What types of tumors are included in the Chompret criteria for Li-Fraumeni syndrome?

Chompret Criteria Tumor Spectrum

The Chompret criteria include Li-Fraumeni syndrome (LFS) spectrum tumors: premenopausal breast cancer, soft tissue sarcomas (STS), brain tumors, adrenocortical carcinoma (ACC), with specific rare tumors (choroid plexus carcinoma and embryonal anaplastic rhabdomyosarcoma) warranting testing regardless of family history. 1

Core LFS Spectrum Tumors in Chompret Criteria

The Chompret criteria specifically identify the following tumor types for TP53 genetic testing consideration:

Primary LFS Spectrum Tumors

• Premenopausal breast cancer - particularly when diagnosed before age 31 years as a standalone criterion, or before age 46 years when combined with family history 1
• Soft tissue sarcomas (STS) - including rhabdomyosarcoma, with embryonal anaplastic subtype rhabdomyosarcoma being a rare tumor warranting testing independent of family history 1
• Brain tumors - including choroid plexus carcinoma (which warrants testing regardless of family history), gliomas, and Sonic Hedgehog (SHH) subtype medulloblastoma 1
• Adrenocortical carcinoma (ACC) - warrants TP53 testing at any age regardless of family history 1

Additional Core Cancers in LFS Spectrum

• Osteosarcoma and bone tumors - considered part of the core cancer spectrum, with up to 10% of children with osteosarcoma having germline TP53 mutations 1

Four Clinical Situations Triggering Chompret Criteria

The 2017 Clinical Cancer Research guidelines define four specific scenarios warranting TP53 testing 1:

1. Familial presentation: Proband with an LFS spectrum tumor (premenopausal breast cancer, STS, brain tumor, ACC) diagnosed before age 46 years AND at least one first- or second-degree relative with an LFS tumor (excluding breast cancer if proband has breast cancer) before age 56 years or with multiple tumors 1

2. Multiple tumors: Proband with multiple malignancies (excluding two breast cancers), with at least two belonging to the LFS spectrum, diagnosed before age 46 years 1

3. Rare tumors: Patients with ACC, choroid plexus carcinoma, or embryonal anaplastic subtype rhabdomyosarcoma independent of family history 1

4. Early-onset breast cancer: Breast cancer diagnosed before age 31 years 1

Broader Tumor Spectrum Beyond Core Criteria

While not specifically listed in Chompret criteria, the wider LFS tumor spectrum includes 1:

• Hematologic malignancies - including leukemias and low-hypodiploid acute lymphoblastic leukemia (ALL), with 40% of children with low-hypodiploid ALL having germline TP53 mutations 1
• Other cancers - lung, skin, gastrointestinal tract, kidney, thyroid, and neuroblastoma 1

Clinical Performance of Chompret Criteria

The Chompret criteria demonstrate superior sensitivity (95%) when combined with classic LFS criteria compared to classic criteria alone (40% sensitivity), with a positive predictive value of 20-35%. 1 This makes them highly effective for identifying TP53 mutation carriers who would otherwise be missed by classic LFS criteria alone.

Key Clinical Pitfall

The NCCN 2021 guidelines emphasize that the Chompret criteria focus on "core" tumor types (sarcoma, breast cancer, adrenocortical carcinoma, brain tumors) diagnosed at specific ages, but clinicians should maintain high suspicion even when patients present outside these strict parameters, as germline TP53 mutations can occur in broader contexts. 1