The estimation of tumor cell percentage for molecular testing by pathologists is not accurate

Alexander J J Smits, J. Alain Kummer, Peter C. De Bruin, Mijke Bol, Jan G. Van Den Tweel, Kees A. Seldenrijk, Stefan M. Willems, G. Johan A Offerhaus, Roel A. De Weger, Paul J. Van Diest, Aryan Vink

Research output: Contribution to journalArticlepeer-review


Molecular pathology is becoming more and more important in present day pathology. A major challenge for any molecular test is its ability to reliably detect mutations in samples consisting of mixtures of tumor cells and normal cells, especially when the tumor content is low. The minimum percentage of tumor cells required to detect genetic abnormalities is a major variable. Information on tumor cell percentage is essential for a correct interpretation of the result. In daily practice, the percentage of tumor cells is estimated by pathologists on hematoxylin and eosin (H&E)-stained slides, the reliability of which has been questioned. This study aimed to determine the reliability of estimated tumor cell percentages in tissue samples by pathologists. On 47 H&E-stained slides of lung tumors a tumor area was marked. The percentage of tumor cells within this area was estimated independently by nine pathologists, using categories of 0-5%, 6-10%, 11-20%, 21-30%, and so on, until 91-100%. As gold standard, the percentage of tumor cells was counted manually. On average, the range between the lowest and the highest estimate per sample was 6.3 categories. In 33% of estimates, the deviation from the gold standard was at least three categories. The mean absolute deviation was 2.0 categories (range between observers 1.5-3.1 categories). There was a significant difference between the observers (P

Original languageEnglish (US)
Pages (from-to)168-174
Number of pages7
JournalModern Pathology
Issue number2
StatePublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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