PMC5792817_01
Clinical and laboratory findings. A: Growth curve. Before admission, the height
gain was approximately 6.5 cm over the preceding 6 mo. After surgery for ACC, the
growth rate improved. B: Gynecomastia present on admission. Breast swelling was
bilateral and the breast glands were palpable below the nipples.
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The growth rate also improved (Fig. 1A).
Radiology and pathology findings of the tumor. A: Abdominal computed tomography. A
large, heterogeneous mass (white arrow) was detected just above the right kidney,
pushing the liver up to the diaphragm. B: Pathological examination of the biopsy
tissue (H & E staining, 200 x). The tumor comprised cells with eosinophilic
cytoplasm and heterogenic nuclei arranged in an alveolar pattern. The mitotic
activity of the cells was high.
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A large, heterogeneous tumor was detected below the liver on computed tomography (Fig. 2A). High nuclear grade, high mitotic rate (43/50 high-power fields), atypical mitosis, eosinophilic tumor cell cytoplasm, diffuse architecture, venous invasion, and capsular invasion were observed (Fig. 2B).
Clinical course after admission.
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Cortisol levels decreased to an insufficient level, and glucocorticoid supplement had been initiated in advance (Fig. 3).
PMC5792817_02
A schematic representation of the pathway of urinary steroid metabolites. A: On
admission, the levels of the metabolites of AD4, DHEA, and estrogens were extremely
high. B: Six months after surgery, the levels of these metabolites were almost
completely suppressed. P5: pregnenolone, 17alpha-OHP5: 17alpha-hydroxypregnenolone, P4:
progesterone, 17alpha-OHP4: 17alpha-hydroxyprogesterone, DHEA: dehydroepiandrosterone, AD4:
androstenedione, E: estrogens, DOC: deoxycorticosterone, 11DOF: 11-deoxycortisol, B:
hydroxycorticosterone, Ald: aldosterone, F: cortisol.
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Metabolites of pregnenolone (P5), progesterone (P4), 17-OHP5, 17-OHP4, cortisol, and estrogens were also elevated (Fig. 4A). After surgery, these metabolites decreased to almost under the 20-percentile levels, reported for 3 to 5-yr-old boys with normal hormone activity (Fig. 4B).
A schematic representation of the steroid metabolic pathway in the patient's ACC
tissue. According to laboratory data and the urine steroid profile generated on
admission, activity of 17alpha-hydroxylase (converted P5 to DHEA through 17alpha-OHP5),
3beta-hydroxysteroid dehydrogenase (converted P5 to P4), and aromatase (converted DHEA
and testosterone to estradiol) is mainly accelerated. StAR: Steroidogenic acute
regulatory protein, SULT2A1: Sulfotransferase family 2A member 1.
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These findings indicated an activated Delta5-steroids metabolic pathway (P5 converted to DHEAS), activated 3beta-hydroxysteroid dehydrogenase (P5 converted to P4), and aromatase (DHEA and T converted to E2) (Fig. 5).
The scheme for TP53 gene analysis. A heterogeneous germline point
mutation was detected in exon 4 (c.215C>G (p.Pro72Arg)).
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A heterozygous point mutation was detected in exon 4 of the TP53 gene (c.215C>G (p.Pro72Arg)) (Fig. 6).