Imaging AnalysisPublication Exclusive

Incidental hypermetabolic, 18F-FDG-avid thyroid nodule on PET scan

A 73-year-old man was sent for consultation for a hypermetabolic thyroid nodule found on 18F-fluorodeoxyglucose PET imaging. The patient had the restaging scan because of a history of renal cell cancer and a growing neck mass felt on exam. He had been diagnosed 13 years earlier with renal cancer after a nephrectomy. He had no history of head and neck radiation or family history of thyroid disease, including thyroid cancer. The patient was unaware of the thyroid nodule and had no symptoms of dysphagia, change in voice or anterior neck pressure.

Exam, imaging

On exam, the patient had a normal thyroid except for a 2-cm mass in the left thyroid lobe that was very firm, nontender and mobile. He had no palpable adenopathy in the neck. Laboratory testing showed a normal thyroid-stimulating hormone level of 1.19 mU/L.

Review of the PET/CT scan demonstrated a 2.5-cm heterogeneous, hypodense nodule in the left thyroid lobe (Figure 1A). No enlarged nodes in the neck were seen. After injection of 18F-fluorodeoxyglucose (18F-FDG), the nodule was hypermetabolic on the single-photon emission CT (SPECT) scan, shown by the accumulation of the isotope with a standardized uptake value of 5.4 (Figure 1B). There were no other sites of FDG uptake. Fusion of the CT and the nuclear SPECT scan (Figure 1C) confirmed the hypermetabolic activity of this nodule.

Stephanie L. Lee

Ultrasound examination in the endocrine clinic demonstrated a 2.9 cm x 2.6 cm x 2.3 cm (sagittal x depth x width) taller-than-wide hypoechoic mass in the left lobe of the thyroid extending into the isthmus (Figure 2). The nodule had several sonographic features that were concerning for malignancy, including infiltrative margins, hypoechogenicity and taller-than-wide shape on transverse view. The nodule had grade 3 intranodular vascular blood flow by Doppler analysis. Sonographic node survey did not reveal any adenopathy.

Figure 1. CT and PET/CT scan of the neck through the thyroid gland. (A) Axial image of CT scan. Heterogeneous nodule is located in the isthmus and left thyroid lobe (yellow arrow). (B) 18F-FDG PET SPECT scan. This nodule is hypermetabolic as shown by excess accumulation of the 18F-FDG with a standardized uptake value of 5.2 (blue arrow). (C) Fused 18F-FDG PET and CT scan.

An ultrasound-guided fine-needle aspiration (FNA) biopsy of the left nodule showed epithelial cells with low nuclear-to-cytoplasmic ratio that stained positive for cytokeratins (CAM5.2 and AE1:3) and epithelial membrane antigen (EMA) and was negative for thyroglobulin and thyroid transcription factor 1 (TTF-1). The vimentin stain was inconclusive.

The morphologic changes and immunohistochemical profile were suggestive of metastatic renal cell carcinoma. After thyroidectomy, the pathology demonstrated a 2-cm left metastatic clear cell renal cell carcinoma that was immunostain-stain-positive for cytokeratins (CAM5.2 and AE1:3) and EMA, focally positive for vimentin and negative for thyroglobulin and TTF-1.

Nonthyroidal cancer metastatic to the thyroid

Imaging of this nodule demonstrated several characteristics associated with an increase in the risk for thyroid malignancy: 18F-FDG uptake, hypoechogenicity and taller-than-wide appearance on ultrasound. 18F-FDG in the thyroid can occur in a diffuse pattern throughout the thyroid or focally within a nodule.

Figure 2. Transverse thyroid ultrasound. Transverse image of the thyroid obtained with a 14 MHz linear probe. The hypoechoic nodule is seen in the left lobe of the thyroid. Concerning sonographic characteristics of this nodule are the hypoechoic echogenicity (darker than the surrounding normal thyroid gland), infiltrative margins (blue arrow), and taller than wide shape. (A) Transverse. (B) Sagittal. TR: trachea

Images: reprinted with permission.

A systematic study of the literature that included 125,575 patients showed an incidental focal uptake of 18F-FDG in a thyroid nodule occurred in about 1.6% of PET scans. More than one-third (34.8%) of the focal metabolic hyperactivity was associated with a risk for thyroid malignancy that ranged in individual studies from 15% to 50%. In this large study, none of the focally hypermetabolic thyroid nodules was a nonthyroidal cancer metastatic to the thyroid.

Metastases from other primary malignancies to the thyroid are clinically uncommon, but autopsy studies show a higher prevalence of 1.9% to 24%. The most common nonthyroid malignancies metastatic to the thyroid are renal cell (48.1%), colorectal (10.4%), lung (8.3%), breast carcinoma (7.8%) and sarcoma (4%). Nonthyroidal metastases commonly occur in nodular thyroid glands (44.2%). The mean and median interval between diagnoses of a nonthyroidal cancer and its thyroid metastases can be a prolonged time at 69.9 and 53 months, respectively. In only 20% of cases was the diagnosis of the nonthyroidal cancer and its metastases to the thyroid synchronous.

FNA biopsy is the most important diagnostic test, but it is critical that the information of the history of a nonthyroidal cancer be provided to the cytopathologist so the appropriate immunohistochemical analysis can be performed.

It is important to remember that the thyroid gland can be a site of metastases of a variety of tumors. This should be considered when a biopsy of a thyroid nodule occurs in a patient with a prior nonthyroidal malignancy regardless of the time since the diagnosis of the primary cancer.

