Pediatric Malignancies Masquerading as Infections
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Chief Academic Officer, Baystate Health Professor of Pediatrics and Dean of the Western Campus of Tufts University School of Medicine, Springfield MA, is Associate Editor for Infectious Disease Alert.
Synopsis: Review of initial infectious disease consultations for children with malignancy showed that prolonged fatigue, bone pain, hepatomegaly, splenomegaly, hematologic abnormalities, or elevated LDH may be the revealing sign of pediatric malignancy.
Source: Forgie SE, Robinson, JL. Pediatric malignancies presenting as a possible infectious disease. BMC Infectious Diseases 2007;7:44 (available at www.biomedcentral.com/1471-2334/7/44).
Among 561 patients diagnosed with malignancy from 1993-2003 in the Northern Alberta Children's Cancer Program, infectious diseases consultation was initially requested for 21 children (<15 years of age) a median of 7 days (range, 0-32 days) prior to definitive diagnosis. The reasons for consultation included suspected musculoskeletal infection (9), fever (4), possible respiratory tract infection (2), possible soft tissue infection (2), splenomegaly and lymphadenopathy (1), leukocytosis (2), and possible neurocysticercosis (1). The patients reported symptoms of fever (15), weight loss of up to 10 kg (7), bone pain (6), fatigue from 1-70 days duration (6), and headache (6). Findings on physical examination included hepatomegaly (4), palpable splenomegaly (8), and a wide variety of rashes (7). Imaging studies revealed hepatomegaly in 2 additional patients and splenomegaly in 3 additional patients. All but 2 patients had an abnormal hemoglobin, white blood cell count, and/or platelet count. Malignancy was considered as probable in the differential diagnosis by both the referring physician and the consultant in 9 cases, and by either the referring physician or the consultant in 9 cases. Malignancy was not considered by either in 1 case of leukemia that was initially diagnosed as suppurative arthritis, and the 2 cases of possible soft tissue infection, which were a fibrous histiocytoma and a rhabdomyosarcoma. Three patients had both infection and malignancy on initial presentation. The types of malignancy included leukemia (13), lymphoma (3), rhabdomyosarcoma (1), Langerhans cell histiocytosis (1), fibrous histiocytosis (1), ependymoma (1), and neuroblastoma (1). Only 2 patients (10%) had a normal hematologic finding on complete blood count, and 10 patients (48%) had elevated lactate dehydrogenase (LDH). Delay in diagnosis that was directly attributable to investigation or therapy for infection occurred in only 2 patients: one patient was treated for suppurative arthritis for 11 days with leukopenia attributed to antibiotics, and one patient was diagnosed with discitis with an MRI scheduled as an outpatient 8 days later. Both patients had abnormalities on complete blood counts.
Malignancy, infection, and collagen vascular diseases are the most common causes of fever of unknown origin among children and are the primary diagnostic considerations for children with ambiguous presentations such as constitutional symptoms and non-specific findings. This study confirms that delayed treatment for pediatric malignancies because of misdiagnosis of an infectious disease is rare.
There are several clinical caveats from this report. Bone pain, which was present in about one-third of these children, is common in leukemia and malignancy, which should be considered along with infection for all children with vague musculoskeletal symptoms. Abdominal imaging for hepatomegaly and splenomegaly was an important diagnostic tool, and when positive with an uncertain diagnosis suggests malignancy. Abnormal results of the complete blood count were present in 90% of patients, and physicians should be cautious in attributing these abnormalities to non-malignant processes. An elevated LDH, indicative of rapid cell turnover in malignancy and cell damage in other processes, was present in about half of patients. In summary, prolonged fatigue, bone pain, hepatomegaly, splenomegaly, hematologic abnormalities, or elevated LDH, even when only one of these is present, suggest malignancy even when the consultation is requested because of a possible infectious disease.