Skeletal metastases from renal cell carcinoma: diagnostic uncertainty with molecular imaging

Description

A 54-year-old patient underwent right radical nephrectomy for what was then diagnosed as a Stage-II (T2bN0M0) renal cell carcinoma (RCC). Four months after surgery, the patient reported of pelvic pain and had a rising serum alkaline-phosphatase level. The tecnetium-99 m-methylene-diphosphate (Tc99m-MDP) bone scan then demonstrated a focus of uptake in the right ischium, corresponding to the locus of pain (figure 1). As part of further metastatic work-up, a whole body ¹⁸F-fluorodeoxyglucose positron-emission tomography (FDG-PET) scan was performed; this however could not demonstrate any anomalies (figure 2). Six months after surgery (2 months after the first scan) the patient complained of generalised bony pains. Then, metastatic disease was confirmed when reimaging (with chest radiograph and a repeat bone scan) showed pulmonary and vertebral metastases (figure 3).

Figure 1.

Tecnetium-99m-methylene-diphosphate bone scan image showing an area of increased tracer uptake in the right hemi-pelvis, corresponding to the clinical locus of pain (4 months after surgery).

Figure 2.

¹⁸F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) maximum-intensity projection view (A) and FDG-PET/CT fusion (B) images visualising no anomalous uptake in the pelvis (4 months after surgery).

Figure 3.

Right-sided lung metastasis (A) and a repeat bone scan image (B) revealing progressive metastatic disease (6 months after surgery).

Two commonly used molecular-imaging techniques in the general evaluation of skeletal metastases are the bone scan and the FDG-PET scan. Whereas the bone scan is dependent on bone turnover, the FDG-PET scan depends on increased glucose uptake by cancerous cells, often accompanied by upregulated glucose transporter 1 (GLUT-1) expression. With RCC, however, FDG-PET uptake is less likely to have a correlation with GLUT-1 expression, hence limiting the role of FDG-PET in RCC.^{1 2}

In conclusion, an investigation of possible bone metastasis from RCC warranted in the presence of bone pains and/or elevated alkaline-phosphatase levels. Bone scan is a common first-line investigation, although FDG-PET is another option. However, one should appreciate that there is a 30% false-negative rate associated with both.³ Further, since both the tests rely on different molecular-uptake mechanisms, the results of either test may or may not concur with the other.

Learning points.

• X-ray radiography and a serum alkaline phosphatase level measurement should be the first investigations in patients with suspected skeletal metastases from renal cell carcinoma.

• Skeletal metastases from renal cell carcnioma may not be readily demonstrable with the use of FDG-PET scans.

• The bone scan and the FDG-PET scan are both associated with a 30% false-negative rate in the detection of skeletal metastatic disease from renal cell carcinoma.