Primary Orbital Liposarcoma in Li-Fraumeni Cancer Family Syndrome: A Case Report

2005 ◽  
Vol 91 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Tito Poli ◽  
Francesco Laganà ◽  
Luigi Caradonna ◽  
Roberta Gobbi ◽  
Domenico Corradi ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Genetic Disorder ◽  
Molecular Profile ◽  
Prognostic Information ◽  
Upper Eyelid ◽  
Li Fraumeni Syndrome ◽  
Clinical Criteria ◽  
Li Fraumeni ◽  
Cellular Markers ◽  
The Right

Aims and background The aim of this study was to describe a case of primary orbital liposarcoma in Li-Fraumeni syndrome. Methods and study design In July 1998 a 20-year-old woman with a histological diagnosis of orbital myxoid liposarcoma underwent surgical treatment in our department. Since the patient's family pedigree met the clinical criteria for the diagnosis of LFS, molecular analysis was performed, which resulted in a molecular profile consistent with Li-Fraumeni syndrome. Results The patient underwent orbital exenteration extended to the upper eyelid; surgical reconstructive steps were performed to permit placement of an orbital prosthesis. Two years after primary surgery the patient underwent a quadrantectomy with lymphadenectomy of the right axilla because of the presence of a nodule of 1.5 cm in diameter in the upper-lateral quadrant of the right breast. One year after the last surgery, the patient is disease free. Conclusion The diagnosis of an orbital malignancy in a young patient with a family history of cancer should suggest the presence of an underlying genetic disorder like LFS; with molecular analysis we can now determine the genetic disorder and the exact location of the mutation, and also obtain important prognostic data using specific cellular markers. More prognostic information increases the chances of adequate personalized treatment.

scholarly journals Li–Fraumeni-szindróma

2019 ◽  
Vol 160 (6) ◽  
pp. 228-234
Author(s):  
Anita Sejben ◽  
László Tiszlavicz ◽  
Kornélia Polyák ◽  
László Kovács ◽  
Anikó Maráz ◽  
...  
Keyword(s):  
Family History ◽  
Adjuvant Chemotherapy ◽  
Inflammatory Myofibroblastic Tumor ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Li Fraumeni Syndrome ◽  
Cancer Types ◽  
Li Fraumeni ◽  
The Individual ◽  
The Right

Abstract: Li-Fraumeni syndrome is a rare genetic disorder predisposing the individual to multiple different cancer types, caused by a germline mutation of the TP53 or CHEK2 genes inherited in an autosomal dominant manner. We hereby describe the case of a family with Li–Fraumeni syndrome. An asymptomatic 40-year-old female was diagnosed with primary lung leiomyosarcoma (T3N0), adenocarcinoma (T1aN0), and inflammatory myofibroblastic tumor, which were surgically removed without further treatment. Twenty months later she underwent surgery for retroperitoneal liposarcoma and even though she received adjuvant chemotherapy, deceased shortly after. Due to family history, the patient underwent TP53 mutation testing, using peripheral blood genomic DNA, which identified a heterozygous, likely pathogenic missense mutation (c.722C>G p.Ser241Cys) in case of the mother and her son. Three years after the patient’s death, her 17-year-old son was diagnosed with a 3.5 cm osteosarcoma of the right second rib, which was surgically removed, followed by adjuvant chemotherapy. However, despite treatment, he deceased after two years. Throughout four generations of the patient’s family, 10 malignant tumors (stomach-, breast-, 2 lung-, and colon cancer, leukemia, leiomyosarcoma, liposarcoma and 2 osteosarcoma) were diagnosed with a mean age of 43.2 (13–70 years) years. The simultaneous appearance of primary lung leiomyosarcoma, inflammatory myofibroblastic tumor and adenocarcinoma in the same organ is extremely rare. When possible, surgical resection should be carried out. Genetic testing for TP53 is recommended when family history is suggestive of Li–Fraumeni syndrome. Prognosis remains poor. Orv Hetil. 2019; 160(6): 228–234.

scholarly journals Osteosarcoma of the Mandible in a Patient with Florid Cemento-Osseous Dysplasia and Li–Fraumeni Syndrome: A Rare Coincidence

