|Year : 2018 | Volume
| Issue : 6 | Page : 740-750
Unusual sites of metastatic and benign I 131 uptake in patients with differentiated thyroid carcinoma
Shanmuga S Palaniswamy, Padma Subramanyam
Department of Nuclear Medicine and Molecular Imaging, Amrita Institute of Medical Sciences, Amrita Vishwavidyapeetham, Cochin, Kerala, India
|Date of Web Publication||4-Dec-2018|
Shanmuga S Palaniswamy
Department of Nuclear Medicine and Molecular Imaging, Amrita Institute of Medical Sciences, Amrita Vishwavidyapeetham, Cochin - 682 041, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Differentiated thyroid carcinoma (DTC) is the most common pathological type of thyroid carcinoma, which includes papillary and follicular subtypes. DTC is usually indolent, characterized by good prognosis, and long-term survival. Total thyroidectomy is the mainstay of treatment in DTC which is followed by diagnostic whole body 131I (WBI) scan. Like other primary malignancies of the head and neck, DTC follows a consistent pattern of spread in the cervical LNs. The central compartment, level VI and VII, is the first sentinel node followed by spread to the lateral compartments levels II–V, followed by the contralateral side. Inspite of nodal involvement, DTC usually have a favourable outcome. Presence of extrapulmonary distant metastases could predict a poor prognosis for high-dose 131I therapy. However, distant metastasis occurs often as a grave event and mortality rates vary depending on metastatic sites. Aim and Objectives: A range of rare 131I concentrating DTC deposits in sella, orbit, choroid, skeletal muscles, liver, skin, costochondral soft tissue, pancreas and kidney, and a few benign 131I concentrating sites are being depicted. Materials and Methods: Metastatic sites from DTC can be easily identified by performing a whole body 131I (WBI) scan along with a stimulated thyroglobulin (Tg) estimation (TSH >30 uIU/ml). Apart from thyroid and thyroid-related diseases, certain benign non-thyroidal pathologies can concentrate radioiodine (131I). From 13,000 of our patients who underwent radioiodine scan for thyroid cancer, we have selected a few cases of 131I concentrating benign and malignant lesions for illustration. Results: Out of 13000 DTC patients who underwent whole body 131I scintigraphy in our department from Jan 2007 till Mar 2018, 25 patients revealed benign sites of 131I uptake. 61 % patients had residual thyroid tissue with or without associated nodal involvement. Remaining patients had distant metastases. Rare sites of functioning thyroid metastases and benign sites of I 131 uptake have been selected for illustration. Conclusion: Apart from the WBI (two-dimensional, planar) images, single-photon emission computed tomography-computed tomography (SPECT-CT) has been incremental in localizing benign lesions which greatly depends on their location. This pictorial review highlights the need to create an awareness to detect metastatic deposits of DTC at unexpected sites. Otherwise patients will need further investigation to rule out unsuspected sites of functioning distant metastases.
Keywords: Benign pathologies, differentiated thyroid carcinoma, metastatic sites, radio iodine, TENIS syndrome, whole body 131I scan
|How to cite this article:|
Palaniswamy SS, Subramanyam P. Unusual sites of metastatic and benign I 131 uptake in patients with differentiated thyroid carcinoma. Indian J Endocr Metab 2018;22:740-50
|How to cite this URL:|
Palaniswamy SS, Subramanyam P. Unusual sites of metastatic and benign I 131 uptake in patients with differentiated thyroid carcinoma. Indian J Endocr Metab [serial online] 2018 [cited 2019 Jul 16];22:740-50. Available from: http://www.ijem.in/text.asp?2018/22/6/740/246855
| Introduction|| |
For many years,131I has played a central role in evaluating thyroid diseases and has an established role in the follow-up and management of differentiated thyroid carcinoma (DTC). Although DTC have a good prognosis, the main metastatic pattern is lymph nodal (LN) metastasis. It has been reported that up to 36% of cases of papillary thyroid carcinoma and 17% of cases of follicular thyroid carcinoma are accompanied with cervical LN metastasis and nodal metastasis is strongly related to higher incidence of recurrence. Appropriate range of cervical lymph node dissection can effectively reduce the local recurrence and improve the prognosis of DTC. Current guidelines and literature recommend performing prophylactic central LN dissection and therapeutic lateral LN dissection in surgical treatment of DTC. The presence of distant metastases from DTC decreases the 10-year survival of patients by 50%. Metastases to the brain, breast, liver, kidney, muscle, skin, and other sites are relatively rare. Recognizing these rare sites of metastases from DTC has a significant impact on the clinical decision making and prognostication. Total thyroidectomy is the mainstay of treatment in DTC which is followed by diagnostic whole body 131I (WBI) scan. Patients undergoing 131I diagnostic scan or high-dose 131I ablation/metastatic therapy are weaned off (for 3–4 weeks) stable iodine-containing foods such as seafood, iodised salt, drugs (cough expectorants, povidone iodine, amiodarone), and iodinated contrast agents 3–6 months prior to the procedure. It is mandatory to stop tablet thyroxine for 3-4 weeks prior to 131I imaging or therapy so as to increase the endogenous thyroid stimulating hormone (TSH) level >30 μIU/ml (micro International unit/milliliter). These salient instructions facilitate the uptake of 131I by thyrocytes so that a higher therapeutic benefit is derived by the patient. Diagnostic WBI scan is usually performed 48–72 h after oral radioiodine administration using high-energy collimators on a Gamma camera. Radioiodine concentration in normal and affected thyrocytes is based on sodium iodide symporter (NIS) uptake mechanism. NIS is known to exist and has an active role also in other tissues as shown in [Table 1]. Many organs including the liver do not exhibit the NIS expression.
