Li Fraumeni syndrome is a rare cancer predisposition hereditary disorder characterized as autosomal dominant. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni, Jr., who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients.
This syndrome is also known as the Sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome.
The syndrome is linked to germline mutations of the TP53
tumor suppressor gene
The mutations can be inherited, or can arise from de novo mutations early in embryogenesis, or in one of the parent’s germ cells.
Malignant astrocytomas occur in approximately 10% of persons with Li-Fraumeni syndrome
The vast majority of gliomas associated with Li-Fraumeni syndrome occur prior to 40 years of age.
Lechien et al. report on a family in which segregation of a TP53 mutation in two generations was associated with two brain tumours, a leiomyosarcoma and a thyroid carcinoma in four male patients. The main patient presented with seizures revealing several primary brain tumours 1)
A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, Yoshimura et al. consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome 2)