2020 ◽  
Author(s):  
Simon Haefliger ◽  
Dorothee Harder ◽  
Michal Kovac ◽  
Karin Linkeschova ◽  
Harald Eufinger ◽  
...  
Keyword(s):  
Root Resorption ◽  
Bilateral Breast Cancer ◽  
Li Fraumeni Syndrome ◽  
Osseous Dysplasia ◽  
Left Posterior ◽  
Bone Biopsies ◽  
Li Fraumeni ◽  
Causative Relation ◽  
High Grade Osteosarcoma ◽  
The Right

Abstract Cemento-osseous dysplasia (COD) is the most common benign fibro-osseous lesion of the jaws and generally considered non-neoplastic and self-limited. Here, we present a 30-year old female who noticed a bilateral swelling of her posterior mandible with irregular periapical mineralization and incomplete root resorption on panoramic radiographs. A biopsy revealed florid COD and no further treatment was initiated. 9 years later, she presented with a progressive expansion of her left posterior mandible after being treated for bilateral breast cancer 4 and 8 years before. CT scans showed expansile and densely mineralized lesions in all four quadrants with the left posterior mandible showing a focal penetration of the buccal cortical bone. Biopsies revealed an osteoblastic high-grade osteosarcoma in the left and a COD in the right mandible, notably with cellular atypia in the spindle cell component. The patient underwent segmental resection of the left mandible with clear margins and adjuvant chemotherapy. Subsequent genetic testing identified a heterozygous germline TP53 mutation (p.V173G) which confirmed the clinically suspected Li–Fraumeni syndrome (LFS). 3 years after the resection, the patient is free of disease and the other foci of COD remained stable in size on follow-up imaging analyses. Our case illustrates LFS-related osteosarcoma developing within florid COD. Given the rarity of this coincidence, a causative relation between the two lesions seems unlikely but in patients with tumor predisposition syndromes it might be advisable to closely monitor even benign lesions like COD.

scholarly journals PEComa in a Young Patient with Known Li-Fraumeni Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Kyriakos Neofytou ◽  
Simone Famularo ◽  
Aamir Z. Khan
Keyword(s):  
Risk Stratification ◽  
Tumour Suppressor Gene ◽  
Malignant Potential ◽  
Renal Lesion ◽  
Epithelioid Angiomyolipoma ◽  
Li Fraumeni Syndrome ◽  
Cancer Predisposition Syndrome ◽  
Rare Tumours ◽  
Li Fraumeni ◽  
The Right

Perivascular epithelioid cells neoplasms (PEComas) constitute a family of rare tumours which have been reported virtually in all anatomic sites. The histological clarification of the malignant potential of these tumours is still problematic despite the proposed risk stratification systems. Li-Fraumeni syndrome (LFS) is caused by a germline mutation in the TP53 tumour suppressor gene. It is a rare but well-characterized cancer predisposition syndrome leading to the development of a variety of different tumour types. To the best of our knowledge, an association between this syndrome and PEComas has not been previously documented. A 24-year-old lady with known LFS presented with two uncertain-in-nature lesions, one within the right part of the liver and one within the upper pole of the right kidney. The patient underwent an uncomplicated open simultaneous right partial nephrectomy and resection of segment 7 of the liver. The morphological and immunohistochemical features of both lesions were of epithelioid angiomyolipoma (PEComa). Although the obvious scenario was that the liver lesion was a metastasis from the renal lesion, the assessment of their malignant potential according to the existing risk stratification systems was rather in favour of two synchronous primary PEComas, pointing out that the histological assessment of malignant potential of PEComas is still problematic.

scholarly journals An aggressive locoregional orbital rhabdomyosarcoma and Li Fraumeni syndrome

2021 ◽  
Vol 19 (1) ◽  
pp. 81-85
Author(s):  
Berrin Erok ◽  
◽  
Kenan Kıbıcı ◽  
Keyword(s):  
P53 Gene ◽  
Early Age ◽  
Past Medical History ◽  
Resonance Imaging ◽  
Rare Presentation ◽  
Orbital Mass ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
Magnetic Resonance Imaging Mri ◽  
The Right

