A Rare Pediatric Case of Li-Fraumeni Syndrome Presenting with Macropenis and Dual Primary Malignancies on MRI and 18F-FDG PET/CT

A Rare Pediatric Case of Li-Fraumeni Syndrome Presenting with Macropenis and Dual Primary Malignancies on MRI and 18F-FDG PET/CT | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Pediatric Case of Li-Fraumeni Syndrome Presenting with Macropenis and Dual Primary Malignancies on MRI and 18F-FDG PET/CT Jiawen Chen, Wei Ouyang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6251040/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract This case report describes a 19-month-old boy presenting with macropenis and increased stature, who was incidentally diagnosed with concurrent choroid plexus carcinoma in the right lateral ventricle and left adrenocortical carcinoma. Subsequent germline testing revealed a pathogenic TP53 mutations, confirming a diagnose of Li-Fraumeni syndrome(LFS). LFS with primary manifestations of macropenis and accelerated linear growth has rarely been documented in the medical literature. This case highlight 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. macropenis adrenocortical carcinoma choroid plexus carcinoma Li-Fraumeni syndrome MRI 18F-FDG PET/CT Figures Figure 1 Figure 2 Figure 3 Introduction Li-Fraumeni syndrome (LFS) is an inherited cancer susceptibility 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, adrenocortical carcinoma, soft tissue sarcomas, bone tumors, hematologic 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 LFS[ 3 ]. While numerous case reports on LFS exist, the application of whole-body 18 F-FDG PET/CT for diagnostic evaluation and longitudinal surveillance remains rare documented, particularly regarding its role in long-term monitoring[ 4 ]. We present a pediatric case presenting with macropenis and accelerated linear growth, leading to the incidental detection of synchronous primary malignancies: a right lateral ventricular choroid plexus carcinoma and left adrenocortical carcinoma. Subsequent germline testing revealed a pathogenic TP53 mutations, confirming LFS diagnosis. Serial PET/CT surveillance over 7 months demonstrated complete metabolic remission without recurrence. Written informed consent was obtained for case publication from his parents. Case report A 19-month-old boy presented to hospital in early 2024 with macropenis and increased stature, X-ray photos of the bone age suggested that the bone age is equivalent to a 7-year-old. Cranial contrast-enhanced MRI (Fig. 1 ) revealed a heterogeneously enhancing mass in the posterior horn of the right lateral ventricle, displaying hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, and uneven enhancement on dynamic contrast-enhanced MRI. Magnetic resonance spectroscopy (MRS) suggested an extraventricular tumor. The patient underwent general anesthesia for resection of the right lateral ventricular lesion. Histopathological examination confirmed choroid plexus carcinoma (WHO grade III) with a Ki-67 index of 80%. Postoperatively, the patient was transferred to the pediatric intensive care unit. Laboratory tests revealed normal adrenocorticotropic hormone (ACTH) levels but significantly elevated 24-hour urinary free cortisol (UFC) levels (15,784 nmol/24h) and mildly elevated growth hormone (GH) levels (8.38 µg/L). Because of such a high level of hormones, we were worried that he still had other lesions. Two weeks later, a whole-body 18 F-FDG PET/CT (Fig. 2 ) identified a large left adrenal mass with significant FDG uptake, containing high-density calcifications and hypodense areas with relatively reduced FDG uptake within the lesion. The lesion caused displacement of adjacent structures, including the liver, left kidney, pancreas, and intestines. Biopsy in favor of an adrenocortical carcinoma. Genetic analysis of the brain tumor specimen revealed a TP53 mutation, and multidisciplinary consultation established a diagnosis of LFS. Given the large size of the adrenal mass, the patient received chemotherapy (DEP regimen) and continuously took Mitotane to reduce tumor volume prior to surgical intervention. After 4 cycles of chemotherapy, the size of tumor had shrunk and laparoscopic 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 4 cycles of adjuvant DEP chemotherapy. Follow-up whole-body 18 F-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 macropenis and accelerated growth, with his height increasing from 86 cm to 98 cm during this period were observed. The patient remains in good clinical condition, continuing taking Mitotane and regular surveillance. Discussion LFS is clinically characterized by the development of malignancies across multiple