Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score—Report from the German MET Studies

Abstract

Background: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management. Patients: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score. Results: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1–17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0–16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS. Conclusions: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score.

Refractory and relapsed paediatric ACC in the MET studies – A challenging situation necessitating novel diagnostic and therapeutic concepts

“…The International Paediatric Adrenocortical Tumour Registry reported on 92 of 259 patients dying of disease progression (including relapse) or being alive with active disease at last follow-up [15]. Most events in paediatric ACC occur within 2 years following diagnosis [13,16,17]. In our study, progression occurred at a median time of 0.6 years.…”

Locally Advanced Adrenocortical Carcinoma in Children and Adolescents—Enigmatic and Challenging Cases

“…Many patients suffer from significant toxicity in the setting of adjuvant systemic treatment [3]. Up to 50% of stage II-III patients still experience disease recurrence [3,[5][6][7]. Given these data, a more sophisticated risk stratification is needed to guide adjuvant treatment.…”

“…Approximately 40-50% of children and adolescents with ACC are diagnosed with locally advanced disease [3,5,6]. Up to 50% of them relapse after complete tumor resection [3][4][5][6][7][8][9].…”

“…Approximately 40-50% of children and adolescents with ACC are diagnosed with locally advanced disease [3,5,6]. Up to 50% of them relapse after complete tumor resection [3][4][5][6][7][8][9]. We have previously reported that only a small proportion of these patients can be rescued by salvage therapy [10].…”

Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms

“… 9 , 10 , 12 , 14 , 15 More recently, Picard et al 1 revisited the role of WC in assessing pediatric ACN, emphasizing that some of these criteria remain poorly defined among pathologists and questioning its prognostic specificity. This group proposed a modified version of the WC (modified WC [mWC] or 5-item microscopic score), defined by a new 2-step scoring algorithm (including Ki67 proliferative index) demonstrating prognostic and therapeutic implications, 16 yet requiring independent validation.…”