Thyroid Cancer
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Cancer of the thyroid is a disease in which malignant (cancerous) cells are found in the tissues of the thyroid gland. The thyroid gland is located at the base of the throat and produces hormones that help the body function normally. Most patients are between 25 and 65 years old, thyroid cancer is more common in women than in men. It is the most common malignancy of the endocrine (hormone) system. There are four main types of thyroid cancer (depending on the type of cell that the cancer developed in); papillary carcinoma, follicular carcinoma, medullary carcinoma and anaplastic carcinoma. Occasionally other types of cancer (lymphoma, sarcoma and carcinosarcoma) can be found in the thyroid gland. Some thyroid cancers are caused by exposure to radiation and some medullary carcinomas are associated with an inherited condition (multiple endocrine neoplasia). However, in the large majority of cases the cause is unknown

Menu: Thyroid Cancer

Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Molecular Biology of Thyroid Cancers
Multiple Endocrine Neoplasia

Information Patients and the Public (17 links)


Information for Health Professionals / Researchers (16 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Xing M, Alzahrani AS, Carson KA, et al.
Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer.
JAMA. 2013; 309(14):1493-501 [PubMed]
IMPORTANCE: BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established.
OBJECTIVE: To investigate the relationship between BRAF V600E mutation and PTC-related mortality.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 1849 patients (1411 women and 438 men) with a median age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. MAIN OUTCOMES AND MEASURES: Patient deaths specifically caused by PTC.
RESULTS: Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) (P < .001) in BRAF V600E-positive vs mutation-negative patients. Deaths per 1000 person-years in the analysis of all PTC were 12.87 (95% CI, 9.61-17.24) vs 2.52 (95% CI, 1.40-4.55) in BRAF V600E-positive vs mutation-negative patients; the hazard ratio (HR) was 2.66 (95% CI, 1.30-5.43) after adjustment for age at diagnosis, sex, and medical center. Deaths per 1000 person-years in the analysis of the conventional variant of PTC were 11.80 (95% CI, 8.39-16.60) vs 2.25 (95% CI, 1.01-5.00) in BRAF V600E-positive vs mutation-negative patients; the adjusted HR was 3.53 (95% CI, 1.25-9.98). When lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant (HR, 1.21; 95% CI, 0.53-2.76). A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center. For example, in patients with lymph node metastasis, the deaths per 1000 person-years were 26.26 (95% CI, 19.18-35.94) vs 5.93 (95% CI, 2.96-11.86) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 4.43 [95% CI, 2.06-9.51]; adjusted HR, 1.46 [95% CI, 0.62-3.47]). In patients with distant tumor metastasis, deaths per 1000 person-years were 87.72 (95% CI, 62.68-122.77) vs 32.28 (95% CI, 16.14-64.55) in BRAF V600E-positive vs mutation-negative patients (unadjusted HR, 2.63 [95% CI, 1.21-5.72]; adjusted HR, 0.84 [95% CI, 0.27-2.62]).
CONCLUSIONS AND RELEVANCE: In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC.


Pushkarev VM, Kovzun OI, Pushkarev VV, Tronko MD
Biochemical effects of combined action of gamma-irradiation and paclitaxel on anaplastic thyroid cancer cells.
Ukr Biokhim Zh. 2013 Jan-Feb; 85(1):51-61 [PubMed]
The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), gamma-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). IR activated common DNA damage-induced signaling and manifested certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There was clear antagonism between Ptx and IR relative to cell cycle regulators--tumor suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but combined action of both agents enhanced caspase-3 and, especially, caspase-8 activation. The Ptx at low (1-25 nM) concentrations caused noticeable radioprotective effect. Thus, in ATC cells the ionizing radiation and Ptx exhibited competitive effects upon phosphorylation of cell cycle controllers: p53, pRb, CHK2, cAbl and expression of Bax. At the same time, the combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases activation and survivin expression. The net effect of these events during the first 48-72 h of cells incubation can be considered as antiapoptotic--Ptx attenuated cytotoxic effect of IR.


