Received: 27 February 2019 Revised: 28 February 2019 DOI: 10.1002/pbc.27710 Pediatric Blood & Cancer The American Society of Pediatric Hematology/Oncology LETTER TO THE EDITOR Reply to “Pathological prognostication of pediatric adrenocortical tumors: Is a gold standard emerging?” To the Editor: In a recently published article in Pediatric Blood & Can- cer, Jehangir et al studied 22 cases of pediatric adrenocortical tumors (ACTs) and found that Wieneke criteria accurately predicted clini- cal outcome. 1 The authors demonstrated correctly how the Wieneke score was superior compared to adult scores to predict malignancy, which is now recognized in the literature. 2 They showed the high sen- sitivity of Wieneke score as no patient categorized as benign (n = 14) had a malignant outcome, which was also assessed with Dehner and Hill criteria. 3 Contemporary to Jehangir et al, we reported a compre- hensive series of 95 cases of pediatric ACTs in the French population. 4 Respective incidences of histologically “benign” (63.1%, n = 60 vs. 63.6%, n = 14), “intermediate” (12%, n = 11 vs. 4.5%, n = 1), and “malig- nant” (25%, n = 24 vs. 32%, n = 7) neoplasms were similar to the present series, illustrating comparable sampling of patients. Results regarding the prognostic value of Wieneke's criteria were similar with two cri- teria being not statistically significant between benign and malignant tumors, namely vena cava invasion and presence of atypical mitosis. The authors argue also the high specificity of the Wieneke score, which allows a better distinction between histologically benign and malignant tumors compared to other systems, and therefore limits deleterious consequences of a “cancer” misdiagnosis for child and fam- ily. However, among seven patients with an ACT classified as malig- nant according to Wieneke score, three were alive with disease and two in complete remission at the end of follow-up. What first deter- mined malignancy in pediatric ACT and therefore guide treatment rec- ommendations is tumor stage (as described by the International Pedi- atric Adrenocortical Tumor Registry). 5 Besides biological data, it is defined by tumor volume, initial disease extension, and integrity of tumor resection, which are known to be central factors in the risk assessment of these tumors. Assessing the prognostic value of Wieneke score in small series of patients has been done few times but appears to us not suffi- cient enough to guide perioperative treatment recommandations. 1,6–9 Pathologists have to primarily focus on how the pathological grad- ing is integrated by clinicians to decide whether or not an adjuvant therapy is needed. Although it has a minor value in treatment algo- rithms for stages I and IV disease, it is of great significance for stages II-III tumors, which are associated with the most unpredictable out- come. Given the significance of choosing an adequate monitoring of these patients, clinicians need precise and relevant criteria from the pathological prognostication. In our study, we showed how the redun- dancy of some Wieneke criteria with tumor staging features artificially upgrades malignancy. 4 We believe that, after tumor staging assess- ment, the use of a simple pathological score that includes the most predictive and discriminant Wieneke microscopic criteria (adrenal cap- sular invasion, venous invasion, confluent necrosis, and mitotic count), in addition to the proliferation index Ki67, would guide more precisely the need of an adjuvant therapy in pediatric localized ACTs. 4 With a cut-off of two items, we showed a significant correlation between “favorable” or “unfavorable” histology tumors with outcome. Further independent studies are necessary to validate these findings. ORCID Cécile Picard https://orcid.org/0000-0001-9284-4531 Daniel Orbach https://orcid.org/0000-0002-2520-139X Cécile Picard 1 Daniel Orbach 2 Frédérique Dijoud 1 1 Institut de Pathology Multisite, Groupement hospitalier Est, Hospices Civils de Lyon, UCBL Lyon 1 University, Lyon, France 2 SIREDO Oncology Center, Institut Curie, PSL University, Paris, France Correspondence Cécile Picard, Department of Pathology, Institut de pathologie multisite, Groupement hospitalier Est, Hospices Civils de Lyon, Lyon 1 University, Lyon, France. Email: cecile.picard@chu-lyon.fr REFERENCES 1. Jehangir S, Nanjundaiah P, Sigamani E, et al. Pathological prognostica- tion of paediatric adrenocortical tumours: is a gold standard emerging. Pediatr Blood Cancer. 2018;66:e27567. 2. Erickson LA. Challenges in surgical pathology of adrenocortical tumours. Histopathology. 2018;72(1):82-96. 3. Dehner LP, Hill DA. Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors. Pediatr Dev Pathol Off J Soc Pediatr Pathol Paediatr Pathol Soc. 2009;12(4):284-291. 4. Picard C, Orbach D, Carton M, et al. Revisiting the role of the patho- logical grading in pediatric adrenal cortical tumors: results from a national cohort study with pathological review. Mod Pathol. 2018. https://doi/org/10.1038/s41379-018-0174-8 5. Ribeiro RC, Pinto EM, Zambetti GP, Rodriguez-Galindo C. The International Pediatric Adrenocortical Tumor Registry initiative: contributions to clinical, biological, and treatment advances in pedi- atric adrenocortical tumors. Mol Cell Endocrinol. 2012;351(1):37- 43. 6. Magro G, Esposito G, Cecchetto G, et al. Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical Pediatr Blood Cancer. 2019;66:e27710. c  2019 Wiley Periodicals, Inc. 1 of 2 wileyonlinelibrary.com/journal/pbc https://doi.org/10.1002/pbc.27710