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A rare pediatric case of Li-Fraumeni syndrome presenting with virilization symptoms and dual primary malignancies on magnetic resonance imaging and [18F]-fluorodeoxyglucose positron emission tomography/computed tomography
Jiawen Chen1 . Wei Ouyang1
Received: 18 March 2025 / Revised: 28 June 2025 / Accepted: 4 July 2025 / Published online: 15 August 2025 @ The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025
Abstract
This case report describes a 19-month-old boy presenting with macropenis, increased stature, and deep voice, who was diag- nosed with concurrent choroid plexus carcinoma in the right lateral ventricle and left adrenocortical carcinoma. Subsequent germline testing revealed pathogenic TP53 mutations, confirming a diagnosis of Li-Fraumeni syndrome. Li-Fraumeni syn- drome with primary manifestations of macropenis and accelerated linear growth has rarely been documented in the medical literature. This case highlights the critical importance of implementing whole-body imaging modalities in pediatric patients with growth-developmental abnormalities, particularly those suggestive of Li-Fraumeni syndrome, to guide therapeutic decision-making and follow-up monitoring.
Keywords Adrenocortical carcinoma . Choroid plexus carcinoma · Li-Fraumeni syndrome . Magnetic resonance imaging . Positron emission tomography computed tomography
Introduction
Li-Fraumeni syndrome is an inherited cancer susceptibil- ity disorder, resulting from germline mutations of the TP53 tumor suppressor gene, which was initially described in 1969 by Frederick Li and Joseph Fraumeni in four families and the original definition was subsequently established in 1988 from 24 families [1]. It represents one of the most aggressive cancer predisposition syndromes in childhood, with a diverse tumor spectrum that includes brain tumors (choroid plexus carcinoma, medulloblastoma), adrenocor- tical carcinoma, soft tissue sarcomas, bone tumors, hema- tologic malignancies, breast cancer, and other tumor types [2]. Timely screening for TP53 mutations in neonates and assessing the associated cancer risk are critical for the early
diagnosis of Li-Fraumeni syndrome [3]. While numerous case reports on Li-Fraumeni syndrome exist, the applica- tion of whole-body [18F]-fluorodeoxyglucose positron emis- sion tomography/computed tomography ([18F]-FDG PET/ CT) for diagnostic evaluation and longitudinal surveillance remains rarely documented, particularly regarding its role in long-term monitoring [4]. We describe a boy presenting with macropenis, accelerated linear growth and deep voice, leading to the incidental detection of synchronous primary malignancies: a right lateral ventricular choroid plexus carcinoma and left adrenocortical carcinoma. Subsequent germline testing revealed pathogenic TP53 mutations, con- firming Li-Fraumeni syndrome diagnosis. Serial [18F]-FDG PET/CT surveillance over 7 months demonstrated complete metabolic remission without recurrence. Informed consent for case publication and associated imaging materials was obtained from the patient’s parents.
☒ Wei Ouyang oyw1963@smu.edu.cn
Jiawen Chen
1 Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, No. 253 Gongye Street, Guangzhou 510280, China
Case report
A 19-month-old boy presented to hospital in early 2024 with macropenis measuring 6 cm in length, increased stature, and deep voice; radiographs of the bone age suggested that the bone age is equivalent to a 7-year-old. Cranial contrast- enhanced magnetic resonance imaging (MRI) revealed a heterogeneously enhancing mass in the posterior horn of the right lateral ventricle, displaying hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imag- ing, and uneven enhancement on dynamic contrast-enhanced MRI (Fig. 1). Magnetic resonance spectroscopy (MRS) sug- gested an extraventricular tumor. The patient underwent gen- eral anesthesia for resection of the right lateral ventricular lesion. Histopathological examination confirmed choroid plexus carcinoma (World Health Organization grade III) with a Ki-67 index of 80%.
Postoperatively, the patient was transferred to the pediatric intensive care unit and he was subjected to serum and urinary laboratory tests. The levels of serum
dehydroepiandrosterone sulfate (DHEA-S, 2,620 µg/ dL), androstenedione (AE, 2.9 ng/ml), and testosterone (6.3 ng/ml) were markedly elevated. The serum cortisol level was not elevated at morning (226 nmol/L), while the 4 pm cortisol level (318 nmol/L) and midnight cortisol level (171 nmol/L) were not suppressed. His 24-h urinary free cortisol (UFC) levels (15,784 nmol/24 h) were increased. His adrenocorticotropic hormone (ACTH) level was below the normal range at 8 am (<1.0 pg/mL), 4 pm (5.82 pg/mL), and midnight (<1.0 pg/mL). The growth hormone (GH, 8.38 µg/L) and 17-hydroxyprogesterone (17-OHP, 0.38 ng/ mL) were within the normal range.
