Synonyms

• LFS
• familial p53 Syndrome

Category

Syndrome

Behaviour

Malignant

Grade

High

Gender

M = F

Tissue of Origin

Other

Epidemiology

• Autosomal dominant cancer susceptibility Syndrome
• TP53 germline mutations
• Incidence 1 in 5,000 - 1 in 20,000
• 80-90% lifetime cancer risk
• Early onset malignancies typical

Clinical Features

• Early-onset malignancies
• Osteosarcoma (age 5-25 years peak)
• Soft tissue sarcomas
• Breast cancer (especially young women)
• Brain tumours
• Leukaemia and lymphomas

Location

• Skeleton: femur, tibia, humerus (osteosarcoma)
• Soft tissues: extremities
• Multiple primary malignancies

Imaging

• Baseline and regular surveillance imaging
• MRI whole spine screening
• Breast MRI (Females)

Pathology

• Histology varies by tumour type
• Associated malignancies often High-grade

Genetics

• TP53 germline mutations
• Autosomal dominant inheritance
• Pathogenic variants identified by sequencing

Treatment

• Surveillance and early detection critical
• Standard oncologic treatment by tumour type
• Avoid unnecessary ionizing radiation
• Avoid chemotherapy agents when possible

Prognosis

• Very poor without surveillance
• Better with early detection
• Multiple primary cancers expected

Key Points

• SYSTEMIC GENETIC Syndrome
• Germline TP53 mutations
• Very High cancer predisposition
• Avoid unnecessary radiation and chemotherapy

Workup - Blood Tests

TP53 sequencing: genetic testing

Workup - Local Imaging

• Annual surveillance: whole-body MRI
• Baseline brain MRI
• Breast MRI annually (Females)
• Spine MRI screening

Workup - Biopsy

Standard histology for detected lesions

Workup - Staging

Full staging by tumour type

Workup - Other

• Genetics consultation mandatory
• Cancer genetics coordination essential
• Family member testing and counselling
• Psychological support

Follow-up Summary

• Annual whole-body MRI surveillance
• Baseline brain and breast MRI (Females)
• Quarterly clinical assessment
• Immediate imaging with any symptoms
• Coordinate care across multiple specialists