Sporadic Parathyroid Carcinoma Treated With Lenvatinib, Exhibiting a Novel Somatic MEN1 Mutation

Author:

Ito Yu1ORCID,Imaizumi Toshinori2ORCID,Daido Hisashi1ORCID,Kato Takehiro2ORCID,Yabe Daisuke234ORCID

Affiliation:

1. Department of Diabetes and Endocrinology, Gifu Prefectural General Medical Center , Gifu 500-8717 , Japan

2. Department of Diabetes, Endocrinology and Metabolism/Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine , Gifu 501-1194 , Japan

3. Center for One Medicine Innovative Translational Research, Gifu University , Gifu 501-1194 , Japan

4. Departments of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto 606-8507 , Japan

Abstract

Abstract Parathyroid carcinoma (PC) is extremely rare and is primarily treated surgically. Chemotherapy is an option for advanced stages, but no standard regimen exists. Emerging research suggests the efficacy of multitarget tyrosine kinase inhibitors (MTKIs) for PC, targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). A 61-year-old Japanese woman presented with a neck mass, diagnosed as PC with pleural and lumbar metastases. After parathyroidectomy and radiation for lumbar metastasis, immunohistochemistry showed VEGFR overexpression, leading to targeted therapy with MTKIs. Despite no actionable mutations on cancer genomic panel test, a novel MEN1 somatic mutation (NM_130801: exon2: c.332delG: p.G111fs*8) was identified, which may affect VEGFR2 expression and tumor epigenetics. Although severe hand-foot syndrome necessitated dose reductions and treatment interruptions, sorafenib treatment managed hypercalcemia with evocalcet and denosumab. Lenvatinib, as second-line therapy, was effective against pleural metastases but caused thrombocytopenia and hematuria, leading to discontinuation and uncontrolled recurrence and metastasis progression. Our case highlights the need for further research on genomic profiling, molecular targets, and therapy response in PC.

Publisher

The Endocrine Society

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