Positron emission tomography/computed tomography imaging features of renal cell carcinoma and pulmonary metastases in a dog

Abstract

A 9-year-old spayed female cocker spaniel dog was referred for hematuria. A large abdominal mass and multiple pulmonary nodules were identified radiographically. A whole-body 2-deoxy-2-[¹⁸F]fluoro-d-glucose positron emission tomography/computed tomography (PET/CT) scan revealed intensely increased uptake in a renal mass and the pulmonary nodules. Renal cell carcinoma was diagnosed on histological examination.

A 9-year-old spayed female cocker spaniel was examined after being referred for recurrent hematuria. The dog had been presented to a local animal hospital 1 mo previously for hematuria and was prescribed cephalexin for suspected cystitis. The clinical signs improved after medical treatment but the dog relapsed shortly thereafter. Subsequently, the dog was referred to the Veterinary Teaching Hospital of the University of Konkuk for further examination.

Case description

At the time of the referral, there were no significant abnormal findings on physical examination. Complete blood (cell) count (CBC) and serum chemistry results were within normal reference ranges, except for mild elevations of alkaline phosphatase [289 U/L; reference range (RR): 15 to 127 U/L] and creatine kinase (418 U/L; RR: 46 to 320 U/L). A urine dipstick test was positive for hematuria (> 250 erythrocytes/μL, 4+) and proteinuria (0.1 g/L, 2+). Specific gravity of the urine sample was 1.050.

Thoracic radiographs revealed multiple round soft-tissue nodules of varying size throughout the lung field. A large soft-tissue mass with irregular contours was identified in the right cranial quadrant on abdominal radiographs (Figure 1). On abdominal ultrasound, the right kidney was replaced by a large irregularly shaped mass with heterogeneous echotexture and containing multiple anechoic to hypoechoic areas.

Figure 1.

Thoracic and abdominal radiographs of the dog on right lateral and ventrodorsal projections. A and B — Multiple round nodules of varying size are present throughout the lung parenchyma, consistent with pulmonary metastases. C and D — In the right upper abdomen, a large soft-tissue opacity of irregular shape (white arrows) is identified corresponding to the right renal mass found on abdominal ultrasonography.

A whole-body 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) scan was performed to evaluate malignancy of the renal mass and pulmonary nodules and to detect any other metastases not visible on radiographic and ultrasonographic images. The patient was fasted for 12 h, after which 85.1 MBq (2.3 mCi) ¹⁸F-FDG was administered intravenously. The dog was kept in a quiet and restricted room for 1 h after the injection to minimize muscle uptake of ¹⁸F-FDG caused by physical activity or anxiety. General anesthesia was induced with intravenous propofol (Anepols; Hana Pharm, Hwasung, Korea) and maintained with 1% to 2% isoflurane (Ifran; Hana Pharm) and 100% oxygen via an endotracheal tube. The CT was performed using an intravenous bolus of 2 mL/kg body weight (BW) iohexol (Omnipaque 300; GE Healthcare, Shanghai, China) for post-contrast images.

The PET/CT was performed with a Philips GEMINI PET/CT system (Philips; Eindhoven, the Netherlands), which includes a Philips ALLEGRO PET scanner (gadolinium oxyorthosilicate crystal, 28 flat modules of a 22 × 29 array, 18-cm axial field of view) and an MX8000 D 2 slice CT scanner. Computed tomographic parameters were 120 kV and 200 mA with a scan speed of 2 rotations/s. The PET and CT slice thicknesses were 4 mm and 3.2 mm, respectively. All acquired images (192 images for PET, 483 images for CT) were reconstructed using the 3D Row Action Maximum Likelihood Algorithm. For semiquantitative evaluation, ¹⁸F-FDG standardized uptake values (SUVs) corresponding to the ratio of concentration of radiotracer activity in a region of interest to mean concentration throughout the body were calculated.

Computed tomographic images revealed an irregularly enlarged mass (51 mm × 66 mm × 58 mm) replacing the right kidney. On unenhanced and contrast-enhanced images, the mass showed heterogeneous attenuation with calcifications and multiple central areas of low attenuation. Invasion of adjacent organs, including the adrenal gland, was not seen, but the ipsilateral renal vein and ureter were not identifiable. There were no other abnormal abdominal findings or metastases to abdominal lymph nodes. Thoracic CT images revealed abundant contrast-enhanced pulmonary nodules corresponding to those on the radiographic images.

