Received: 3 December 2018 Revised: 6 November 2018 Accepted: 10 November 2018 DOI: 10.1002/pbc.27567 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology RESEARCH ARTICLE Pathological prognostication of paediatric adrenocortical tumours: Is a gold standard emerging? Susan Jehangir 1,2 Pratibha Nanjundaiah 1 Elanthenral Sigamani 3 Deepak Burad 3 Marie T. Manipadam 3 Vivienne Lea 4 Theresa Ly 4 Andrew J. A. Holland 2,5 1 Department of Paediatric Surgery, Christian Medical College, Vellore, India 2 Department of Paediatric Surgery, The Children's Hospital at Westmead, Sydney, Australia 3 Department of Clinical Pathology, Christian Medical College, Vellore, India 4 Department of Anatomical Pathology, The Children's Hospital at Westmead, Sydney, Australia 5 University of Sydney School of Medicine, Sydney, Australia Correspondence Susan Jehangir, Level 3, Department of Paediatric Surgery, The Children's Hospital at Westmead, Corner Hawkesbury Road and Hainsworth Street, Westmead, Sydney, NSW, Australia, 2145. Email: susanjehangir@cmcvellore.ac.in Abstract Background: Criteria for the pathological classification of adult adrenocortical tumours (ACTs) have been found to overestimate the malignant potential of childhood ACTs. We sought to evalu- ate the accuracy and utility of criteria developed for paediatric ACT compared to current criteria for adults. Methods: ACTs treated between January 2006 and December 2016 in two paediatric institu- tions were evaluated. Patients classified clinically as malignant (CM) had locally invasive disease at surgery requiring extensive en bloc resection to achieve clear margins, had local recurrence or distant metastasis. Slides were reviewed by pathologists blinded to the clinical outcome. A grade was assigned to each tumor according to the Weiss, Aubert, Wieneke and Dehner-Hill criteria. The pathological grade was compared to the clinical outcome. Results: The median follow-up was 60 months (interquartile range 25-80 months). Based on clin- ical criteria, of 22 patients 14 (64%) had a benign course and eight (34%) behaved malignant. The malignant potential was overestimated by Weiss criteria in 23% and Aubert criteria in 27%. Wieneke and Dehner-Hill criteria showed good clinicopathological correlation; no child who had a benign course was classified as malignant. The Dehner-Hill criteria, however, classified five (23%) children as intermediate risk of which three had a clinically benign and two a CM course. Conclusion: The Wieneke criteria accurately predicts the clinical course in childhood ACTs and could be considered the gold standard in their pathological characterization. KEYWORDS childhood adrenocortical tumours, paediatric adrenocortical tumours, Wieneke criteria 1 INTRODUCTION Adrenocortical tumours (ACTs) remain rare in childhood and con- stitute 0.2% of paediatric malignancies. 1 ACTs show a bimodal distribution, affecting children less than 5 years old and adults in the fourth and fifth decade of life. 2 Paediatric ACTs behave differently from histologically similar tumours in the adult population. In contrast to adult tumours, which are largely asymptomatic, most childhood ACTs present with symptoms of androgen excess. 2 They may occur sporadically or be associated with hereditary cancer syndromes including Li-Fraumeni and Beckwith-Wiedemann syndromes. 3 Even with aggressive histological features, childhood ACTs tend to have a more benign clinical path. 4 Abbreviations: ACTs, adrenocortical tumours; CB, clinically benign; CM, clinically malignant; IVC, inferior vena cava The pathological diagnosis of malignant ACT has been an area of uncertainty worldwide. Weiss and Medeiros in 1989 described a set of nine histological criteria to define the malignant potential in ACT. 5 When applied to adult ACT, these criteria showed good clinicopatho- logical correlation and have subsequently become popular. When applied to childhood ACTs, however, the same criteria tend to overes- timate malignant potential with only 31% clinical correlation. 6 Aubert et al. in 2002 simplified the Weiss criteria by choosing five of the nine criteria that had high inter-observer agreement and eliminating the more subjective or difficult to interpret components but still overrated malignancy in children. 7 Several authors have defined individual char- acteristics including age at presentation, sex, duration of symptoms, stage and localized disease as individual predictors of outcome. 8–10 In 2003, Wieneke et al. studied 83 paediatric ACTs and recom- mended a set of criteria to define malignant potential in children. 6 This Pediatr Blood Cancer. 2018;e27567. c  2018 Wiley Periodicals, Inc. 1 of 5 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.27567