Diagnosis of neuroblastoma metastasis in bone marrow with a panel of monoclonal antibodies

Abstract

Neuroblastoma, along with rhabdomyosarcoma, Ewing's sarcoma, and acute lymphoblastic leukemia/lymphoma, is one of the small, round-cell tumors of childhood. All of these malignancies show a propensity to metastasize to bone marrow. Occasionally when the clinical picture is unclear and the tumor is particularly anaplastic, it can be difficult to arrive at a diagnosis by conventional histological and biochemical procedures. In the present study, a panel of nine monoclonal antibodies was used to undertake a detailed analysis of seven bone marrows contaminated with tumor cells: six cases of stage IV neuroblastoma, and one case of stage IV-S neuroblastoma. The antibody profiles obtained were compared with those deduced from the studies of over 20 marrows from patients with acute lymphoblastic leukemia. A comparison of these data with those obtained from the studies of rhabdomyosarcoma and Ewing's sarcoma cell lines and tissues suggests that when high levels of tumor cells are present in the marrow, it is possible to obtain a confident diagnosis of either neuroblastoma or acute lymphoblastic leukemia. In addition, the immunocytological identification of neuroblasts in bone marrow enables accurate staging without histological examination.

Contribution of Multiparameter Flow Cytometry Immunophenotyping to the Diagnostic Screening and Classification of Pediatric Cancer

“…Despite this, early studies in neuroblastoma patients already showed BM infiltration by CD45 − /CD56 + tumor cells, in the absence of proteins denoting hematopoietic commitment [29], [33]. Because of the relatively high frequency of metastatic BM involvement in neuroblastoma, this is by far the non-hematopoietic pediatric tumor mostly studied by MFC.…”

“…Thus, usage of flow cytometry in pediatric solid tumors has been almost restricted to the evaluation of tumor cell DNA contents in both paraffin-embedded and frozen tissue specimens, in combination or not with simultaneous staining for one or a few phenotypic markers [19]–[24]. Consequently, while immunophenotypic studies are routinely applied in most pediatric lymphomas for the differential diagnosis between B- and T-cell precursor lymphoblastic lymphomas and Burkitt lymphoma 25–28, few studies have been reported so far, in which MFC is systematically applied to the study of the phenotypic characteristics of pediatric solid tumors [29]–[31]. In addition, the few reported studies have mainly focused on descriptive analyses of the staining patterns for one or a few markers, usually in a single diagnostic subtype of the disease.…”

Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force

“…Many NB-associated antigens are inappropriate for detection of MD and MRD because of their heterogeneous expression in individual tumours or co-expression by normal cells (Sugimoto et al, 1988). In contrast, disialoganglioside G D2 is reported to be homogeneously and strongly expressed on neuroblastic tumours (Schulz et al, 1984;Cheung et al, 1985;Shochat et al, 1988), but not on normal haematopoietic cells (Cheung et al, 1986) and is therefore regarded as ideal for specific and sensitive detection of MD and MRD by IC and FC (Warzynski et al, 2002, Swerts et al, 2004.…”

CD10+ cell population in the bone marrow of patients with advanced neuroblastoma

“…The monoclonal antibodies UJ-13A and UJ-127-1 1 were used to detect neuroblasts in the bone marrow. These antibodies were kindly given to us by Dr. Kemshead [9,14]. These monoclonal antibodies bind specifically to neuroblastoma cells but not to normal BM cells and to leukemic cells.…”