Gültekin SS, Sahmaran T
The efficacy of patient-dependent practices on exposure rate in patients undergoing iodine-131 ablation.
Health Phys. 2013; 104(5):454-8 [PubMed]
The authors investigated the efficacy of the patient-dependent practices (micturition, defecation, and taking a shower) after I ablation therapy in patients with thyroid cancer. Exposure rates were measured from a 1-m distance at 2, 4, and 24 h after the I administration. The comparisons for 2-4 h and 2-24 h time intervals were carried out among the patients with good and poor compliance, according to the relative amount of the patient-dependent practices, over mean values calculated for an effective half-life (h) or exposure rate decline ratio (%). In the 2-4 h interval, the mean values for good versus poor compliance were found to be: 4.16 h versus 8.14 h and 31% versus 17% in micturition; 5.70 h versus 6.84 h and 26% versus 21% in defecation; and 6.68 h versus 5.69 h and 24% versus 24% in taking a shower. Among patients with good versus poor compliance during a 2-24 h interval, the mean values were: 11.63 h versus 16.62 h and 74% versus 61% in micturition; 12.75 h versus 15.88 h and 71% versus 63% in defecation; and 13.77 h versus 14.21 h and 68% versus 67% in taking a shower.


Unlü S, Ozdemir S, Sümer S, et al.
Investigation of DNA damage by the alkaline comet assay in 131I-treated thyroid cancer patients.
Anal Quant Cytol Histol. 2013; 35(1):36-40 [PubMed]
OBJECTIVE: To assess the possible applicability of comet assay in the evaluation of DNA damage caused by ionizing radiation. The alkaline comet assay or single-cell gel electrophoresis has been used as a standard method for measuring and analyzing DNA damage.
STUDY DESIGN: Peripheral blood samples were collected from papillary thyroid cancer patients who received 131I by oral administration. Blood samples were taken just before the treatment, on the first day of treatment, and 1 week posttreatment. To determine the radiation-induced DNA damage, alkaline comet assay was performed.
RESULTS: It was found that significantly high levels of DNA damage occurred in first day samples when compared to control samples according to tail moment measurements. Also, a decrease in the level of damage was observed in the 1-week samples.
CONCLUSION: Our observations and data confirmed that treatment with 131I for papilloma thyroid cancer can cause DNA damage in circulating lymphocytes, and the comet assay seemed suitable to assess the effect of radioactive iodine for the patients.


Mweempwa A, Prasad J, Islam S
A rare neoplasm of the thyroid gland.
N Z Med J. 2013; 126(1369):75-8 [PubMed]
Burkitt's lymphoma of the thyroid gland is a rare malignancy. We present a case of a 58-year-old female who developed a rapid enlargement of her thyroid gland. Core biopsy confirmed the diagnosis of Burkitt's lymphoma. The tumour resolved after three cycles of chemotherapy. This case report emphasises the importance of considering lymphoma when dealing with thyroid nodules and goitres, as its management is different from that of other thyroid pathologies and delaying treatment has an impact on prognosis.


North DL
Uptake of ¹³¹I in households of thyroid cancer patients.
Health Phys. 2013; 104(4):434-6 [PubMed]
Fifty persons and pets living with thyroid cancer patients who were treated with large administered activities of I have been surveyed to ascertain their uptake of radioiodine from the domestic environment. All patients had been hospitalized for one night after the therapeutic administration, and the thyroids of the cohabitants were assayed 3-10 d after the patients returned home. Seven of the assays were positive for I in the thyroid gland. The transmitted quantities absorbed by the cohabitants were all less than 10 of the patients' burdens at discharge.


