Terminal Deoxynucleotidyl Transf erase Positivity in Neuroblastoma

Anne O’Meara, Fin Breatnach, Theresa Finn, Emer Lawlor, Children’s Research Centre, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12 (Republic of Ireland) Since the discovery of the enzyme terminal deoxynucleotidyl transferase (TdT) in calf thymus [1] this ‘marker’ has come to play a major role in the interpretation and classification of the leukaemias [2]. We would like, however, to report strong TdT positivity in marrow aspirate of a child with a non-haematolog-ical malignancy. A 5-year-old girl was admitted with a 3-week history of lethargy and flitting aches. Physical examination revealed obvious pallor and a low grade fever. There were no other abnormal physical findings. Haematological investigations included HB 9.6 g/dl, WCC 3.9 × 109/1 of which 42% were neutro-phils, 54% lymphocytes, 2% monocytes and 2% eosin-ophils; platelet count was 177×109/1. May-Grün-wald-Giemsa staining of initial marrow aspirate showed reduction in erythroid and megakaryocytic cell lines, but no evidence of a malignant process. Repeat marrow aspirate demonstrated malignant cells distributed both singly and in clumps permeating and replacing normal marrow elements. The cell morphology was consistent with acute lymphatic leukaemia (ALL) of L2 type using the FAB classification. Periodic acid Schiff and Sudan black stains were negative and the acid phosphatase stain revealed an atypical diffuse granular positivity. Immunophenotyp-ing of the marrow cells with a panel of monoclonal antibodies gave the following result: UCHT-l(P. Beverly), la”, cALLA (J5)-, OKTÓ-, VIM-D5” and VIB-C5” (W. Knapp), My7and My9(J. Griffin) an-timonocyte-, slg-. A TdT immunofluorescence (IF) assay (Bethesda Research Laboratories) of bone marrow smear revealed greater than 90% positivity of bone marrow cells. A tentative diagnosis of ALL was made, probably of early T cell lineage. Subsequent clinical investigation, however, proved this not to be the case. A skeletal survey was normal apart from multiple lucent areas in the skull vault and there was downward and lateral displacement of the left kidney on IVP. CT scan of abdomen confirmed a small calcified mass (not seen on plain film) in the upper left quadrant extending medially and downward. 24-hour urinary estimation of VMA was normal. A repeat marrow aspirate reacted strongly with monoclonal antibody UJ13A [3], indicating presence in the marrow of cells of neuroectodermal origin. A diagnosis of stage IV neuroblastoma was thus confirmed. The child was commenced on three weekly courses of vin-cristine, cyclophosphamide, cisplatinum and VM26. After two courses, the marrow was free of neuroblastoma cells and removal of the primary tumour was carried out after a further four courses. Histology of the tumour confirmed a