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Arquivos Brasileiros de Endocrinologia & Metabologia

versão On-line ISSN 1677-9487

Arq Bras Endocrinol Metab vol.58 no.3 São Paulo abr. 2014

http://dx.doi.org/10.1590/0004-2730000002913 

artigos originais

Rare renal metastases from differentiated thyroid carcinoma: early clinical detection and treatment based on radioiodine

Metástases renais raras de carcinoma diferenciado da tireoide: detecção clínica precoce e tratamento com radioiodoterapia

Zhong-Ling Qiu1 

Yan-Li Xue1 

Quan-Yong Luo1 

1Department of Nuclear Medicine, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China

ABSTRACT

Objective

: The aim of this study was to explore the clinical characteristics of renal metastatic cancer, the methods for its detection by radioiodine (131I), and the response to 131I treatment in fourteen patients with renal metastases from differentiated thyroid carcinoma (DTC).

Subjects and methods

: DTC patients (n = 2,955) that received treatment with 131I were retrospectively analyzed. Scans (131I-WBS, 31I-SPECT/CT and/or 18F-FDG-PET/CT) were performed after an oral therapeutic dose of 131I. Therapeutic efficacy was evaluated based on changes in Tg and anatomical imaging changes at renal lesions.

Results

: Among these 14 patients, 11 had avidity for 131I, but three patients did not accumulate 131I after 131I treatment. In the 11 131I-positive renal lesions, 10 cases were detected by 131I-SPECT/CT combined with another imaging modality and one case by 131I-WBS combined with ultrasonography (US). In the three 131I-negative renal lesions, two cases were detected by 18F-FDG-PET/CT and one case by computed tomography (CT). In 11 patients with 131I-avid renal metastases, Serum Tg levels in 81.82% (9/11) patients showed a gradual decline, and 18.18% (2/11) of the patients showed a significant elevation. There was no marked difference in serum Tg before the last 131I treatment (Z = 0.157; p = 0.875). Only one patient presented partial response, eight patients exhibited stable disease, and renal metastases progressed in two patients showing progressive disease. No patients reached complete response.

Conclusion

: 131I-SPECT/CT, combined with another imaging modality after 131I-WBS, can contribute to the early detection of renal metastases of DTC. 131I therapy is a feasible and effective treatment for most DTC renal metastases with avidity for 131I. Arq Bras Endocrinol Metab. 2014;58(3):260-9

Key words: Differentiated thyroid cancer; renal metastases; radioiodine therapy; 131I-SPECT/CT; 18F-FDG-PET/CT

RESUMO

Objetivo

: O objetivo deste estudo foi analisar as características clínicas de metástases renais, os métodos para sua detecção por radioiodo (131I) e a resposta ao tratamento com 131I em 14 pacientes com metástases renais de carcinoma diferenciado da tireoide (DTC).

Sujeitos e métodos

Pacientes com DTC (n = 2.955) que receberam tratamento com 131I foram analisados retrospectivamente. 131I-PCI, 31I-SPECT/CT e/ou 18F-FDG-PET/CT foram feitos após uma dose terapêutica oral de 131I. A eficácia terapêutica foi baseada nas alterações da Tg e nas imagens anatômicas das lesões renais.

Resultados

: Dos 14 pacientes, 11 apresentaram lesões ávidas por 131I, mas três pacientes não acumularam 131I depois do tratamento com 131I. Nas 11 lesões renais positivas para 131I, 10 casos foram detectados por 131I-SPECT/CT combinado com outra modalidade de exame de imagem e um caso por 131I-WBS combinado com US. Nas três lesões renais negativas para 131I, dois casos foram detectados por 18F-FDG-PET/CT e um caso por tomografia computadorizada (TC). Em 11 pacientes com metástases renais ávidas por 131I, os níveis séricos de Tg em 81,82% (9/11) dos pacientes mostraram um declínio gradual e 18,18% (2/11) apresentaram uma elevação significativa. Não houve diferenças marcadas na Tg sérica antes do último tratamento com 131I (Z = 0,157; p = 0,875). Apenas um paciente apresentou resposta parcial, oito pacientes apresentaram doença estável e as metástases renais progrediram em dois pacientes que apresentaram doença progressiva. Nenhum dos pacientes apresentou resposta completa.

