P2A295: Atypical Presentation of Juvenile Myelomonocytic leukemia in a Pediatric Patient

Introduction: Juvenile Myelomonocytic Leukemia (JMML) is an extremely rare disorder in pediatric patients. Patients classically present with fever, cough, infections, pallor, hepatosplenomegaly, lymphadenopathy, and rash. Diagnosis is achieved by typical clinical picture and hematological findings.

Case Description: 1 y/o female with non-significant past history presents with 1.5 months of intermittent hesitance to sustain weight on the left leg after trauma and limping associated with fever and irritability for 48 hours. Patient with history of rash in back and red conjunctiva 1 week prior to ER arrival. Patient admitted with suspected left ankle septic arthritis, fever, leukocytosis and increased inflammatory markers with edema, erythema, and warmth of left ankle. Arthrocentesis performed and Clindamycin started. Despite antibiotic therapy and negative synovial fluid culture, high fever persisted and 48 hours later developed edema and pain of the left elbow. Working diagnosis was Atypical Kawasaki due to prolonged fever, increased CRP and ESR, leukocytosis, thrombocytosis, rash, and conjunctival injection, swelling and redness of the left ankle and bilateral elbows. Echocardiogram was suggestive of coronary artery dilation. Blood cultures, U/A, CXR, and abdominal ultrasound were negative. Patient had irritability and severe joint pain. Received one dose of IVIG with decreased leukocytosis and inflammatory markers, symptoms resolution and discharged home on Aspirin. Febrile episodes and polyarthralgia recurred 48 hours after discharge. She had leukocytosis, increased inflammatory markers, admitted to PICU with suspected Macrophage Activation Syndrome (MAS) vs. severe infection vs. malignancy vs. JIA. Second dose of IVIG and Solumedrol pulse administered without resolution of fever or leukocytosis. Bone marrow biopsy revealed JMML. Upon diagnosis, patient found with hepatomegaly and splenomegaly, pain, irritability, fever, night sweats with leukocytosis, and mild thrombocytopenia. Patient started on Hydroxyurea, Mercaptopurine, and Azacytidine. By day #3 of treatment, patient was clinically stable with resolved fever, no pain, and improved irritability.

Discussion: JMML is characterized by abnormal production of myeloid progenitors and monocytes, deregulation of intracellular RAS signal transduction pathway, aggressive clinical course, and poor outcomes. Clinical presentation includes splenomegaly (prerequisite for diagnosis), hepatomegaly, lymphadenopathy; interstitial infiltrates on CXR; abdominal symptoms, and cutaneous signs. Peripheral blood smear findings: anemia with presence of nucleated red blood cells, leukocytosis, monocytosis, immature granulocytes shift, and thrombocytopenia. Bone marrow findings: myeloid predominance and hypercellularity from myelomonocytic proliferation, reduction of megakaryocytes, and moderate increase of blasts ( < 20%). Due to similarities in clinical presentation to other diseases, a diagnostic approach is crucial. Allogeneic hematopoietic stem cell transplantation is curative treatment.

Conclusion: JMML can present without typical signs and symptoms. The atypical presentation of this disorder, with the diversity of symptoms, can delay diagnosis and early treatment. This case demonstrates that a high index of suspicion is of foremost importance to reach a diagnosis and provide treatment.