The role of 18-Flurodeoxyglucose positron emission computed tomography-computed tomography (18F FDG PET/CT) in thyroid cancer remains in evolution. There is no role for FDG PET/CT in the initial evaluation of DTC. However, FDG PET/CT is a well-established imaging modality in the evaluation of patients with TENIS syndrome (thyroglobulin elevated negative iodine scan) to look for occult disease. The use of FDG PET/CT in the initial staging and response evaluation of aggressive and poorly DTCs is also well known.
Prognosis of 131I negative DTC metastasis (TENIS), the so-called non-functioning metastasis (I 131 non concentrating), is significantly worse. In these patients, an early diagnosis of non-functioning metastasis and their surgical extirpation remains to be the optimal therapeutic approach. At this stage there is an activation of cellular glucose metabolism, enabling FDG uptake in these dedifferentiated cells. By virtue of their increased growth rate and subsequent increased utilization of glucose, these lesions then become detectable by the FDG PET/CT imaging.
This pattern of differential radiotracer (131I negative but FDG positive) uptake is called “flip-flop phenomenon.” The WBI and the FDG PET/CT scans are, therefore, complementary in this clinical scenario. Most often, a lesion will take up either only radioiodine or FDG, although a patient can have both the radioiodine and FDG avid lesions depending on varying grades of differentiation among various lesions. Poorly differentiated or progressively dedifferentiated thyroid cancer do not express NIS gene and thereby exhibit negative WBI scan indicating a grave prognosis. These are usually refractory to high-dose 131I therapy and may need advanced redifferentiation therapies and tyrosine kinase inhibitors. Feine et al. have shown that there can be a flip-flop in scan uptake patterns in thyroid cancers, first being 131I positive, FDG negative, and with disease progression and dedifferentiation becoming FDG positive, iodine negative. It is these latter tumors, those that are iodine negative, in which FDG PET appears to be most potentially beneficial. Here, we illustrate rare sites of solitary 131I concentrating distant metastases and a few sites of benign 131I uptake.
| Materials and Methods|| |
We retrospectively analyzed 13,000 patients who underwent WBI in the Nuclear Medicine Department of Amrita Institute of Medical Sciences, Cochin from 2007 onwards. Lymph nodes, lungs, and bones are the common sites of distant metastases in DTC that can be managed palliatively with multiple doses of high-dose 131I therapy. In this pictorial review, a range of rare 131I concentrating DTC metastatic deposits in sella, orbit, choroid, skeletal muscles, liver, skin, costochondral soft tissue, pancreas and kidney, and a few benign 131I concentrating sites are being illustrated. A few of these patients also underwent whole body FDG PET/CT imaging as part of their workup which is also being depicted here.
A 49-year-old male, diagnosed case of follicular carcinoma of thyroid and cervical lymph nodal metastases, underwent total thyroidectomy. Patient received high-dose 131I therapy on three occasions with a cumulative dosage of 349 mCi. Later he developed recurrent headache and progressively worsening double vision for 2 weeks [Figure 1]. Follow-up WBI scan showed no abnormal 131I uptake in anterior neck, sella region, or elsewhere but stimulated Tg was elevated (167 ng/ml, normal is <2 ng/ml). Patient was thus categorised as a case of TENIS syndrome. Brain magnetic resonance imaging (MRI) T1 contrast coronal image showed an enhancing metastatic deposit in sella with suprasellar extension. Solitary brain metastases from DTC are extremely rare i.e. approximately 1% of all DTC. It typically affects older patients with aggressive thyroid cancer, with a reported incidence of 0.15–1.3%. The reported median survival of patients diagnosed with brain metastasis varies between 4 months to 33 months. Because of its rarity, the impact of brain metastasis on the survival of patients with DTC is unknown, and there are no clear guidelines for their management. For brain metastasis in general, although treatment guidelines can differ based on the prognosis of the patients and its extent, surgery remains the preferred treatment modality. Brain metastasis is associated with very poor prognosis even with combined treatment using high-dose 131I therapy, external radiotherapy, and chemotherapy.
