⁶⁸Ga-DOTATATE PET/CT may detect renal lesions in pheochromocytoma and paraganglioma patients and renal-cell carcinoma in a subgroup of patients with SDHB and SDHD germline mutations

Background: Pheochromocytomas/paragangliomas (PHEO/PGL) are extremely rare and their evaluation and management is very challenging. Currently, ⁶⁸Ga-DOTATATE PET/CT is the imaging of choice for the evaluation and the management of patients with PHEO/PGL. Moreover, germline mutations in Von Hippel-Lindau (VHL), succinate dehydrogenase subunit B (SDHB), SDHC, and SDHD have been detected in individuals with synchronous or metachronous PHEO/PGL and renal cell carcinoma (RCC).

Objectives: To determine the ability of ⁶⁸Ga-DOTATATE PET/CT to detect renal lesions in patients with PHEO/PGL, and RCC in a subgroup of patients with SDHB and SDHD mutations, which is not yet defined.

Methods: 60 consecutive PHEO/PGL patients who underwent ⁶⁸Ga-DOTATATE PET/CT in an alphabetically arranged database starting in January 2014 were evaluated for the presence of renal lesions. The gold reference standard for the comparison was contrast-enhanced CT and MRI (CE-CT/MRI) done within three months of the ⁶⁸Ga-DOTATATE PET/CT scan. 8 patients were excluded as they had undergone CT/MRI beyond three months. The final cohort is 52 patients, 26 females, 26 males; mean age; 44.0±15.9 years. The mean duration between ⁶⁸Ga-DOTATATE PET/CT and CE-CT/MRI was 8.8±19.8 days. 44/52 patients had information about their germline mutations for SDHB, SDHC, and SDHD; and 7 patients had additional information about SDHA.

Results: Twenty-six of the 52 patients were positive for SDHB (n=20) or SDHD (n=6) mutations; one was positive for SDHA. A total of 23 suspicious renal lesions in 10 patients ranging from 0.6cm to 4.5cm were detected on ⁶⁸Ga-DOTATATE PET/CT scan. Two of these renal lesions are ⁶⁸Ga-DOTATATE avid on PET/CT studies of 2 patients with germline mutations. One of these was proven to be renal PGL on histopathologic examination. The second lesion was not histopathologically confirmed. A total of 37 renal lesions in 12 patients were identified on CE-CT/MRI ranging from 0.2cm to 4.7cm. On comparing with the reference standard, 20/23 renal lesions in 10 patients on ⁶⁸Ga-DOTATATE PET/CT were true positive with a void of activity on 19 of these 20 lesions, whereas 3 renal lesions in 2 patients were false positive with a void of activity on 2 of these 3 lesions. 17 out of 37 lesions on CE-CT/MRI in 6 patients could not be identified by ⁶⁸Ga-DOTATATE PET/CT and considered as false negative on ⁶⁸Ga-DOTATATE PET/CT. The size of these missed lesions on ⁶⁸Ga-DOTATATE PET/CT ranged from 0.2cm to 0.5cm.

Conclusions: In patients with PHEO/PGL, renal lesions greater than 0.6cm and lesions with increased or void of DOTATATE activity might be detected in ⁶⁸Ga-DOTATATE PET/CT studies. Although the incidence may not be very high, because of reported association of RCC with SDHB and SDHD germline mutations, detection of increased DOTATATE renal activity in PET/CT might warrant further evaluation to rule out probable malignant renal lesions. Renal cysts were visualized as void of activity in ⁶⁸Ga-DOTATATE PET/CT studies. In our cohort, the incidence of RCC was found to be very low.