organ systems, typically occurring at a young age. It is reported that approximately 50% of individuals carrying TP53 mutations will develop cancer by the age of 30, with lifetime risks reaching up to 70% in males and nearly 100% in females[ 5 ]. Due to the elevated cancer risk and substantial 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 endocrine abnormalities but also in its multidisciplinary diagnostic approach integrating advanced imaging and genetic analysis. Macropenis and accelerated linear growth in this patient may be associated with adrenocortical carcinoma, which can lead to peripheral precocious puberty, resulting in virilization signs such as pubic hair development, penile or clitoral enlargement, and hirsutism. In rare cases, excessive cortisol secretion may induce Cushing syndrome[ 6 ]. In our case, despite complete tumor resection and no recurrence, the patient exhibited persistent accelerated growth (12 cm height increase over 7 months), suggesting advance to central precocious puberty after surgery[ 7 ]. In this case, whole-body 18 F-FDG PET/CT not only monitored the postoperative status of the brain tumor but also incidentally identified the adrenal lesion, highlighting its unique value in screening for multiple primary malignancies in LFS 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 (SUVmax < 1.5), providing objective evidence of therapeutic efficacy. Declarations Author Contribution Jiawen Chen wrote the main manuscript text and prepared figures 1-3. Jiawen Chen and Wei Ouyang reviewed the manuscript. References Li FP, Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747–752 Kratz CP, Achatz MI, Brugières L et al (2017) Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. Clin cancer research: official J Am Association Cancer Res 23:e38–e45 Wasserman JD, Novokmet A, Eichler-Jonsson C et al (2015) Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study. J Clin oncology: official J Am Soc Clin Oncol 33:602–609 Gosangi B, Dixe de Oliveira Santo I, Keraliya A et al (2024) Li-Fraumeni Syndrome: Imaging Features and Guidelines. Radiographics: Rev publication Radiological Soc North Am Inc 44:e230202 McBride KA, Ballinger ML, Killick E et al (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat reviews Clin Oncol 11:260–271 Ilanchezhian M, Varghese DG, Glod JW et al (2022) Pediatric adrenocortical carcinoma. Front Endocrinol 13:961650 Kim MS, Yang EJ, Cho DH et al (2015) Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery. Korean J family Med 36:150–153 Kan Y, Si Y, Wang W et al (2022) Simultaneous Detection of 2 Types of Malignancies in a Pediatric Patient on FDG PET/CT Led to Diagnosis of Li-Fraumeni Syndrome. Clin Nucl Med 47:912–913 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 15 May, 2025 Reviews received at journal 08 Apr, 2025 Reviewers agreed at journal 29 Mar, 2025 Reviewers invited by journal 24 Mar, 2025 Editor assigned by journal 20 Mar, 2025 Submission checks completed at journal 20 Mar, 2025 First submitted to journal 18 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6251040","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":432992856,"identity":"50465482-48ed-43a8-a498-62c64e92bb95","order_by":0,"name":"Jiawen Chen","email":"","orcid":"","institution":"Zhujiang Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiawen","middleName":"","lastName":"Chen","suffix":""},{"id":432992857,"identity":"a12098fd-0735-4e62-a694-ff0b735bb215","order_by":1,"name":"Wei Ouyang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYJCCAx8qauQgTDbidDAenHHmmDFJWpgP87YwJzYQrYVfIsfgMG8DW/r8aWcMGD6UHWbgn92AX4vkjByDg3N3yORuuJ1jwDjj3GEGiTsH8GsxuJG74cDbM2y5G6RzDJh52w4zGEgkEKGFt405XX42UMtfYrUcBGpJYAA6jJmRGC2SPe8/gALZcMPttIKDPefSeSRuENDCz56W/AEYlfLys5M3PvhRZi3HP4OAFgYBJAUHgJiHgHqQNQcIqxkFo2AUjIIRDgCmhklGSiKIoQAAAABJRU5ErkJggg==","orcid":"","institution":"Zhujiang Hospital of Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Wei","middleName":"","lastName":"Ouyang","suffix":""}],"badges":[],"createdAt":"2025-03-18 08:38:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6251040/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6251040/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79263169,"identity":"125fc9ca-3c1b-452d-b702-1253f8b3a89b","added_by":"auto","created_at":"2025-03-26 09:49:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":919503,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI findings in a 19-month-old boy presenting with macropenis, adult voice and accelerated growth of stature. Brain MRI (A,T1-weighted; B,T2-weighted; C,DWI) demonstrate a 55×45 mm lesion in the right lateral ventricular posterior horn (arrows), highly