|Figure 1: Follicular carcinoma of thyroid and cervical lymph nodal metastases s/p total thyroidectomy. Patient has been treated three times with radioiodine (cumulative dosage 349 mCi). Later patient developed recurrent headaches and progressively worsening double vision for 2 weeks. (a) Follow-up whole body 131I (WBI) scan was negative, stimulated thyroglobulin was high (167ng/ml), diagnosed as TENIS syndrome, thyroglobulin elevated negative iodine scan. (b) MRI T1 contrast coronal image showed an enhancing metastatic deposit in sella with suprasellar extension (Red arrow)|
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Ocular (uveal) metastasis
A 56-year-old male with metastatic papillary carcinoma of thyroid s/p total thyroidectomy was referred for WBI scan. Scan showed extensive 131I concentrating skeletal metastases. He was treated twice with high-dose 131I therapy [Figure 2]a. Follow-up WBI scan after second dose showed abnormal focal 131I uptake corresponding to lesion in right orbit. After 2 weeks, patient developed sudden onset of diminished vision on the right side. Ophthalmic examination was performed [Figure 2]b. Ultrasound B scan showed two choriodal mass lesions in lower and posterior quadrants with homogenous internal opacity. Scan confirmed associated posterior uveal (choroidal) metastases on the right side. An urgent ophthalmic examination revealed a visual acuity of 6/24 of the right eye with right relative afferent papillary defect and choroidal lesions causing exudative retinal detachment on the right side. Ocular metastases secondary to thyroid cancer are extremely uncommon, typically affecting the orbit rather than the globe and uvea. Within the uveal structures, the choroid is more commonly involved than the iris and ciliary body. The literature review, shows that posterior uvea (choroid) is most commonly involved (88%), followed by anterior uvea [i.e., iris (9%) and ciliary body (2%)].
|Figure 2: A 56-year-old male patient with metastatic papillary carcinoma of thyroid underwent total thyroidectomy. WBI scan showed extensive 131I concentrating skeletal metastases. He was treated twice with high-dose 131I therapy. (a) Post therapy WBI scan after second dose of 131I therapy showed extensive functioning distant metastases (arrow showing right frontal & Right supraorbital metastases). After 2 weeks, patient developed sudden onset of diminished vision on the right eye. Ophthalmic examination was performed. (b) Ultrasound B scan showed two choriodal mass lesions in lower and posterior quadrants with homogenous internal opacity (A and B denote the two choroidal mass lesions, C denotes retinal detachment). Scan confirmed associated uveal metastases on the right side|
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A 58-year-old male with histologically proven papillary thyroid cancer s/p total thyroidectomy underwent high-dose 131I residual thyroid ablation. Patient later presented with swelling close to lateral aspect of the right eye. MRI of orbit showed enhancing soft tissue mass measuring 3.2 × 2 cm along the superolateral aspect of right orbit, abutting lateral rectus muscle and lacrimal gland, displacing the globe medially. Lesion erodes the posterolateral wall of orbit, extends to lateral aspect of middle cranial fossa with no involvement of neuroparenchyma. Plain CT of paranasal sinuses revealed lesion in the posterolateral aspect of right orbit with wall erosion. Patient also showed associated frontal, left maxillary, and anterior ethmoidal sinusitis [Figure 3]. WBI scan showed functioning metastases at superolateral aspect of right orbit corresponding to the CT-detected lesion. Stimulated Tg was 1670 ng/ml. Patient received three sittings of high-dose 131I therapy. Recent WBI scan showed complete resolution of right orbital soft tissue mass with no new functioning metastases elsewhere. Orbit and globe are not common sites of thyroid cancer metastases. Ocular symptoms usually arise in patients with long-standing thyroid cancer or those with widely disseminated disease. It is more common in patients with Follicular Ca thyroid and indicates a hematogenous spread of the malignancy.
|Figure 3: A 58-year-old male with papillary thyroid cancer s/p total thyroidectomy and high-dose 131I residual thyroid ablation with the right eye swelling. MRI of orbit was done which showed enhancing soft tissue mass measuring 3.2 × 2 cm along the superolateral aspect of right orbit. WBI scan showed functioning metastases at superolateral aspect of right orbit (Arrow depicting lesion). SPECTCT showed lesion abutting the lateral rectus muscle and lacrimal gland, displacing the globe medially. Stimulated Tg was 1670 ng/ml|
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A 47-year-old woman with multifocal papillary thyroid carcinoma, underwent total thyroidectomy. WBI scan was performed and patient was orally ablated with 70 mCi of 131I sodium iodide solution. Post-therapy WBI scan showed a focal site of abnormal 131I uptake in the right lower chest [Figure 4]. SPECT-CT thorax localized the lesion to lower outer quadrant of right mammary gland raising the suspicion of a co-existing primary breast malignancy or a metastastic deposit from DTC. An ultrasound-guided fine-needle aspiration cytology (FNAC) confirmed metastases from DTC. Isolated breast metastasis from DTC are extremely rare.131I uptake in both lactating and non-lactating breasts has been described. In the lactating breast, as well as in the thyroid gland, NIS mediates iodine uptake. Radioiodine uptake in benign breast pathologies can be seen with gynecomastia, supernumerary breasts, and lactational duct cyst or galactocele. Increased 131I uptake is also associated with hyperprolactinemia. To date, only 11 cases of breast metastases arising from DTC have been described in the literature, but these are invariably associated with other sites of DTC metastasis.
