A 7-month-old girl presents to her pediatrician’s office with a 1-week history of fevers and upper respiratory symptoms.
The infant had no past medical history and her immunizations were up-to-date. She had some decreased appetite and occasional fussiness, but was otherwise acting appropriately for her age. She had normal urine output. Because of the 1-week history of fevers and rhinorrhea, the pediatrician obtained laboratory studies revealing normocytic anemia and thrombocytosis. The infant was then referred to the emergency department (ED) for further evaluation.
On initial presentation, the patient was febrile to 102.56°F; heart rate was 185 beats per minute; respiratory rate of 36 breaths per minute; blood pressure of 97/49 mm Hg; and oxygen saturation of 99% on room air. Physical exam revealed an active 7-month-old girl in no acute distress but found to be pale and nonjaundiced. She had a regular cardiac rate and rhythm without a murmur. Lungs were clear to auscultation bilaterally without increased work of breathing, wheezing, or crackles. Abdomen was soft, nontender, nondistended with active bowel sounds, and with no hepatosplenomegaly or palpable masses. Her remaining physical exam was normal and appropriate for age.
Labs and hospital course
Initial laboratory results demonstrated a white blood cell count (WBC) of 9.1 K/mcL; absolute neutrophil count (ANC) of 0.3 K/mcL; hemoglobin of 7.8 gm/dL with mean corpuscular volume (MCV) of 79.9 fL; hematocrit, 24.3%; and platelets, 633 K/mcL. Comprehensive metabolic panel was normal, specifically aspartate aminotransferase (AST), 23 unit/L; alanine aminotransferase (ALT), 17 unit/L; alkaline phosphatase, 142 unit/L; and total bilirubin, 0.2 mg/dL.
Inflammatory markers were elevated with C-reactive protein (CRP) of 26.8 mg/dL and erythrocyte sedimentation rate (ESR) greater than 120 mm/h. Iron studies were: iron, 9 mcg/dL; total iron binding capacity (TIBC), 114 mcg/dL; iron saturation, 8%; and ferritin, 434 ng/mL, not exclusively consistent with iron-deficiency anemia. A blood culture and nasopharyngeal respiratory pathogen panel was obtained.
The patient was admitted to the general pediatric unit for febrile neutropenia and was started on cefepime for empiric bacterial antibiotic coverage. Due to potential malignancy, the patient had an abdominal ultrasound that showed a 6.4-cm hepatic mass, confirmed with an abdominal computed tomography (CT) scan (Figure 1).
The patient’s main abnormal vital sign/physical exam finding was fever. She had several initial laboratory abnormalities including severe neutropenia, normocytic anemia, thrombocytosis, and elevated inflammatory markers. Also, she was found to have a nonspecific hepatic mass on imaging, although nonpalpable on physical exam.
This patient’s presentation was concerning for sepsis and malignancy, and thorough evaluation was needed. Such patients require consultation with pediatric subspecialists at the time of presentation, which may require transferring the patient to a tertiary care center. This infant was admitted to a tertiary children’s hospital where subspecialty consultation was readily available. In a patient with fever and neutropenia, prompt initiation of antibiotic therapy for potential sepsis is important, and this empiric coverage should continue until an infectious bacterial process has been ruled out.
For any child who presents with a liver mass, benign or malignant tumors are highly suspected, with malignant tumors being most concerning and requiring prompt evaluation. Hemangioma and hamartoma are the most common liver masses in infants aged younger than 1 year. These lesions often are visualized on abdominal ultrasound, CT, or magnetic resonance imaging (MRI). Hepatoblastoma and hepatocellular carcinoma also are on the differential, which requires a confirmatory biopsy when the patient is clinically stable. Additional imaging may be warranted if there is concern for metastatic disease.
Given the patient's fever, an infectious etiology was suspected, such as abscesses or viral hepatitis, and required further laboratory studies. Although uncommon, Entamoeba histolytica should be considered because of its propensity to form liver abscesses, especially with a history of international travel.
Further evaluation and diagnosis
Febrile neutropenia can be caused by viral suppression of bone marrow function. However, given the additional abnormal findings in this patient (ie, elevated inflammatory markers and hepatic mass), timely involvement of pediatric subspecialists and further workup were needed. The Hematology/Oncology team was consulted for febrile neutropenia, anemia, and thrombocytosis with concerns for a possible oncologic etiology, and the Infectious Disease team for possible infectious process as the cause of her signs and symptoms.
The patient continued to be febrile while on cefepime. Her blood culture was negative. She was found to have enterovirus/rhinovirus on her respiratory viral polymerase chain reaction (PCR) panel, likely the source of her fever. Her remaining infectious disease workup was negative, specifically for hepatitis, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Entamoeba histolytica. Sepsis was ruled out given that her blood culture was negative. The child remained well appearing throughout her hospitalization and had a negative infectious disease workup.
She underwent a bone marrow biopsy that was negative for malignancy. A fine needle biopsy of the hepatic lesion was performed initially, but this was not diagnostic. Subsequently, she had an open liver biopsy, which demonstrated a right-lobe hepatic mass with pathology showing abundant mixed lymphoplasmacytic infiltrate and positive immunoglobulin (Ig) G4 plasma cells, consistent with inflammatory pseudotumor (Figure 2).
Additional laboratory studies including normal alpha-fetoprotein and beta-hCG levels were negative, but showed positive granulocyte antibodies. Genetic congenital neutropenia panel was also negative. All immunoglobulin levels (IgG, IgM, and IgA) were elevated.
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