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Case Reports
. 2024 Jul 24;2(8):luae121.
doi: 10.1210/jcemcr/luae121. eCollection 2024 Aug.

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

Yu Ito  1 , Toshinori Imaizumi  2 , Hisashi Daido  1 , Takehiro Kato  2 , Daisuke Yabe  2   3   4
Affiliations
Case Reports

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

Yu Ito et al. JCEM Case Rep. .

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.

Keywords: MEN1; VEGF receptor; multi-target tyrosine kinase inhibitors; parathyroid carcinoma.

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Figures

Figure 1.
Figure 1.
Neck ultrasonography identified a well-defined, heterogeneous lesion measuring 26 × 24 × 16 mm in the left inferior parathyroid gland (A). Chest computed tomography showed multiple pleural lesions (B). 99mTc-MIBI scintigraphy (C) and FDG-PET (D) showed significant uptake in the parathyroid tumor, the area of pleural thickening, and fifth lumbar vertebra, suggesting left inferior parathyroid carcinoma with pleural and lumber metastasis. Abbreviations: FDG-PET: fluorodeoxyglucose-positron emission tomography; MIBI: methoxy-isobutyl-isonitrile; Tc: technetium.
Figure 2.
Figure 2.
Summary of the clinical course of the PTH and serum calcium levels from the diagnosis of parathyroid carcinoma. The reference ranges for serum calcium (8.8-10.1 mg/dL [2.19-2.52 mmol/L]) and intact PTH (10-65 pg/mL [1.06-6.89 pmol/L]) are indicated by green and yellow bands, respectively. Treatment initiated with evocalcet in the outpatient setting failed to adequately correct the hypercalcemia, necessitating hospitalization. Left parathyroidectomy and left thyroid lobectomy were undertaken. Thereafter, a regimen of evocalcet, denosumab, and radiation (3 Gy/20 Fr) to the fifth lumbar vertebra was subsequently implemented. The patient then received sorafenib, but due to the onset of hand-foot syndrome, a dose reduction of sorafenib was required, and with disease progression, lenvatinib was introduced. However, lenvatinib was discontinued owing to thrombocytopenia and hematuria, following which there was a local recurrence of the parathyroid carcinoma with skin infiltration. Despite neck radiation, the treatment response was limited, and the patient died at the age of 62.
Figure 3.
Figure 3.
Pathological findings of the surgical excision specimen of parathyroid carcinoma. Immunostaining for VEGFR2 (monoclonal; Santa Cruz Biotechnology, Dallas, USA) and PDGFRα (monoclonal; Abcam, Cambridge, UK), which can be highly expressed in parathyroid carcinoma, was performed to investigate therapeutic targets. The results suggested that VEGFR2 was expressed, and we selected sorafenib as therapy targeting VEGFR2. Abbreviations: PDGFRα: platelet-derived growth factor alpha receptor; VEGFR: vascular endothelial growth factor.
Figure 4.
Figure 4.
Time course of computed tomography findings of primary lesion and pleural metastasis. The primary lesion did not recur for a certain period of time after parathyroidectomy, but a local recurrence was noted around 12 months and showed a tendency to increase. On the other hand, the pleural lesions were gradually increasing, but after the introduction of lenvatinib, some areas showed a tendency to shrink.
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