Conclusão

: 131I-SPECT/CT, combinada com outra modalidade de diagnóstico por imagem após 131I-PCI, pode contribuir para a detecção precoce de metástases renais de DTC. O tratamento com 131I é passível de ser feito e eficiente para o tratamento da maior parte das metástases renais ávidas por 131I. Arq Bras Endocrinol Metab. 2014;58(3):260-9

INTRODUCTION

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and accounts for less than 1% of malignant neoplasms in humans (1). The overall prognosis for DTC patients is one of the best among all types of cancer, with a 10-year survival rate over 85-90%, but its incidence is gradually increasing in different parts of the world (2,3). Although DTC is generally characterized by an indolent course with low mortality, patients with distant metastases have strong prognosis of mortality, and more than 50% of these DTC patients die from distant metastatic disease during follow-up (4). Distant metastases derived from DTC occur in 5-23% of patients at presentation and during follow-up (5,6).

The major sites of distant metastases from DTC are the lungs and bones, while minor sites include the brain, liver, skin, and muscle. In contrast, renal metastases from DTC are extremely rare. Ahmed and cols. (7) reported that from December 1975 to September 2005, only one case of DTC metastasizing to the kidney was found among 3,500 DTC patients at their institution. To the best of our knowledge, only 26 cases have been reported in the literature to date.

131I has been used as a therapy for distant metastases from DTC for over 60 years and has been an important component in the management of DTC. Traditionally, 131I whole-body scans (131I-WBS) have been performed to localize 131I uptake and detect residual (or recurrent) disease and distant metastases after 131I treatment. However, the precise anatomical localization of foci with increased 131I uptake is difficult on planar images because of the lack of anatomical landmarks. By precisely localizing 131I uptake, 131I single photon emission computed tomography/computed tomography (131I-SPECT/CT) might improve the diagnostic accuracy of 131I scanning, thus improving the management of diseases in patients (8,9). Scans based on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) are well established for detecting recurring or metastatic DTC in patients with a negative 131I-WBS and elevated serum Tg (10,11). Moreover, noninvasive imaging tools, including ultrasonography (US), enhanced CT, and magnetic resonance imaging (MRI), are useful for the detection of distant metastases (suspected according to clinical symptoms) in the follow-up of DTC.

Because of its limited and rare appearance, renal metastasis from DTC has only been occasionally reported, mainly as case reports or a small case series. Therefore, the diagnosis and efficacy of 131I therapy have not been clearly defined and need further research. In this study, we retrospectively reviewed 14 patients treated with 131I at Shanghai Sixth People’s Hospital in China. We explored their clinical characteristics, as well as methods for 131I-based detection and treatment of renal metastases from DTC.

SUBJECTS AND METHODS

Subjects

A total of 2,955 DTC patients were enrolled in this study at the Department of Nuclear Medicine of Shanghai Sixth People’s Hospital, a major referral site in China for 131I treatment. All patients were treated with 131I for the ablation of postsurgical thyroid remnants, or treatment of metastases after total or near-total thyroidectomy from January 1998 to January 2012. Among them, 14 patients had diagnosis of renal metastases from DTC.

Methods for 131I therapy and follow-up

All patients stopped taking thyroid hormone medication and began a low iodine diet 3-4 weeks before radioiodine therapy (thyroid stimulating hormone (TSH) reaching levels of ≥ 30 mIU/L). The patients received an oral administration of 131I after examinations, including FT3, FT3, FT4, TSH, Tg and anti-Tg antibody (TgAb) tests, neck ultrasonography, X-ray, CT, MRI, and whole-body bone scans. 131I-WBS or 131I-SPECT/CT fusion imaging was performed 5 days after 131I administration. The first oral dose of 3.7 GBq of 131I was given to remove thyroid remnants. The oral administration of 7.4 GBq of 131I was then given each time for the treatment of renal metastases. The treatment interval varied from 4 to 12 months, and the treatment was repeated 2-8 times. The time diagnosing renal metastases was established from 0.4 yrs. to 14.3 yrs. with a median time of 5.8 yrs. after the initial thyroid surgical treatment

