Am J Med Genet A. 2025 Nov 8:e64305. doi: 10.1002/ajmg.a.64305. Online ahead of print.
ABSTRACT
Neurofibromatosis 1 (NF1) is caused by pathogenic variants of the NF1 gene and increases the risk of tumor development. Phyllodes tumors are rare fibroepithelial neoplasms of the breast, for which the malignant forms exhibit high recurrence and metastasis rates. Herein, we report the case of a 19-year-old female with NF1 who developed a malignant phyllodes tumor of the breast. She noticed a breast mass 3 years before referral, which was diagnosed as a fibroadenoma. However, rapid tumor growth was observed 3 months prior to her hospital visit. Magnetic resonance imaging of the breast revealed a 9-cm tumor, and lumpectomy confirmed the malignancy. Recurrence necessitated a total mastectomy and pectoralis major resection. One year after surgery, metastases were detected in the left axillary lymph nodes and femoral head, requiring surgical intervention and denosumab treatment. No relapses were observed after 18 months. Comprehensive genomic profiling revealed a germline NF1 nonsense variant with loss of heterozygosity (LOH) in tumor cells. Additional somatic variants of TP53 and SMARCB1 have been identified. The TP53 variant is listed in the Catalogue of Somatic Variants in Cancer as a breast cancer-associated variant, whereas a splice site variant in SMARCB1 and LOH suggests a loss of SMARCB1 function. This case highlights the increased risk of malignancy in NF1 patients and underscores the need for comprehensive genomic profiling.
PMID:41204772 | DOI:10.1002/ajmg.a.64305
