The spectrum of lipomatous tumors differs in the adult and pediatric populations, with liposarcoma being rare in children. Nearly 10% of individuals with Li-Fraumeni syndrome develop sarcomas in the first 2 decades of life; however, the frequency of sarcoma types and subtypes in this syndrome is unknown. Two atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLS) were identified in the pathology files of our institution in young children from “classical” Li-Fraumeni and Li-Fraumeni variant kindreds with a known germline TP53 mutation (Y220C) in one of the families. The patients were 5 and 6 years of age and the ALT/WDLSs were the first expression of the syndrome. The tumors had a high degree of cellular atypia and differed from sporadic ALT/WDLS by strong nuclear immunoreactivity for p53 and absent mdm2 expression. This is the first report of 2 ALT/WDLSs presenting in children before 10 years of age, both in association with Li-Fraumeni syndrome/variant. ALT/WDLS in a young child should raise the possibility of a cancer predisposition syndrome and, in this setting, the p53+/mdm2− immunophenotype might be characteristic. Recognition of this lesion and its association is important for early diagnosis and subsequent tumor surveillance in the proband and affected family members.
Myhre-JensenO. A consecutive 7-year series of 1331 benign soft tissue tumours. Clinicopathologic data. Comparison with sarcomas. Acta Orthop Scand1981;52:287–293.
2.
CoffinCMDehnerLP. Soft tissue tumors in first year of life: a report of 190 cases. Pediatr Pathol1990;10:509–526.
3.
CoffinCMWilliamsRA. Congenital lipoblastoma of the hand. Pediatr Pathol1992;12:857–864.
4.
CollinsMHChattenJ. Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 25 tumors. Am J Surg Pathol1997;21:1131–1137.
5.
MentzelTCalonjeEFletcherCD. Lipoblastoma and lipoblastomatosis: a clinicopathological study of 14 cases. Histopathology1993;23:527–533.
6.
MillerGGYancharNLMageeJFBlairGK. Lipoblastoma and liposarcoma in children: an analysis of 9 cases and a review of the literature. Can J Surg1998;41:455–458.
7.
ShmooklerBMEnzingerFM. Liposarcoma occurring in children. An analysis of 17 cases and review of the literature. Cancer1983;52:567–574.
8.
AlaggioRCoffinCMWeissSW. Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age. Am J Surg Pathol2009;33:645–658.
9.
KauffmanSCStoutAP. Lipoblastic tumors of children. Cancer1959;12:912–925.
10.
KuhnenCMentzelTFisseler-EckhoffADebiec-RychterMSciotR. Atypical lipomatous tumor in a 14-year-old patient: distinction from lipoblastoma using FISH analysis. Virchows Arch2002;441:299–302.
11.
StorlazziCTMertensFDomanskiHFletcherCDWiegantJMandahlN. Ring chromosomes and low-grade gene amplification in an atypical lipomatous tumor with minimal nuclear atypia. Int J Oncol2003;23:67–71.
12.
LiFPFraumeniJFJrMulvihillJJ. A cancer family syndrome in twenty-four kindreds. Cancer Res1988;48:5358–5362.
13.
VarleyJMMcGownGThorncroftMKelseyAMBirchJM. Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families. Cancer Res1997;57:3245–3252.
14.
MalkinDLiFPStrongLC. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science1990;250:1233–1238.
15.
VarleyJM. Germline TP53 mutations and Li-Fraumeni syndrome. Hum Mutat2003;21:313–320.
16.
HisadaMGarberJEFungCYFraumeniJFJrLiFP. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst1998;90:606–611.
17.
OlivierMGoldgarDESodhaN. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res2003;63:6643–6650.
18.
PetitjeanAMatheEKatoS. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat2007;28:622–629.
19.
PoliTLaganàFCaradonnaLGobbiRCorradiDSesennaE. Primary orbital liposarcoma in Li-Fraumeni cancer family syndrome: a case report. Tumori2005;91:96–100.
