localized LCH may require little to no
intervention in the ED but need only close oncologic follow-up.
Pulse oximetry should be checked to screen for hypoxia and a chest x-ray
obtained if hypoxia is detected. Laboratory evaluation should include CBC, liver
function testing, electrolytes to screen for DI, and inflammatory markers such as
erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In HLH,
laboratory analysis may reveal a markedly high serum ferritin as well as
transaminitis, hypertriglyceridemia, hypofibrinogenemia, and cytopenias. Bone
marrow evaluation may show characteristic hemophagocytosis. Oncologic
consultation can guide the evaluation and management of systemically ill patients,
as in the case of HLH, or allow for careful follow-up of more stable patients with
suspected LCH.

TUMORS OF THE CENTRAL NERVOUS SYSTEM
Goals of Treatment


CNS tumors span a wide range of clinical presentations. The most critical goal is the
timely identification and management of cord compression and increased ICP. The
goal of early identification of CNS tumors needs to be balanced against exposure to
ionizing radiation from CT given that many children present with nonspecific
symptoms including headache and/or vomiting. Careful recognition of atypical

features and/or concerning associated signs or symptoms can assist in decision
making regarding advanced imaging.
CLINICAL PEARL AND PITFALLS
Clinical clues for increased ICP may include a bulging fontanel in infants,
or headache with early morning vomiting in older children.
Measurement of sodium levels is particularly important in patients with
CNS tumors.

Current Evidence
Brain tumors represent the most common solid tumor in the pediatric population and
the second most frequent pediatric cancer overall. There are approximately 2,000
new malignant brain tumors diagnosed annually in children. These tumors can affect
children and adolescents of any age group, but the peak incidence is in children 5 to
10 years old. Supratentorial tumors are more common in children younger than 1
year and older than 10 years. Infratentorial lesions are more common between ages
of 1 and 10 years. Unlike in adults, brain tumors in children are usually primary, not
metastatic. Since tumor location usually drives the presenting signs and symptoms,
this is the most useful categorization in the ED ( Table 98.4 ).

Clinical Considerations
Clinical Recognition
Some of the symptoms of brain tumors in children are nonspecific, and
nonlocalizing complaints occur with a variety of tumor types. Examples include
headache, altered behavior, vision changes, altered growth or weight, somnolence,
and altered school performance. The diagnosis of brain tumor may be delayed in
such patients. Once patients develop signs and symptoms more easily referred to the
CNS, their presentations tend to hinge on the tumor location ( Table 98.4 ).
Infratentorial tumors may present with cranial nerve deficits, such as facial nerve
palsies, dysphagia, or paresis of cranial nerve VI, causing diplopia or strabismus.
Ependymomas of the fourth ventricle may present with hydrocephalus and increased

ICP. Cerebellar lesions can cause truncal ataxia and a reeling gait when located on
the midline. When only one cerebellar hemisphere is involved, patients may display