Detection and diagnosis of renal metastases from DTC

The detection of renal metastases was carried out by means of one of two approaches: (1) if 131I-WBS (with or without SPECT/CT) demonstrates 131I uptake in the renal lesions, an imaging tool (US, enhanced CT, or MRI ) can be used to indicate renal metastasis (serum levels of Tg should also be elevated), and (2) if 131I-WBS reveals no 131I uptake, 18F-FDG-PET/CT, enhanced CT, MRI, or US scans that are positive (with elevated serum Tg) may indicate renal metastases from DTC. The diagnosis of renal metastases was confirmed by pathology results and clinical follow-up of renal lesions from DTC.

Evaluation of efficacy

The therapeutic effects of 131I therapy for renal metastases from DTC were evaluated based on changes in serum Tg levels and alterations in the anatomical imaging of renal metastatic lesions. Serum Tg levels were measured with the Immulite chemiluminescent immunoassay system (Diagnostic Products Corporation, Los Angeles, CA, USA). Serum TSH and anti-Tg antibody (TgAb) levels were also measured. The evaluation of anatomical images was performed based on methods established by RECIST 1.1. The responses defined by RECIST 1.1 are as follows: complete response (CR): disappearance of all target lesions, any pathological lesions (target or non-target) must have a reduction in short axis to < 10 mm; partial response (PR): at least a 30% decrease in the diameters of target lesions; progressive disease (PD): at least a 20% increase in the diameters of target lesions, combined with an absolute increase of at least 5 mm in the sum of diameters (in addition, appearance of one or more new lesions was also considered progression); stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increases to qualify for PD.

Statistical analysis

SPSS17.0 was used for statistical analysis. Tg changes were estimated by the Wilcoxon signed rank test. A p value < 0.05 was considered a statistically significant difference.

RESULTS

Demographic features of the patients

Fourteen patients were diagnosed with renal metastases from DTC with multimodality imaging, with an incidence of 0.47% (14/2955). The characteristics of these 14 DTC patients are summarized in table 1. Their ages ranged from 17 to 74 years, with a mean of 43 years. Seven subjects were over 45 years of age, and seven were less than 45 years. Eight subjects were males and six were females (male-to-female ratio of 1.3:1). The distribution of DTC pathological types included nine cases of papillary thyroid cancer and five cases of follicular thyroid cancer. Of the 14 cases, only one (case 14) had a single renal metastasis, whereas 13 cases presented combined metastases to other organs: 11 patients had lung metastases, seven had bone metastases, three had mediastinal metastases, and there was one case each of metastasis to the brain, muscle, liver, and parapharyngeal region. Renal metastases were asymptomatic in nine patients, but found on imaging follow-up studies. Three patients had symptoms of lower back pain, and two had hematuria.

Table 1 Characteristics and related data of patients with renal metastases from differentiated thyroid carcinoma 

