Peripheral precocious puberty in Li-Fraumeni syndrome: a case report and literature review of pure androgen-secreting adrenocortical tumors

Abstract

Introduction: Pure androgen-secreting adrenocortical tumors are a rare but important cause of peripheral precocious puberty.

Case presentation: Here, we report a pure androgen-secreting adrenocortical tumor in a 2.5-year-old boy presenting with penile enlargement, pubic hair, frequent erections, and rapid linear growth. We confirmed the diagnosis through laboratory tests, medical imaging, and histology. Furthermore, genetic testing detected a pathogenic germline variant in the TP53 gene, molecularly confirming underlying Li-Fraumeni syndrome.

Discussion: Only 15 well-documented cases of pure androgen-secreting adrenocortical tumors have been reported so far. No clinical or imaging signs were identified to differentiate adenomas from carcinomas, and no other cases of Li-Fraumeni syndrome were diagnosed in the four patients that underwent genetic testing. However, diagnosing Li-Fraumeni syndrome is important as it implies a need for intensive tumor surveillance and avoidance of ionizing radiation.

Conclusion: In this article, we emphasize the need to screen for TP53 gene variants in children with androgen-producing adrenal adenomas and report an association with arterial hypertension.

Keywords: Hypertension; Li–Fraumeni syndrome; Pediatric endocrinology; Peripheral precocious puberty; Pure androgen-secreting adrenocortical tumor.

Fig. 1

Imaging studies. A Abdominal ultrasound showed a hypoechoic lesion in the left adrenal. B MRI confirmed the presence of a well-defined 26 × 23 × 31 mm nodule (dotted red circle) with limited but homogeneous contrast accumulation, and no evidence of invasion into adjacent organs or vessels

Fig. 2

Pathology. A Macroscopic image of the adrenal tumor with an intact thin capsule. Weight 11.2 g (after fixation), dimensions 4.5 cm × 3 × 2.5 cm, and maximum diameter 2.5 cm B Low magnification and C high magnification image of H&E staining showing a solid population of eosinophilic cells with granular cytoplasm, vesicular nuclei with moderate pleomorphism, and some giant nuclei. No hemorrhagic or necrotic zones. D, E Positive immunostaining for (D) inhibin and (E) Melan-A. F Low mitotic activity with a Ki67 positive cell ratio of approximately 10%. G Strong and diffuse P53 immunoexpression (100% of positive cells)

Fig. 3

Genetic testing. A Integrative Genomics Viewer (IGV) graphic showing a single nucleotide variant (SNV) in the TP53 gene (G>A), producing p.Arg158His alteration. The reference sequence used is NM_000546.5. B TP53 gene diagram shows that the R158H variant hits the functional part of the DNA-binding domain of P53 and imparts a transcriptional activity comparable to null variants. C Domain structure of p53. Adapted from Tanaka et al. [40]