Evaluation of bone marrow (BOM) minimal residual disease (MRD) after treatment in children with disseminated neuroblastoma (NB)

M. Brisigotti, M. F. Bonetti, L. Bereich, D. Medicina, G. Fabbretti, A. Garaventa, E. Magrini, B. De Bernard, E. Lanino, C. Rosanda, F. Callea

Research output: Contribution to journalArticle


Our aims were (1) to optimize the histological evaluation; (2) to correlate aspiration cytology with histology; (3) to clarify the prognostic implication of MRD. Materials were 201 biopsies, 391 smears from 41 consecutive NB children with BOM involvement at onset, obtained after aggressive chemotherapy with and without BOM or peripheral blood stem cell graft enrolled from June 1995 to May 1996. Methods were routine histology, cytology, and immunocytochemistry (ICC) (polyclonal and monoclonal antibodies NSE, SYN, CROM, S100, MiB1, UJ13A, CD56, and CD45 were used in all cases). Histological parameters included presence of NB cells, degree of differentiation, and type of related stroma. Correlation studies were carried out for 39 of 41 patients on the total number of corresponding samples (176 biopsies versus 300 aspirations) as well as on individual samples from the corresponding site (crista). Sixtythree of 185 representative biopsies (34.6%) were positive (patterns: focal, diffuse, multiple nonconfluent foci, either differentiated or undifferentiated). Up to 100 serial sections were required in 13 of 63 samples from three cases before detecting NB cells. Thirty-five of 391 smears were positive (9% ), 5 of which could be detected only by ICC. The comparison between BOM biopsy and aspiration (b/a) led to the following results: b+/a- in 49 samples; b+/a+ in 14; b-/a+ in 1; b-/a-in 112. In the 49 b+/asamples, the localization pattern was mostly focal (either differentiated or undifferentiated); in the 14 b+/a-f samples it was mainly diffuse undifferentiated. Conclusions: (1) BOM histology is by far more effective than aspiration cytology (34.6% versus 9%) in detecting MRD in treated NB; (2) aspiration cytology is likely to miss the focal (either differentiated or undifferentiated) involvement; (3) the long-term follow-up is expected to clarify the prognostic implications of MRD with special regard to focal involvement after chemotherapy and late relapse.

Original languageEnglish
Pages (from-to)519
Number of pages1
JournalPediatric Pathology and Laboratory Medicine
Issue number3
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Pediatrics, Perinatology, and Child Health

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