Diagnostic and prognostic utility of SF1, IGF2 and p57 immunoexpression in pediatric adrenal cortical tumors

Guntiboina, Vinay Anand; Sengupta, Moumita; Islam, Nelofar; Barman, Shibsankar; Biswas, Soumali; Chatterjee, Uttara; Mishra, Prafulla Kumar; Roy, Paromita; Mallick, Mamata Guha; Datta, Chhanda

doi:10.1016/j.jpedsurg.2018.12.002

Cited by 10 publications

(12 citation statements)

References 29 publications

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“…In our experience, one of the three patients who experienced metastatic disease obtained complete remission with platinum-based chemotherapy and mitotane. Overexpression of the IGF2 and IGF1R genes was described in ACT also in the pediatric setting ( 41 ), but trials testing the utility of insulin like growth factor receptor 1 inhibitors (e.g., linsitinib) have failed to provide advantage for adulthood ACC treatment ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

et al. 2020

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Background and Aims: Pediatric adrenocortical tumors (ACTs) are very rare endocrine neoplasms in childhood. In this study, we performed a retrospective analysis of children with ACT treated at our institution by examining clinical and genetic disease features, treatment strategies, and outcomes. Methods: We retrospectively analyzed a cohort of 13 children treated at the Bambino Gesù Children's Hospital from November 2010 to March 2020. Results: The median age at diagnosis was 17 months (range = 0-82 months). The female: male ratio was 3.3/1. Mixed symptomatology (>1 hormone abnormality) was the most common presentation (46.1%). In three cases, the tumor was detected during prenatal or perinatal echographic screening. All patients presented with localized disease at diagnosis and underwent total adrenalectomy. Six patients were identified as having malignancies according to the Wieneke scoring system, five benign, and two undetermined. Seven patients underwent mitotane adjuvant therapy for 12 months. There was metastatic disease in three patients, with no correlation with age or Wieneke score. The most common sites of metastases were the liver and lungs. Metastatic patients were treated with surgery (n = 2), mitotane (n = 1), chemotherapy (n = 2) associated with anti-EGFR (n = 1), or immunotherapy with anti-PD1 (pembrolizumab) (n = 1); two patients achieved complete disease remission. Overall 2-and 5-year survival rates were 100%, with a median follow-up of 5 years (range = 2-9.5 years). Two-and 5-year disease free survival was 76.9 and 84.6%, respectively (95% confidence interval = −66.78-114.76 months). All patients are alive, 12 without disease, and one with stable disease. Genetic analyses showed TP53 germline mutations in six of eight patients analyzed (five inherited, one de novo). One patient had Beckwith-Wiedemann syndrome, with mosaic paternal uniparental disomy of chromosome 11, in both neoplastic and healthy adrenal tissue. Miele et al. Adrenocortical Tumors in Children Conclusion: We report the cases of 13 patients treated for ACT, including 12 aged <4 years at diagnosis, with a relative short time from symptoms onset. Our cohort experienced an excellent prognosis. TP53 mutation was found in 75% of tested patients (6/8) confirming the need to perform genetic tests and familial counseling in this disease.

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Section: Discussionmentioning

confidence: 99%

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

et al. 2020

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“…As of this, a separate scoring system proposed by Wieneke et al combine nine macroscropic and microscopic features of pediatric adrenal cortical neoplasms associated to clinically malignant cases. This model has since been reproduced by other groups and could potentially also benefit from the inclusion of P53, IGF2, and Ki-67 immunostainings [146][147][148]. ACCs are regularly uniformly positive for synaptophysin and SF1 and usually exhibit some grade of calretinin and melan A expression.…”

