Detection of metastatic neuroblastoma in bone marrow: When is routine marrow histology insensitive? Journal Article


Authors: Cheung, N. K. V.; Heller, G.; Kushner, B. H.; Liu, C.; Cheung, I. Y.
Article Title: Detection of metastatic neuroblastoma in bone marrow: When is routine marrow histology insensitive?
Abstract: Purpose: To measure the sensitivity of histologic examination in detecting metastatic solid tumor in bone marrow. Patients and Methods: A total of 145 patients with stage 4 neuroblastama underwent 840 marrow examinations, each consisting of six sites [four aspirates and two biopsies), from October 1990 to June 1996 at Memorial Sloan-Kettering Cancer Center. Metastasis was detected by either histology (aspirate by Wright-Giemse and biopsy by Hematoxylin-Eosin stains) or immuno-staining of aspirates using anti-G(D2) monoclonal antibodies. Results: The absence of tumor by histology at a single marrow site was a poor guarantee of the absence of disease. The number of false-negative sites increased as the percent of G(D2)-positive tumor cells in the marrow decreased: zero of six if tumor Cell count was ≤ 1%, and approximately six of six sites if ≤ 0.003%. Sensitivity was comparable between marrow aspirate and biopsy. A lower bound (LB) for the probability of false-negative histology was calculated from the (1) discordance among the six marrow samplings and (2) comparison with immunofluorescence. When disease was extensive (eg, at diagnosis), the LB was 0.13 and 0.3, respectively. After treatment, it increased to 0.37 and 0.8. Examining multiple marrow sites can decrease the LB to 0.15. However, at least three sites have to be negative at relapse, six at diagnosis, and more than 50 during treatment or offtherapy follow-up. The marginal decrease in the LB by additional samplings rapidly diminished to less than 0.05 after two sites. Conclusion: Except at diagnosis and relapse when gross disease is present, marrow sampling by histology has limited sensitivity. Current practice grossly underestimates the true prevalence of marrow disease.
Keywords: immunohistochemistry; child; controlled study; human tissue; major clinical study; sensitivity and specificity; bone marrow; tumor markers, biological; relapse; clinical protocol; immunofluorescence; neuroblastoma; bone marrow biopsy; biopsy, needle; predictive value of tests; false negative reactions; bone marrow neoplasms; gangliosides; bone marrow metastasis; humans; human; priority journal; article; giemsa stain
Journal Title: Journal of Clinical Oncology
Volume: 15
Issue: 8
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1997-08-01
Start Page: 2807
End Page: 2817
Language: English
PUBMED: 9256123
PROVIDER: scopus
DOI: 10.1200/JCO.1997.15.8.2807
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Brian Kushner
    311 Kushner
  2. Glenn Heller
    399 Heller
  3. Nai-Kong Cheung
    648 Cheung
  4. Irene Y Cheung
    96 Cheung
  5. Chong-Yuan Liu
    11 Liu