Usefulness of PET/CT in the diagnosis of recurrent or metastasized differentiated thyroid carcinoma.

The aim of the present study was to determine the usefulness of the positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) in the detection of recurrence or metastasization of differentiated thyroid carcinoma (DTC) in patients with abnormal thyroglobulin levels and negative findings on the 131I-diagnostic whole-body scanning (dWBS). Fifteen patients with DTC, abnormal thyroglobulin levels, and negative 131I-dWBS findings were scanned using the 18F-FDG PET/CT. Positive diagnosis was based on postoperative histologic findings, and clinical and imaging follow-up results obtained in the subsequent 6 months. In addition, preoperative and postoperative thyroglobulin levels were compared. Using the findings of 18F-FDG PET/CT and data on confirmed positive diagnosis, sensitivity and positive predictive value (PPV) were calculated. Sensitivity and PPV of PET/CT in detecting recurrence or metastasisization of DTC were 93.30 and 91.40%, respectively. Furthermore, postoperative thyroglobulin levels were markedly lower compared to the preoperative levels (respectively, 4.67±1.71 vs. 58.53±18.34 ng/ml; p<0.05). PET/CT scan with 18F-FDG is an informative technique for the detection of recurrent or metastasized DTC in patients with abnormal thyroglobulin levels and negative 131I-dWBS findings.

Introduction

The incidence of thyroid carcinoma is the highest among head and neck carcinomas. Differentiated thyroid carcinoma (DTC) accounts for 90% of thyroid cancers, with 20% of patients experiencing disease relapse, which decreases survival rates (1). A timely diagnosis of thyroid cancer recurrence is critical. Evaluation of serum thyroglobulin and 131I-diagnostic whole-body scanning (dWBS) are the most commonly employed detection techniques. However, 15–20% of patients with abnormal thyroglobulin levels show negative findings on 131I-dWBS (2,3). Furthermore, it is difficult to differentiate the recurrence of DTC from cicatricial tissue by computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), or ultrasound (4). Subsequently, PET/CT has been introduced in the diagnostics of DTC, since PET/CT shows metabolic activity and anatomical abnormalities, characteristic of the tumour.

Between December 2005 and June 2013, 18F-fluorodeoxyglucose (FDG) PET/CT was utilized to diagnose 15 patients with DTC. The results identified 18F-FDG PET/CT as a valuable detecting technique for the recurrence or metastasization of DTC.

Materials and methods

Patients

Fifteen patients with DTC were admitted to the Department of Nuclear Medicine of the Xuzhou Central Hospital (Xuzhou, China) between December 2005 and June 2013. There were 3 male and 12 female patients, aged 25–58 years, with a median age of 46 years (Table I). The patients were diagnosed with DTC, and underwent total or subtotal thyroidectomy.

Table I.

Demographic and clinical data of 15 study patients.

Patient, no.	Gender	Age, years	Histological type of the tumour	PET/CT diagnosis	Surgery/follow-up confirmation	Preoperative thyroglobulin, ng/ml	Postoperative thyroglobulin, ng/m
1	Female	36	Papillary carcinoma	2 cervical lymph nodes	2 in neck	53.36	4.34
2	Female	45	Papillary carcinoma	2 cervical lymph nodes	2 in neck	34.51	2.47
3	Male	33	Papillary carcinoma	2 cervical lymph nodes	2 in neck	61.74	5.02
4	Female	48	Follicular carcinoma	4 cervical lymph nodes	4 in neck	66.85	5.77
5	Female	25	Papillary carcinoma	3 cervical lymph nodes	2 in neck	56.27	4.73
6	Female	58	Papillary carcinoma	4 cervical lymph nodes	3 in neck	72.02	6.08
7	Male	55	Papillary carcinoma	2 cervical lymph nodes	2 in neck	42.25	3.34
8	Female	29	Papillary carcinoma	2 cervical lymph nodes	2 in neck	58.13	4.86
9	Female	52	Papillary carcinoma	2 cervical lymph nodes	2 in neck	49.61	3.53
10	Female	40	Papillary carcinoma	1 cervical lymph node	1 in neck	26.68	1.18
11	Female	50	Papillary carcinoma	5 cervical lymph nodes	4 in neck	83.43	6.71
12	Female	42	Papillary carcinoma	3 cervical lymph nodes	3 in neck	92.62	7.29
13	Female	52	Papillary carcinoma	3 cervical lymph nodes	3 in neck	63.45	5.43
14	Female	49	Papillary carcinoma	3 in the lung and 2 in the mediastinum	3 in lung and 2 in mediastinum	475.03	–
15	Male	46	Papillary carcinoma	Negative	1 in neck	46.02	–

PET, positron emission tomography; CT, computed tomography.

The pathological types comprised 14 cases of papillary carcinoma and 1 case of follicular carcinoma. The patients received 1 or several courses of postoperative treatment with 131I: 1 patient was treated once, 4 patients were treated twice, 6 patients were treated three times, 2 patients were treated four times, 1 patient was treated six times, and the remaining patient was treated eight times. At the follow up after the treatment, elevated levels of thyroglobulin (>20 ng/ml) and negative 131I-dWBS findings were present in each of these patients. Subsequently, tumour recurrence or metastasization was suspected. The patients underwent PET/CT examination. Patients continued receiving thyroidin pills following surgery, including during PET/CT, to avoid deterioration of the tumour.