suggestive of malignancy. On dynamic contrast-enhanced MRI (D-F: axial, coronal, and sagittal T1-weighted images), the tumor displayed uneven enhancement with no significant ventricular dilatation observed in the surrounding structures\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6251040/v1/54585f886cef39e1a3d68cb1.png"},{"id":79263170,"identity":"2f8c0397-9148-452a-9821-d7161f16c1e8","added_by":"auto","created_at":"2025-03-26 09:49:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":991654,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT findings 2 weeks after the brain tumor resection. The MIP (A) revealed a hypermetabolic lesion in the right upper abdomen (A, arrow). Axial brain images (B: PET; C: CT; D: fusion) revealed complete resection of the primary lesion with residual surgical cavity (arrows) in the right lateral ventricular posterior horn, with decreased FDG uptake. On the axial upper abdominal images (E: PET; F: CT; G: fusion), a large left adrenal mass measuring approximately 112×92 mm was observed, showing significant FDG uptake and SUVmax up to 11.9 (arrows), containing high-density calcifications and hypodense areas with relatively reduced FDG uptake within the lesion. On the sagittal pelvic images (H: PET; I: CT; J: fusion), macropenis was identified, with a length of approximately 6 cm (arrows)\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6251040/v1/989e805b566dd79114cea149.png"},{"id":79265070,"identity":"83ab7356-5f5e-4971-a48f-81026bb0140b","added_by":"auto","created_at":"2025-03-26 09:57:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1000207,"visible":true,"origin":"","legend":"\u003cp\u003e\u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT findings 7 months after the first PET/CT examination. The MIP (A) showed no hypermetabolism after the resection of adrenocortical carcinoma. Axial brain images (B: PET; C: CT; D: fusion) and axial upper abdominal images (E: PET; F: CT; G: fusion) revealed no evidence of recurrence in the right lateral ventricle and left adrenal gland. The sagittal pelvic images (H: PET; I: CT; J: fusion) showed persistent macropenis, with a length of approximately 7 cm (arrows)\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6251040/v1/fa2c267e678cac0d8ffaa4b3.png"},{"id":79265073,"identity":"563e8dd1-1a40-4c72-ab6a-83a35d915ca6","added_by":"auto","created_at":"2025-03-26 09:57:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3081934,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6251040/v1/6a66ea3b-1fba-42da-9f2c-c78abd4f2b42.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Pediatric Case of Li-Fraumeni Syndrome Presenting with Macropenis and Dual Primary Malignancies on MRI and 18F-FDG PET/CT","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLi-Fraumeni syndrome (LFS) is an inherited cancer susceptibility disorder, resulting from germline mutations of the \u003cem\u003eTP53\u003c/em\u003e 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[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It represents one of the most aggressive cancer predisposition syndromes in childhood, with a diverse tumor spectrum that includes brain tumors, adrenocortical carcinoma, soft tissue sarcomas, bone tumors, hematologic malignancies, breast cancer, and other tumor types[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Timely screening for \u003cem\u003eTP53\u003c/em\u003e mutations in neonates and assessing the associated cancer risk are critical for the early diagnosis of LFS[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. While numerous case reports on LFS exist, the application of whole-body \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT for diagnostic evaluation and longitudinal surveillance remains rare documented, particularly regarding its role in long-term monitoring[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. We present a pediatric case presenting with macropenis and accelerated linear growth, leading to the incidental detection of synchronous primary malignancies: a right lateral ventricular choroid plexus carcinoma and left adrenocortical carcinoma. Subsequent germline testing revealed a pathogenic \u003cem\u003eTP53\u003c/em\u003e mutations, confirming LFS diagnosis. Serial PET/CT surveillance over 7 months demonstrated complete metabolic remission without recurrence. Written informed consent was obtained for case publication from his parents.