Patient No Sex Age of total thyroidectomy(years) Age of diagnosing renal metastases of DTC Years after detection of primary tumor (years) Histology Other synchronous distant metastases Detecting modality Confirmation modality Localization of renal metastases (diameter) cm) Symptoms NO. of RIT courses 131 131
1 F 51 65 14.3 F Lungs, bones, liver 131I-WBS, ultrasonography FNAB Left 5.2 Low back pain 8 Yes 59.2
2 F 25 34 9.2 P Lungs, mediastinum 131I-SPECT/CT, MRI FNAB Left 1.2 No 6 Yes 40.7
3 M 29 29 0.4 P Lungs, erector spinae 131I-SPECT/CT, enhanced CT Follow-up Right 0.9 No 5 Yes 35.15
4 M 28 40 12.6 P Lungs, mediastinum 131I-SPECT/CT, MRI Follow-up Left 0.6 No 7 Yes 49.95
5 F 43 51 8.1 F Lungs and Bones Biopsy, CT FNAB Left 3.1 Low back pain, hematuria 1 No 11.1
6 F 48 52 4.3 F Lungs, bones 131I-SPECT/CT FNAB Right 1.8 No 5 Yes 35.15
7 M 34 35 1.2 F Lungs 131I-SPECT/CT, MRI Follow-up Bilateral L: 0.4 R: 0.6; 0.4 No 5 Yes 31.45
8 M 11 19 8.6 P Lungs, bones 131I-SPECT/CT FNAB Bilateral L: 3.2 R: 2.8 Hematuria 3 Yes 22.2
9 M 21 24 3.2 P Lungs, bone 131I-SPECT/CT, ultrasonography FNAB Left 1.1 No 4 Yes 14.8
10 F 63 66 3.7 P Lungs, bone 131I-SPECT/CT FNAB Left 3.3 No 3 Yes 12.95
11 M 57 62 5.4 F Bones 18F-FDG-PET/CT,MRI FNAB Right 1.9 No 1 No 11.1
12 M 24 25 0.9 P Mediastinum 131I-SPECT/CT, Ultrasonography FNAB Right 2.4 No 4 Yes 18.5
13 M 67 74 7.9 P Brain, lungs, parapharyngeal, lung mediastinum 18F-FDG-PET/CT FNAB Left 2.3 Low back pain 1 No 22.2
14 F 30 31 1.4 P 131I-SPECT/CT, ultrasonography Follow-up Left 0.5 No 4 Yes 11.1

DETECTION OF RENAL METASTASES FROM DTC

Discovery of functional renal metastases

Renal metastases from DTC that were detected with multimodality imaging are shown in figure 1. In the detection of renal metastases from DTC after 131I treatment, 131I-WBS found 21 lesions (indicating abnormal 131I uptake) in the abdomen of 11 DTC patients, suggesting distant metastases from DTC, of which a total of 10 patients with 13 lesions were located in the kidneys after 131I-SPECT/CT. Four cases with four lesions were found in the left kidneys, four cases with four lesions were found in the right kidneys, and two cases with five lesions were bilateral; among them, one case (case 7) with three lesions was found bilateral in the kidneys, one lesion in the left kidney and two lesions in the right kidney. Of those 10 patients with 13 renal metastatic lesions revealed by 131I-SPECT/CT, all patients were SPECT-positive; but only three patients with five lesions (cases 6, 8, and 10) were CT-positive, with the remaining eight lesions of seven DTC patients (cases 2, 3, 4, 7, 9, 11, and 14) presenting equivocal or negative CT, suggesting early or small renal metastases. In these seven patients, three (cases 2, 4, and 7) were synchronous with MRI (Figure 2), three (cases 9, 12, and 14) with US, and one case (case 3) with enhanced CT. Among the remaining eight 131I-uptake foci, one renal metastatic lesion in a DTC patient with lower back pain (case 1) was shown by 131I-WBS combined with US, and others were excluded and identified as five intestinal uptake sites, one liver metastasis, and one erector spinae by 131I-SPECT/CT.

Figure 1 Renal metastases from DTC detected with multimodality imaging. 

Figure 3 A 74-year-old male patient with lower back pain was given 131I treatment after total thyroidectomy. No abnormal 131I uptake was found in the post-therapeutic 131I-WBS with elevated serum Tg and 18F-FDG-PET/CT was performed to search for potential metastatic lesions. Maximum intensity projections in 18FDG-PET revealed more intense 18FDG uptake lesions in the chest and abdomen (A: arrow). 18F-FDG-PET/CT revealed a prominent 18FDG uptake lesion with a diameter of 23 mm in the upper pole of the left kidney (B-D: arrow). 

