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Updated: May 12, 2025

Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells

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Osteosarcoma Arising in Noonan Syndrome/RASopathy Complex: First Case Report.

Najwa Yousef¹, John Basile^1,2, Michael E Kallen³

¹Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD, USA.

Head and Neck Pathology

|May 8, 2025

Summary

This summary is machine-generated.

Noonan syndrome (NS), a RASopathy, is linked to various malignancies. This report details the first documented case of osteosarcoma in the mandible of a male patient with NS and polyostotic fibrous dysplasia.

Keywords:

PTPN11 mutation Fibrous dysplasia Noonan syndrome Osteosarcoma RASopathy

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Area of Science:

Genetics and developmental biology
Oncology
Rare diseases

Background:

Noonan syndrome (NS) is a RASopathy characterized by genetic heterogeneity, with PTPN11 mutations in ~50% of cases.
NS is associated with various malignancies, but osteosarcoma has not been previously reported.
Polyostotic fibrous dysplasia (FD) is a rare bone disorder affecting multiple bones.

Purpose of the Study:

To report the first case of osteosarcoma in a patient with Noonan syndrome.
To highlight the potential association between NS, fibrous dysplasia, and osteosarcoma development.

Main Methods:

Case report of a male patient with Noonan syndrome.
Detailed clinical history and diagnostic findings.
Review of literature for similar cases.

Main Results:

The patient presented with osteosarcoma of the mandible.
The osteosarcoma developed in the context of long-standing polyostotic fibrous dysplasia of craniofacial bones.
This represents the first reported instance of osteosarcoma in a Noonan syndrome patient.

Conclusions:

This case expands the known spectrum of malignancies associated with Noonan syndrome.
The co-occurrence of NS, FD, and osteosarcoma warrants further investigation into potential underlying mechanisms.
Clinicians should consider osteosarcoma in the differential diagnosis for patients with NS and craniofacial abnormalities.