The patient was a 23-year-old female who had hypertension during a routine medical visit in 2009 at age 11 years. Examination for causes of hypertension revealed a large, and well-defined mass in the left upper quadrant above the left kidney and deep to the spleen. The mass was approximately 8.7 × 9.7 × 9.7 cm and was relatively round. The kidneys and liver were normal in appearance. There was no regional adenopathy. Laboratory investigation showed remarkably elevated levels of deoxycorticosterone, aldosterone, and dehydroepiandrosterone. The mass was removed one month later, and weighed 388 g and measured 11 × 10 × 6 cm. There was a 3 × 3 cm defect on the surface suggestive of tumor rupture. The tumor was composed of nests of moderate-sized cells with round nuclei, prominent nucleoli, and moderate to abundant foamy to amphophilic non-foamy cytoplasm. There was only one mitosis per ten 400× fields and there was no atypical mitosis. However, the tumor demonstrated prominent venous invasion, necrosis, and extracapsular extension. Calcifications were noted. Immunohistochemical stains were positive for melan-A, vimentin, and cytokeratin (focal). Epithelial membrane antigen, chromogranin, and inhibin-α were negative. Ki-67 LI was <5%. Occasional areas of the tumor showed moderate nuclear staining for p53. The patient was referred to St. Jude for treatment. At that time, her adrenal hormones had returned to normal levels. She underwent comprehensive imaging studies, including FDG-PET scans. There was no evidence of residual disease. The recommendation was observation. She remains disease free 12 years from diagnosis.\nMolecular findings: Blood and tumor DNA of this patient was analyzed by whole genome sequencing (WGS) (). The patient had a wild type sequence for TP53 in both germline and tumor DNA (, ). ACT was wild type for ATRX and acquired the p.G34E variant in CTNNB1 and p.R201H in GNAS (). In addition, the patient harbored the germline p.R307* variant in the PDE11A (). WES analysis of blood-derived DNA was not sufficiently sensitive to detect chromosome 11p15 UPD, but MS-MLPA revealed a mosaic pattern of paternal 11p15 UPD.
The patient was a 21-year-old female with past history of stage 3 ACT diagnosed at 4.9 years. Her development was normal except for an incidental note per the family of longer and larger right upper and lower extremities throughout her life that had not been specifically investigated as far as the patient and her family were aware, but was associated with chronic left-leaning posture and asymmetric shoe size. She had been in her usual state of good health until the age 4 years when she complained of abdominal pain. She also had weight loss, increased headaches, decreased activity and energy, increased tiredness, and sweating. Given the persistence of symptoms, she was examined by a physician who palpated an abdominal mass and noted hypertension and slight androgen elevations. Magnetic resonance imaging showed a large abdominal mass in the right adrenal gland, with direct extension into the inferior vena cava and nearly completely filling of the right atrium. She underwent a partial sternotomy, and extraction of the caval portion of the adrenal tumor and resection of the right retroperitoneal tumor. The tumor weight was 550 g and measured 13.5 × 10.5 × 6.0 cm. The pathology confirmed ACC (low Ki-67 LI, rare mitotic figures and negative for inhibin-α). There were large areas of necrosis, and vascular invasion with tumor penetration through the capsule. Immunohistochemistry analysis was negative for p53 and positive for beta-catenin. She was treated with the combination of cisplatin, doxorubicin, etoposide, and mitotane. Features of right-sided lateral overgrowth, including right-sided tongue enlargement as well as increased right vs. left arm circumferences (51 cm vs 50 cm), calf circumferences (39 cm vs 37 cm), and a slight leg length discrepancy (88 cm vs 85 cm) were first noted during exams performed at St. Jude as part of a multidisciplinary rare endocrine tumor clinic when she was 18 years old, and led to additional testing subsequently confirming chromosome 11p15 UPD. She has been alive and tumor free for 17 years.\nMolecular findings: Blood DNA of this patient was analyzed by whole exome sequencing (WES). No reportable structural, single nucleotide variants, and indel or copy number changes were identified in APC, CDKN1C, MEN1, PRKAR1A, and TP53. Chromosome paternal 11p15 UPD was confirmed by MS-MLPA.