Introduction. Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with 10 % of the cases occuring in the orbit. Patients often present with a rapidly developing proptosis and globe displacement. Aim. We aimed to present a very rare presentation of orbital RMS, with a giant exophytic orbital mass, a very rare presentation occuring in more advanced cases. Description of the case. A 3-year old girl presented to our hospital with a rapidly enlarging tissue like ulcerative mass. Her past medical history was remarkable with the diagnosis of embryonal rhabdomyosarcoma (RMS) and treatment with chemoradiotherapy at the age of 15 months. On magnetic resonance imaging (MRI), there was a giant heterogenously enhancing mass filling the right orbit and extending to the intracranial region. Li Fraumeni syndrome (LFS) was considered due to her sister death from neuroblastoma at an early age. Cytogenetic analysis revealed mutations of p53 gene, which supported our consideration. Conclusion. RMS is a highly malignant tumor which usually occurs sporadiacally. However, some rare syndromes are associated with increased incidence of RMS, such as LFS.

TP53, a gene for colorectal cancer predisposition in the absence of Li-Fraumeni-associated phenotypes

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321825
Author(s):  
Mariona Terradas ◽  
Pilar Mur ◽  
Sami Belhadj ◽  
Emma R Woodward ◽  
George J Burghel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
International Agency ◽  
Loss Of Function ◽  
Total N ◽  
Li Fraumeni Syndrome ◽  
Clinical Criteria ◽  
Panel Testing ◽  
Background Population ◽  
Li Fraumeni

ObjectiveGermline TP53 pathogenic (P) variants cause Li-Fraumeni syndrome (LFS), an aggressive multitumor-predisposing condition. Due to the implementation of multigene panel testing, TP53 variants have been detected in individuals without LFS suspicion, for example, patients with colorectal cancer (CRC). We aimed to decipher whether these findings are the result of detecting the background population prevalence or the aetiological basis of CRC.DesignWe analysed TP53 in 473 familial/early-onset CRC cases and evaluated the results together with five additional studies performed in patients with CRC (total n=6200). Control population and LFS data were obtained from Genome Aggregation Database (gnomAD V.2.1.1) and the International Agency for Research on Cancer (IARC) TP53 database, respectively. All variants were reclassified according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), following the ClinGen TP53 Expert Panel specifications.ResultsP or likely pathogenic (LP) variants were identified in 0.05% of controls (n=27/59 095) and 0.26% of patients with CRC (n=16/6200) (p<0.0001) (OR=5.7, 95% CI 2.8 to 10.9), none of whom fulfilled the clinical criteria established for TP53 testing. This association was still detected when patients with CRC diagnosed at more advanced ages (>50 and>60 years) were excluded from the analysis to minimise the inclusion of variants caused by clonal haematopoiesis. Loss-of-function and missense variants were strongly associated with CRC as compared with controls (OR=25.44, 95% CI 6.10 to 149.03, for loss of function and splice-site alleles, and OR=3.58, 95% CI 1.46 to 7.98, for missense P or LP variants).ConclusionTP53 P variants should not be unequivocally associated with LFS. Prospective follow-up of carriers of germline TP53 P variants in the absence of LFS phenotypes will define how surveillance and clinical management of these individuals should be performed.

scholarly journals Identification of the TP53 p.R337H Variant in Tumor Genomic Profiling Should Prompt Consideration of Germline Testing for Li-Fraumeni Syndrome

2021 ◽  
pp. 1141-1150
Author(s):  
Renata Lazari Sandoval ◽  
Cibele Masotti ◽  
Mariana Petaccia de Macedo ◽  
Maurício Fernando Silva Almeida Ribeiro ◽  
Ana Carolina Rathsam Leite ◽  
...  
Keyword(s):  
Founder Mutation ◽  
Care Center ◽  
Tertiary Care ◽  
Brazilian Population ◽  
Genomic Profiling ◽  
Li Fraumeni Syndrome ◽  
Clinical Criteria ◽  
Worldwide Population ◽  
Li Fraumeni ◽  
Germline Testing

