Late recurrent renal cell carcinoma presenting as a solitary gallium-68 DOTATATE-avid pancreatic mass with polycythemia

Abstract

Pancreatic metastasis of renal cell carcinoma (RCC) is rare and can present many years after nephrectomy. It can exhibit radiological characteristics very similar to those of a pancreatic neuroendocrine tumor (pNET). Here, we present a case of an 81-year-old female who presented with an incidentally discovered solitary hypervascular pancreatic head mass with intense gallium-68-DOTA-OCTREOTATE positron emission tomography/computed tomography (Ga-68 DT-PET/CT) uptake 15 years after her initial nephrectomy for an RCC. The mass continued to grow despite somatostatin analog (SSA) therapy, prompting endoscopic ultrasound (EUS)-guided biopsy, which revealed metastatic RCC.

Introduction

The majority of pancreatic neuroendocrine tumors (pNET) are nonfunctioning and are diagnosed incidentally on imaging studies [1, 2]. They are typically hypervascular on computed tomography (CT) and magnetic resonance imaging (MRI) and demonstrate intense uptake on gallium-68-DOTA-OCTREOTATE positron emission tomography/CT (Ga-68 DT-PET/CT) [3]. However, there are some mimickers that should not be overlooked. We describe the case of an 81-year-old female who was referred to our center for an incidental solitary pancreatic head mass 15 years after her initial left nephrectomy. It appeared as a hypervascular mass on the initial abdominal CT scan and demonstrated intense Ga-68 DT uptake on PET/CT, resembling a pNET.

Case presentation

An 81-year-old woman with multiple comorbidities and a history of renal cell carcinoma (RCC) status post left nephrectomy and adrenalectomy in 2006 was referred in 2021 for evaluation of an incidentally discovered pancreatic mass identified during assessment of abdominal pain. She reported no symptoms suggestive of a functioning pNET, including no hypoglycemia, flushing, diarrhea, peptic ulcers, or unexplained weight loss.

Diagnostic assessment

Baseline laboratory studies showed normal serum chromogranin A (CgA) 51 ng/mL (51 µg/L) (normal reference range: <76 ng/mL; <76 µg/L), carcinoembryonic antigen 3.8 ng/mL (3.8 µg/L) (normal reference range: <5.0 ng/mL; <5.0 µg/L), pancreatic polypeptide 928 pg/mL (0.928 µg/L) (normal reference range: 56-480 pg/mL; 0.056-0.480 µg/L), and carbohydrate antigen 19-9 62 U/mL (62 kU/L) (normal reference range: <35 U/mL; <35 kU/L). Renal function indices revealed mild impairment with serum creatinine (Cr) of 1.40 mg/dL (124 µmol/L) (normal reference range: 0.57-1.11 mg/dL; 50-98 µmol/L) and estimated glomerular filtration rate of 38 mL/min/1.73 m² (normal reference >60 mL/min/1.73 m²). Hematologic parameters showed polycythemia with hemoglobin (Hb) of 17.6 g/dL (176 g/L) (normal reference range: 12.0-16.0 g/dL; 120-160 g/L), hematocrit (Hct) 55% (0.55 L/L) (normal reference range: 33–47%; 0.33-0.47 L/L), and platelets (Plt) 294 × 10³/µL (294 × 10⁹/L) (normal reference range: 150-400 × 10³/µL; 150-400 × 10⁹/L). Polycythemia workup revealed a normal erythropoietin (EPO) level of 7.6 mIU/mL (7.6 IU/L) (normal reference range: 2.6-18.5 mIU/mL; 2.6-18.5 IU/L) and lack of JAK2 and MPL gene mutations.

Contrast-enhanced CT demonstrated a 2.4-cm hypervascular mass in the pancreatic head (Fig. 1). Ga-68 DT-PET/CT showed intense radiotracer uptake with a maximum standardized uptake value of 24.7, consistent with a Krenning score of 3 (Fig. 1). Serial MRIs over follow-up revealed progressive growth of the pancreatic lesion without additional suspicious sites of disease.

Figure 1.

Ga-68 DT-PET (left), fused PET/CT (middle), and axial arterial phase enhanced CT through the pancreatic head showing an intensely Ga-68 DT-PET/CT avid pancreatic head/neck hypervascular mass (solid arrows; standardized uptake value maximum [SUVmax = 24.7; Krenning score 3]).

Treatment

In view of the patient's advanced age and comorbidities, surgery was deemed high-risk. Based on its solitary presentation and intense Ga-68 DT-PET/CT uptake, the mass was considered to be most consistent with a pNET. Accordingly, treatment with the somatostatin analog (SSA), lanreotide 120 mg every 4 weeks, was initiated. However, after 14 months—despite dose intensification—the lesion continued to grow, approaching 6.0 cm (Fig. 2). Endoscopic ultrasound (EUS)-guided biopsy was, therefore, performed, and histopathology confirmed metastatic clear cell renal cell carcinoma.