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 19-month-old boy presented to hospital in early 2024 with macropenis and increased stature, X-ray photos of the bone age suggested that the bone age is equivalent to a 7-year-old. Cranial contrast-enhanced MRI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) revealed a heterogeneously enhancing mass in the posterior horn of the right lateral ventricle, displaying hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, and uneven enhancement on dynamic contrast-enhanced MRI. Magnetic resonance spectroscopy (MRS) suggested an extraventricular tumor. The patient underwent general anesthesia for resection of the right lateral ventricular lesion. Histopathological examination confirmed choroid plexus carcinoma (WHO grade III) with a Ki-67 index of 80%.\u003c/p\u003e\u003cp\u003ePostoperatively, the patient was transferred to the pediatric intensive care unit. Laboratory tests revealed normal adrenocorticotropic hormone (ACTH) levels but significantly elevated 24-hour urinary free cortisol (UFC) levels (15,784 nmol/24h) and mildly elevated growth hormone (GH) levels (8.38 µg/L).\u003c/p\u003e\u003cp\u003eBecause of such a high level of hormones, we were worried that he still had other lesions. Two weeks later, a whole-body \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) identified a large left adrenal mass with significant FDG uptake, containing high-density calcifications and hypodense areas with relatively reduced FDG uptake within the lesion. The lesion caused displacement of adjacent structures, including the liver, left kidney, pancreas, and intestines. Biopsy in favor of an adrenocortical carcinoma. Genetic analysis of the brain tumor specimen revealed a \u003cem\u003eTP53\u003c/em\u003e mutation, and multidisciplinary consultation established a diagnosis of LFS.\u003c/p\u003e\u003cp\u003eGiven the large size of the adrenal mass, the patient received chemotherapy (DEP regimen) and continuously took Mitotane to reduce tumor volume prior to surgical intervention. After 4 cycles of chemotherapy, the size of tumor had shrunk and laparoscopic retroperitoneal tumor resection was performed. Histopathology confirmed adrenocortical carcinoma with no lymph node metastasis, with a Ki-67 index of 8%.\u003c/p\u003e\u003cp\u003eThe patient completed an additional 4 cycles of adjuvant DEP chemotherapy. Follow-up whole-body \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT 7 months after the first examination (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) showed no evidence of recurrence in the left adrenal gland or right lateral ventricle. However, persistent macropenis and accelerated growth, with his height increasing from 86 cm to 98 cm during this period were observed.\u003c/p\u003e\u003cp\u003eThe patient remains in good clinical condition, continuing taking Mitotane and regular surveillance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLFS is clinically characterized by the development of malignancies across multiple organ systems, typically occurring at a young age. It is reported that approximately 50% of individuals carrying \u003cem\u003eTP53\u003c/em\u003e mutations will develop cancer by the age of 30, with lifetime risks reaching up to 70% in males and nearly 100% in females[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Due to the elevated cancer risk and substantial 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 endocrine abnormalities but also in its multidisciplinary diagnostic approach integrating advanced imaging and genetic analysis.\u003c/p\u003e \u003cp\u003eMacropenis and accelerated linear growth in this patient may be associated with adrenocortical carcinoma, which can lead to peripheral precocious puberty, resulting in virilization signs such as pubic hair development, penile or clitoral enlargement, and hirsutism. In rare cases, excessive cortisol secretion may induce Cushing syndrome[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In our case, despite complete tumor resection and no recurrence, the patient exhibited persistent accelerated growth (12 cm height increase over 7 months), suggesting advance to central precocious puberty after surgery[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this case, whole-body \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT not only monitored the postoperative status of the brain tumor but also incidentally identified the adrenal lesion, highlighting its unique value in screening for multiple primary malignancies in LFS patients. By evaluating metabolic activity, PET/CT enables early detection of occult lesions and postoperative recurrence, particularly before significant anatomical changes occur[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Postoperative PET/CT in this patient demonstrated complete metabolic remission (SUVmax\u0026thinsp;\u0026lt;\u0026thinsp;1.5), providing