Metachronic Breast and Cerebellar Neoplasm in a Young Patient

AbstractSeveral factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Being a special atypical subtype of invasive carcinoma, it most frequently affects women of advanced age and represents 1 to 7% of all breast cancers. The reported case aims to show the rarity of the occurrence of desmoplastic medulloblastoma and mammary mucinous carcinoma in a young patient in a short period of time, in different sites, without direct anatomical attachment and without occurrence of metastasis. Initially, this patient had a desmoplastic medulloblastoma and was treated with lumpectomy and radiotherapy. After 13 months, the patient was diagnosed with a mucinous breast carcinoma, underwent mastectomy, adjuvant chemotherapy and is currently undergoing endocrinotherapy. We conclude, based on the metachronous characteristic of the neoplasia and clinical characteristics, that the patient is likely to have Li-Fraumeni syndrome, an autosomal dominant disease with mutation of the TP53 gene, which is the the main involved. Because the patient does not present all the characteristics of the phenotype of the syndrome, she can thus be classified as having Li-Fraumeni variant or Li-Fraumeni-like syndrome.

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Pediatric Case of Li–Fraumeni Syndrome in Honduras

Case Reports in Pediatrics ◽

10.1155/2021/6612802 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

R. Martínez-Beckerat ◽

C. Alas-Pineda ◽

M. Melgar-Gonzales ◽

B. Mejía-Raudales ◽

N. Andino-Paz ◽

...

Keyword(s):

Autosomal Dominant ◽

Tp53 Gene ◽

Pediatric Case ◽

Choroid Plexus Tumor ◽

Li Fraumeni Syndrome ◽

Left Lateral Ventricle ◽

Dominant Disease ◽

History Of ◽

Li Fraumeni ◽

Increased Susceptibility

Li–Fraumeni syndrome is an inherited, autosomal dominant disease. It is categorized as a rare disease caused by mutations of the TP53 gene, which causes increased susceptibility of the patients and their children to many types of cancer. Choroid plexus tumor is rare, which occurs in 0.3 cases per 1,000,000 people, of which 40% turn out to be carcinomas. We present a 12-year-old boy with a history of worsening headaches of more than one month, gait disturbance, projectile vomiting, and right hemiparesis. An intraventricular tumor was identified in the occipital of the left lateral ventricle, which turned out to be a TP53-mutant choroidal plexus carcinoma.

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The TP53 gene promoter is not methylated in families suggestive of Li-Fraumeni syndrome with no germline TP53 mutations

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2009.04.014 ◽

2009 ◽

Vol 193 (1) ◽

pp. 63-66 ◽

Cited By ~ 2

Author(s):

Alena Finkova ◽

Alzbeta Vazna ◽

Ondrej Hrachovina ◽

Sarka Bendova ◽

Kamila Prochazkova ◽

...

Keyword(s):

Gene Promoter ◽

Tp53 Gene ◽

Tp53 Mutations ◽

Li Fraumeni Syndrome ◽

Li Fraumeni

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Li-Fraumeni Syndrome and p53 in 2015: Celebrating their Silver Anniversary

Clinical & Investigative Medicine ◽

10.25011/cim.v39i1.26328 ◽

2016 ◽

Vol 39 (1) ◽

pp. 37 ◽

Cited By ~ 7

Author(s):

David Malkin

Keyword(s):

Wilms Tumor ◽

Cancer Genetics ◽

Tp53 Gene ◽

Pleuropulmonary Blastoma ◽

Li Fraumeni Syndrome ◽

Von Hippel Lindau ◽

Von Hippel Lindau Disease ◽

Li Fraumeni ◽

Sick Children ◽

Risk Of Cancer

In a typical morning in the Cancer Genetics Clinic at The Hospital for Sick Children in Toronto, the following array of patients and families might be seen: a family of three children, all harbouring a mutation of the succinyl dehydrogenase C gene inherited from their father who had had extensive surgery several years ago for a secreting paraganglioma; three families with Li-Fraumeni syndrome, each with at least one child harbouring a TP53 gene mutation conferring a lifetime risk of cancer approaching 100% and currently undergoing surveillance for early tumour detection; two children with Li-Fraumeni syndrome undergoing treatment for cancer – one having had three cancer diagnoses before 19 months of age and the other just completing therapy for metastatic adrenocortical carcinoma at age 3; two children with von Hippel-Lindau disease being monitored for persistent pancreatic neuroendocrine tumors and cerebellar hemangioblastomas, respectively; and one child with Beckwith-Wiedeman syndrome and Wilms tumor and another child completing therapy for a pleuropulmonary blastoma (PPB).

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Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome

Journal of Medical Genetics ◽

10.1136/jmedgenet-2017-104976 ◽

2017 ◽

Vol 55 (3) ◽

pp. 173-180 ◽

Cited By ~ 32

Author(s):

Mariette Renaux-Petel ◽

Françoise Charbonnier ◽

Jean-Christophe Théry ◽

Pierre Fermey ◽

Gwendoline Lienard ◽

...

