The reticulin algorithm for adrenocortical tumor diagnosis: a multicentric validation study on 245 unpublished cases

Am J Surg Pathol. 2013 Sep;37(9):1433-40. doi: 10.1097/PAS.0b013e31828d387b.


The pathologic diagnosis of adrenocortical carcinoma (ACC) still needs to be improved, because the renowned Weiss Score (WS) system has a poor reproducibility of some parameters and is difficult to apply in borderline cases and in ACC variants. The "reticulin algorithm" (RA) defines malignancy through an altered reticulin framework associated with 1 of the 3 following parameter: necrosis, high mitotic rate, and vascular invasion. This study aimed at validating the interobserver reproducibility of reticulin stain evaluation in an unpublished series of 245 adrenocortical tumors (61 adenomas and 184 carcinomas) from 5 Italian centers, classified according to the WS. Eight pathologists reviewed all reticulin-stained slides. After training, a second round of evaluation on discordant cases was performed 10 weeks later. The RA reclassified 67 cases (27%) as adenomas, including 44 with no reticulin alterations and 23 with an altered reticulin framework but lacking the subsequent parameters of the triad. The other 178 cases (73%) were carcinomas according to the above-mentioned criteria. A complete (8/8 pathologists) interobserver agreement was reached in 75% of cases (κ=0.702), irrespective of case derivation, pathologists' experience, and histologic variants, and was further improved when only those cases with high WS and clinically malignant behavior were considered. After the training, the overall agreement increased to 86%. We conclude that reticulin staining is a reliable technique and an easy-to-interpret system in adrenocortical tumors; moreover, it has a high interobserver reproducibility, which supports the notion of using such a method in the proposed 2-step RA approach for ACC diagnosis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms / chemistry*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Adenoma / chemistry*
  • Adrenocortical Adenoma / pathology
  • Adrenocortical Carcinoma / chemistry*
  • Adrenocortical Carcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Biomarkers, Tumor / analysis*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Italy
  • Male
  • Middle Aged
  • Observer Variation
  • Predictive Value of Tests
  • Prognosis
  • Reproducibility of Results
  • Reticulin / analysis*
  • Staining and Labeling / methods
  • Young Adult


  • Biomarkers, Tumor
  • Reticulin