The PET images showed abnormal ¹⁸F-FDG uptake in the renal mass, lung nodules, and ileum compared with normal dog reference values in 1 study (1). On the PET/CT fused images, the right renal mass displayed intensely increased uptake (SUV_max, 7.4) in parenchymal regions, with regions of less intense uptake corresponding to the areas of lower attenuation on CT, presumably representing necrosis (Figure 2A). Pulmonary nodules (diameter 2.4 to 14.6 mm) showed various SUVs (SUV_max, 1.1 to 5.5). The larger nodules [mean diameter 10.3 mm; 95% confidence interval (CI): 8.5 to 12.6 mm] represented true-positive uptake (mean SUV_max, 3.0). On the contrary, small nodules (mean diameter 3.7 mm; 95% CI: 3.2 to 4.3 mm) did not show increased uptake and were false-negative results (Figure 2B). Small intestinal loops filled with gas just orad to the large intestine, presumably ileum, showed intensely increased uptake (SUV_max, 8.2) without any abnormal findings on CT images (Figure 2A).

Figure 2.

2-Deoxy-2-[¹⁸F]fluoro-d-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) images. A — Dorsal CT, PET, and fused PET/CT images of the whole body. The large irregular renal mass shows intense ¹⁸F-FDG uptake (red arrow) together with necrotic regions of no uptake (asterisk). Another region of high metabolic activity (dotted line) on the PET scan corresponds to loops of small-intestine that appeared normal on CT, suggesting physiologic or inflammatory uptake. Note physiologic uptake in muscle (yellow arrows) and intensive uptake in the urinary bladder consistent with the excretion of ¹⁸F-FDG (blue arrow). B — Transverse fused PET/CT images of the thorax in a cranial-to-caudal sequence. Variably increased uptake by pulmonary nodules is noted on the PET/CT scan. Misregistration between some nodules on CT images and ¹⁸F-FDG uptake on PET images due to respiratory motion is identified.

For histopathologic study, tissue samples of the right renal mass were obtained after PET/CT by using a 14-gauge automated biopsy needle (Bard biopsy gun; CR Bard, Covington, Georgia, USA) with ultrasound guidance. Necrotic regions showing relatively low SUV_max on PET/CT images were avoided during biopsy. Histopathologic examination revealed many abnormal irregular-sized glandular structures, composed of cells with basally located dark nuclei and abundant eosinophilic cytoplasm embedded in fibrotic tissue, surrounding the glomeruli and invading adjacent tissues. The histopathologic interpretation was renal cell carcinoma.

The presence of metastases resulted in a guarded prognosis, and the owner elected symptomatic therapy for ongoing care of the dog in consultation with the local referring hospital. As the condition progressed, the dog showed dyspnea, vomiting, and hematochezia, and died 5 mo later.

Discussion

The use of PET/CT has become widespread in human medicine as a useful tool in diagnosis and staging of malignancies, treatment planning, and monitoring after therapy (2,3). Positron emission tomography/computed tomography combines the accurate anatomic localization in CT images with the functional information provided by PET (2,4). Recently, PET/CT has been introduced into veterinary medicine and has been described as a useful modality for diagnosis of neoplastic and inflammatory lesions (5–10). Renal cell carcinoma and pulmonary metastases in a dog could be illustrated through PET/CT in this case.

Primary renal tumors are rare in dogs, accounting for 1.7% of all canine neoplasms. Renal cell carcinoma, which was diagnosed histopathologically in this case, is the most common primary renal neoplasm in dogs, usually occurring in middle to old age (11). Renal cell carcinoma is highly aggressive and readily spreads via both hematogenous and lymphangitic routes, resulting in distant metastases to organs including the lungs, distant lymph nodes, liver, and bone, and local invasion of adjacent structures such as the renal vein, caudal vena cava, regional lymph nodes, and adrenal gland (12). The multiple pulmonary metastases found in this case were consistent with the metastatic tendency of renal cell carcinoma.

On PET images, the right renal mass displayed markedly increased ¹⁸F-FDG uptake compared with the left kidney. Considering the high SUV of a malignant renal lesion in another study (13), the SUV of this renal mass was high enough to be suspicious for malignancy. Although PET is a significant imaging modality in oncology, it has limitations when applied in urological cancers because ¹⁸F-FDG is excreted through the urinary tract (14). To minimize accumulation of ¹⁸F-FDG in urological organs, studies using hydration or diuretics before image acquisition have been performed with relevant results (15,16). In the case of renal cell carcinoma, significant variability in ¹⁸F-FDG uptake can be seen, ranging from normal to intensely increased uptake. This variation in uptake level in renal cell carcinoma might be caused by varying degrees of expression of glucose transporter 1 and the lack of ¹⁸F-FDG uptake in regions of necrosis (17). Certain studies have revealed that PET is not superior to CT in detecting primary renal cell carcinoma lesions because of low sensitivity (18,19) and a high rate of false-negative results for primary renal cell carcinoma; sensitivity, specificity, and accuracy were 47%, 80%, and 51% in PET and 97%, 95%, and 83% in CT (19). Despite the low sensitivity of PET for primary renal cell carcinoma, the malignant renal lesion in this dog was identified with intense metabolic activity on PET images owing to its high grade of malignancy and large size. A study comparing certain biological characteristics of renal cell carcinomas by using ¹⁸F-FDG uptake found that malignant lesions with high SUVs had a higher tumor grade, higher degree of expression of glucose transporter 1, and larger size than lesions with low SUVs (20). Another study revealed an association between SUV_max of lesions and survival time in advanced renal cell carcinoma patients; patients with high SUV_max of primary or metastatic lesions had poor prognosis with short survival time (21). The SUV_max of the renal mass in this dog was relatively high though slightly lower than the cut-off value for statistical significance in the aforementioned study; the survival time and poor prognosis of the dog appeared to correspond to the results of the study.

