Neuroblastoma cells in bone marrow.a Characteristic clumps of cells (three to several hundred cells) closely adhering to each other.The cell size approximates two to three red blood cell diameters and appears a little bit larger and more polymorphic than hematopoietic blasts. High nucleus/cytoplasm ratio.The round-to-moderately oval nucleus contains fine grainy chromatin characteristically with small areas of higher density ("pepper-and-salt structure").Nucleoli are not often visible.The basophilic cytoplasm is purely confined and the cell margins even invisible in cell clumps.Vacuoles are rarely seen,and granulation is never seen.Some neuroblastoma cells may demonstrate phagocytosis phenomena (not shown). b Homer-Wright rosette:typical neuroblastoma cells form a ring of cells around cytoplasmic material (neuropil) in the center. c Atypical "ALL like" neuroblastoma cells in bone marrow with many single cells of only one 1-2 red blood cell diameter size, but typical structure of the nucleus and ill-defined, fringed cytoplasm, no or only small clumps. d Small tumor clump consisting of cells with distinct membrane staining for GD2 (antibody 14G2a).Due to unspecific GD2 staining to other cell elements (e.g., some megakaryocytes, histocytes phagocytosing neuroblastoma cells), the morphology of the stained cell must be compatible with a neuroblastoma cell to be regarded as such. (Courtesy of R. Schumacher-Kuckelkorn, Cologne)
tyrosine hydroxylase. It is agreed that patients who meet the International Neuroblastoma Staging System (INSS) criteria for stages 1 - 3 should not be upstaged to stage 4 or stage 4S because of the detection of a few immunocytologically positive cells in the bone marrow in the absence of morphological evidence of disease by light microscopy (Brodeur et al. 1993).
The amount of marrow involvement in most infants with stage-4S disease is minimal (<1% tumor cells per nucleated marrow cells). An upper limit of 10 % has been defined. If this is exceeded, an upstaging from stage 4S to stage 4 is recommended (Brodeur et al. 1993).
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