|Figure 4: A 47-year-old woman with multifocal papillary thyroid carcinoma, underwent total thyroidectomy and high-dose 131I residual thyroid ablation. Post-therapy WBI scan showed a focal site of abnormal 131I uptake in the right lower chest (Arrow indicating I 131 uptake in right breast lesion). SPECT-CT thorax localized the lesion to lower outer quadrant of right mammary gland raising the suspicion of a co-existing primary breast malignancy or a metastastic deposit from DTC. Ultrasound guided FNAC confirmed breast lesion to be metastases from DTC|
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A 45-year-old male presented with multinodular goiter. FNAC from thyroid was reported as a follicular neoplasm. He underwent total thyroidectomy and right neck dissection. Histopathology revealed a papillary thyroid carcinoma – conventional type (pT3N1bMx). WBI scan showed 131I concentrating residual thyroid tissue with suspicious cervical nodal metastases. Patient was ablated with 120 mCi of 131I orally. Four months later patient developed small painless, purple-colored skin nodules [Figure 5]. Tg while on T4 was found to be elevated. Whole body FDG PET/CT off T4 for 3 weeks (TSH >30 uIU/ml) was suggested. Images showed focal FDG avidity in multiple intramuscular deposits (left 6th intercostal space, left gluteus intermedius, paravertebral muscle on left side at level of L4/L5, right pectoralis major anterior to 3rd rib, right psoas muscle, left longissimus colli, and bilateral latissmus dorsi). Stimulated Tg was also performed which was significantly elevated (845 ng/ml). Cutaneous and intramuscular nodules cytopathology was positive for metastatic papillary thyroid carcinoma. In view of extensive cutaneous and intramuscular nodular metastases, patient was treated with 170 mCi of 131I. On review, patient had further deterioration of the disease clinically and based on the thyroid tumor board decision, patient was started on tyrosine kinase inhibitors. Presentation of cutaneous metastases is associated with advanced disease. Dahl et al. reported that papillary thyroid carcinoma was most common (41%) followed by follicular (28%), anaplastic (15%), and medullary carcinomas (15%), respectively. The scalp was the most common site of metastasis in that series.
|Figure 5: A 45-year-old male with multinodular goiter s/p total thyroidectomy and right neck dissection. Histopathology was reported as papillary thyroid carcinoma – conventional type treated with 120 mCi of 131I. Four months later developed small painless, purple-colored skin nodules. Whole body FDG PET/CT was suggested. Images showed focal FDG avidity in multiple intramuscular deposits (left 6th intercostal space, left gluteus intermedius, paravertebral muscle on left side at level of L4/L5, right pectoralis major anterior to 3rd rib, right psoas muscle, left longissimus colli, and bilateral latissmus dorsi). Stimulated Tg was 845 ng/ml. (c) FDG PETCT scan - arrow showing FDG positive cutaneous and muscle deposits, (d) Biopsy of Right psoas muscle deposit - shows infiltarting neoplasm composed of cells arranged in a papillary pattern, separated by fibrinous stroma. Each cell has round to oval clear nuclei, with nuclear overlapping, moderate eosinophilic cytoplasm. Neoplastic cells are CK 7 and thyroglobulin positive and negative for CK 20.|
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A 40-year-old man, with papillary carcinoma of thyroid with cervical lymph nodal metastases post-total thyroidectomy, central compartmental neck dissection, and radioiodine ablation, presented to our department with rising Tg. Follow-up WBI scan was negative. He was orally ablated with 184 mCi of 131I [Figure 6]. Post-131I therapy WB scan showed a solitary functioning right lobe of liver metastasis (confirmed with SPECT-CT) and histopathology. Liver metastasis from DTC is a rare event, with a reported frequency of 0.5%. Only 10 cases have been documented in the literature so far.
|Figure 6: Papillary carcinoma of thyroid and cervical lymph nodal metastases post-total thyroidectomy and central compartmental neck dissection, presented with rising Tg. Follow-up WBI scan was negative. Post-131I therapy WB scan showed a solitary site of abnormal 131I uptake in right lobe of liver as confirmed with SPECT-CT (Arrow depicting the lesion on planar whole body image & cross hair on SPECTCT).|
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Pancreas and kidney metastases
A 60-year-old female patient with follicular carcinoma of thyroid and lymph nodal metastases underwent total thyroidectomy. About 3 weeks later WBI scan was done which was negative [Figure 7]a. Stimulated Tg was >1000 ng/ml with TSH of only 1.2 uIU/ml. Recombinant human TSH (rhTSH) assisted whole body FDG PET/CT was performed (TSH >100 uIU/ml). Images showed FDG avid metastatic deposits in the pancreas [Figure 7]b, and the right kidney [Figure 7]c. Patient was treated with 182 mCi of 131I. Clinical detection of DTC metastasis of the kidney is infrequent. Both the kidney and pancreatic involvement are unusual and extremely rare without any nodal or other sites of distant metastases. To the best of our knowledge, only 25 cases have been reported in the literature.