18F-FDG PET/CT imaging

The Philips GXL 16 PET/CT scanning instrument (Philips Medical Systems, Inc., Cleveland, OH, USA) was used. The patients fasted for ≥6 h prior to scanning. Strict blood glucose levels (non-diabetic patients, <6.1 mmol/l; patients with diabetes, <8.3 mmol/l) were maintained. The patients were intravenously administered 270–370 MBq of 18F-FDG (4.4 MBq/kg). After 60 min and prior to the scanning, the patients were required to empty their bladders.

Collection ranges were from the basilar part to the proximal femur. The 16-slice helical CT scanning parameters were 140 kV, 320 mA, with flat sweeping. Data were analyzed by image fusion following iterative reconstruction, obtaining coronal, sagittal and cross-sectional CT, PET and PET/CT fusion images. The PET/CT images were reviewed independently by two radiologists who calculated a standardized uptake value of radioactive hot lesion. A standardized uptake value of ≥2.5 localized in metastatic regions was considered as indicative of tumour metastasization.

Diagnostic criteria of tumour recurrence or metastasization

Based on the positive results of PET/CT scanning, the lesions located in the neck underwent surgical excision, and postoperative histopathology was carried out. The patients were monitored for their serum thyroglobulin levels for 1 month. If the lesions were located in the organs where surgical excision was problematic, the status was determined by clinical situation and the follow-up imaging results within 6 months after the initial PET/CT examination.

Data analysis

The PET/CT images were qualitatively ranked as true positive, false negative, and false positive. Sensitivity and positive predictive value (PPV) for the diagnosis of recurrence and metastasization of DTC were calculated.

Statistical analysis

The SPSS 13.0 statistical software (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Data were presented as mean ± standard deviation. The differences were tested using the paired t-test. P<0.05 was considered to indicate a statistically significant difference.

Results

In 14 patients, PET/CT scanning had a sensitivity of 93.33%. The 14 patients were found to have 40 tumour recurrences or metastases, of which 35 were cervical lymph node metastases (Fig. 1). The tumours were excised and were identified by postoperative pathology as being tumour metastases in 32 cases and as inflammatory changes in 3 cases. Thus, PPV comprised 91.43%. In 1 patient, 5 lumps were located in the lungs and the mediastinum. No biopsy or surgical intervention were conducted in this patient. The lumps increased during the follow up for 6 months, confirming their metastatic nature.

Figure 1.

Cervical lymph node metastasis revealed by positron emission tomography/computed tomography (PET/CT) scanning. (A) CT imaging shows no significant neck mass. (B) PET imaging shows two lumpy abnormal radioactive concentration shadows on the right side of the neck. (C) PET/CT imaging shows two abnormal fluorodeoxyglucose hypermetabolism areas in the sternocleidomastoid region of the right side of the neck, which were considered lymph node metastases.

One patient had negative PET/CT findings and developed neck lumps after 6 months of follow up, which were confirmed as tumour metastases.

A total of 13 patients with preoperative serum thyroglobulin levels of 58.53±18.34 ng/ml underwent surgery. Their postoperation serum thyroglobulin levels were 4.67±1.71 ng/ml (p<0.05 vs. preoperative).

Discussion

Examination of thyroglobulin levels and 131I-dWBS following treatment is important for tumour monitoring and the detection of metastasization in DTC (5). Elevated thyroglobulin levels indicate recurrence or metastasization, resulting in 131I-dWBS scans being able to locate the tumour. When 131I-dWBS shows negative findings, B-mode ultrasound, CT, MRI, PET or other imaging techniques are used to localize recurrent or metastatic tumour. The first three methods are mainly used to locate the tumour by anatomical abnormalities, while PET reveals the tumour through metabolic abnormalities (6). Each of these techniques has its advantages and limitations. By contrast, PET/CT imaging can simultaneously reveal metabolic status and anatomical location of the lesion, thus combining the advantages of PET and CT (7). This technique is useful in difficult diagnoses, such as that for postoperative scars or nodules, which lack typical benign or malignant signs. Malignant tumours consume glucose at 10-fold higher rates than normal or scar tissue, and this feature enables precise differential diagnosis in those cases (8). Therefore, combined functional and morphological examination during PET/CT can improve the ability to detect recurrent and metastatic tumours (9).

The diagnostic efficiency of 18F-FDG PET/CT imaging in the postoperative follow up of patients with DTC depends on patient selection, sample size, thyroglobulin levels, and thyroid-stimulating hormone levels (10). Sensitivity and PPV for recurrence and metastasization of DTC range from 66 to 93.3% and from 87.5 to 100%, respectively (11–13). These values are significantly higher than those achieved by B-mode ultrasound, CT, MRI, or PET alone. In the present study, sensitivity and PPV were 93.33 and 91.43%, respectively, for patients with positive thyroglobulin levels and negative 131I-dWBS findings. This is in agreeement with previous findings (14–19). In such patients, metastatic tumour is more aggressive, which leads to elevation of the sensitivity of 18F-FDG PET/CT imaging. However, tumours that uptake iodine do not uptake FDG, therefore, 18F-FDG PET/CT cannot fully replace 131I-dWBS and should not be recommended for routine screening for recurrent or metastatic DTC.

In conclusion, findings of the present study indicate that 18F-FDG PET/CT imaging is an informative technique for the detection of recurrence or metastasization of DTC in patients with positive thyroglobulin levels and negative 131I-dWBS.