The patient was an 8.5-year-old female with presumptive diagnosis of BWS who presented to the local physician in 2003 with new onset of herculean habitus, clitoromegaly, pubic hair, acne, and apocrine odor. Abdominal computed tomography imaging revealed synchronous bilateral adrenal masses. There was no evidence of disease elsewhere. The patient underwent laparotomy with excision of the left adrenal gland and tumor enucleation of the right gland. The left tumor weighed 21.5 g and measured 5.5 × 1.5 × 0.7 cm, and right tumor measured 1.3 × 1.2 × 1.0 cm. Sections of both tumors showed similar cellular constituents. Tumors were composed of a uniform population of cells with ample acidophilic cytoplasm and moderate anisonucleosis that recapitulated the zona reticularis, consistent with the diagnosis of adrenocortical adenoma. The p53 staining was negative and Ki-67 labeling index (LI) was less than 2%. Inhibin-α was positive in a subset of cells. No chemotherapy was indicated. The patient remained asymptomatic until 2008, and then developed bilateral small breast nodules. The right breast mass measured 3.5 × 2.5 × 2.0 cm and the left inferior breast mass measured 3.0 × 2.0 × 2.0 cm and both were surgically removed. Histology of the first mass had features of tubular adenoma and that of the left mass of juvenile fibroadenoma. The patient remained clinically stable until the age of 18 years when she was taken off the protocol.\nMolecular findings: Blood and tumor DNA of this patient was examined by whole exome sequencing (WES) (). Results showed that the patient had a wild type sequence for TP53 in both germline and tumor DNA as well as wild type sequence for CTNNB1 and ATRX in the tumor (, ). Additional findings included the somatic p.E150K variant in the imprinted MKRN3 and the p.D155fs in the cytochrome P450 Family 17 Subfamily A Member 1, CYP17A1. Of note, the patient harbored a germline p.E257K variant in EGFR () and the p.M595T variant in the regulator of epigenetic gene silencing SIRT1. Both variants were present in the tumor in the heterozygous state (). The variant in EGFR was classified as likely benign in CLINVAR (variant ID 1123013) and the SIRT1 variant was not reported. Therefore, both variants have been reported in the Genome Aggregation Database (gnomAD) originated from unrelated individual sequences as part of population genetic studies supporting lack of biological significance for both variants in the context of adrenocortical tumors. WES analysis of blood-derived DNA did not detect 11p15 UPD. However, a pattern of homozygosity at chromosome 11p15 was verified by microsatellite markers analyses and confirmed by MS-MLPA consistent with paternal uniparental disomy (UPD) in the germline sample ().
Patient was a 2.4-year-old male with a past medical history consistent with BWS (hemihypertrophy) who had an abdominal mass in the left adrenal gland during surveillance for abdominal tumors. In addition, a hepatic mass was noted. The patient underwent laparotomy with resection of the left adrenal gland and partial hepatectomy. The adrenal tumor weighed 56 g and measured 5.9 × 5.9 × 3.6 cm. The liver lesion weighed 73 g and measured 6.5 × 4.5 × 4.0 cm. Tumors in adrenal gland and liver were histologically identical. The immune profile of both tumors was positive for pan keratin, vimentin, synaptophysin, melan-A, and was negative for inhibin-α, chromogranin, and alpha-feto protein, anti-endomysial antibody (EMA), and calretinin. Liver and adrenal masses were also negative for p53, and Ki-67 LI was <5% in both tumors. There was vascular invasion in the adrenal tumor. Peri-aortic lymph nodes were negative. Tumor margins were free of tumor. The patient was not treated with chemotherapy and remains free of disease 11 years after the diagnosis of adrenocortical carcinoma (ACC).\nMolecular findings: Molecular studies were done for the germline sample and the patient was wild type for TP53. Microsatellite analysis covering the position 1,061,991 to 4,539,851 at chromosome 11p15 (GRCh37/hg19) revealed a heterozygous pattern for all studied markers but MS-MLPA revealed a pattern consistent with mosaic paternal UPD.