Discovery of non-functional renal metastases

Of the 14 DTC cases with renal metastases, three patients with three lesions failed to accumulate 131I after 131I treatment. Among them, two DTC patients (cases 11 and 13) with renal metastases were observed with 18F-FDG-FET/CT (Figure 3); one lesion in one patient (case 11) was 18F-FDG-FET–positive but CT-equivocal and confirmed by MRI, and one patient was positive by 18F-FDG-FET and CT (case 13) (Figure 3). The remaining patient (case 5), who had lower back pain and hematuria, but was negative in 131I-WBS with elevated serum Tg, had renal metastasis identified by CT.

Figure 2 A 40-year-old male patient who presented mediastinal lymph node and pulmonary metastases from papillary thyroid cancer was treated with 131I for postsurgical thyroid remnants and metastases. An unexpected lesion with 131I uptake in the left abdomen, mediastinal lymph node, and lungs (suggesting metastasis) was observed on a 131I-WBS 5 days after an oral therapeutic dose of 131I (A: arrow). To localize this unexpected lesion of 131I uptake, a subsequent low-dose 131I-SPECT/CT scan was performed using a GE Hawkeye Millennium. Fusion images showed that the lesion was located in the left kidney (B-D: crossing line). Further examination with MRI revealed a solitary metastatic lesion with a diameter of 8 mm in the upper pole of the left kidney (E-F: arrow). 

Diagnosis of renal metastases from DTC

Among 14 DTC patients with renal metastases, ten cases (71.43%) were diagnosed based on pathological results (cases 1, 2, 5, 6, 8, 9, 10, 11, 12, and 13) and the remaining four cases (28.57%) with renal metastases also should be considered by clinical follow-up because lesions were considered too small for a fine-needle aspiration biopsy. Moreover, 131I-SPECT/CT combined with MRI (cases 4 and 7), enhanced CT (case 3), or US (case 14) showed the existence of renal lesions after several 131I therapy.

Responses to 131I therapy

Among 14 patients, three patients with renal metastases did not accumulate 131I after 131I treatment; therefore, responses to 131I therapy were ineffective for them.

Changes in serum Tg

All eleven 131I-avid patients received approximately three to eight courses of 131I treatment at an interval of 4-12 months. The median stimulated serum Tg level was 4659 ng/mL (range 87-18191 ng/mL) before the first 131I treatment, and 4194 ng/mL (range 31701-19 ng/mL) before the last 131I treatment. There were no marked differences in serum Tg before and after 131I treatments (Z = 0.157; p = 0.875). Serum Tg levels in 81.82 % (9/11) of the patients showed a gradual decline, while 18.18% (2/11) of the patients showed a significant elevation. In one patient (case 14), serum Tg level was normal and stabilized at about 2.56 and 9.3 ng/mL; however, TgAbs were obviously high and changed from 327 to 92 u/mL after several 131I treatments (Table 2).

Table 2 Response of DTC patients with renal metastases after 131I treatment 

Patient nº Stimulated Tg before first 131131I treatment(ng/mL) 131 131
1 8,752 6,923 PD
2 640.7 289 SD
3 567 19 SD
4 401 123 SD
6 5,463 6,376 SD
7 18,191 602 PR
8 17,016 31,701 PD
9 87 22 SD
10 39.38 22.64 SD
12 94 52 SD
13 13,562 17,817 PD
14 2.56 9.3 SD

Anatomical imaging changes after 131I therapy

Of the 11 cases with renal metastases, only one patient presented PR and eight patients exhibited SD; these findings suggest that the disease remains stable. The renal metastases progressed in two patients showing PD. No patient reached CR (Table 2).

DISCUSSION

Differentiated thyroid cancer (DTC) has been reported to present initially distant metastases in about 4% of cases. During follow-up, distant metastases develop in 2-34% of cases (12). The presence of distant metastases reflects advanced clinical presentation, associated with higher mortality rate, especially in elderly patients (13). However, 131I-WBS combined with elevated serum Tg can contribute to the early detection of distant metastases (at a time when other radiological studies are negative), and the disease is potentially curable by means of 131I therapy (14,15).