Although CT has been more effective than PET for identifying primary renal tumors, PET is superior in the detection of distant metastases and local recurrence, which is critical to the choice of treatment and to monitoring after therapy (22). In the present case, elevated SUVs were found in multiple pulmonary metastases, especially the larger masses, that were identified on CT images. Large pulmonary nodules were more likely to have high SUVs, and nodules less than 5 mm in diameter showed false-negative results with no increased metabolic activity. Furthermore, among true-positive nodules, mean SUV_max of larger nodules (diameter 10.5 to 17.8 mm) was 4, while that of smaller nodules (diameter 5.7 to 9.8 mm) was 2.4. These results are consistent with the findings of a study (21) of metastatic renal cell carcinoma in human medicine in which pulmonary metastatic lesions with true-positive ¹⁸F-FDG uptake were larger (mean diameter 20 mm; 95% CI: 13 to 27 mm) than lesions with false-negative results (mean diameter 8 mm; 95% CI: 5 to 12 mm). It is noteworthy that nodules with the same diameter (5 to 12 mm) as those that showed false-negative results in the aforementioned study were detected as true-positive in this case. Therefore, small pulmonary metastases could be detected better in the present case through PET. Various factors affecting PET quantification might have brought about this difference, including physical and biological differences as well as advances in scan protocol and modality (23).

Regarding ¹⁸F-FDG uptake by intestinal components, especially small intestines, few studies have been reported (24–27). Small intestines have a wide range of uptake, but this is mostly low grade. Increased ¹⁸F-FDG uptake in the intestines can occur with primary tumors, such as adenocarcinoma and lymphoma, as well as with metastasis. Highly varying degrees of uptake have also been associated with non-malignant causes, including inflammatory, infectious, and benign lesions, as well as with normal physiologic activity such as active smooth muscle and mucosa, swallowed secretions, and microbial uptake (25). In a study in humans, 61%, 17%, 8%, and 13% of patients with unexpectedly high ¹⁸F-FDG uptake in the gastrointestinal tract were diagnosed with cancerous/precancerous, inflammatory, benign, and false-negative lesions, respectively, on endoscopic and histopathologic examinations (26). Thus, incidental finding of high ¹⁸F-FDG uptake in the gastrointestinal tract warrants further investigation. The PET/CT imaging characteristics including the PET uptake pattern and CT image features of the uptake region might aid in narrowing the list of differential diagnoses. Short segmental or intense focal ¹⁸F-FDG uptake of the small intestine tends to indicate primary or metastatic neoplasm, while longer segmental or a diffuse pattern of intestinal uptake is likely to represent non-malignant lesions (28). The SUV of intestinal uptake is of negligible value in differentiating inflammation, infection, and malignancy, which show similar values for intensity of ¹⁸F-FDG uptake (29). On CT, intestinal neoplasia commonly appears as a soft-tissue mass or intestinal thickening with contrast enhancement (30). However, inflammation and infection can also show intestinal wall enhancement (25). Although further histopathologic examinations were declined by the owner, the uptake of intestinal loops in the present case was considered inflammatory, infectious, or physiological on the basis of the elongated segmental uptake pattern on PET and normal appearance on CT images. Furthermore, small-intestinal metastases in renal cell carcinoma are rare, and primary tumors of the colon, ovary, uterus, and stomach commonly involve the small intestine (12,28).

In conclusion, PET/CT imaging features of primary renal cell carcinoma and presumed pulmonary metastases were described. With PET alone, there were limitations in detection of small-sized pulmonary nodules, precise localization of increased uptake regions, and differentiation of physiologic from pathologic uptake. Combined PET/CT, providing anatomical detail and lesion characteristics together with functional information, allowed more accurate image interpretation. CVJ