Li-Fraumeni syndrome is a rare autosomal dominant genetic ailment that represents a predisposition toward several malignant diseases. Mutations in the tumor protein (TP) 53 tumor suppressor gene are the underlying cause of this syndrome. It is clinically recognized when an individual develops a sarcoma before 45 years of age and has a first-degree relative with any kind of malignancy before 45 years of age. To make a definite diagnosis, molecular genetic studies that confirm TP53 mutations are necessary.
Li-Fraumeni syndrome is rarely encountered in clinical practice, with approximately 500 families described in the medical literature so far . Because of the identified mutations of the TP53 gene (missense, nonsense, frameshift, and splice mutations have all been described), the main component of the presentation is the appearance of one or more malignant tumors before the age of 45 years    . Specifically, sarcomas are the predominant tumor type encountered in this patient population . Osteosarcoma is the most common subtype seen in Li-Fraumeni syndrome, followed by rhabdomyosarcoma (embryonal type), which possesses a very low incidence rate (1 in 2.6 million cases) and is predominantly diagnosed in younger children and adolescents . Additional tumors that are regarded as "hallmarks" of Li-Fraumeni syndrome arise from the breast, the brain, the kidneys (adrenal cortical carcinoma, or ACC), and the hematopoietic system (leukemias)   . However, studies in the past years have recognized a range of other cancers that develop in Li-Fraumeni syndrome, including those of the gastrointestinal tract (the colon and the stomach), the breast, lungs, prostate, ovaries, pancreas, kidneys (Wilms tumor), but also the skin (melanoma), lymphomas and choroid plexus carcinoma, mainly because of their very young onset in these cases compared to the general population  .
The diagnosis of Li-Fraumeni syndrome may be difficult to attain without clinical suspicion. For this reason, the physician must obtain a detailed history that focuses on the age of malignancy onset and if more than one neoplastic disorder is present  . A family history is perhaps the crucial component of the patient interview, as the diagnostic criteria mandate the presence of a first-degree relative with any form of malignancy before the age of 45 years and a first or second-degree relative with a malignant disease diagnosed before 45 years of age or a sarcoma recognized at any age    . Some authors have established criteria for a "Li-Fraumeni-like" syndrome, which comprise a patient having a childhood cancer (for example, a brain tumor, sarcoma, or adrenocortical carcinoma), a first- or second-degree relative with any of the malignancies that are typical for Li-Fraumeni syndrome, and a first- or second-degree relative with any kind of cancer developing before 60 years of age   . When clinical criteria are met and when appropriate histopathological studies confirm the tumor types , a more detailed investigation should be employed. To make a definite diagnosis, it is necessary to perform molecular genetic studies that evaluate the TP53 gene and associated mutations  . However, only 70% of cases exhibit severe TP53 mutations that are known to cause the disease .