Because of such a high level of serum DHEA-S, AE, and testosterone, we suspected a hormonally active adrenal tumor. Two weeks later, a whole-body [18F]-FDG PET/CT (Fig. 2) identified a large left adrenal mass with significant [18F]-FDG uptake, containing high-density calcifications and hypodense areas with relatively reduced [18F]-FDG uptake within the lesion. The lesion caused displacement of adja- cent structures, including the liver, left kidney, pancreas, and intestines. Genetic analysis of the brain tumor specimen
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revealed a TP53 mutation, and multidisciplinary consulta- tion established a diagnosis of Li-Fraumeni syndrome.
Given the large size of the adrenal mass, the patient received doxorubicin liposome-etoposide-methylpredni- solone (Qilu Pharmaceutical, Jinan, China) chemotherapy regimen and continuously took Mitotane (Laboratoire HRA Pharma, Paris, France) to reduce tumor volume prior to surgical intervention. After four cycles of chem- otherapy, the size of the tumor had shrunk and laparo- scopic retroperitoneal tumor resection was performed. Histopathology confirmed adrenocortical carcinoma with no lymph node metastasis, with a Ki-67 index of 8%.
The patient completed an additional four cycles of doxorubicin liposome-etoposide-methylprednisolone chemotherapy. Follow-up whole-body [18F]-FDG PET/CT 7 months after the first examination (Fig. 3) showed no
evidence of recurrence in the left adrenal gland or right lateral ventricle. However, persistent accelerated growth, with his height increasing from 86 to 98 cm during this period, was observed.
The patient remains in good clinical condition (con- tinuing taking Mitotane) with regular surveillance.
Discussion
Li-Fraumeni syndrome is clinically characterized by the development of malignancies across multiple organ sys- tems, typically occurring at a young age. It is reported that approximately 50% of individuals carrying TP53 muta- tions will develop cancer by the age of 30, with lifetime risks reaching up to 70% in males and nearly 100% in
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females [5]. Due to the elevated cancer risk and substan- tial associated morbidity and mortality, there is an urgent need to enhance clinical recognition of these syndromes. The uniqueness of this case lies not only in its rare endo- crine abnormalities but also in its multidisciplinary diag- nostic approach integrating advanced imaging and genetic analysis.
Macropenis, deep voice, accelerated linear growth, and advanced bone age are indicative of virilization in this patient and correspond to peripheral precocious puberty. This presentation should raise clinical suspicion for adren- ocortical carcinoma. In some patients, hormonally active adrenal tumors secrete not only androgens but also excess cortisol, leading to Cushing’s syndrome [6]. In our case, despite complete adrenal tumor resection and no recurrence, the patient exhibited persistent accelerated growth (12 cm height increase over 7 months), suggesting advance to cen- tral precocious puberty after surgery [7].
In this case, whole-body [18F]-FDG PET/CT not only monitored the postoperative status of the brain tumor but also identified the adrenal lesion, highlighting its unique
CT (d) brain images show no recurrence in the right lateral ventric- ular posterior horn (arrows). e-g Axial upper abdominal images of PET (e), CT (f), and PET/CT (g) reveal no evidence of recurrence in left adrenal gland. h-j Sagittal PET (h), CT (i), and PET/CT (j) images of pelvic show persistent macropenis (arrows)
value in screening for multiple primary malignancies in Li-Fraumeni syndrome patients. By evaluating metabolic activity, PET/CT enables early detection of occult lesions and postoperative recurrence, particularly before significant anatomical changes occur [8]. Postoperative PET/CT in this patient demonstrated complete metabolic remission, provid- ing objective evidence of therapeutic efficacy.
Author Contribution Jiawen Chen wrote the main manuscript text and prepared Figs. 1-3 and revised the manuscript. Jiawen Chen and Wei Ouyang reviewed the manuscript.
Data Availability No datasets were generated or analysed during the current study.
Declarations
Competing interests The authors declare no competing interests.
References
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