Incidental brain uptake of Gallium-68 DOTATATE positron emission tomography/computed tomography scan in patients with neuroendocrine tumors: a case report and literature review

Introduction

Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that arise from cells of neuroendocrine origin (1). These tumors can present in different organs and include: carcinoid tumors, gastroenteropancreatic tumors [gastrinoma, insulinoma and VIPoma (VIP, vasoactive intestinal peptide)], small cell lung cancer and catecholamine-secreting tumors (pheochromocytomas and paragangliomas) (1). The diagnosis of NETs is often challenging due to nonspecific presentations, such as abdominal pain, diarrhea, flushing and shortness of breath (2). The slow growth of the tumors further adds to the exciting challenges of diagnosis and early detection (2).

Somatostatin (SST) is a small cyclical neuropeptide that is found in notably high concentrations in neurons, endocrine cells, the gastrointestinal tract and the endocrine pancreas (3). The majority of NETs express somatostatin receptors (SSTRs), which can be targeted by certain Gallium-68-labelled SST analogues with positron emission tomography (PET) imaging for diagnosis and staging (4,5).

Gallium-68 DOTATATE (⁶⁸Ga-DOTATATE) PET/computed tomography (CT) scan is the predominantly used imaging modality for accurate diagnosis and staging of NETs. This Gallium-68-labelled SST analogue exhibits high affinity for SSTRs, which are expressed highly in NETs (5). Additionally, meningiomas express SSTR subtype 2, which can show an area of uptake on ⁶⁸Ga-DOTATATE PET/CT scan (3). Meningiomas are the most prevalent benign primary brain tumors and they arise from the meningothelial cells of the arachnoid membranes, which are attached to the inner layer of the dura mater (6,7).

The expression of meningiomas of SSTRs impacts the interpretation of ⁶⁸Ga-DOTATATE PET/CT scans when there is an incidental uptake in the brain in patients with NETs. The scan findings can be interpreted as tumor metastasis, which may lead physicians to move to a more aggressive management and investigations, such as biopsy, resection and radiation therapy. Previous to initiating treatment of metastasis or malignant tumors, it is advisable to do supplementary imaging techniques such as CT scan or magnetic resonance imaging (MRI) to definitively confirm the cause of the lesion on ⁶⁸Ga-DOTATATE PET/CT scan before starting management of metastasis or malignant tumors.

This case report highlights the importance of incidental brain uptake of ⁶⁸Ga-DOTATATE PET/CT scans in patients with NETs and demonstrates the different causes of this uptake. Additionally, this study aims to review the current literature on incidental brain uptake in NET patients to provide a comprehensive understanding of its implications for clinical practice and patient management. We present this article in accordance with the CARE reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-25-18/rc).

Case presentation

Case 1

A 48-year-old female with a past medical history of obesity treated with gastric sleeve, history of congenital pulmonary stenosis, cerebrovascular accident, hyperthyroidism and a 1 cm benign lung nodule for more than 3 years presented to the hospital with shortness of breath. Initial investigations done by the cardiologist and pulmonologist did not reveal any significant abnormalities. However, one month later, the patient started experiencing excessive acne on the face, back and chest along with high blood pressure.

Later, she was admitted to the hospital for hypertension and hypokalemia, which were accompanied by edema in her extremities. Further investigations showed a high level of 24-hour urinary cortisol, at 388 mcg/24 hours, and failed dexamethasone suppression test. An evaluation revealed a diagnosis of Cushing’s syndrome and further testing was done to localize the source. A CT scan of the chest revealed a 1.2 cm right upper lobe nodule. A ⁶⁸Ga-DOTATATE PET/CT scan showed an avid 1 cm uptake in the right upper lobe with peak standardized uptake value (SUV) 1.4 (Figure 1).

Figure 1 Coronal ⁶⁸Ga-DOTATATE PET/CT scan showing an uptake in the right side lateral to the physiological uptake of the pituitary gland. ⁶⁸Ga-DOTATATE PET/CT, Gallium-68 DOTATATE positron emission tomography/computed tomography.

Bronchoscopic biopsy confirmed the presence of a carcinoid tumor in the right upper lobe. Following lobectomy, the patient recovered well with physiotherapy, resulting in an improvement in the initial shortness of breath. The post-surgery patient went into remission.

Six months after the surgery, a follow-up ⁶⁸Ga-DOTATATE PET/CT scan revealed focal activity in the right skull lateral to the pituitary, suspicious of tumor uptake. Further laboratory tests were done to rule out recurrence of Cushing’s syndrome, given the initial concern for tumor metastasis; however, given the low tumor grade, this was very unlikely. A brain MRI scan documented a lesion in the tentorium near the right Meckel’s cave, suggestive of meningioma (Figure 2). The follow-up MRI was compared to the previous images from 18 years ago and showed the presence of a stable meningioma.

Figure 2 A cross-sectional brain MRI showing a lesion in the tentorium near the right Meckel’s cave (highlighted by the red circle), suggestive of meningioma. MRI, magnetic resonance imaging.

