Figure 1
MRI brain and orbits
Li Fraumeni syndrome
SectionPaediatric radiology
Case TypeClinical Cases
AuthorsZubair Syed, Visad Patel, Kabir Gandhi, Greg Gerasymchuk
Connected authors
3 years, female
Clinical History
3-year-old girl with past medical history history of virilization at 1 year of age secondary to adrenal carcinoma. Adrenal mass was surgically removed and symptoms subsided. Patient currently presents with left-sided facial swelling.
Other history: The patient's mother was diagnosed with breast cancer at age 34.
Other history: The patient's mother was diagnosed with breast cancer at age 34.
Imaging Findings
Original ultrasound showed a mass arising from the left adrenal gland. The follow-up MRI of the abdomen showed a left adrenal mass with no significant enhancement which was found to be an adrenal carcinoma.
MRI of the brain and orbits was performed 2 years later and showed an enhancing mass adjacent to the left masseter which on biopsy was found to be a rhabdomyosarcoma.
After genetic workup, patient was found to have a p53 mutation.
MRI of the brain and orbits was performed 2 years later and showed an enhancing mass adjacent to the left masseter which on biopsy was found to be a rhabdomyosarcoma.
After genetic workup, patient was found to have a p53 mutation.
Discussion
Li-Fraumeni Syndrome (LFS) is an autosomal dominant genetic mutation in the p53 gene predisposing affected individuals to a variety of cancers including adrenal cortical carcinomas, soft tissue sarcomas, osteosarcomas, breast cancers, brain tumours, and leukaemia. Prior studies have demonstrated that over half of all cancers associated with the syndrome occur before the age of 30 [1]. Unfortunately, incidence still remains undetermined.
The classic Li-Fraumeni Criteria [2] for diagnosis requires:
1. Diagnosis of a sarcoma before the age of 45
2. Diagnosis of any cancer in a first-degree relative before the age of 45
3. Another first- or second-degree relative diagnosed with any cancer before the age of 45 or the diagnosis of sarcoma at any age
While clinical presentation is dependent on the specific cancer the patient presents with, any suspicion with the aforementioned criteria should motivate the clinician to gather a family history over at least 3 generations to investigate genetic causation. In the case of LFS, patients with the genetic abnormality have a 57% probability of developing a second primary malignancy within 30 years of the first primary malignancy [3, 4]. Additionally, due to the aggressive nature of the neoplasms, a thorough radiological work up is often indicated to decrease patient morbidity and mortality [1]. Finally, it is appropriate to point out that mothers of children diagnosed with soft-tissue sarcomas or osteosarcomas have a 3-fold increase in the risk for breast cancer at a younger age [5]. Early MRI driven screening modalities for breast cancer have shown early promise for LFS screening and will continue to be researched [6].
Genetic testing using sequence analysis of selected exons for the TP53 mutation or deletion is indicated for those satisfying the above criteria and additionally in women <30 years old with BRCA 1/2 negative breast cancers, individuals with adrenal cortical carcinoma, and individuals with choroid plexus carcinomas [7, 8].
Surveillance of additional primary neoplasms is paramount in patients with known TP53 mutation. Patients with LFS should have an annual physical examination with additional attention to the dermatologic and the neurological tests. Current criteria for surveillance for breast cancer should begin at 18-20 years and diagnostic imaging should begin at ages 20-25. For colorectal cancer, an initial screening colonoscopy should be performed at age 25 and subsequently every 2-5 years [9, 10].
Treatment goals for patients with LFS are specific for individual neoplasms with emphasis put on early detection of additional neoplasms.
The classic Li-Fraumeni Criteria [2] for diagnosis requires:
1. Diagnosis of a sarcoma before the age of 45
2. Diagnosis of any cancer in a first-degree relative before the age of 45
3. Another first- or second-degree relative diagnosed with any cancer before the age of 45 or the diagnosis of sarcoma at any age
While clinical presentation is dependent on the specific cancer the patient presents with, any suspicion with the aforementioned criteria should motivate the clinician to gather a family history over at least 3 generations to investigate genetic causation. In the case of LFS, patients with the genetic abnormality have a 57% probability of developing a second primary malignancy within 30 years of the first primary malignancy [3, 4]. Additionally, due to the aggressive nature of the neoplasms, a thorough radiological work up is often indicated to decrease patient morbidity and mortality [1]. Finally, it is appropriate to point out that mothers of children diagnosed with soft-tissue sarcomas or osteosarcomas have a 3-fold increase in the risk for breast cancer at a younger age [5]. Early MRI driven screening modalities for breast cancer have shown early promise for LFS screening and will continue to be researched [6].
Genetic testing using sequence analysis of selected exons for the TP53 mutation or deletion is indicated for those satisfying the above criteria and additionally in women <30 years old with BRCA 1/2 negative breast cancers, individuals with adrenal cortical carcinoma, and individuals with choroid plexus carcinomas [7, 8].
Surveillance of additional primary neoplasms is paramount in patients with known TP53 mutation. Patients with LFS should have an annual physical examination with additional attention to the dermatologic and the neurological tests. Current criteria for surveillance for breast cancer should begin at 18-20 years and diagnostic imaging should begin at ages 20-25. For colorectal cancer, an initial screening colonoscopy should be performed at age 25 and subsequently every 2-5 years [9, 10].
Treatment goals for patients with LFS are specific for individual neoplasms with emphasis put on early detection of additional neoplasms.
Differential Diagnosis List
Li Fraumeni syndrome
Li Fraumeni syndrome
Gardner\'s syndrome
Familial adenomatous polyposis
Retinoblastoma
Final Diagnosis
Li Fraumeni syndrome
References
[1] Shinagare AB, Giardino AA, Jagannathan JP et-al. (2011) Hereditary cancer syndromes: a radiologist\'s perspective. AJR Am J Roentgenol 197 (6): W1001-7 (PMID: 22109313)
[2] Li FP, Fraumeni JF Jr, Mulvihill JJ, et al. (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358-62 (PMID: 3409256)
[3] Hisada M, Garber JE, Fung CY, Fraumeni JF, Li FP (1998) Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst 90(8):606-11 (PMID: 9554443)
[4] Hwang SJ, Lozano G, Amos CI, Strong LC (2003) Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk. Am J Hum Genet 72(4):975-83 (PMID: 12610779)
[5] Birch JM, Hartley AL, Marsden HB, et al. (1984) Excess risk of breast cancer in the mothers of children with soft tissue sarcomas. Br J Cancer 49(3):325-31 (PMID: 6704308)
[6] Saslow D, Boetes C, Burke W, et al. (2007) American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57(2):75-89 (PMID: 17392385)
[7] Mccuaig JM, Armel SR, Novokmet A, et al. (2012) Routine TP53 testing for breast cancer under age 30: ready for prime time?. Fam Cancer 11(4):607-13 (PMID: 22851211)
[8] Seidinger AL, Mastellaro MJ, Paschoal fortes F, et al. (2011) Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil. Cancer 117(10):2228-35 (PMID: 21192060)
[9] Villani A, Tabori U, Schiffman J, et al. (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12(6):559-67 (PMID: 21601526)
[10] National Comprehensive Cancer Network (2014) NCCN Guidelines: Li-Fraumeni Syndrome.
Case information
| URL: | https://www.eurorad.org/case/11636 |
| DOI: | 10.1594/EURORAD/CASE.11636 |
| ISSN: | 1563-4086 |
