¹⁸F-fluorodeoxyglucose-positron-emission tomography/computed tomography staging of mucinous tubular and spindle cell carcinoma of the kidney

INTRODUCTION

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) was first described in 1998, and classified as a variant of renal cell carcinoma (RCC) in the classification of World Health Organization (WHO) in 2004.[1] Currently, there are approximately 100 cases of MTSCC-K reported in the literature.[2] This tumor occurs throughout life (age range: 17-82 years) and is more frequent in females.[1] These tumors possess histological components involving mucin, tumor cells forming tubules, and spindle cells and resemble papillary RCC. However, chromosome 7 and 17 defects and chromosome Y deletion, typical of papillary RCC, are not observed in MTSCC-K.[3] The majority of these tumors are accidentally discovered during abdominal imaging studies due to other indications. The major symptoms include flank pain and hematuria that occur when the lesions reach large sizes. The cases with MTSCC-K reported in the literature had tumors measuring between 1 and 18 cm. The treatment of the disease involves complete surgical excision.[2] As a variant of RCC, the staging of medial tibial stress syndrome of the kidney using ¹⁸F-fluorodeoxyglucose-positron-emission tomography/computed tomography (¹⁸FDG-PET/CT) has not been previously reported in the literature. The current case is significant due to the demonstration of the utility of PET/CT in primary staging of MTSCC-K.

CASE REPORT

A 62-year-old female patient was evaluated due to the incidental finding of a renal mass. Ultrasound (US), CT, magnetic resonance imaging (MRI), and ¹⁸FDG-PET/CT revealed a mass lesion in the left kidney measuring 4 cm in diameter. The physical examination and laboratory tests were not remarkable. The patient was using gliclazide due to type II diabetes mellitus. The patient never smoked. The patient underwent radical nephrectomy, and the immunohistopathological examination of the specimen revealed MTSCC-K. The patient was regarded to have stage PT1aN0M0 tumor according to RCC staging system, and she was placed on a follow-up program.

The pathological examination of the radical nephrectomy material revealed a centrally located necrotic tumor measuring 4 cm in diameter and confined within the renal capsule. The pathological tumor stage was T1A-weighted. The immunohistochemical examination revealed spindle cells with tubular structures in the mucinous background, and the tumor showed positive staining for cytokeratin 7 and RCC. The tumor had negative staining for AMACR, CD10, and vimentin. These immunohistochemical features and findings suggested the diagnosis of MTSCC-K [Figure 1].

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Figure 1 Tumors areas with tubular and spindle cells (H and E, ×100)

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The US revealed a hyperechogenic mass lesion in the left kidney measuring 4 cm in diameter. CT revealed an isodense mass lesion measuring 4 cm in diameter and located in the posterior and central part of the left kidney. MRI revealed a solid primary kidney carcinoma located in the central and posterior part of the left kidney, measuring 44 × 32 × 35 mm with a hyperintense appearance contrast uptake in T2A-weighted sequences. FDG-PET/CT examination revealed a left renal mass located in the central and posterior segment, measuring 40 × 30 × 40 mm and with pathological FDG uptake. The maximum standard uptake value (SUV_max) was 6.7 [Figure 2].

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Figure 2 (a) Magnetic resonance imaging, mass in the central posterior part of the left kidney, diffuse contrast uptake (arrow), (b) ¹⁸F-fluorodeoxyglucose-positron-emission tomography/computed tomography (¹⁸FDG-PET/CT), left renal mass with a standard uptake value of 6.7 (arrow), (c) ¹⁸FDG-PET/CT, the coronal reconstruction shows left renal mass (arrow), (d) Maximum intensity projection images of a patient, (arrow: Left renal mass)

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DISCUSSION

Kidney cancers account for 3% of all cancers, and 5-year survival is 68.4%. Clear cell RCC accounts for 90% of all RCCs.[34] The treatment of the local disease involves radical or partial nephrectomy. RCC has been shown to be resistant to radiation therapy and chemotherapy. Therefore, early diagnosis and treatment are considerably important. MTSCC-K remained as one of the unclassified tumors until 2004; however, in 2004, the WHO classified the tumor as a variant of the RCC. This tumor is extremely rare and mostly occurs in adult females. The mean age is reported to be 53-year in the literature. These tumors are associated with a good prognosis.[2]

USG, contrast-enhanced CT, MRI, ¹⁸FDG-PET/CT, ¹¹C-acetate PET, ¹⁸F-fluoroethylcholine PET/CT, and immune-single-photon emission computed tomography can be used in the diagnosis of RCC. The diagnosis of the tumors involving the urinary system is complicated using ¹⁸FDG-PET due to the physiological activity of the urinary tract. The physiological ¹⁸FDG excretion of the renal collecting system should be differentiated from malignant pathological activity. Renal parenchymal lesions can be differentiated from physiological ¹⁸FDG uptake by acquiring late phase images and/or after diuretic injection. Focally increased activity in the ureter and renal pelvis can be observed as a variant of ¹⁸FDG activity. Furthermore, calyceal diverticula and megacalycosis may appear as increased renal ¹⁸FDG activity. The excretion of ¹⁸FDG from the pelvicalyceal system limits the sensitivity and specificity of the procedure in diagnosing renal cancers. Another factor decreasing the sensitivity is that primary renal tumors can express low levels of glucose transporters-1 (GLUT-1), which are responsible for the accumulation of ¹⁸FDG. The low sensitivity of ¹⁸F-FDG-PET in some reports has been attributed to ¹⁸FDG excretion through the kidneys and collecting systems, decreasing contrast between renal lesions and normal tissues, as well as being due to the significant variability of ¹⁸F-FDG uptake that may be related to the variable expression of GLUT-1, tumor grade, presence of central necrosis, and/or lack of accessibility of ¹⁸F-FDG.[5]

