Atypical ductal hyperplasia: Interobserver and intraobserver variability

Rohit K. Jain, Rutika Mehta, Rosen Dimitrov, Lisbeth G. Larsson, Paul M. Musto, Kurt B. Hodges, Thomas M. Ulbright, Eyas M. Hattab, Narasimhan Agaram, Muhammad T. Idrees, Sunil Badve

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69 Scopus citations


Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter- and intraobserver variability and the impact of the addition of an immunostain for high- and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair (κ-value=0.34). The intraobserver-value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall-value=0.50) was observed (P=0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter- and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions.

Original languageEnglish (US)
Pages (from-to)917-923
Number of pages7
JournalModern Pathology
Issue number7
StatePublished - Jul 1 2011


  • atypical ductal hyperplasia
  • ductal carcinoma in situ
  • immunohistochemistry
  • interobserver variation
  • usual ductal hyperplasia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Jain, R. K., Mehta, R., Dimitrov, R., Larsson, L. G., Musto, P. M., Hodges, K. B., Ulbright, T. M., Hattab, E. M., Agaram, N., Idrees, M. T., & Badve, S. (2011). Atypical ductal hyperplasia: Interobserver and intraobserver variability. Modern Pathology, 24(7), 917-923.