|Figure 7: A 60-year-old female patient with follicular carcinoma of thyroid with lymph nodal metastases underwent total thyroidectomy. Three weeks later (a) WBI scan was done which was negative stimulated serum thyroglobulin was >1000 ng/ml with TSH of only 1.2 uIU/ml. Recombinant human TSH (rhTSH) assisted whole body FDG PET/CT was performed (TSH was >100 uIU/ml after two intramuscular rhTSH injections). Images showed FDG avid metastatic deposits in the pancreas (b), and the right kidney (c) Cross hair shows FDG avid pancreatic and renal metastatic deposit|
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Muscle (deltoid) metastasis
A 66-year-old male, a case of multinodular goiter underwent total thyroidectomy. Histopathology revealed completely intrathyroidal widely invasive follicular thyroid carcinoma (3.3 × 2.5 × 2 cm) in the left upper lobe with micropapillary carcinoma in the right lobe. Diagnostic WBI scan was done and patient was treated with 70 mCi of 131I [Figure 8]a. Six months later WBI scan showed no abnormal 131I uptake in anterior neck and rest of whole body but stimulated Tg was high (124 ng/ml). Whole body FDG PET/CT (non-contrast study) was suggested to look for any occult site of metastases. [Figure 8]b 18-F FDG PET/CT showed no local recurrence but an isolated FDG avid lesion in left deltoid muscle suggestive of a metastatic deposit. Ultrasound examination of the lesion showed an echogenic nodule measuring 12.8 mm in the deltoid muscle anteriorly. Excision biopsy revealed a neoplasm of follicular and papillary patterns amidst skeletal muscle fibers with nuclear clearing and many intranuclear pseudoinclusions. Neoplasm showed diffuse positivity for cytokeratin 19 (CK19), TTF-1, and Tg on immunohistochemistry (IHC). The literature review shows that hematogenous metastasis from DTC to skeletal muscle is extremely rare. A retrospective review of the literature revealed only 10 reports of DTC muscle metastases.
|Figure 8: A 66-year-old male, a case of multinodular goiter underwent total thyroidectomy – case of completely intrathyroidal widely invasive follicular carcinoma. WBI scan was done and patient was administered 70 mCi of 131I [(a), post-therapy WBI scan]. Six months later follow-up WBI scan was negative with stimulated Tg of 124 ng/ml. FDG PET/CT (b) showed no local recurrence but an isolated FDG avid lesion in left deltoid muscle suggestive of a metastatic deposit|
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Costochondral and soft tissue metastases
A 62-year-old patient with follicular Ca thyroid s/p total thyroidectomy and high-dose 131I therapy presented with swelling in chest region of 2 months duration. WBI scan was negative [Figure 9]a with stimulated Tg of 346 ng/ml. Whole body FDG PET/CT [Figure 9]b off T4 showed a large FDG avid lesion in left 1st costal cartilage (SUV Max 40.9) (b) anterior to left 4th costal cartilage (SUV Max 29.0), and a small subcutaneous deposit in anterior chest wall at parasternal region toward left side [Figure 9]c. No other FDG avid lesions seen in thyroid bed and elsewhere. Patient was treated empirically with 150 mCi of 131I. Patient is lost to follow-up.
|Figure 9: A 62-year-old patient with follicular ca thyroid s/p total thyroidectomy and high dose 131I therapy presented with swelling in chest region of 2 months. (a) WBI scan was negative with stimulated Tg of 346 ng/ml. Whole body FDG PET/CT (b) off T4 showed a large FDG avid lesion in (A) left 1st costal cartilage (SUV Max 40.9) (B) anterior to left 4th costal cartilage (SUV Max 29.0) and a small subcutaneous deposit in anterior chest wall at parasternal region toward left side (C) (Arrows and crosshair depict the lesions as described)|
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Although occasionally soft tissue metastases may present themselves as painful masses, they are usually asymptomatic. Therefore, they may be an unexpected finding in imaging studies. Besides the possibility of underdiagnosis, several factors have been implicated in the rare occurrence of soft tissue metastases, such as muscle motion, mechanical tumor destruction, muscle ability to remove tumor-produced lactic acid, changes in pH, accumulation of metabolites, and local temperature of the soft tissue sites. In addition, blood flow is variable, influenced by adrenergic receptors, and subject to variations in tissue pressure affecting cancer implantation. Whether traumatic injury to soft tissue is a risk factor for soft tissue metastases remains undetermined.
Solitary bone metastases
Sacral metastases – A 68-year-old male with papillary Ca thyroid s/p completion thyroidectomy operated in 1999. Patient was on T4 and had not received any 131I therapy. Patient had persistent severe pain at left gluteal region and urinary incontinence. MRI LS spine with contrast was done. A well-defined expansile lesion was present, measuring 3.6 × 3.2 × 2.6 cm involving S3, S4 vertebrae at left paramedian region with anterior exophytic component likely to be a chordoma. Patient was referred for WBI scan. Scan showed focal 131I uptake in sacral vertebrae in planar and SPECT-CT imaging confirming functioning thyroid metastases in sacrum. WBI scan helped in the diagnosis as chordomas are iodine-negative lesions. Patient underwent S2–S5 sacrectomy followed by high-dose 131I therapy [Figure 10]. Histopathology reported features suggestive of moderate to poorly DTC favoring metastasis. IHC reported CK7: positive, CK20: negative, TTF-1: positive, Tg: positive, CEA: negative. Patient received two doses of high-dose 131I therapy at an interval of 6 months. Patient was kept on regular follow up and was found to be doing well and pain free. Radioiodine is highly specific and concentrates in presence of active NIS.
