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Imaging Studies in Early Diagnosis of Childhood Leukemia

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Imaging Studies in Early Diagnosis of Childhood Leukemia Dra. Viviana Riquelme S y col. Revista Chilena de Radiología. Vol. 18 Nº 1, año 2012; 24-29. Imaging studies in early diagnosis of childhood leukemia Drs. Viviana Riquelme S(1), Cristián García B(2). 1. Physician, School of Medicine Graduate, Pontificia Universidad Católica, Santiago, Chile. 2. Departments of Radiology and Pediatrics. School of Medicine, Pontificia Universidad Católica, Santiago, Chile. Imaging studies in early diagnosis of childhood leukemia Abstract: Leukemia is the most commonly encountered cancer in children under the age of 15 and accounts for approximately 35-40% of all cancers at that age. Acute lymphoblastic leukemia (ALL) is the most com- mon type of leukemia affecting young children between the ages of 2 and 5 years; it accounts for around 80 % of all childhood leukemia cases. Initial clinical and laboratory findings may be non-specific. Imaging studies in patients with bone pain and extramedullary involvement may provide the clinician with valuable supplementary information when the first symptoms result from tissue infiltration and haematological series show a discrete and asymptomatic involvement. The purpose of this work is to review the initial radiological manifestations of leukemia in children. Given the systemic nature of this disease, the goal is to identify the key elements found in the study of the different affected organs, in order to facilitate an early diagnosis of this condition. Late-stage alterations or treatment complications, such as osteonecrosis, infections by opportunistic pathogens, graft-versus-host disease, etc. –where magnetic resonance imaging (MRI) and computed tomography (CT) play a fundamental role– will not be reviewed. Keywords: Child, Imaging, Leukemia, Pediatrics. Resumen: La leucemia es el cáncer más frecuente en niños menores de 15 años y corresponde aproxi- madamente al 35-40% de todos los cánceres a esa edad. Se presenta con mayor frecuencia entre los 2 y 5 años de edad y la forma más frecuente es la leucemia linfoblástica aguda, que corresponde al 80% de los casos. Las manifestaciones clínicas y de laboratorio pueden ser inicialmente inespecíficas. El estudio imagenológico en pacientes con dolor óseo y compromiso extramedular, puede entregar valiosa información complementaria al clínico cuando los primeros síntomas derivan de la infiltración de los teji- dos y el compromiso de las series hematológicas es discreto y asintomático. El propósito de este trabajo es revisar las manifestaciones radiológicas iniciales de la leucemia en el niño. Considerando que es una enfermedad sistémica, el objetivo es identificar los elementos claves en el estudio de los distintos órganos comprometidos, que permitan al radiólogo sospechar el diagnóstico en la etapa precoz de la enfermedad. No se revisarán las alteraciones de la fase tardía o de complicaciones del tratamiento, como osteonecro- sis, infecciones por gérmenes oportunistas, enfermedad de injerto vs. huésped, etc., donde la resonancia magnética (RM) y la tomografía computada (TC) juegan un rol fundamental. Palabras clave: Imágenes, Niño, Leucemia, Pediatría. Riquelme V y cols. Estudios de imágenes en el diagnóstico precoz de leucemia en pediatría. Rev Chil Radiol 2012; 18(1): 24-29. Corresponding. Dr. Cristián García B. / [email protected] Manuscript received November 24th, 2011; accepted for publication March 19th, 2012. Introduction Since the beginning of the Program Cancer in The expected incidence of cancer in children the Child in 1988, an average of 100-110 new cases under 15 years is 110-150/1.000.000 children a year, of lymphoblastic leukemia and 30 cases of myeloid being slightly more common in men(1). Leukemia is the leukemia per year have been reported in the public most commonly encountered cancer and accounts for health sector(1). around 35-40% of all cancers at that age(1). The signs and symptoms that suggest leukemia are U.S. statistics establish an incidence rate of one varied and recommendations for diagnostic suspicion case of leukemia every 7,000 children per year(2). are clearly detailed in the Clinical Guide: Leukemia in In Chile, the preliminary report of the National Re- Children Under 15 years, Chilean Ministry of Health(1). gistry of Childhood Cancer Population (RENCI) revealed In general, diagnosis should be suspected in any in 2007 an incidence of leukemias of 42.7/1.000.000(1). child with anemia not associated with bleeding, fever 24 Revista Chilena de Radiología. Vol. 18 Nº 1, año 2012; 24-29. IMÁGENES PEDIÁTRICAS associated or not with pallor, visceromegaly and CBC The purpose of this paper is to review the initial with anemia and/ or neutropenia (sometimes leuko- radiological manifestations of leukemia in children. cytosis), bone pain not associated with trauma, with Whereas it is a systemic disease, the goal is to identify CBC with cytopenia. the key elements in the study of the various organs Leukemia should be included in the differential involved, thus allowing the radiologist to suspect diagnosis in the presence of combination of the