Pediatric Adrenal Tumors Research Articles

FRI193 Early Presentation Of Pediatric Oncocytic Adrenal Tumor Associated With Germline TP53 Pathogenic Variant—Report Of Three Cases

Abstract Disclosure: R.R. Oppenheimer: None. L.P. Lins: None. C.P. Oliveira: None. I.P. Magalhaes: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. A.W. Kuhn: None. H. Charchar: None. M.C. Fragoso: None. Oncocytic adrenal tumors (OAT) are uncommon and usually nonfunctional. In the pediatric age group, OAT are extremely rare and less than 20 cases have been reported. Herein we report the clinical presentation and follow up of 3 non-related children with Li-Fraumeni syndrome with a germline TP53 pathogenic variant (PV) (p.R337H) who developed secreting OAT. Case 1. A 19 month old male presented with moon face, weight gain, irritability and pubic hair (Tanner stage P3) for over 4 months. He had no family history of neoplasms and his parents were unrelated to each other. Hormonal data revealed serum cortisol 33 mcg/dL with a suppressed ACTH. Testosterone was elevated (242 ng/dL - RR <12 ng/dL) with low plasma gonadotropins. Androstenedione 3,08 (RR<0,5ng/mL). Abdominal CT revealed a left adrenal tumor (5.0 x 4.4 x 4.0cm). He underwent a left laparoscopic adrenalectomy and histopathologic analysis confirmed OAT Wieneke score 2/9. Immunohistochemistry was positive for inhibin, p53 and Ki67 (10-15%). The postoperative clinical course was uneventful. The TP53 p.R337H PV was inherited from his father. He is now prepubertal and there is no evidence of relapse in 14 months of monitoring. Case 2. An 18 month old female presented with acne, clitoromegaly, pubic hair (Tanner stage 2), axillary odor, axillary hair and weight gain. Hormonal study showed elevated total testosterone of 624.7 ng/dL, androstenedione, DHEA-S and prepubertal gonadotropins. 17OHP and cortisol were normal. Abdominal CT confirmed a heterogeneous solid nodule of 5.5 x 4.5 x 3.7 cm in the right adrenal topography. The patient underwent a right adrenalectomy and OAT was identified by histopathology (Wieneke score 3/9). Immunohistochemistry was positive for p53, inhibin and Ki67 (30%). The TP53 p.R337H PV was inherited from her mother. She had remission of secondary sexual characteristics and he is now prepubertal. Case 3. A 2 years and 8 months old girl was referred with precocious pubarche and clitoromegaly (2,6cm). She had a right flank palpable mass and tanner 1 breasts. Hormonal studies showed elevated testosterone (70ng/dL), androstenedione (3.81ng/mL) and DHEA-S (13490ng/mL), with LH 0.3IU/L and FSH 3.4IU/L. The cortisol after DST was 5.8mcg/dL and ACTH was suppressed. Abdominal MRI revealed a 5 cm tumor at the right adrenal gland. She underwent laparoscopic adrenalectomy. The histopathologic analysis revealed an OAT Wieneke score 1/9. Immunohistochemistry was positive for p53 and Ki67 (13%). The TP53 p.R337H PV was inherited from her father. Conclusion: Although rare, functional OATs have been reported in children. Herein we describe the first patients with the TP53 p.R337H PV to present with OATs. These are the youngest cases of OAT published so far. The clinical presentation, hormonal data and follow-up were not different from those of other pediatric adrenal tumors. So far there is no evidence of disease relapse during follow-up. Presentation: Friday, June 16, 2023

Imaging of pediatric adrenal tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up.

Laparoscopic approach of pediatric adrenal tumors.

