Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and therefore be candidates for experimental therapies. In addition, there have been few other molecular pathways identified aside from the Ras/MAPK pathway to serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia in order to expand our knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, gene splicing, the polycomb repressive complex 2 (PRC2) and transcription. Importantly, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.
Cutaneous Ewing sarcoma is a rare variant that has been poorly characterized and has no standard therapy. We report 2 patients with cutaneous Ewing sarcoma and review 76 other cases reported in the literature for demographics, presentation, treatment, and outcome. Only 2 patients presented with metastatic disease, and only 8 patients developed metastatic disease. Ninety-one percent of all patients are alive despite wide variations in treatment regimens. On the basis of this summary, treatment consisting of local control with surgery and/or radiation and abbreviated chemotherapy is proposed as a treatment option for this less aggressive Ewing sarcoma.
A 3-year-old girl with acute lymphocytic leukemia (ALL) in remission developed lower extremity paraparesis and areflexia 15 days after receiving intrathecal methotrexate, cytarabine, and hydrocortisone. Cerebrospinal fluid protein was 107 mg/dl. Compound muscle action potential amplitudes were reduced, F waves were absent, and sensory conduction studies were normal. Needle electromyography (EMG) revealed reduced motor unit potential recruitment. Magnetic resonance imaging (MRI) showed lumbosacral ventral root enhancement. She was treated with intravenous immunoglobulin and slowly recovered. Nerve conduction and EMG abnormalities correlated with MRI root enhancement, facilitated early diagnosis, and distinguished this from a myelopathy or distal polyneuropathy. These findings could represent selective ventral nerve root vulnerability to intrathecal chemotherapy. A selective autoimmune process cannot be excluded.
Within the pediatric age group, chylothorax is rare and has been reported almost exclusively in the setting of thoracic surgical procedures or central venous hypertension secondary to central venous catheter thrombosis. We report on the development of central venous thrombosis and chylothorax in the absence of the usual risk factors in a patient with septic shock, and we expand on the role that procoagulant states, such as those induced by sepsis, might play in the development of this complication. This case reminds the practitioner that central venous thromboses and their complications may occur in the absence of the usually reported risk factors and must therefore still be considered when other clinical events suggest their presence.
We present the case of an 11.5-year-old girl with M1 acute myelogenous leukemia (AML) who had isolated extramedullary relapse develop in both breasts 12 months after diagnosis and 7 months off chemotherapy. She received further chemotherapy, focal radiation therapy, then underwent a matched, unrelated bone marrow transplant and continues in remission 37 months later. Review of the literature revealed 10 cases in other children younger than 21-years-old with AML and breast involvement. These cases are summarized, and potential pathophysiologic mechanisms of spread are discussed. Breast involvement in AML is rare in children. However, regular breast examinations should be performed as part of routine follow-up in all girls with AML.
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