Acute Myelogenous Leukemia
A 6-month-old boy presented with a history of 4 days of fever and emesis and maximum-recorded temperature of 40°C. Vital signs at presentation indicated a temperature of 38.2°C with tachycardia and hypertension, and physical examination results revealed a pale, lethargic infant with diaper rash predominantly around the anus. Visualization of the anus showed laxity of the sphincter, surrounding erythema, and purulent discharge from rectal fissures at anterior and posterior aspects of the anus (Figure 1). The differential at this time included traumatic injury, anal abscess, and pyoderma gangrenosum. Laboratory tests were conducted, and the complete blood count revealed pancytopenia. White blood cell count was 3600/µL (reference range for age 6 months, 6000-17,500/µL), hemoglobin was 7.6 g/dL (reference range 9.5-13.5 g/dL), and platelets were 10 × 103/µL (reference range 150-250 × 103/µL). Cefipime was begun for neutropenic fever and clinical diagnosis of sepsis.
On day 2, bone marrow aspirate and biopsy were performed for histology, flow cytometry, and cytogenetics. The Wright-Giemsa stain demonstrated atypical bone marrow with interstitial fibrosis (Figure 2). Bone marrow biopsy and aspirate revealed normocellular marrow with atypical fibrosis in a fibrohistiocytic background. Flow cytometry results were unremarkable, and cytogenetics were positive for 9:11q23 translocation, consistent with acute myelogenous leukemia (AML). The boy was diagnosed as having acute myeloid leukemia with leukemia cutis of the anus. Parenteral antibiotic therapy with meropenem, vancomycin, and gentamycin was begun for worsening of the anal lesion and continued fever. Granulocyte-colony stimulating factor 5 µg/kg was given intravenously daily until neutrophil counts recovered to greater than 3000.
On hospital day 7, a central venous line was placed under general anesthesia, and the results of a rectal examination revealed a worsening rectal lesion with prolapse, absent sphincter tone, and deep anal and rectal fissures at 12 and 6 o’clock position with signs of granulation. On day 14, after resolution of neutropenia, a single intrathecal injection of 20 mg of cytarabine and a topical nitrogen mustard (mechlorethamine) gel (0.016%) was administered for 5 days with significant resolution of the rectal lesion.1 On day 21, systemic low-dose intravenous cytarabine at 75 mg/m2 for 4 days was begun as preinduction. On day 31, induction chemotherapy was initiated per protocol Japan Acute Non-Lymphocytic Leukemia-91.2 To date, the patient has successfully completed preinduction and 4 courses of chemotherapy; he remains in remission as assessed by cytogenetics and flow cytometry on follow-up bone marrow examinations.
Diverse cutaneous presentations of AML can make determination of the etiology challenging and may be responsible for misclassifications.3 Although the most commonly encountered childhood cancer is AML, less than 5% of AML cases are diagnosed in the first year of life.4 AML often presents with lethargy, difficulty feeding, or fever, and may have cutaneous changes.
Leukemia cutis is a broad term used to describe cutaneous infiltrations of lymphoid or myeloid leukemia cells, and it can occur concomitantly with systemic leukemia or often herald acute leukemia.5 Leukemia cutis is frequently associated with a high tumor burden and indicates a worse prognosis. Suspicious lesions should be followed by hematologic studies and bone marrow biopsy. Skin biopsy may be required to diagnose leukemia cutis; however, concerns exist when obtaining tissue in areas harboring gram negative rods, as this may cause an ensuing sepsis.6
Close clinical monitoring may be warranted as spontaneous regression occurs, or as patients develop hematologic disease months and even years later.5 Cytogenetic studies are an important tool because 11q23 rearrangement is aggressive and may need more intensive treatment.7
Infant AML with leukemia cutis is currently controversial in terminology, diagnosis, and management of the condition. No consensus currently exists, and treatment of the condition can include observation, systemic chemotherapy, or allogenic stem cell transplant.
For the general pediatrician, it is important to remember that infantile leukemia cutis presentation is variable and that physicians should maintain a high index of suspicion of cutaneous lesions in infants.
Katie Dowd; Sana Mohiuddin, MD; Janet Meller, MD; Vijay Tonk, PhD; and Curtis W. Turner, MD, are with the Department of Pediatrics as Texas Tech University Health Sciences Center School of Medicine in Amarillo, Texas.
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