|Figure 10: Solitary functioning sacral metastasis in a 68-year-old male with papillary Ca thyroid s/p completion thyroidectomy. WBI scan showed focal 131I uptake in sacral vertebrae, confirmed with SPECT-CT, confirming functioning thyroid metastases in sacrum. MRI LS spine (arrow shows the sacral lesion) with contrast reported: Well-defined expansile lesion measuring 3.6 × 3.2 × 2.6 cm involving S3, S4 vertebrae at left paramedian region with anterior exophytic component likely to be a chordoma. Patient had S2–S5 sacrectomy and high-dose 131I therapy. HPR reported moderate to poorly differentiated carcinoma favoring metastasis|
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Humeral metastases [Figure 11] – A 38-year-old lady presented with long-standing goiter. FNAC reported papillary carcinoma thyroid. Total thyroidectomy along with left radical neck dissection was performed. Histopathology revealed metastasis to left level II cervical and left recurrent laryngeal nodes. Residual thyroid and WBI scan showed moderate to significant residual thyroid tissue. She was orally ablated with 113 mCi of 131I. A post-therapy WBI scan showed significant 131I uptake in thyroid bed as expected and a new focal 131I uptake in left humerus raising a suspicion of unsuspected solitary skeletal metastases. Patient was further investigated with a plain CT scan for the left humeral lesion. Stimulated Tg was 179 ng/ml. Based on the location of the lesion and need for metastaectomy and additional shoulder stabilisation, patient opted for second dose of high-dose 131I therapy.
|Figure 11: Solitary functioning humeral metastasis in a 38-year-old lady with papillary carcinoma thyroid s/p total thyroidectomy and left radical neck dissection. Residual thyroid and WBI scan showed moderate to significant residual thyroid tissue. She was orally ablated with 113 mCi of 131I. A post-therapy WBI scan showed significant 131I uptake in thyroid bed and a new focal 131I uptake in left humerus raising a suspicion of unsuspected solitary skeletal metastasis. Stimulated Tg was 179 ng/ml|
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Scapular deposit [Figure 12] – A 56-year-old lady presented with goiter. She was investigated and underwent total thyroidectomy with central compartmental neck dissection. Histopathology suggested papillary thyroid carcinoma with lymph nodal metastases. WBI scan revealed minimal residual thyroid tissue with left lower cervical nodal metastases and unsuspected 131I concentrating right scapular deposit. As stimulated Tg was 659 ng/ml, whole body FDG PET/CT was suggested. PET/CT confirmed FDG avid left thyroid bed lesion, highest mediastinal nodal and right scapular metastatic deposit.
|Figure 12: Scapular deposit in a 56-year-old patient s/p total thyroidectomy and central compartmental neck dissection. Patient is a proven case of papillary thyroid carcinoma with lymph nodal metastases. WBI scan revealed minimal residual thyroid tissue with left lower cervical nodal metastases and 131I concentrating right scapular deposit. Stimulated Tg was 659 ng/ml. PET/CT showed FDG avid left thyroid bed lesion, highest mediastinal nodal and right scapular metastatic deposit. Note: Patient shows same number of positive lesions in both Whole body I 131 and FDG PETCT scan suggesting varying grades of cellular differentiation in the same patient|
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Bone metastases represent a frequent complication especially of follicular thyroid cancer. Palliative treatment is frequently the only option at diagnosis. These osteolytic lesions reduce severely the quality of life causing pain, fractures, and spinal cord compression. More than 80% of bone metastases from all tumors including DTC are located in axial skeleton red marrow where blood flow is high (vertebrae, ribs, and hips). Surgical option is preferred wherever feasible. Higher dose of 131I (150–200 mCi) is recommended in presence of skeletal metastatic deposits. Patients usually need multiple doses of high-dose 131I therapy. External radiotherapy is also indicated in these cases.
Benign sites of I 131 uptake
Benign causes of 131I have been encountered in day-to-day practice. False-positive radioiodine uptake can be classified according to the underlying mechanism as follows; (1) Physiological uptake (breast, blood-pool activity, gastric and colonie mucosa). (2) Pathological activity (lung, pleura, pericardium, thymus, meninges). (3) Internal retention of body secretions (esophagus, trachea). (4) External contamination (skin, hair, garment). The uptake in soft tissues has been reported at the following sites and disease conditions; in fat necrosis of the breast, lactating breasts, patient on hormonal therapy, or oral contraceptive pills ([Figure 13] thick arrow). Patients display false positive I131 uptake in tracheostomy, inflamed cysts like ovarian/lymphoepithelial cyst, skin burns, skin wound, and even in a psoriatic plaque. Iodine uptake in rib may be due to benign causes also. Iodine uptake in the pleura and mediastinum has also been described in pleuropericardial cyst, saliva and esophageal-retained saliva (thin arrow [Figure 13]), Barrets esophagus, Zenker's diverticulum, and sites of ectopic thyroid tissue, can also produce false-positive scans with radioiodine. Benign 131I uptake has been reported in pericardial effusion and myocardial infarction. It is also seen in infective and inflammatory lung diseases. Inflamed tissues undergo certain biological events like increased blood flow and capillary permeability. Increased permeability can result in an abundance of cells in tissue or vessels, and stasis of radio-iodinated blood can also occur due to an increase in the concentration of cells within blood. All these lead to false-positive WBI scan. Tg estimation serves as a robust tumor marker to identify any such benign cause of 131I uptake from a malignant thyroid deposit.