The major sites of distant metastases from DTC are the lungs and bones, while other sites infrequently involved include the brain, liver, skin, pleura, and muscle. Metastasis to the kidneys is not an uncommon incidental finding at autopsy; 4.6-7.6% of patients have metastases in the kidneys, with frequencies of bilaterality and multiplicity being as high as 71-81% (16). Metastases to the kidney from papillary and follicular thyroid cancer are found in 2.8-3.8% and 6-20% of cases, respectively (17). However, the clinical detection of DTC metastasis to the kidneys is quite rare; a retrospective review of the literature revealed only 26 case reports of renal metastases arising from DTC. Of the 26 cases of renal metastasis associated with DTC, full-text studies of three patients were not found using the PubMed and EMBASE databases; the other 23 patients are reviewed in table 3 (7,16-36). We previously reported one case of renal metastases from DTC, a 29-year-old man with concomitant metastases to the erector spinae and lungs (case 7) (19). Most subjects were females over 45 years of age; nine cases were FTC, 10 cases PTC, three cases a follicular variant of PTC, and one case of Hurthle cell thyroid cancer. However, because of its limited expression and rarity, renal metastasis from DTC has only been occasionally reported, mainly as case reports or a small case series. Here, a relatively large number of DTC cases from renal metastasis were described in this study. The overall prevalence of renal metastasis from DTC was about 0.47% (14 of 2,955). Similar to our patients, most of the previously reported patients had advanced DTC with metastases to other organs when renal metastases were found. In our study, a 31-year-old female with a single left renal metastasis from DTC was the only case detected by 131I-SPECT/CT and US after 131I treatment.

Table 3 Renal metastases from differentiated thyroid cancer previously reported in the literature 

No. Author Publication (year) Age/sex Histopathology Diagnostic methods Localization of renal metastases (size, cm) Other synchronous distant metastases Years
1 Borde and cols. (16) 2011 56/M Papillary 131I-WBS, F-FDG PET, SPECT, CT, biopsy Bilateral (L: 5.5; R: 1.4, 1.5)
2 Malhotra and cols. (17) 2010 30/M Papillary 131I-SPECT/CT, biopsy R (1.5) Lungs, liver, bones, mediastinum, and adrenal 20
3 Djekidel and cols. (18) 2010 75/M Hurthle cell Biopsy R (5) Bone 9
4 Luo and cols. (19) 2008 29/M Papillary 131I-SPECT/CT R Erector spinae
5 von Falck and cols. (20) 2007 64/F Follicular 131I-SPECT/CT L Lungs and bone 20
6 Ahmed and cols. (7) 2006 24/F Papillary Ultrasonography R (1.3) 26
7 Kumar and cols. (21) 2005 66/F Follicular 131I-WBS, biopsy L Adrenal
8 Iwai and cols. (22) 2005 76/F Follicular CT, MRI, biopsy R (3) Muscle, lung 13
9 Liou and cols. (23) 2005 50/F P/F CT, biopsy R (1.9) Lungs, and bone -
10 Inahara and cols. (24) 2002 66/M Papillary Hematuria, biopsy Bilateral 11
11 Smallridge and cols. (25) 2001 61/F Papillary 131I-WBS, CT L (3) Muscle
53/F Papillary CT R (3.5) Lungs
12 Garcia-Sanchis and cols. (26) 1999 65/F Follicular 131I-WBS L (10) Lungs and bones
13 Benchekroun and cols. (27) 1999 56/M Papillary Low back pain L (5.6) 3
14 Lam and cols. (28) 1996 91/F Papillary L (5) -
15 Graham and cols. (29) 1995 75/M P/F IVP L (7.7) < 1
16 Ro and cols. (30) 1995 47/F Follicular Hematuria R (1.2) 7
17 Tur and cols. (31) 1994 72/F P/F 131I-WBS Bilateral Liver 3
18 Sardi and cols. (32) 1992 53/M Papillary Hematuria R (12) Lungs 7
19 Marino and cols. (33) 1991 -/ F Follicular 201T , 123I scan R 26
20 Johnson and cols. (34) 1982 66/F Follicular Hematuria L Lungs 37
21 Davis and Corson (35) 1979 49/F Follicular Bilateral (R: 3.5; L: 4.4) 18
22 Takayasu and cols. (36) 1968 44/F Follicular IVU Bilateral Bone 3