In 1997, Goldberg et al. showed successful utility of ¹⁸FDG-PET/CT in the evaluation of renal masses.[6] In a meta-analysis conducted by Wang et al. in 2012, the authors reported 88% specificity and 91% sensitivity for ¹⁸FDG-PET/CT in diagnosing both RCC and extra-renal metastases.[7]

The specificity and sensitivity of ¹⁸FDG-PET/CT in diagnosing renal masses are based on the size and location of the renal mass. Kumar et al. analyzed 63 patients who underwent 103 PET/CT scans with a sensitivity of 90%, specificity of 91%, and accuracy of 90% in diagnosing recurrent disease.[8] Several reports in the literature have also previously assessed the differences in the metabolic properties of various subtypes of RCC using either ¹⁸F-FDG-PET or ¹⁸F-FDG PET/CT. Ye et al. evaluated 12 patients with RCC (7 patients with clear cell and 5 with other subtypes) and 12 patients with lymphoma using ¹⁸FDG-PET/CT, and they observed higher FDG uptake in lymphoma patients compared to the patients with clear cell RCC (mean SUV 6.37 ± 2.28). However, mean SUV was not different between other subtypes of the renal carcinoma and lymphoma. The SUV was 6.37 for lymphoma and 6.27 for the subtypes of RCC.[9] The mean SUV of 6.7 for the current patient was similar to that reported in the literature. Kumar et al. examined 28 patients, 10 of which had primary RCC with a maximum SUV of 7.9 and mean SUV of 6.0 for ¹⁸FDG activity.[8] Khandani et al. evaluated 26 patients with RCC (19 with clear cell subtype and 7 with nonclear cell subtype) using ¹⁸F-FDG-PET/CT and reported an average SUV of 3.9 for clear cell RCC and maximum SUV of 7.9 for nonclear cell RCC, and the difference was borderline significant.[6] Nakoda et al. found a faster metabolic rate in clear cell RCC compared to papillary RCC.[6]

Bertagna et al. compared the relationship between histological subtype and PET/CT findings. The positivity in PET/CT was 61% in clear cell RCC, 66% in papillary RCC, 100% in the carcinoma of the collecting ducts, and 69% in the other subtypes.[6] MTSCC-K are considered low-grade tumors associated with a good prognosis. Metastasis to the lymph nodes and recurrence rarely occur. However, widespread lung and bone metastases have been described in 2 cases with sarcomatoid differentiation reported in the literature.[2] MTSCCs generally appear as hypovascular lesions on MRI and CT. The number of mitosis is lower compared to other types of RCC, and these tumors are associated with a good prognosis; however, PET/CT with ¹⁸FDG does not contribute to a diagnosis. In the current case, the diagnosis and primary staging were established by PET/CT with a high-SUV value. There are a limited number of studies in the literature demonstrating the sensitivity of PET/CT in the diagnosis of variant kidney tumors. In some studies in the literature, increased GLUT-1 expression, and high-Fuhrman grade were detected in patients with positive ¹⁸FDG uptake among those (n = 11) evaluated with ¹⁸FDG-PET/CT.[5] However, there are studies in the literature that did not support these findings. Miyakita et al. (n = 19) employed ¹⁸F-FDG-PET in RCC cases and reported that there was no correlation between GLUT-1 expression and ¹⁸F-FDG-PET positivity.[5] A similar study was conducted by Aide et al. (n = 35) using ¹⁸FDG-PET for the characterization and staging of a suspicious renal mass, and they reported that the distribution of the Fuhrman histological grade among visualized and nonvisualized RCC on ¹⁸FDG-PET was not statistically significant.[6] Furthermore, Bertagna et al. examined 68 patients, and they did not report a correlation between Fuhrman histological grade and ¹⁸FDG-PET/CT findings.[6] There are studies in the literature suggesting that the PET/CT could change the treatment decision in the management of renal masses. Ramdave et al. examined 17 patients diagnosed with a kidney tumor who were planned to undergo radical nephrectomy; however, PET/CT changed the treatment decision in 6 cases (35%), three of which underwent partial nephrectomy and the other 3 patients underwent follow-up due to the presence of a benign tumor. This finding suggested that PET/CT could change the treatment decision in renal masses. A SUV value of 6.7 for PET/CT in the current patient facilitated the decision of radical nephrectomy.[10]

CONCLUSION

¹⁸F-fluorodeoxyglucose PET/CT shows 88% sensitivity in diagnosing known solid renal masses despite the urinary excretion of ¹⁸FDG. ¹⁸FDG-PET/CT may be helpful in diagnosing the subtypes of RCC and variant tumors due to their different metabolic activity. PET/CT can be used in the diagnosis and staging of MTSCC-K due to its high SUV. Considering the paucity of cases with MTSCC-K in the literature, further studies are warranted to support these findings.