fo- diagnosis in the early stages of the disease. llowing signs and symptoms: Fever of unknown origin; Late-stage alterations or treatment complications, bone pain not associated with trauma; spontaneous such as osteonecrosis, infections by opportunistic bruising or associated with minor trauma; nasal or pathogens, graft-vs host disease, etc., where magnetic gingival bleeding; recurrent infections; lymphadeno- resonance imaging (MRI) and computed tomography pathy (persisting for more than 4 weeks; lymph nodes (CT) play a fundamental role will not be reviewed. larger than 3 cm; generalized palpable lymph nodes), and splenomegaly(1-4). Leukemia. Bone and extramedullary manifestations There are genetic as well as environmental fac- Due to extramedullary tissue infiltration, viscero- tors associated with its pathogenesis. Clearly, there megaly (hepatomegaly, splenomegaly, nephromegaly, is an increased risk associated with genopathies enlargement of the pancreas), polyadenopathies, such as Klinefelter syndrome and Down syndrome, central nervous, renal and testicular system involve- the latter posing a relative risk 15 times higher than ment may be observed(1,3,4), the latter being the least that faced by the general population (2.3). Exposu- common pathology. Its frequency varies depending re to chemicals, such as benzene, pesticides and on the type of leukemia. ionizing radiation are modifiable factors involved in Imaging findings on those most frequently affected its etiology(2). organs, will be reviewed. Acute lymphoblastic leukemia (ALL) is defined by the presence of more than 20% lymphoblasts in Liver, spleen, kidneys bone marrow(2,3) and represents the most common An estimated 60-70% of patients with ALL present type of leukemia in childhood, accounting for 80% with hepatosplenomegaly(3), while AML occurs in no of cases(3,4) It predominates in men and occurs most more than half of the cases(5). It is often a finding on often between the ages of 2 and 5 years(3.4). physical examination and rarely causes functional Acute myeloid leukemia (AML) represents 17% of impairment(1). Bilateral nephromegaly is also a com- leukemias(2). Its occurrence is similar in both sexes mon finding, though less frequent. with no predominance for any given age range(4). Ultrasonography (US) studies allow depiction of Initial clinical manifestations are usually nonspecific increased size of these organs, which may be asso- and the most common clinical presentation includes: ciated with decreased liver and splenic parenchymal pallor, fatigue, bleedings, fever and recurrent infections echogenicity and increased echogenicity of the renal as a result of an existing spinal cord dysfunction(2,4). The parenchyma, conditions that can be reversed with CBC may reveal anemia, thrombocytopenia and / or treatment(6.7) (Figure 1). Along with nephromegaly, neutropenia with normal, decreased or increased WBC CT scans reveal multiple low- attenuation areas in the count(3,4). In 95% of cases, ALL manifests itself with renal parenchyma, usually presenting bilaterally(7,8) some cytopenia in the CBC, whilst anemia is present in (Figure 2). 99% of cases. The WBC is normal in 50% of children(3), being anemia the alarm symptom in these cases. In AML, 44% of patients present with anemia at diagnosis, while 69% has neutropenia and 25% exhibits leukocytosis with CBC count over 100.000/microliter(3); complications such as cerebral, lung and liver infarction as a result of leukocytosis may be present(1,3). Although definitive diagnosis is achieved by studying the bone marrow, the imaging study, mainly in patients with bone pain and extramedullary involvement, may provide the clinician with valuable complementary in- formation when the first symptoms derive from tissue infiltration and involvement of haematological series appears discrete and asymptomatic. The chance of cure depends on the type of leu- Figure 1. Six-month infant with ALL. Abdominal ultrasound kemia, the presence of associated adverse factors revealed bilateral nephromegaly. On a sagittal section of the and the response to treatment, being about 73% for right flank, enlarged kidney on that side (sagittal diameter of lymphoblastic leukemia and 50% for myeloid leukemia(1). 9.0 cm) and slightly increased echogenicity are observed. 25 Dra. Viviana Riquelme S y col. Revista Chilena de Radiología. Vol. 18 Nº 1, año 2012; 24-29. 2a nodes are usually hypoechoic and nodal hilum may be absent or eccentrically placed due to tumor invasion(10,11). On color Doppler studies it usually shows hilar vascular flow within it. Though none of the aforementioned signs is pathognomonic of leukemia, their presence in the appropriate clinical context increases the index of suspicion(11). Bone involvement Bone pain is the most commonly encountered symptom secondary to proliferation of neoplastic cells in the bone marrow(7,12,13). An estimated 30% of patients with ALL present with bone pain(4) and sometimes this may be the only alarm symptom in the presence of a CBC without 2b leukocytosis, which may occur in 1% of cases(3). It may affect any part of the skeleton, being the pelvis, vertebrae and long bones of lower extremities the most commonly affected sites(3).
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