The 131I-WBS is indispensable for finding distant metastases because of their ability to accumulate 131I through the sodium iodide (Na+/I-) symporter after an oral dose of 131I. In our series, most DTC patients (11/14) with renal metastases have the ability to take up 131I. However, the accurate localization of focal activity by 131I-WBS is difficult because of the lack of anatomical markers. Therefore, renal metastases from DTC are easily misinterpreted as an intestinal physiological uptake frequently observed through 131I-WBS in DTC patients. In recent years, 131I-SPECT/CT has emerged in this setting as a useful tool for accurately locating sites of pathological uptake and identifying physiological mimics of disease, thus providing a more accurate staging of prognostic information for risk stratification which, in its turn, tailors management and follow-up regimens (37). 131I-SPECT/CT for anatomic localization of renal metastases has been reported in past reviews (19,20). In our cases, 10 DTC patients with renal metastases were detected by 131I-WBS combined with 131I-SPECT/CT, suggesting that the additional diagnostic information provided by 131I-SPECT/CT over 131I-WBS could detect renal metastases from DTC patients. Patients with renal metastases are usually asymptomatic and most are less than 45 years old, as seen in our cases, also suggesting that avid 131I metastatic foci of renal metastasis could be detected at an early stage by 131I-SPECT/CT scan.

Due to dedifferentiation, about 20-50% of metastatic DTC have no ability to take up 131I. The definitive role of 18F-FDG-PET/CT in DTC patients with serum Tg levels and negative 131I-WBS has been consistently demonstrated (38). The discrepancy between the two imaging tools is attributable to the flip-flop phenomenon of 131I and 18F-FDG (39). Three patients with three lesions did not accumulate 131I after 131I treatment. Among them, two DTC patients had renal metastases discovered on 18F-FDG-FET/CT (originally done to evaluate elevated Tg). Moreover, Borde and cols. also described renal metastases that had no uptake of 131I but were detected by 18F-FDG-FET/CT in a 56-year-old male PTC patient (16). Tumors with 131I non-avidity and FDG uptake suggest their high grade (38).

In clinical settings, most conventional imaging such as US, enhanced CT, and MRI are performed for the evaluation of symptoms, disease staging, or the evaluation of treatment response. Therefore, renal metastases from DTC cannot be considered for these conventional imaging scans without clinical symptoms or clinical suspicion prior to the initiation of various therapies. For example, because of lower back pain and hematuria, a 51-year-old female patient with no avid 131I was found to have a left renal metastasis from DTC by CT combined with biopsy in our study.

Renal metastatic foci from DTC (regardless of 131I avidity) can be accurately localized with 131I-SPECT/CT or 18F-FDG-FET/CT; however, renal lesions less than 1.0 cm are too small for detection by CT scans. Moreover, Blum and cols. (40) reported a sixty-three-year-old woman (with a history of PTC) treated with surgery and then ablation with 100 mCi of 131I. Post-treatment WBS demonstrated an equivocal signal in the upper right abdomen that 131I-SPECT/CT later confirmed as 131I accumulation within a benign renal cyst. These are strong reminders that 131I-SPECT/CT and 18F-FDG-FET/CT images are valuable in finding, but not completely in diagnosing, rare renal metastases from DTC. Thus, other imaging modalities need to be applied for finding renal metastases when metastatic foci are positive in 131I-SPECT or 18F-FDG-FET, but negative or equivocal in CT scans in the follow-up of DTC. These other modalities, including US, enhanced CT, and MRI, are especially useful tools to detect small (< 1 cm) or cryptic renal lesions unseen on CT scans. Of the 14 patients here, four were further identified by MRI scan, four by US, one by enhanced CT, and one by biopsy. Therefore, multimodality imaging is essential to accurately assess the extent of renal metastases from DTC to guide treatment, prevent tumor progression, and improve survival.

