Ganglioneuroblastoma infiltrating the bone marrow in an adult

Ganglioneuroblastomas belong to the group of neuroblastic tumours. They are embryonal neoplasms derived from primordial neuroectodermal cells of the neural cord as a part of the sympathetic neural system. Patients suffering these tumours are usually children aged between 2 and 4 years. Ganglioneuroblastomas are usually located in the abdomen, mediastinum, neck and lower extremities but, especially in adults, local invasion and lymph node metastases are not rare. Although the skeleton is not a typical site for ganglioneuroblastomas, paediatric patients do show bone marrow infiltration. We here report a 37-year-old patient who initially presented with bone pain and involvement of the skeleton finally resulting in a diagnosis of ganglioneuroblastoma, mixed type, stage IV according to the International Neuroblastoma Staging System (INSS). At relapse following chemotherapy, he presented with a left-shifted differential blood count (WBC count 4AE2 · 10/l), bicytopenia (Hb 62 g/l; platelet count 15 · 10/l) and elevated lactate dehydrogenase (LDH, 788 iu/ l). Urinary dopamine, metanephrine, and normetanephrine were increased. Morphological examination of bone marrow biopsy sections (left) and aspirates (right) showed clusters of immature neuroblastoma cells with pale-blue cytoplasm, distinct cell borders, round, sometimes eccentric nuclei and inconspicuous nucleoli. Immunohistochemical analysis showed strong positivity of tumour cells for neuron-specific enolase and chromogranin, whereas results with anticytokeratin antibodies were negative. The patient died from progressive disease 4 years after diagnosis despite surgery, radiation and chemotherapy, including high-dose chemotherapy and allogeneic haematopoietic stem cell transplantation. Adult cases showing a similar pattern have been described, but the frequency of bone marrow infiltration by ganglioneuroblastoma is difficult to determine due to the rarity of this tumour in adults. Bone marrow infiltration by ganglioneuroblastoma can mimic leukaemia with regard to cytopenia, elevated LDH and the presence of constitutional symptoms. This report strengthens the case for bone marrow investigation in adults with ganglioneuroblastoma. Furthermore, ganglioneuroblastoma should be considered when bone marrow infiltration is obvious but the primary tumour is unclear.