objective evidence of therapeutic efficacy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJiawen Chen wrote the main manuscript text and prepared figures 1-3. Jiawen Chen and Wei Ouyang reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLi FP, Fraumeni JF Jr (1969) Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med 71:747\u0026ndash;752\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKratz CP, Achatz MI, Brugi\u0026egrave;res L et al (2017) Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. Clin cancer research: official J Am Association Cancer Res 23:e38\u0026ndash;e45\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWasserman JD, Novokmet A, Eichler-Jonsson C et al (2015) Prevalence and functional consequence of TP53 mutations in pediatric adrenocortical carcinoma: a children's oncology group study. J Clin oncology: official J Am Soc Clin Oncol 33:602\u0026ndash;609\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGosangi B, Dixe de Oliveira Santo I, Keraliya A et al (2024) Li-Fraumeni Syndrome: Imaging Features and Guidelines. Radiographics: Rev publication Radiological Soc North Am Inc 44:e230202\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcBride KA, Ballinger ML, Killick E et al (2014) Li-Fraumeni syndrome: cancer risk assessment and clinical management. Nat reviews Clin Oncol 11:260\u0026ndash;271\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIlanchezhian M, Varghese DG, Glod JW et al (2022) Pediatric adrenocortical carcinoma. Front Endocrinol 13:961650\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim MS, Yang EJ, Cho DH et al (2015) Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery. Korean J family Med 36:150\u0026ndash;153\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKan Y, Si Y, Wang W et al (2022) Simultaneous Detection of 2 Types of Malignancies in a Pediatric Patient on FDG PET/CT Led to Diagnosis of Li-Fraumeni Syndrome. Clin Nucl Med 47:912\u0026ndash;913\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prad","sideBox":"Learn more about [Pediatric Radiology](http://link.springer.com/journal/247)","snPcode":"247","submissionUrl":"https://submission.nature.com/new-submission/247/3","title":"Pediatric Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"macropenis, adrenocortical carcinoma, choroid plexus carcinoma, Li-Fraumeni syndrome, MRI, 18F-FDG PET/CT","lastPublishedDoi":"10.21203/rs.3.rs-6251040/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6251040/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis case report describes a 19-month-old boy presenting with macropenis and increased stature, who was incidentally diagnosed with concurrent choroid plexus carcinoma in the right lateral ventricle and left adrenocortical carcinoma. Subsequent germline testing revealed a pathogenic \u003cem\u003eTP53\u003c/em\u003e mutations, confirming a diagnose of Li-Fraumeni syndrome(LFS). LFS with primary manifestations of macropenis and accelerated linear growth has rarely been documented in the medical literature. This case highlight 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.\u003c/p\u003e","manuscriptTitle":"A Rare Pediatric Case of Li-Fraumeni Syndrome Presenting with Macropenis and Dual Primary Malignancies on MRI and 18F-FDG PET/CT","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-26 09:49:28","doi":"10.21203/rs.3.rs-6251040/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-15T09:49:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-08T19:58:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330394733643901316381926690221735177484","date":"2025-03-29T07:55:41+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-24T07:42:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-20T23:58:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-20T23:57:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Radiology","date":"2025-03-18T08:26:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-radiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prad","sideBox":"Learn more about [Pediatric Radiology](http://link.springer.com/journal/247)","snPcode":"247","submissionUrl":"https://submission.nature.com/new-submission/247/3","title":"Pediatric Radiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b808a78a-c5c5-44e4-aa3b-92ac4dc38444","owner":[],"postedDate":"March 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-04T21:38:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-26 09:49:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6251040","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6251040","identity":"rs-6251040","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}