The use of temozolomide in paediatric metastatic phaeochromocytoma/paraganglioma: A case report and literature review

Abstract

There is increasing evidence to support the use of temozolomide therapy for the treatment of metastatic phaeochromocytoma/paraganglioma (PPGL) in adults, particularly in patients with SDHx mutations. In children however, very little data is available. In this report, we present the case of a 12-year-old female with a SDHB-related metastatic paraganglioma treated with surgery followed by temozolomide therapy. The patient presented with symptoms of palpitations, sweating, flushing and hypertension and was diagnosed with a paraganglioma. The primary mass was surgically resected six weeks later after appropriate alpha- and beta-blockade. During the surgery extensive nodal disease was identified that had been masked by the larger paraganglioma. Histological review confirmed a diagnosis of a metastatic SDHB-deficient paraganglioma with nodal involvement. Post-operatively, these nodal lesions demonstrated tracer uptake on ¹⁸F-FDG PET-CT. Due to poor tumour tracer uptake on ⁶⁸Ga-DOTATATE and ¹²³I-MIBG functional imaging studies radionuclide therapy was not undertaken as a potential therapeutic option for this patient. Due to the low tumour burden and lack of clinical symptoms, the multi-disciplinary team opted for close surveillance for the first year, during which time the patient continued to thrive and progress through puberty. 13 months after surgery, evidence of radiological and biochemical progression prompted the decision to start systemic monotherapy using temozolomide. The patient has now completed ten cycles of therapy with limited adverse effects and has benefited from a partial radiological and biochemical response.

Keywords: SDHB = SDH enzyme complex subunit B; paraganglioma; pheochromocytoma; succinate dehydrogenase (SDH); temozolomide.

Figure 1

(A), This is an axial diffusion-weighted MRI image showing a right sided heterogeneous suprarenal mass. (B), MRI spectroscopy acquired from a voxel placed within the right suprarenal mass demonstrated a high succinate concentration. (C, D), show fused axial and coronal images from a ⁶⁸Ga-DOTATATE PET/CT scan showing heterogeneous uptake in the right suprarenal mass. (E), Fused coronal image from a post operative ¹⁸FDG-PET/CT, demonstrating FDG avid nodal metastases near the liver hilum and aortocaval region (F), Fused coronal image from a post operative ⁶⁸Ga-DOTATATE PET/CT, demonstrating minimal uptake in the identified nodal metastases (G), Post-operative ¹²³I-MIBG whole body scan, which showed no significant MIBG uptake in the known metastatic deposits.

Figure 2

Family tree of the patient’s family. Black square/circle: male/female with paraganglioma and confirmed SDHB mutation. White square/circle with circle within: male/female with confirmed SDHB mutation, but no known paraganglioma. Asterisk: indicates patient has not undergone tumour screening. White square/circle: male/female with no known SDHB mutation or paraganglioma. Question mark: indicates patient has not undergone genetic testing for SDHB.

Figure 3

Axial contrast-enhanced CT images for this patient from the following time points: (A): September 2020 (post operation), (B): October 2021 (temozolomide therapy commenced), (C): January 2022, (D): April 2022, (E): July 2022.