Keyword(s):

Sanger Sequencing ◽

De Novo ◽

Multiple Primary Cancers ◽

Breast Cancers ◽

De Novo Mutations ◽

Li Fraumeni Syndrome ◽

Medical Laboratories ◽

Li Fraumeni ◽

Adrenocortical Carcinomas ◽

Generation Sequencing

BackgroundDevelopment of tumours such as adrenocortical carcinomas (ACC), choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of the familial history, highly suggestive of a germline TP53 mutation. The aim of this study was to determine the contribution of de novo and mosaic mutations to LFS.Methods and resultsAmong 328 unrelated patients harbouring a germline TP53 mutation identified by Sanger sequencing and/or QMPSF, we could show that the mutations had occurred de novo in 40 cases, without detectable parental age effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA by next-generation sequencing, performed at a depth above 500X, from 108 patients suggestive of LFS without detectable TP53 mutations, allowed us to identify 6 additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21 children with CPT, in 1/31 women with breast cancer before age 31 and in a patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast sarcoma at age 35.ConclusionsThis study performed on a large series of TP53 mutation carriers allows estimating the contribution to LFS of de novo mutations to at least 14% (48/336) and suggests that approximately one-fifth of these de novo mutations occur during embryonic development. Considering the medical impact of TP53 mutation identification, medical laboratories in charge of TP53 testing should ensure the detection of mosaic mutations.

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Identification and characterization of TP53 gene Allele Dropout in Li-Fraumeni syndrome and Oral cancer cohorts

Scientific Reports ◽

10.1038/s41598-018-30238-7 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Mohammed Moquitul Haque ◽

Pradnya Kowtal ◽

Rajiv Sarin

Keyword(s):

Oral Cancer ◽

Tp53 Gene ◽

Li Fraumeni Syndrome ◽

Allele Dropout ◽

Li Fraumeni ◽

Identification And Characterization

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Atypical fibroxanthoma arising in a young patient with Li-Fraumeni syndrome

Journal of Cutaneous Pathology ◽

10.1111/cup.12274 ◽

2013 ◽

Vol 41 (3) ◽

pp. 303-307 ◽

Cited By ~ 7

Author(s):

Sun Mi Lee ◽

Wei Zhang ◽

Martin P. Fernandez

Keyword(s):

Young Patient ◽

Li Fraumeni Syndrome ◽

Atypical Fibroxanthoma ◽

Li Fraumeni

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Efficacy of oral metformin in a patient with metastatic adrenocortical carcinoma: Examination of mechanisms and therapeutic implications

Rare Tumors ◽

10.1177/2036361317749645 ◽

2018 ◽

Vol 10 ◽

pp. 203636131774964 ◽

Cited By ~ 2

Author(s):

RD Peixoto ◽

LM Gomes ◽

TT Sousa ◽

DJ Racy ◽

M Shigenaga ◽

...

Keyword(s):

Adrenocortical Carcinoma ◽

Tp53 Mutation ◽

Germ Line ◽

Objective Response ◽

Tp53 Gene ◽

Li Fraumeni Syndrome ◽

Therapeutic Implications ◽

Treatment Regimens ◽

First Line Therapy ◽

Li Fraumeni

Although rare, adrenocortical carcinoma is among the most common tumors found in children with Li-Fraumeni syndrome and Li-Fraumeni-like syndrome, associated with germ-line mutations in the TP53 gene. In southern Brazil, one form of Li-Fraumeni syndrome, associated with childhood adrenocortical carcinoma, is caused by a mutation in the R337H TP53 tetramerisation domain and is attributed to a familial founder effect. Adrenocortical carcinoma is considered an aggressive neoplasm, usually of poor prognosis and is generally unresponsive to systemic chemotherapy. Optimal treatment regimens remain to be established. We report the case of a young woman with metastatic adrenocortical carcinoma, who achieved stable disease with mitotane, cisplatin, doxorubicin, and etoposide as first-line therapy, but then had an objective response to oral metformin that lasted 9 months. The presence of the R337H TP53 mutation suggests a mechanism for the observed response to metformin.

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Recurrent Pleomorphic Myxoid Liposarcoma in a Patient With Li-Fraumeni Syndrome

International Journal of Surgical Pathology ◽

10.1177/1066896919878804 ◽

2019 ◽

Vol 28 (2) ◽

pp. 225-228 ◽

Cited By ~ 3

Author(s):

Somaye Y. Zare ◽

Mariah Leivo ◽

Oluwole Fadare

Keyword(s):

Young Patients ◽

B Cell Lymphoma ◽

Myxoid Liposarcoma ◽

Tp53 Gene ◽

Anterior Chest Wall ◽

Second Primary ◽

Mdm2 Gene ◽

Li Fraumeni Syndrome ◽

First Case ◽

Li Fraumeni

Pleomorphic myxoid liposarcoma is an extremely rare, clinically aggressive subtype of liposarcoma that has been primarily reported in young patients. In this article, we report a case of a pleomorphic myxoid liposarcoma that presented as a second primary neoplasm in a 34-year-old man with history of primary mediastinal large B-cell lymphoma. During the clinical workup, the patient was diagnosed with a germline TP53 gene mutation and Li-Fraumeni syndrome. The tumor, a 2.9 × 2.3 × 2.0 cm well-demarcated and solid mass, was centered in the anterior chest wall soft tissue. Histologically, most of the tumor displayed abundantly myxoid stroma, low cellularity of mostly bland spindle cells, delicate branching capillaries, and lipoblasts; these areas transitioned to small areas whose features were reminiscent of pleomorphic liposarcoma. As assessed by fluorescence in situ hybridization, the tumor showed no DDIT3 ( CHOP) (12q13) rearrangements or MDM2 gene amplification. Clinically, the tumor progressed with multiple recurrences and metastasis to the humerus bone. To our knowledge, this is the first case of pleomorphic myxoid liposarcoma diagnosed in an adult with Li-Fraumeni syndrome.

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