Section: Histological Evaluation Of Malignant Behaviormentioning

confidence: 97%

What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics

et al. 2021

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Approximately one-tenth of the general population exhibit adrenal cortical nodules, and the incidence has increased. Afflicted patients display a multifaceted symptomatology-sometimes with rather spectacular features. Given the general infrequency as well as the specific clinical, histological, and molecular considerations characterizing these lesions, adrenal cortical tumors should be investigated by endocrine pathologists in high-volume tertiary centers. Even so, to distinguish specific forms of benign adrenal cortical lesions as well as to pinpoint malignant cases with the highest risk of poor outcome is often challenging using conventional histology alone, and molecular genetics and translational biomarkers are therefore gaining increased attention as a possible discriminator in this context. In general, our understanding of adrenal cortical tumorigenesis has increased tremendously the last decade, not least due to the development of next-generation sequencing techniques. Comprehensive analyses have helped establish the link between benign aldosterone-producing adrenal cortical proliferations and ion channel mutations, as well as mutations in the protein kinase A (PKA) signaling pathway coupled to cortisol-producing adrenal cortical lesions. Moreover, molecular classifications of adrenal cortical tumors have facilitated the distinction of benign from malignant forms, as well as the prognostication of the individual patients with verified adrenal cortical carcinoma, enabling high-resolution diagnostics that is not entirely possible by histology alone. Therefore, combinations of histology, immunohistochemistry, and next-generation multi-omic analyses are all needed in an integrated fashion to properly distinguish malignancy in some cases. Despite significant progress made in the field, current clinical and pathological challenges include the preoperative distinction of non-metastatic low-grade adrenal cortical carcinoma confined to the adrenal gland, adoption of individualized therapeutic algorithms aligned with molecular and histopathologic risk stratification tools, and histological confirmation of functional adrenal cortical disease in the context of multifocal adrenal cortical proliferations. We herein review the histological, genetic, and epigenetic landscapes of benign and malignant adrenal cortical neoplasia from a modern surgical endocrine pathology perspective and highlight key mechanisms of value for diagnostic and prognostic purposes.

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“…However, reliably distinguishing ACC from ACA is difficult on FNAC and CB in absence of capsular and vascular invasion. These become even more difficult in paediatric patients where cytological features alone are not an adequate guide in favour of malignancy 14‐17 …”

Section: Discussionmentioning

confidence: 99%

Utility of cell block preparation in diagnosis of paediatric abdominal neoplasms

Kanjilal

Das²,

Chatterjee

et al. 2020

Diagnostic Cytopathology

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Background Paediatric abdominal neoplasms are fairly common. Fine needle aspiration cytology (FNAC) is used for the initial evaluation of paediatric abdominal neoplasms. However, sometimes FNA interpretation can be difficult on limited material, owing to tumour heterogeneity and overlapping features. Therefore, we attempted to obtain additional information using cell block (CB) preparation from residual aspiration material along with immunohistochemistry (IHC) to enhance the diagnostic accuracy. Aim To evaluate the correlation between CB preparation and FNAC in diagnosis of paediatric abdominal tumours with the help of an extended panel of IHC markers and to highlight some of the diagnostic difficulties. Materials and methods A total of 113 cases of paediatric abdominal masses were studied. In addition to routine FNA smears, CBs were prepared from the residual material for IHC analysis as considered appropriate. Results This study included a total of 113 children with abdominal masses. Histopathology following surgical resection was available in 53 cases. Histology was taken as gold standard to measure the diagnostic accuracy with reference to sensitivity (Sn), specificity (Sp), positive predictive value and negative predictive value. The Sn of FNA alone was 87.5% and Sp was 97.78%. The Sn and Sp increased with use of CB alone and were 100% and 97.78% respectively. The highest Sn and Sp were observed when CB was combined with IHC where both the values were 100%. Conclusion CB with IHC is a useful adjunct to the routine FNA smears that further contributes to enhance the accuracy of the cytopathological diagnosis and is useful for choosing pre‐operative chemotherapeutic regimen.

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Diagnostic and prognostic utility of SF1, IGF2 and p57 immunoexpression in pediatric adrenal cortical tumors

Cited by 10 publications

References 29 publications

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

Clinical, Genetic, and Prognostic Features of Adrenocortical Tumors in Children: A 10-Year Single-Center Experience

What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics

Utility of cell block preparation in diagnosis of paediatric abdominal neoplasms

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