|Figure 13: Young patient with DTC underwent total thyroidectomy. WBI scan shows residual thyroid tissue along with diffuse 131I uptake in bilateral breast parenchyma (thick arrow). On close interrogation patient was found to be on prolonged oral contraceptive pills. She also shows 131I uptake in retained saliva in esophagus (thin arrow) which clears after gulping water.|
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Retroverted uterus/ovarian neoplasm or cysts
Retroverted uterus: A premenopausal patient with papillary Ca thyroid underwent total thyroidectomy for goiter. WBI scan showed moderate to significant residual thyroid tissue with focal 131I uptake in pelvis. SPECT-CT localized this focus to retroverted uterus [Figure 14]. No obvious lesion was seen on CT pelvis. The 131I uptake in this case is most likely physiological in uterus being a vascular organ.
|Figure 14: A 45-year-old papillary Ca thyroid s/p total thyroidectomy. WBI scan showed moderate to significant residual thyroid tissue. Incidentally focal 131I uptake is also seen in retroverted uterus which is confirmed with SPECT-CT (arrow). No obvious lesion seen on CT at the corresponding to that site. The 131I uptake is most likely physiological being a vascular organ|
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Ovarian etiology: Two cases of papillary Ca thyroid, post-total thyroidectomy are being described. A case of papillary Ca thyroid [Figure 15]a, post-thyroidectomy shows focal 131I uptake in left upper cervical nodal metastases on WBI scan. An additional site of focal 131I uptake is revealed intrapelvically. SPECT-CT of pelvis localized the uptake to ovary raising a suspicion of left ovarian pathology. Further investigation with ultrasound and CT confirmed inflamed corpus luteal cyst. Another case [Figure 15]b of DTC depicting 131I uptake in bilateral ovaries, confirmed on further investigation to be bilateral ovarian teratomas.
|Figure 15: Two cases of papillary Ca thyroid, post-total thyroidectomy. The first case (a) shows focal 131I uptake in left upper cervical nodal metastases. There is additional site of focal 131I uptake intrapelvically. SPECT-CT of pelvis localized the uptake to ovary indicating left ovarian pathology (Arrow indicating I 131 uptake in left ovary). Further investigation confirmed inflamed corpus luteal cyst. (b) Another case depicting 131I uptake in bilateral ovaries (arrows), confirmed on further investigation to be bilateral ovarian teratomas|
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Teratomas are slow-growing tumors that contain elements from multiple germ cell layers and are best assessed with ultrasound. They usually occur in young women 20–30 years of age. Uncomplicated ovarian teratomas tend to be asymptomatic and are often discovered incidentally. Mature cystic teratomas are encapsulated tumors with mature tissue or organ components. They are composed of well-differentiated derivatives from at least two of the three germ cell layers (i.e., ectoderm, mesoderm, and endoderm). They, therefore, contain developmentally mature skin complete with hair follicles and sweat glands, sometimes with luxuriant clumps of long hair, and often pockets of sebum, blood, fat, bone, nails, teeth, eyes, cartilage, and thyroid tissue. They can be bilateral in 10–15% cases. Being slow-growing tumors, a non-surgical conservative management is generally implemented.
Ovarian cysts are fluid-filled sacs which are usually asymptomatic. Most ovarian cysts are related to ovulatory cycles, being either follicular or corpus luteal cysts. Other types include cysts due to endometriosis and cystadenomas apart from teratomas. Pelvic inflammatory disease and polycystic ovarian disease can also result in ovarian cysts.
Other cystic structures known to show false-positive findings on radioiodine, include nasolacrimal sac, pleuropericardial, bronchogenic, thymic, breast, hepatic, renal, ovarian, epithelial, and sebaceous cysts. Entry of radioiodine into cysts occurs via passive diffusion or partially active transport. Due to the slow exchange of water and chemical elements between the cysts and their surrounding extracellular/extravascular environment, radioiodine gets trapped within the cysts producing false-positive scans.