Case 2

A 65-year-old female presented to the clinic with epigastric abdominal pain and nausea. She was initially diagnosed as gastroesophageal reflux disease (GERD), however, further testing including esophagogastroduodenoscopy (EGD), showed a 0.4 cm well-differentiated polypoid NET in gastric body in a bed of multiple fundic gland polyps with Ki-67 proliferation index of 1%, consistent with a grade 1 gastrointestinal NET. Molecular testing was negative for Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), human epidermal growth factor receptor 2 (HER2), and microsatellite instability (MSI). Additional biochemical testing for chromogranin A, serotonin, gastrin and urine 5-hydroxyindoleacetic acid (5HIAA), were within the normal limit.

Further testing to assess for metastatic disease, including a ⁶⁸Ga-DOTATATE PET/CT scan, which showed no evidence of disease within the gastrointestinal tract. However, it incidentally revealed two avid lesions in the right temporal lobe and in the left occipital lobe (Figure 3). Meningioma was initially suspected, but the brain MRI came back negative. The patient was assured and advised to follow-up with neurosurgery every 12 months for ongoing surveillance.

Figure 3 A ⁶⁸Ga-DOTATATE PET/CT scan showing two uptakes, one in the right temporal lobe and one in the brain lateral to the pituitary in the left occipital lobe. ⁶⁸Ga-DOTATATE PET/CT, Gallium-68 DOTATATE positron emission tomography/computed tomography.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patients or their relatives after all possible attempts were made.

Discussion

In this paper, we discussed two patients with low-grade NETs with incidental brain uptake of ⁶⁸Ga-DOTATATE PET/CT scan. Follow-up imaging with MRI ruled out metastasis but confirmed the possible diagnosis of meningioma in one of the patients. Metastasis in NETs is rare, with a prevalence of 1.5–5% (8). Although the second patient’s MRI did not confirm the presence of the two lesions demonstrated on the ⁶⁸Ga-DOTATATE PET/CT scan. This may be explained by the possible presence of a small meningioma that is difficult to visualize on the MRI.

Meningiomas are known to show uptake on ⁶⁸Ga-DOTATATE PET/CT scans due to the high affinity of ⁶⁸Ga-labeled peptides for SSTRs, which are highly expressed in meningiomas. This explains the observed uptake (3,9). A previous study by Nakasu et al. revealed that PET scans are more sensitive in detecting meningiomas compared to brain MRIs, which may miss them if used alone (10).

Traditionally, MRI is considered the gold standard for meningioma diagnosis and follow-up (4). Some studies, such as Rachinger et al.’s study and Afshar-Oromieh et al.’s study, presented that SST analogue PET scans can be more sensitive for detecting meningiomas than MRIs (11,12). A prospective study done by Rachinger et al. (12) compared findings of MRI and ⁶⁸Ga-DOTATATE PET/CT scans with tissue biopsies of suspected meningiomas in 21 patients. The findings were that MRI could differentiate tumor from tumor-free tissue with a sensitivity of 79%, while ⁶⁸Ga-DOTATATE PET/CT scan concluded a sensitivity of 90.1%.

This can possibly explain why, in the second case, there were two areas of uptake suggestive of possible meningioma on the ⁶⁸Ga-DOTATATE PET/CT scan, where the MRI was negative. The most common sites for false negative brain MRI and positive ⁶⁸Ga-DOTATATE PET/CT scan for meningioma, where visualization can be challenging, are the sagittal sinus, parasagittal varix, peripheral draining veins—the sylvian and frontal veins.

The reported prevalence of incidental brain uptake of ⁶⁸Ga-DOTATATE PET/CT scan varied between the different studies, 11% by Albano et al. (9), 6.7% by Cleary et al. (4) and 1.6 by Parghane et al. (3). The reported prevalence of meningioma confirmed on MRI in patients with NETs was 9% by Albano et al. (9), 3.5% by Cleary et al. (4) and 1.6% by Parghane et al. (3). In Albano et al. (9) study, 5 cases out of the 48 incidental brain uptakes were confirmed by MRI as metastasis from gastro-entero-pancreatic neuroendocrine tumors (GEP NET). On the other hand, Cleary et al. (4) reported a case of brain uptake of ⁶⁸Ga-DOTATATE PET/CT in a patient with von-Hippel-Lindau disease (VHL). Follow-up MRI was consistent with probable NET metastasis rather than meningioma. Thus, obtaining a brain MRI is a crucial step to confirm the diagnosis.

The incidental detection of brain lesions on ⁶⁸Ga-DOTATATE PET/CT scan poses significant diagnostic challenges. Misinterpreting these findings as metastasis can lead to an aggressive, and potentially unnecessary, approach in diagnosis, such as biopsy, radiation and tumor resection.

Conclusions

Our study highlights two cases of incidental brain uptake on ⁶⁸Ga-DOTATATE PET/CT: one confirmed as a meningioma via MRI and the other, not visible on MRI, suspected to be a meningioma. The literature review emphasizes that while incidental brain uptake is frequently indicative of meningioma, it can occasionally represent NET metastases or venous varices. These cases illustrate the critical need for follow-up imaging, such as MRI, to accurately determine the nature of such lesions and guide appropriate management before considering invasive procedures.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-25-18/rc

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-25-18/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-25-18/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patients or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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