Li-Fraumeni Syndrome

KEY FACTS

TERMINOLOGY

• Li-Fraumeni syndrome (LFS)

• Autosomal-dominant familial cancer syndrome

○ 75% of LFS cases have loss of function mutations in TP53

tumor suppressor gene

○ Lifelong ↑ risk of osteosarcoma, soft tissue sarcoma,

leukemia, breast cancer, brain tumors, melanoma,

adrenal cortical tumors

IMAGING

• Astrocytoma: Cerebrum > cerebellum > spine

• Choroid plexus carcinoma: Lateral ventricle > > 4th ventricle

TOP DIFFERENTIAL DIAGNOSES

• Hereditary syndromes causing familial cancers, including

brain tumors

• Tuberous sclerosis

• von Hippel-Lindau

• Medulloblastoma

• Basal cell nevus syndrome

• Turcot

• Neurofibromatosis type 1

• Carney complex

• Melanoma-astrocytoma syndrome

PATHOLOGY

• p53: Transcription factor important in apoptosis, cell cycle

control; frequently mutated in tumors

• Breast cancer (24-30%), soft tissue sarcoma (12-18%), brain

tumors (12-14%), bone sarcoma (12-13%), adrenocortical

carcinoma (6%)

CLINICAL ISSUES

• Propensity to develop additional primary neoplasms

• Brain tumors: High prevalence below 10 years of age

(Left) A 38-year-old woman

with a history of breast cancer

presented to the ER with

several months of increasingly

severe headache and visual

difficulties. NECT scan shows a

large hyperdense mass ﬈ in

the right occipital region.

(Right) Axial T1 C+ FS in the

same patient shows a large,

intensely enhancing right

occipital mass ﬊.

(Left) Sagittal T1 C+ FS MR

shows that the welldemarcated, intensely

enhancing mass ﬊ abuts the

dura. (Right) Axial presurgical

contrast-enhanced SPGR

shows a subtle dural "tail"

along the tentorium cerebelli

ſt. Preoperative diagnosis of

meningioma was confirmed at

surgery. Further evaluation

disclosed TP53 germline

mutation, and Li-Fraumeni

syndrome was diagnosed.

Trauma, and Stroke

Brain: Pathology-Based Diagnoses: Malformations,

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