PURPOSE Li-Fraumeni syndrome (LFS) is rare in the worldwide population, but it is highly prevalent in the Brazilian population because of a founder mutation, TP53 p.R337H, accounting for 0.3% of south and southeastern population. Clinical criteria for LFS may not identify all individuals at risk of carrying the Brazilian founder mutation because of its lower penetrance and variable expressivity. This variant is rarely described in databases of somatic mutations. Somatic findings in tumor molecular profiling may give insight to identify individuals who might be carriers of LFS and allow the adoption of risk reduction strategies for cancer. MATERIALS AND METHODS We determined the frequency of the TP53 p.R337H variant in tumor genomic profiling from 755 consecutive Brazilian patients with pan-cancer. This is a retrospective cohort from January 2013 to March 2020 at a tertiary care center in Brazil. RESULTS The TP53 p.R337H variant was found in 2% (15 of 755) of the samples. The mutation allele frequency ranged from 30% to 91.7%. A total of seven patients were referred for genetic counseling and germline testing after tumor genomic profiling results were disclosed. All the patients who proceeded with germline testing (6 of 6) confirmed the diagnosis of LFS. Family history was available in 12 cases. Nine patients (9 of 12) did not meet LFS clinical criteria. CONCLUSION The identification of the TP53 p.R337H variant in tumor genomic profiling should be a predictive finding of LFS in the Brazilian population and should prompt testing for germline status confirmation.

scholarly journals Bilateral renal angiomyolipomas in tuberous sclerosis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Bushra Jawaid ◽  
Abdul Hafeez Qureshi ◽  
Nadeem Ahmed ◽  
Nousheen Yaqoob
Keyword(s):  
Tuberous Sclerosis ◽  
Genetic Disorder ◽  
Abdominal Mass ◽  
Mtor Inhibitors ◽  
Percutaneous Biopsy ◽  
The Body ◽  
Clinical Criteria ◽  
Contralateral Kidney ◽  
Multiple Organs ◽  
The Right

Abstract Background Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign hamartomas in multiple organs of the body. Renal angiomyolipomas (AML) are commonly associated with TSC. They are mostly asymptomatic. But large and rapidly growing AMLs with the presence of an aneurysm cause symptoms and pose a life-threatening risk for hemorrhage. Case presentation Our patient is a 25-year-old female who presented to us as an undiagnosed case of tuberous sclerosis having a large abdominal mass. She fulfilled the clinical criteria required for the diagnosis of TSC. The CT scan revealed an 18 × 13 × 33 cm fat-containing lesion in the right kidney with an adjacent aneurysm measuring around 16 cm in diameter. Due to the large size of the AML and associated aneurysm, surgical exploration was mandated. On the contralateral kidney, multiple contrast-enhancing soft-tissue densities were present that appeared suspicious on radiology. So a percutaneous biopsy of those lesions was done. Fortunately, it had the same histopathology as an Angiomyolipoma. Nephrectomy of the right-sided kidney with AML has been done. The left-sided lesions that are less than 2 cm and asymptomatic are kept on close surveillance. Any change in size will prompt therapy with mTOR inhibitors. Conclusion When dealing with bilateral renal AML, it is important to adopt a conservative approach. When intervention is indicated, the least invasive strategy should be sought and enacted. Radical surgery should be the last resort.

scholarly journals Multiple meningiomas arising within the same hemisphere associated with Li-Fraumeni syndrome

2021 ◽  
Vol 12 ◽  
pp. 99
Author(s):  
Christopher S. Hong ◽  
E. Zeynep Erson-Omay ◽  
Jennifer Moliterno
Keyword(s):  
Right Hemisphere ◽  
Neurofibromatosis Type ◽  
World Health ◽  
Li Fraumeni Syndrome ◽  
Multiple Meningiomas ◽  
Radiation History ◽  
Li Fraumeni ◽  
Health Organization ◽  
The Right ◽  
Time Of Presentation

Background: While meningiomas are some of the most common intracranial tumors, the presence of multiple ones at the time of presentation is rare and can most commonly be observed in patients with well-described syndromes (i.e., neurofibromatosis type 2) or those with prior cranial radiation history. In others, however, the pathophysiology remains unclear. Case Description: A 49-year-old female with no significant personal or familial oncologic medical history presented with a generalized seizure and was found to have ten meningiomas arising within the right hemisphere. She underwent a two-staged resection of all tumors, with pathology revealing the World Health Organization Grade I meningioma. Whole-exome sequencing revealed somatic NF2 mutations and heterozygous deletion of chromosome 22 overlapping with NF2, and analysis of the germline uncovered mutations of TP53, rendering a diagnosis of Li-Fraumeni Syndrome. Conclusions: This case represents a novel presentation of multiple meningiomas in a patient with newly diagnosed Li-Fraumeni syndrome, suggesting meningioma may be considered as part of this tumor-predisposed patient population.