131I uptake in recent fracture
67 year old lady with follicular carcinoma thyroid following post total thyroidectomy underwent diagnostic WBI scan. In view of her age, histology and presence of minimal residual thyroid tissue, patient was treated with high dose 131I therapy. Image [Figure 16]a shows minimal residual thyroid tissue in anterior neck 5 days after high-dose 131I therapy, on the day of her scheduled post-therapy WBI scan, patient sustained a fall 1 h prior to her arrival at the center. Scan shows 131I uptake in residual thyroid tissue as expected in an immediate post-therapy setting. There was an abnormal diffuse 131I uptake in the right clavicular region corresponding to her site of injury. Subsequent X-ray confirmed fracture of lateral third clavicle on right side.
|Figure 16: 131I uptake in recent fracture: A 67-year-old case of follicular Ca thyroid, post-total thyroidectomy. WBI scan (a) shows minimal residual thyroid tissue. Five days after high-dose 131I therapy on the day of scan, patient sustained a fall 1 h before her arrival. (b) Scan shows 131I uptake in residual thyroid tissue as expected in an immediate post-therapy setting. There was an abnormal diffuse 131I uptake in right clavicular region (arrow). Subsequent chest X-ray confirmed fracture of lateral third clavicle on right side|
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Inflammation and infection attribute a major chunk of false-positive 131I uptake sites. It is thought that leukocytes stimulate the formation of inflammatory exudates in chronic inflammatory processes. It alters blood vessels to permit migration of leukocytes outside of the vessels into the tissue. As part of their bactericidal effect, leukocytes are known to induce iodide organification by means of a myeloperoxidase. Therefore, retention of radioiodine in leukocytes in clotted blood and tissues may also explain various reports of false-positive uptake in sites of inflammation.
| Conclusion|| |
DTC, which ordinarily behaves in an indolent manner, can have unusual metastatic presentations and patterns. Increasing importance should be given to rare metastases in DTC patients. This pictorial review highlights the need to create an awareness to detect metastatic deposits of DTC at unexpected sites. Care should be taken to determine whether 131I uptake found at an unexpected site is DTC metastasis or false-positive uptake.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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| References|| |
Mazzaferri EL. Management of a solitary thyroid nodule. New Engl J Med 1993;328:553-9.
Reddy RM, Grigsby PW, Moley JF, Hall BL. Lymph node metastases in differentiated thyroid cancer under 2 cm. Surgery 2006;140:1050-4; discussion 1054-55.
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al
. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.
Shaha AR, Shah JP, Loree TR. Differentiated thyroid cancer presenting initially with distant metastasis. Am J Sur 1997;174:474-6.
Aggarwal V, Bhargav PR, Mishra A, Agarwal G. Clinico-pathological characteristics and long-term outcome in patients with distant metastases from differentiated thyroid carcinoma. World J Sur 2007;31:246-7.
Feine U, Lietzenmayer R, Hanke JP, Wöhrle H, Müller-Schauenburg W.18
FDG whole-body PET in differentiated thyroid carcinoma. Flip flop in uptake patterns of 18
FDG and 131
I. Nuklearmedizin 1995;34:127-34.
Parker LN, Wu SY, Kim DD, Kollin J, Prasasvinichai S. Recurrence of papillary thyroid carcinoma presenting as a focal neurologic deficit. Arch Intern Med 1986;146:1985-7.
Ritland JS, Eide N, Walaas L, Hoie J. Fine-needle aspiration biopsy diagnosis of a uveal metastasis from a follicular thyroid carcinoma. Acta Ophthalmol Scand 1999;77:594-6.
Arat YO, Boniuk M. Red lesions of the iris, choroid, and skin secondary to metastatic carcinoma of the thyroid: A review. Surv Ophthalmol 2007;52:523-8.
Hammami MM, Bakheet S. Radioiodine breast uptake in nonbreastfeeding women: Clinical and scintigraphic characteristics. J Nucl Med 1996;37:26-31.
Shim HK, Kim MR. Incidental findings of intense radioiodine uptake in struma ovarii and bilateral nonlactating breasts simultaneously on postablation 131I SPECT/CT for papillary thyroid cancer. Nucl Med Mol Imaging 2016;50:353.
Dahl PR, Brodland DG, Goellner JR, Hay ID. Thyroid carcinoma metastatic to the skin: A cutaneous manifestation of a widely disseminated malignancy. J Am Acad Dermatol 1997;36:531-7.
Salvatori M, Perotti G, Rufini V, Maussier ML, Summaria V, Fadda G, et al
. Solitary liver metastasis from Hurthle cell thyroid cancer: A case report and review of the literature. J Endocrinol Invest 2004;27:52-6.
Liou MJ, Lin JD, Chung MH, Liau CT, Hsueh C. Renal metastasis from papillary thyroid microcarcinoma. Acta Oto-Laryngologica 2005;125:438-42.
Pucci A, Suppo M, Lucchesi G, Celeste A, Viberti L, Pellerito R, et al
. Papillary thyroid carcinoma presenting as a solitary soft tissue arm metastasis in an elderly hyperthyroid patient. Case report and review of the literature. Virchows Archiv 2006;448:857-61.
Itani M, Lewis HD. I 131 uptake in fat necrosis. Radiol Case Rep 2016;12:161-7.
Oh JR, Ahn BC. False-positive uptake on radioiodine whole-body scintigraphy: Physiologic and pathologic variants unrelated to thyroid cancer. Am J Nucl Med Mol Imaging 2012;2:362-85.
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