Figure 2.

Contrast-enhanced T1-weighted fat-saturated MR image acquired 4 years later shows a marked interval increase in size of the mass with the development of internal necrosis (arrow).

Outcome and follow-up

The patient remained stable and asymptomatic throughout the 4-year follow-up period. She was referred to the Genitourinary Oncology service. Repeat EUS biopsy showed signs of pancreatic inflammation rendering her at increased risk of gastric outlet obstruction, so she did not receive radiation. Instead, she was started on combination immunotherapy with ipilimumab and nivolumab of which she has currently completed 2 cycles with continued stable follow up.

Discussion

Pancreatic NETs are predominantly nonfunctioning and usually identified incidentally following imaging studies performed for different indications [1, 2]. On contrast-enhanced CT and MRI, they typically appear hypervascular with early arterial enhancement [3]. Their high somatostatin receptor (SSTR) expression underpins the diagnostic value of Ga-68 DT-PET/CT, which generally demonstrates 81-100% sensitivity and 90-100% specificity for well-differentiated neuroendocrine tumors [3]. Nevertheless, multiple pancreatic entities can share similar anatomic and functional imaging features, creating diagnostic pitfalls. These include focal physiologic Ga-68 DT uptake in the pancreatic head or uncinate process, intrapancreatic accessory spleen, and more rarely, pancreatic ductal adenocarcinoma [4-6]. An additional key mimic is pancreatic metastasis from RCC. While RCC most often metastasizes to the lungs, lymph nodes, bone, and liver, pancreatic involvement is uncommon, representing less than 5% of cases [7]. When it occurs, pancreatic RCC metastasis can be solitary, hyperenhancing on CT/MRI, and critically, can also express SSTR and demonstrate intense uptake on Ga-68 DT-PET/CT imaging, thereby resembling a pNET [8-11]. These lesions may manifest many years after nephrectomy; very late presentations, approaching 3 decades, have been described [12]. RCC can also produce paraneoplastic syndromes; polycythemia—seen predominantly with the clear-cell subtype—occurs in a small minority of patients (∼2-4%) [13]. The diagnostic utility of serum EPO in RCC-associated erythrocytosis is limited. In large case series, circulating EPO is elevated in only ∼34% of patients with RCC-related erythrocytosis [14].

From a management standpoint, pancreatic RCC metastases often pursue an indolent course and are associated with prolonged survival and favorable outcomes compared with metastases to other anatomic sites [15, 16]. For solitary pancreatic metastasis, surgical resection is generally preferred when feasible and has the strongest survival data. When surgery is not possible, alternative local and systemic approaches may be considered, including radiotherapy, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitor-based regimens, or a combination of TKIs and immunotherapy. Available evidence suggests these non-surgical strategies can provide clinically meaningful disease control in appropriately selected patients, although outcomes are generally best when complete surgical resection can be achieved [17]. To our knowledge, no studies have systematically evaluated outcomes of polycythemia following metastasectomy. However, in a retrospective cohort of 254 patients with RCC, nephrectomy was associated with a significant improvement in paraneoplastic syndromes, including polycythemia [18]. One study has shown reversal of polycythemia in metastatic RCC post systemic therapy with the combination of pembrolizumab and axitinib [19].

Our case illustrates this diagnostic convergence. An isolated, hyperenhancing pancreatic head mass with avid Ga-68 DT-PET/CT uptake presenting 15 years after nephrectomy, initially indistinguishable from a pNET on imaging alone. Concurrent polycythemia further supported RCC as an alternative diagnosis. Histologic confirmation established pancreatic RCC metastasis, underscoring the limitation of imaging in this context and the importance of integrating clinical history (remote RCC), paraneoplastic clues, and tissue diagnosis.

Accordingly, an accurate distinction from pNET is not merely academic; it guides counseling, therapy sequencing, and surgical planning. Clinicians should maintain a high index of suspicion for RCC metastasis in any hypervascular pancreatic lesion with strong SSTR imaging uptake in a patient with prior RCC—regardless of the interval since nephrectomy—and should pursue tissue diagnosis to guide definitive management.

Learning points

• Pancreatic RCC metastases can mimic pNET radiologically, even demonstrating high SSTR DOTATATE uptake, and may present many years after nephrectomy.

• Histological diagnosis should be pursued in any pancreatic metastatic lesion, if feasible, in any patient with a history of an RCC.

• As demonstrated in multiple cases, metastatic RCC to the pancreas appears to have an indolent course and a favorable outcome.

Contributors

All authors made individual contributions to authorship. M.A. and S.E.: were involved in the diagnosis and management of this patient and manuscript submission. U.M.: prepared imaging studies. All authors reviewed and approved the final draft.

Funding

No public or commercial funding.

Disclosures

None declared.

Informed patient consent for publication

Signed informed consent obtained directly from the patient.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.