Due to the rare occurrence of renal metastases from DTC, the best management for this condition is unclear. Since most cases are associated with metastases at other sites, surgical excision, with its risks and limited efficacy, is not a practical solution. Although external beam radiotherapy can provide local tumor control in a high percentage of cases, its efficacy is transient and dose-dependent. To obtain a longer lasting efficacy, a high dose of irradiation may be required and adverse effects must be considered. In addition, it is usually applied to treat a single metastasis and is unsuitable for the treatment of multiple metastases.

Sorafenib is a multikinase inhibitor that targets several molecular signals involved in the pathogenesis of DTC, and that has been used in the treatment of advanced or metastatic 131I-refractory DTC (41). However, it has only been reported as an anti-cancer drug for DTC with distant metastases, but not avid 131I lung metastases, in recent years. Therefore, these treatments have not been applied in this group of patients. Currently, 131I therapy is the treatment of choice for most DTC patients with distant metastases after thyroidectomy. If renal metastases from DTC have excellent 131I uptake, they can be differentiated from other malignant neoplasms based on this feature, and be treated with 131I. However, there are no data showing the efficacy of 131I for the treatment of renal metastases from DTC due to their rarity. Here, the therapeutic effects of 131I therapy on renal metastases from DTC were evaluated based on changes in serum Tg and alterations in anatomical imaging of metastatic renal lesions. In our study, among the 14 DTC patents with renal metastases, 11 patients showed avidity for 131I.

Serum Tg is a highly sensitive and specific marker of DTC metastasis and recurrence, which also reflects tumor burden. Serum Tg is usually significantly elevated in DTC patients with distant metastases. Thus, the pronounced reduction in Tg (at roughly the same TSH level) indicates that 131I therapy can eliminate some tumor cells after multiple treatments (4). In our study, serum Tg levels in 81.82% (9/11) patients showed a gradual decline and 18.18% (2/11) patients showed a significant elevation, suggesting that 131I is partly effective for the treatment of DTC patients with renal metastases. Because the detection of Tg may be disturbed by TgAbs, we measured serum levels of Tg and TgAbs simultaneously in all patients. In only one patient in this study, serum TgAb levels increased to a certain extent (> 100 ng/mL) but Tg levels were normal and stabilized at about 2.56 and 9.3 ng/mL. After 131I therapy, serum levels of TgAbs decreased markedly.

After 131I therapy, MRI examinations revealed statistically significant shrinking of metastatic renal lesions in only one patient. This improvement may be due to small lesions or those that were at an early stage. The anatomical imaging of renal metastases with excellent avidity for 131I showed insignificant changes in eight patients (72.73%), indicating that those lesions were stable. Though renal metastatic foci accumulated 131I, US still showed PD in a patient, suggesting renal metastasis in this DTC patient may exhibit dedifferentiation (42). Renal metastatic foci in the remaining three patients gradually increased without 131I uptake after 131I treatment. Therefore, 131I treatment is ineffective for patients with a relatively poor prognosis.

CONCLUSION

In summary, renal metastasis is an extremely rare pattern of invasion from DTC with an incidence of 0.47%. 131I-SPECT/CT, combined with other imaging modalities after 131I-WBS, can contribute to the early detection of renal metastases and is essential to accurately assess the extent of renal metastases from DTC to guide treatment and prevent tumor progression. 131I therapy can significantly decrease serum Tg, and shrink or stabilize renal metastatic lesions with excellent avidity for 131I.

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Received: August 2, 2013; Accepted: August 23, 2013

Correspondence to: Quan-Yong Luo Department of Nuclear Medicine, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, P. R. China lqyn@sh163.net

Conflict of interest disclosure: Zhong-Ling Qiu and Yan-Li Xue contributed equally to this work. This study was sponsored by the National Natural Science Foundation of China (No: 81201115).

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