To analyze the role of laparoscopic surgery for the management of pediatric adrenal tumors (AT). Retrospective analysis of children diagnosed with AT, operated laparoscopically during 2003-2020. The strategy differed according to tumor extension. AT < 6cm were resected. Locally advanced tumors (L2) or > 6cm were biopsied. N = 28. Complete tumor resection (R0) in 20 (71%), tumor biopsy in 8 (R2). Age (median): 28.8months (2months-18years). 14/28 left-sided, 2 bilateral. Median operating time: 78min (45-180). Mean tumor size (for resections): 4cm (2.5-6). Tumor pathology: neuroblastoma (n = 17), Ganglioneuroma (n = 7), Adrenocortical carcinoma (n = 1), Osteosarcoma metastasis (n = 1), Pheochromocytoma (n = 1), Venous malformation (n = 1). Mean hospital stay: 2.5days (1-3). Mean follow up: 65.5months (24-192). Overall survival and event-free survival were 86 and 75%, respectively (5years event-free survival for neuroblastoma: 33% [intermediate risk], 16.6% [high risk]. No surgery-related mortality. Laparoscopic surgery for adrenal tumors is safe. Laparoscopic biopsy is useful for unresectable tumors when a percutaneous approach is not possible. With the proposed selection criteria, the laparoscopic approach should be the first option for resection of small and localized AT in pediatrics.

Adrenal Tumors in Children - Clinicopathological Experience

Abstract Objective To document general baseline data on the patterns of childhood adrenal tumors. Design, setting, and participants This is a retrospective analysis of 10 cases of pediatric adrenal tumors (age group 0–12 years) in surgical pathology encountered over a period of 5 years. Results In the adrenal gland, adrenal medullary tumors were more common than adrenal cortex with neuroblastoma as common individual tumor. Two were tumors of adrenal cortex and 8 were of adrenal medulla with ratio of medullary to cortical adrenal neoplasms as 4:1. Conclusion Different types of tumors were seen in the adrenal gland. A high index of suspicion should be maintained with an aim of surgical treatment. Histological type is important for understanding etiology and progression of disease.

KCNQ1OT1 hypomethylation: A Novel disguised genetic predisposition in sporadic pediatric adrenocortical tumors?

Pediatric adrenal tumors, other than neuroblastoma, are rare and can be associated with a genetic predisposition. In this report we describe two patients with an isolated and apparently sporadic adrenocortical tumor; one girl with a carcinoma, the other girl with an adenoma. In both patients genetic screening revealed hypomethylation of the KCNQ1OT1 gene, well-known for its association with the Beckwith-Wiedemann syndrome. This represents a likely novel genetic predisposition in patients with adrenocortical tumors without clear phenotypic features of the Beckwith-Wiedemann syndrome.

Unusual Adrenal Cortical Tumor of Unknown Biologic Potential: A Nodule in a Nodule in a Nodule

Adrenocortical tumors are uncommon neoplasms in childhood. Most pediatric adrenal tumors are virilizing and carcinomas are more common than adenomas. Recent molecular data suggest an adenoma-to-carcinoma progression sequence in adrenal cortical neoplasms. We report a case of a 5-year-old boy who presented with virilizing symptoms secondary to an adrenal tumor that was resected laparoscopically. The bulk of the tumor was a large, yellow mass with typical features of an adrenal cortical adenoma. In the center was a well-circumscribed tan-brown nodule that was distinct from the adenoma and had oncocytic features. A third minute focus (3.0 mm) was noted that was not circumscribed or encapsulated, but showed marked pleomorphism and abundant mitoses, including atypical forms and increased Ki67 compared with the outer 2 nodules. Molecular analysis to assess the clonality and mutation rates of the 3 distinct areas showed only 2 genetic loci with allelic imbalances.

Adrenal cortical tumors in childhood — clinicopathological features of six cases

Six cases of adrenal cortical tumors are presented with a discussion of the clinical features and histological findings. Five of the 6 children, aged between 6 mths and 6 yrs, presented with symptoms of hyperadrenalism, 4 with virilization and 1 with Cushingoid features. The remaining infant presented with an asymptomatic abdominal mass. In each case there was a unilateral tumor separated from the residual adrenal gland by a thin fibrous capsule. Surgical resection was the treatment employed and, in the 5 cases with functional tumors, perioperative hydrocortisone was given. None of the children received post-operative chemotherapy or radiotherapy. Bizarre cellular morphology, a high mitotic count and extensive necrosis were all seen in clinically benign disease, demonstrating not only the efficacy of local resection but also the difficulty in applying the usual histological criteria of malignancy to these pediatric adrenal tumors. At follow-up, 5 of the 6 patients are alive with no evidence of recurrent disease. The only death resulted from measles pneumonitis in the 1 child who presented with Cushing's syndrome.