Leukaemic alveolar rhabdomyosarcoma

Abstract

A 13-year-old previously well girl presented with a five-week history of lethargy, loss of weight and left upper quadrant pain radiating to her thoracolumbar spine. Examination revealed pallor, left upper quadrant tenderness and bilateral lower limb weakness with brisk lower limb and extensor plantar reflexes together with bilateral clonus. Peripheral blood counts showed pancytopenia: haemoglobin concentration 70 g/l, platelet count 70 · 10/l and neutrophil count 0AE8 · 10/l, and a blood film was leucoerythroblastic. She was in acute renal failure and her lactate dehydrogenase, calcium and urate were elevated at 1886 u/l (230–600), 2AE84 mmol/l (2AE15–2AE65) and 925 umol/l (150–330), respectively. Chest and spine radiographs were normal, as was abdominal ultrasonography. A bone marrow aspirate demonstrated an infiltrate of large cells with prominent nucleoli and basophilic cytoplasm with multiple vacuoles (top left). Flow cytometric analysis showed these cells to be CD56/CD45 (top right). Whole body magnetic resonance imaging revealed a diffusely abnormal bone marrow signal throughout the axial skeleton and a soft tissue lesion centred on T9/T10 with an epidural extension compressing the spinal cord (bottom right). Urinary catecholamines were negative. A T9-10 laminectomy/biopsy yielded a histological diagnosis of alveolar rhabdomyosarcoma with desmin, vimentin, myogenin and myoD1 positivity together with fluorescence in situ hybridization confirmation of the PAX3-FOXO1 fusion gene (bottom left). Immediate treatment with hyperhydration, rasburicase and dexamethasone restored normal renal function and calcium levels. Chemotherapy with ifosfamide/vincristine/actinomycin-D/doxorubicin produced an excellent clinical and tumour response. Rhabdomyosarcoma, especially of alveolar histology has a propensity to metastasize to the bone marrow. Not infrequently, rhabdomyoblasts are mistaken for the blast cells of acute leukaemia. Immunophenotyping usually shows these cells to be CD56/CD45 and they express desmin, vimentin, myoglobin and MyoD1. The cytogenetic hallmarks are the translocations t(2;13)(q35;q14)/PAX3-FOXO1 and t(1;13) (p36;q14)/PAX7-FOXO1, seen in approximately 60% and 20% of cases respectively.