COMPLEX CHROMOSOMAL ABNORMALITIES IN A CHILD WITH ADVANCED NEUROBLASTOMA. H.O. Shah^1,2, N. Chen¹, Q. Tao¹, Y. Zhong¹, J.H. Lin^1,2. 1) Dept Pathology, Cytogenetics, Nassau Univ Medical Ctr, East Meadow, NY; 2) Health Science Center, State University of New York, Stony Brook, NY.
   A 6 year-old girl with negative family history was admitted with proptosis of both eyes, vomiting and abdominal pain. CT scan revealed a large right retroperitoneal mass and multiple metastatic lesions to spine, lung, brain and bone marrow. Fine needle aspirate of retroperitoneal mass, and bone marrow aspirate and biopsy showed small blue cells that were negative for CD45, CD99, cytokeratin, desmin, NSE, neurofilaments and positive for CD56, synaptophysin and chromogranin. FISH performed on interphase nuclei were negative for amplification of MYCN (chromosome 2p24.1) and negative for rearrangement or loss of MLL (chromosome 11q23). Cytogenetic analysis of metaphase tumor cells revealed multiple chromosomal abnormalities with many cell-to-cell variations. The composite karyotype of tumor cells disclosed, female, 46-47,XX,add(4)(q31.1),-6,del(6)(p21.3p25),+7,add(11)(p11.2),del(11)(p11.2p15),add(19)(p13.1),+1-7mar[cp9]/89,idemx2[1]. The primary adrenal tumor was resected after four cycles of chemotherapies and the immunostain of tumor cells are positive for NSE, chromogranin and synaptophysin. Neurofilament is randomly positive in stroma and S-100 is strongly positive in Schwannian stroma. Final diagnosis is Neuroblastoma, Stage 4. In this patient, there are no N-myc amplifications nor LOH of 11q (MLL) detected. However, there are notable structural anomalies on chromosome 4, 6, 11 and 19 in this patient. The genes involved in this patients genome regions of the chromosomal structural abnormalities involve numerous factors and oncogenes reported in other malignancies, including BAK, TNFSF2, WT2, ST5, CDKN1C, NUP98 and IGF2, which may trigger this patients tumorigenesis. Various molecular and cytogenetic factors have been implicated in the pathogenesis of neuroblastoma and useful in predicting clinical behavior and outcome. Chromosomal structural changes are found in more than 50% of neuroblastomas. Therefore molecular and cytogenetic characterizations of neuroblastoma become a routine part of the clinical evaluations that influence the clinical treatment and outcome.