20.
DebelenkoLVPerez-AtaydeARMullikenJBLiangMGArchibaldTHKozakewichHP. D2–40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma. Mod Pathol2005;18:1454–1460.
21.
KrutilkovaVTrkovaMFleitzJ. Identification of five new families strengthens the link between childhood choroid plexus carcinoma and germline TP53 mutations. Eur J Cancer2005;41:1597–1603.
22.
BirchJMHartleyALTrickerKJ. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res1994;54:1298–1304.
23.
EelesRABartkovaJLaneDPBartekJ. The role of TP53 in breast cancer development. Cancer Surv1993;18:57–75.
24.
Dei TosAPPedeutourF. Atypical lipomatous tumor/well differentiated liposarcoma. In: FletcherCDMUnniKKMertensF, eds. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARCPress, 2002;35–37.
25.
PilottiSTorreDelia GLavarinoC. Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms. J Pathol1997;181:14–24.
26.
Schneider-StockRWalterHRadigK. MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas. J Cancer Res Clin Oncol1998;124:532–540.
27.
BinhMBSastre-GarauXGuillouL. MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data. Am J Surg Pathol2005;29:1340–1347.
28.
MelhemMFLawJCel-AshmawyL. Assessment of sensitivity and specificity of immunohistochemical staining of p53 in lung and head and neck cancers. Am J Pathol1995;146:1170–1177.
29.
SoussiTBeroudC. Significance of TP53 mutations in human cancer: a critical analysis of mutations at CpG dinucleotides. Hum Mutat2003;21:192–200.
30.
VarleyJMMcGownGThorncroftM. Are there low-penetrance TP53 alleles? Evidence from childhood adrenocortical tumors. Am J Hum Genet1999;65:995–1006.
31.
VarleyJMThorncroftMMcGownG. A detailed study of loss of heterozygosity on chromosome 17 in tumours from Li-Fraumeni patients carrying a mutation to the TP53 gene. Oncogene1997;14:865–871.
32.
MilnerJMedcalfEACookAC. Tumor suppressor p53: analysis of wild-type and mutant p53 complexes. Mol Cell Biol1991;11:12–19.
33.
LangGAIwakumaTSuhYA. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell2004;119:861–872.
34.
RibeiroRCSandriniFFigueiredoB. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA2001;98:9330–9335.
35.
DiGiammarinoELLeeASCadwellC. A novel mechanism of tumorigenesis involving pH-dependent destabilization of a mutant p53 tetramer. Nat Struct Biol2002;9:12–16.
36.
Schneider-StockRZiegelerAHaeckelCFrankeDSRysJRoessnerA. Prognostic relevance of p53 alterations and Mib-1 proliferation index in subgroups of primary liposarcomas. Clin Cancer Res1999;5:2830–2835.
37.
Dei TosAPDoglioniCPiccininS. Molecular abnormalities of the p53 pathway in dedifferentiated liposarcoma. J Pathol1997;181:8–13.
38.
Dei TosAPPiccininSDoglioniC. Molecular aberrations of the G1-S checkpoint in myxoid and round cell liposarcoma. Am J Pathol1997;151:1531–1539.
39.
Dal CinPKoolsPSciotR. Cytogenetic and fluorescence in situ hybridization investigation of ring chromosomes characterizing a specific pathologic subgroup of adipose tissue tumors. Cancer Genet Cytogenet1993;68:85–90.
40.
OlinerJDKinzlerKWMeltzerPSGeorgeDLVogelsteinB. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature1992;358:80–83.
41.
LeachFSTokinoTMeltzerP. p53 Mutation and MDM2 amplification in human soft tissue sarcomas. Cancer Res1993;53(10 Suppl):2231–2234.
42.
Cordon-CardoCLatresEDrobnjakM. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res1994;54:794–799.
43.
LimacherJMFrebourgTNatarajan-AmeSBergeratJP. Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer2001;96:238–242.