A 73-year-old man was sent for consultation for a hypermetabolic thyroid nodule found on 18F-fluorodeoxyglucose PET imaging. The patient had the restaging scan because of a history of renal cell cancer and a growing neck mass felt on exam. He had been diagnosed 13 years earlier with renal cancer after a nephrectomy. He had no history of head and neck radiation or family history of thyroid disease, including thyroid cancer. The patient was unaware of the thyroid nodule and had no symptoms of dysphagia, change in voice or anterior neck pressure.

Exam, imaging

On exam, the patient had a normal thyroid except for a 2-cm mass in the left thyroid lobe that was very firm, nontender and mobile. He had no palpable adenopathy in the neck. Laboratory testing showed a normal thyroid-stimulating hormone level of 1.19 mU/L.

Review of the PET/CT scan demonstrated a 2.5-cm heterogeneous, hypodense nodule in the left thyroid lobe (Figure 1A). No enlarged nodes in the neck were seen. After injection of 18F-fluorodeoxyglucose (18F-FDG), the nodule was hypermetabolic on the single-photon emission CT (SPECT) scan, shown by the accumulation of the isotope with a standardized uptake value of 5.4 (Figure 1B). There were no other sites of FDG uptake. Fusion of the CT and the nuclear SPECT scan (Figure 1C) confirmed the hypermetabolic activity of this nodule.

Stephanie L. Lee

Ultrasound examination in the endocrine clinic demonstrated a 2.9 cm x 2.6 cm x 2.3 cm (sagittal x depth x width) taller-than-wide hypoechoic mass in the left lobe of the thyroid extending into the isthmus (Figure 2). The nodule had several sonographic features that were concerning for malignancy, including infiltrative margins, hypoechogenicity and taller-than-wide shape on transverse view. The nodule had grade 3 intranodular vascular blood flow by Doppler analysis. Sonographic node survey did not reveal any adenopathy.

Figure 1. CT and PET/CT scan of the neck through the thyroid gland. (A) Axial image of CT scan. Heterogeneous nodule is located in the isthmus and left thyroid lobe (yellow arrow). (B) 18F-FDG PET SPECT scan. This nodule is hypermetabolic as shown by excess accumulation of the 18F-FDG with a standardized uptake value of 5.2 (blue arrow). (C) Fused 18F-FDG PET and CT scan.

An ultrasound-guided fine-needle aspiration (FNA) biopsy of the left nodule showed epithelial cells with low nuclear-to-cytoplasmic ratio that stained positive for cytokeratins (CAM5.2 and AE1:3) and epithelial membrane antigen (EMA) and was negative for thyroglobulin and thyroid transcription factor 1 (TTF-1). The vimentin stain was inconclusive.

The morphologic changes and immunohistochemical profile were suggestive of metastatic renal cell carcinoma. After thyroidectomy, the pathology demonstrated a 2-cm left metastatic clear cell renal cell carcinoma that was immunostain-stain-positive for cytokeratins (CAM5.2 and AE1:3) and EMA, focally positive for vimentin and negative for thyroglobulin and TTF-1.

Nonthyroidal cancer metastatic to the thyroid

Imaging of this nodule demonstrated several characteristics associated with an increase in the risk for thyroid malignancy: 18F-FDG uptake, hypoechogenicity and taller-than-wide appearance on ultrasound. 18F-FDG in the thyroid can occur in a diffuse pattern throughout the thyroid or focally within a nodule.

Figure 2. Transverse thyroid ultrasound. Transverse image of the thyroid obtained with a 14 MHz linear probe. The hypoechoic nodule is seen in the left lobe of the thyroid. Concerning sonographic characteristics of this nodule are the hypoechoic echogenicity (darker than the surrounding normal thyroid gland), infiltrative margins (blue arrow), and taller than wide shape. (A) Transverse. (B) Sagittal. TR: trachea

Images: reprinted with permission.

A systematic study of the literature that included 125,575 patients showed an incidental focal uptake of 18F-FDG in a thyroid nodule occurred in about 1.6% of PET scans. More than one-third (34.8%) of the focal metabolic hyperactivity was associated with a risk for thyroid malignancy that ranged in individual studies from 15% to 50%. In this large study, none of the focally hypermetabolic thyroid nodules was a nonthyroidal cancer metastatic to the thyroid.

Metastases from other primary malignancies to the thyroid are clinically uncommon, but autopsy studies show a higher prevalence of 1.9% to 24%. The most common nonthyroid malignancies metastatic to the thyroid are renal cell (48.1%), colorectal (10.4%), lung (8.3%), breast carcinoma (7.8%) and sarcoma (4%). Nonthyroidal metastases commonly occur in nodular thyroid glands (44.2%). The mean and median interval between diagnoses of a nonthyroidal cancer and its thyroid metastases can be a prolonged time at 69.9 and 53 months, respectively. In only 20% of cases was the diagnosis of the nonthyroidal cancer and its metastases to the thyroid synchronous.

FNA biopsy is the most important diagnostic test, but it is critical that the information of the history of a nonthyroidal cancer be provided to the cytopathologist so the appropriate immunohistochemical analysis can be performed.

It is important to remember that the thyroid gland can be a site of metastases of a variety of tumors. This should be considered when a biopsy of a thyroid nodule occurs in a patient with a prior nonthyroidal malignancy regardless of the time since the diagnosis of the primary cancer.