scholarly journals Prevalence of Germline TP53 Mutations in a Prospective Series of Unselected Patients with Adrenocortical Carcinoma

2013 ◽  
Vol 98 (1) ◽  
pp. E119-E125 ◽  
Author(s):  
Victoria M. Raymond ◽  
Tobias Else ◽  
Jessica N. Everett ◽  
Jessica M. Long ◽  
Stephen B. Gruber ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Family History ◽  
Adrenocortical Carcinoma ◽  
Genetic Counselor ◽  
Tp53 Gene ◽  
Age At Diagnosis ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
Clinical Criteria ◽  
Li Fraumeni

Abstract Purpose: Adrenocortical carcinoma (ACC) is a hallmark cancer in families with Li Fraumeni syndrome (LFS) caused by mutations in the TP53 gene. The prevalence of germline TP53 mutations in children diagnosed with ACC ranges from 50–97%. Although existing criteria advocate for TP53 testing in all patients with ACC regardless of age at diagnosis, the overall prevalence of germline mutations in patients diagnosed with ACC has not been well studied. Patients and Methods: A total of 114 patients with confirmed ACC evaluated in the University of Michigan Endocrine Oncology Clinic were prospectively offered genetic counseling and TP53 genetic testing, regardless of age at diagnosis or family history. Ninety-four of the 114 patients met with a genetic counselor (82.5%), with 53 of 94 (56.4%) completing TP53 testing; 9.6% (nine of 94) declined testing. The remainder (32 of 94; 34%) expressed interest in testing but did not pursue it for various reasons. Results: Four of 53 patients in this prospective, unselected series were found to have a TP53 mutation (7.5%). The prevalence of mutations in those diagnosed over age 18 was 5.8% (three of 52). There were insufficient data to estimate the prevalence in those diagnosed under age 18. None of these patients met clinical diagnostic criteria for classic LFS. Three of the families met criteria for Li Fraumeni-like syndrome; one patient met no existing clinical criteria for LFS or Li Fraumeni-like syndrome. Three of the four patients with mutations were diagnosed with ACC after age 45. Conclusions: Genetic counseling and germline testing for TP53 should be offered to all patients with ACC. Restriction on age at diagnosis or strength of the family history would fail to identify mutation carriers.

scholarly journals Bilateral Cryptophthalmus: First Case Report from Nepal

2021 ◽  
Vol 13 (2) ◽  
pp. 211-218
Author(s):  
Nayana Pant ◽  
Subash Bhatta ◽  
Gulshan Bahadur Shrestha ◽  
Madhu Thapa
Keyword(s):  
Case Report ◽  
Genetic Disorder ◽  
Ocular Tissue ◽  
Amniotic Membrane Transplantation ◽  
Upper Eyelid ◽  
First Case ◽  
Continuous Sheet ◽  
Male Neonate ◽  
The Right ◽  
Orbital Region

Introduction: Cryptophthalmus is characterized by a partial or complete casing of the eyeball by the skin. Cryptophthalmus alongside other systemic abnormalities is well-known as Fraser syndrome. It is an unusual genetic disorder with limited literature. The complexities of disease and limited experience pose challenges in its management. Case: A two-day-male neonate was brought by his parents with a complaint of swelling in the right orbital region and deformed left eye since birth. Examination revealed bilobed globular swelling in the right orbital region covered by a continuous sheet of skin from forehead to cheek with no visible ocular tissue. On the left side, there was absence of upper lid margin and eyelashes and superior symblepharon. He also had bilateral ear abnormalities and right renal agenesis. Surgical intervention was done. On the right side, removal of the globe and cyst was done. On the left side, upper eyelid reconstruction with symblepharon release was done with amniotic membrane transplantation. Conclusions: The management of cryptophthalmus is challenging. Reconstructive surgeries allow cosmesis but useful vision is rarely gained. This is the first case report from Nepal to date to the best of our knowledge.

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