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 Genomic and Clinical Correlates of Adrenocortical Carcinoma in an Adult Patient with Li-Fraumeni Syndrome: A Case Report

2020 ◽  
Vol 28 (1) ◽  
pp. 226-232
Author(s):  
Suraya Bondy ◽  
Camilla Tajzler ◽  
Sebastien J. Hotte ◽  
Anil Kapoor ◽  
Kevin Zbuk ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Ductal Carcinoma ◽  
Disease Recurrence ◽  
Tumour Suppressor Gene ◽  
Bilateral Mastectomy ◽  
Tissue Samples ◽  
Li Fraumeni Syndrome ◽  
Li Fraumeni ◽  
The Right

Li-Fraumeni Syndrome (LFS) is defined by germline mutations of the p53 tumour suppressor gene. Adrenocortical carcinoma (ACC) is a rare aggressive malignancy that is commonly associated with LFS. Most LFS-linked ACC cases occur in children, and limited research has been dedicated to the clinical outcomes and genomics of adult cases with LFS-linked ACC. We report on a 34-year-old female who was diagnosed with three separate malignancies: stage III invasive ductal carcinoma of the right breast, metastatic ACC from the right adrenal gland, and grade 2 pleomorphic sarcoma of the left hand. Her invasive breast ductal carcinoma was treated with neoadjuvant chemotherapy, and she received a bilateral mastectomy after her LFS was confirmed with genetic blood testing. Adrenal ACC was initially treated with a right nephrectomy and adrenalectomy, followed by adjuvant mitotane and two lines of chemotherapy after disease recurrence. Her hand sarcoma was treated by second ray amputation. Further, we conducted deep next-generation sequencing of each of her unique tumour tissue samples using FoundationONE CDx. A whole-genome shot capture followed by in vitro sequencing performed by the Illumina® HiSeq platform revealed a germline P191fs*18 TP53 mutation across all three tissue samples. This case provides insight into the genomics and clinical characteristics of LFS-linked adult-onset ACC and demonstrated that p53 mutations were preserved throughout each malignancy, without apparent treatment pressures on genomic profiling. This case reinforces the critical importance of adopting best practices for LFS, which include the implementation of highly vigilant screening and management of care in a multidisciplinary setting.

scholarly journals Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0251639
Author(s):  
Camila Matzenbacher Bittar ◽  
Yasminne Marinho de Araújo Rocha ◽  
Igor Araujo Vieira ◽  
Clévia Rosset ◽  
Tiago Finger Andreis ◽  
...  
Keyword(s):  
Soft Tissue Sarcomas ◽  
Pathogenic Variant ◽  
Southern Brazil ◽  
Premenopausal Breast Cancer ◽  
Li Fraumeni Syndrome ◽  
Cancer Predisposition Syndrome ◽  
Pathogenic Variants ◽  
Li Fraumeni ◽  
Group B ◽  
Adrenocortical Carcinomas

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Information on TP53 germline pathogenic variant (PV) prevalence when using Chompret criteria in South America and especially in Brazil is scarce. Therefore, the aim of this study was to characterize patients that fulfilled these specific criteria in southern Brazil, a region known for its high population frequency of a founder TP53 variant c.1010G>A (p.Arg337His), as known as R337H. TP53 germline testing of 191 cancer-affected and independent probands with LFS phenotype identified a heterozygous pathogenic/likely pathogenic variant in 26 (13.6%) probands, both in the DNA binding domain (group A) and in the oligomerization domain (group B) of the gene. Of the 26 carriers, 18 (69.23%) were R337H heterozygotes. Median age at diagnosis of the first tumor in groups A and B differed significantly in this cohort: 22 and 2 years, respectively (P = 0.009). The present study shows the clinical heterogeneity of LFS, highlights particularities of the R337H variant and underscores the need for larger collaborative studies to better define LFS prevalence, clinical spectrum and penetrance of different germline TP53 pathogenic variants.

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 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.

scholarly journals Is CHEK2 a moderate-risk breast cancer gene or the younger sister of Li-Fraumeni?

2020 ◽  
Vol 13 (9) ◽  
pp. e236435
Author(s):  
Dilanka L De Silva ◽  
Ingrid Winship
Keyword(s):  
Breast Cancer ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Pathogenic Variant ◽  
Treatment Modalities ◽  
Cancer Gene ◽  
Li Fraumeni Syndrome ◽  
Multiple Cancers ◽  
Li Fraumeni ◽  
Breast Cancer Gene

The CHEK2 gene is mostly considered as a moderate breast cancer gene with the result that many clinicians have a narrow focus. We present the 10-year journey of a man who had five different cancers and had iterative genetic testing including for Li-Fraumeni syndrome, eventually to discover a pathogenic variant in the CHEK2 gene, possibly explaining his numerous cancers. This diagnosis offered him closure which he had desperately sought for well over a decade. A pathogenic variant in the CHEK2 gene can potentially explain these cancers because of its function as a tumour suppressor gene. Consideration is warranted of what this means for individuals with CHEK2 variants who may develop multiple cancers, their prognosis and whether different treatment modalities such as chemotherapy, radiotherapy or target agents would need modification. We encourage more research into the many faces of the CHEK2 gene and the potential for predisposition to multiple cancers.

scholarly journals Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes

2020 ◽  
Vol 28 (10) ◽  
pp. 1379-1386 ◽  
Author(s):  
Thierry Frebourg ◽  
◽  
Svetlana Bajalica Lagercrantz ◽  
Carla Oliveira ◽  
Rita Magenheim ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Brain Mri ◽  
Soft Tissue Sarcomas ◽  
Abdominal Ultrasound ◽  
Dominant Negative ◽  
Whole Body ◽  
Breast Cancers ◽  
Li Fraumeni Syndrome ◽  
Cancer Predisposition Syndrome ◽  
Li Fraumeni

Abstract Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years.

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.

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.

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