Inter-Institutional Second Opinion Pathologic Review of Lymphoproliferative Disorders After WHO Classification.

Reviewer: M. Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 8, 2001

Presenter: Jonathon Silberstein
Affiliation: Memorial Sloan-Kettering Cancer Center


The World Health Organization (WHO) classification of lymphoproliferative disorders is the most recent classification scheme available. It incorporates recent advances in diagnosis and biology, including immunohistochemistry and genetic analysis. In order to assess possible inter-institution variability in diagnosis using this new classification system, the diagnoses of 628 biopsies from 389 patients who were referred to a major academic center were reviewed.

Materials and Methods

  • 389 patients with 628 outside biopsies were referred to Memorial Sloan-Kettering Cancer Center over a six-month period.
  • The outside biopsy specimens were reviewed by one of two institutional hematopathologists.
  • Attention was paid to any new tests performed on outside material. Discrepancies were graded as major, minor, or no change in diagnosis with significant clinical impact.
  • 66/628 specimens were referred from NCI comprehensive cancer centers, 3 from clinical cancer centers, and 558 from undesignated institutions.


  • There were 89/628 (13%) cases in 61/389 (16%) patients of major discrepancies; in 8 cases (1%) (6 pts) new tests were performed on outside material.
  • There were 33/628 cases (5%) in 26/389 pts (7%) of minor discrepancies; in 2 cases (2 pts) new tests were performed.
  • 482/628 biopsies (77%) in 270/389 (70%) of patients there was no discrepancy.
  • There were an additional 24 cases (4%) with an outside report still pending.
  • Major discrepancies included: non-diagnostic, incomplete, ambiguous, or suspicious versus diagnostic or definitive (n=52); benign vs. malignant (n=8); indolent vs. aggressive (n=18); Large-cell vs. Burkitt-like (n=6); and B-cell vs. T-cell (n=1).
  • Major discrepancies were seen in 5/66 (7.57%) of cases referred from NCI comprehensive cancers, compared with 83/558 (14.87%) of cases from undesignated institutions.

Author's conclusions:

  • Discrepancy between institutions for lymphoproliferative disorders remains high, despite the new WHO classification system. Discrepancy rates in cases from NCI comprehensive cancer were significantly lower than those from undesignated institutions.
  • Additional resources are needed to train expert hematopathologists given the importance of obtaining a correct diagnosis for treatment The value of second opinions in hematopathology remains significant.

Clinical/Scientific Implications:

  • In this study, the inter-institutional variability in hematopathologic diagnoses was significant, in both referrals from NCI comprehensive cancer centers as well as those from undesignated institutions. The concordance between the reviewing institution and the NCI comprehensive cancer centers was greater than the concordance between the reviewing institution and undesignated institutions.
  • Given this variability, a second opinion from an expert hematopathologist may be a valuable contribution to patient care.

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