⁶⁸Ga-DOTATATE Avid Metastatic Vertebral Renal Cell Carcinoma in the Setting of von Hippel-Lindau Syndrome

Abstract

Although rare, a metastatic renal cell carcinoma could present with ⁶⁸Ga-DOTATATE avidity. A 66-year-old man with von Hippel-Lindau syndrome (VHL) presented with ⁶⁸Ga-DOTATATE uptake in the pancreatic head, splenic hilar region, and multiple osseous sites, including the right lateral portion of the T9 vertebrae. Biopsy of the T9 lesion confirmed metastatic renal cell carcinoma. Various VHL-associated cancers may display ⁶⁸Ga-DOTATATE avidity, which can change and guide clinical decisions for the patient.

Fig. 1.

A 66-year-old man with von Hippel-Lindau (VHL) syndrome implicated by a germline pathogenic variant in the VHL gene (c.499C>T, p.Arg167Trp) presented with ataxic symptoms. He underwent magnetic resonance imaging (MRI) of the brain and spine revealing cerebellar (Figure 1a, axial post-contrast T1w image) and spinal (1b, sagittal STIR image) hemangioblastomas (HBLs), both were resected improving his ataxic symptoms. The spine MRI also revealed a T9 vertebral body lesion (1c, sagittal fat-suppressed post-contrast image). Two months after HBL resection, a whole-body computed tomography (CT) revealed a left adrenal tumor (1d blue arrow, axial post-contrast abdomen), a perigastric nodule (1d orange arrow, axial post-contrast abdomen), fibroadipose tissue adjacent to the spleen (1d cross-mark, axial post-contrast abdomen), a mass in the pancreatic head (1e yellow arrow, axial post-contrast abdomen), a left renal cell tumor (1e red arrow, axial post-contrast abdomen), and the T9 vertebral lesion (1f green arrow, axial abdomen). Functional ¹²³I-MIBG imaging showed uptake in the left adrenal PHEO (blue arrow on 1g, anterior planar). The abdominal tumors (Figures 1d-1e) were excised two months after the CT study and confirmed by histopathology to be left RCC, left PHEO, metastatic PHEO with surrounding nests of NET in the pancreatic head, and benign fibroadipose tissue. Two months after abdominal surgery, normetanephrine and norepinephrine remained slightly elevated. ⁶⁸Ga-DOTATATE PET/CT showed uptake in the recurrent pancreatic head mass with a SUV_max 106.1 (yellow arrow on, 1h sagittal PET/CT fusion, 1i anterior maximum intensity projection, and 1j axial PET/CT fusion) and the vertebral T9 metastasis with a SUV_max of 9.3 (green arrow, on 1h, 1i, and 1k), which was confirmed to be RCC on biopsy (Figure 2).

Fig. 2.

Histology displayed prominent capillary network, nests of cells with predominantly eosinophilic cytoplasm, and nuclei with inconspicuous nucleoli (2a). Immunohistochemistry depicted diffuse nuclear PAX8 staining supporting renal origin (2b) and diffuse membranous CAIX staining supporting diagnosis of clear cell renal carcinoma (2c) [1, 2]. A neuroendocrine neoplasm was ruled out with negative synaptophysin staining in the tumor cells (2d). The patient was diagnosed at an advanced age, despite his own awareness of an extensive family history of VHL syndrome and VHL-related cancers. Initial workup for ataxia led to the diagnosis of HBLs, and syndromic surveillance revealed visceral tumors, RCC, PCC, and PNETs, typical of VHL disease. Given the abdominal tumors and VHL syndrome, functional imaging and tissue diagnoses were considered to differentiate between a single histology with multiple metastases versus multiple, concurrent new cancer diagnoses. VHL syndrome is an autosomal dominant disorder presenting with HBL, papillary cystadenomas, pancreatic NET (PNETs), PCC/paraganglioma (PCC/PGL), and RCC [3, 4]. HBL, RCC, PNET, and PCC/PGL overexpress somatostatin transmembrane receptors (SSTRs), which can be imaged using ⁶⁸Ga-DOTATATE PET/CT [5–13]. While the ⁶⁸Ga-DOTATATE avid vertebral lesion could have been a benign vertebral hemangioma [10], the history pointed towards a metastatic VHL-related cancer. The expression of SSTRs in osseous RCC metastases have been reported, with one case identifying ⁶⁸Ga-DOTATATE avid metastatic RCC in the vertebral column [14–17], which potentiates treatment with somatostatin analogs and peptide radionuclide receptor therapy [5, 6, 13].

Author Contribution

MP and AJ conceptualized, drafted, and finalized the manuscript and imaging. KP conceptualized and finalized the manuscript. TA performed pathologic diagnosis and provided histologic images. SMN and JEC were the initial care and referring team. AL performed radiologic evaluation.

Funding

This work was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development and was funded by National Institutes of Health (grant number: Z1AHD008735).

Declarations

Conflict of Interest

Mayank Patel, Abhishek Jha, Tatjana Antic, Sarah M. Nielsen, Jane E. Churpek, Alexander Ling, and Karel Pacak declare no conflict of interest.

Ethics Approval

All procedures performed in the study involving the human participant were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent to Participate

Informed consent was obtained from the participant included in the study.