Avram AM, Fig LM, Frey KA, et al.
Preablation 131-I scans with SPECT/CT in postoperative thyroid cancer patients: what is the impact on staging?
J Clin Endocrinol Metab. 2013; 98(3):1163-71 [PubMed]
CONTEXT: The utility of preablation radioiodine scans for the management of differentiated thyroid cancer remains controversial.
OBJECTIVE: To determine the contribution of preablation Iodine 131 (131-I) planar with single-photon emission computed tomography/computed tomography (SPECT/CT; diagnostic [Dx] scans) to differentiated thyroid cancer staging.
DESIGN: Prospective sequential series at university clinic.
METHODS: Using American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging, seventh edition 320 patients post-total thyroidectomy were initially staged based on clinical and pathology data (pTN) and then restaged after imaging (TNM). The impact of Dx scans with SPECT/CT on N and M scores, and TNM stage, was assessed in younger, age <45 years, n = 138 (43%), and older, age ≥ 45 years, n = 182 (57%) patients, with subgroup analysis for T1a and T1b tumors.
RESULTS: In younger patients Dx scans detected distant metastases in 5 of 138 patients (4%), and nodal metastases in 61 of 138 patients (44%), including unsuspected nodal metastases in 24 of 63 (38%) patients initially assigned pathologic (p) N0 or pNx. In older patients distant metastases were detected in 18 of 182 patients (10%), and nodal metastases in 51 of 182 patients (28%), including unsuspected nodal metastases in 26 of 108 (24%) patients initially assigned pN0 or pNx. Dx scans detected distant metastases in 2 of 49 (4%) T1a, and 3 of 67 (4.5%) T1b patients.
CONCLUSIONS: Dx scans detected regional metastases in 35% of patients, and distant metastases in 8% of patients. Information acquired with Dx scans changed staging in 4% of younger, and 25% of older patients. Preablation scans with SPECT/CT contribute to staging of thyroid cancer. Identification of regional and distant metastases prior to radioiodine therapy has significant potential to alter patient management.


Xing M
Molecular pathogenesis and mechanisms of thyroid cancer.
Nat Rev Cancer. 2013; 13(3):184-99 [PubMed]
Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer.


Durmaz E, Barsal E, Parlak M, et al.
Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report.
J Pediatr Endocrinol Metab. 2012; 25(9-10):997-1000 [PubMed]
Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.


Torfs A, Laureyns G, Lemkens P
Outpatient hemithyroidectomy: safety and feasibility.
B-ENT. 2012; 8(4):279-83 [PubMed]
OBJECTIVE: In Belgium, thyroidectomy is currently an inpatient procedure because of potential life-threatening post-operative complications that include hypocalcemia, laryngeal nerve damage and haemorrhage. Thyroidectomy can only be performed on an outpatient basis if the complication rate is low. The purpose of this study was to determine the feasibility and safety of outpatient hemithyroidectomy.
METHODOLOGY: Between March 2008 and September 2010 we selected 54 patients who met our inclusion criteria for outpatient hemithyroidectomy. The procedure was carried out through a standard cervicotomy under general anaesthesia. No drains were used. We analysed patient outcome based on complications, unplanned admissions and readmissions.
RESULTS: The mean age of the 54 patients was 46 years, and most of them were women (81%). The mean duration of surgery was 64 minutes, and there were no intra-operative complications. After an observation period of at least 3 hours, 44 patients (81.5%) were discharged as planned. Ten patients (18.5%) required admission for urine retention (n = 1), social circumstances (n = 1), persistence of nausea (n = 3), delayed anaesthesia recovery (n = 4) and patient preference (n = 1). All 10 were discharged the next day, and none were readmitted.
CONCLUSIONS: Our study shows that outpatient hemithyroidectomy performed by experienced surgeons in carefully selected patients can be safe and is associated with a low complication rate. However, this series is small and larger studies are needed to confirm the results.


Ho AL, Grewal RK, Leboeuf R, et al.
Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.
N Engl J Med. 2013; 368(7):623-32 [PubMed] Article available free on PMC after 14/08/2013
BACKGROUND: Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known.
METHODS: We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib.
RESULTS: Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia.
CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.).


Smith JJ, Chen X, Schneider DF, et al.
Cancer after thyroidectomy: a multi-institutional experience with 1,523 patients.
J Am Coll Surg. 2013; 216(4):571-7; discussion 577-9 [PubMed]
BACKGROUND: The incidence of thyroid cancer in patients treated operatively for thyroid disease has been historically low (<5%). Previous series have not specifically addressed cancer rates in both euthyroid and hyperthyroid patients. This study examined cancer frequency in patients referred for removal of benign thyroid disease in a multi-institutional series.
STUDY DESIGN: A total of 2,551 patients underwent thyroidectomy at 3 high-volume institutions. Indeterminate/malignant fine-needle aspiration diagnosis was excluded (n = 1,028). Cancer cases were compared among 1,523 patients with Graves' disease (n = 264), nodular goiter (n = 1,095), and toxic nodular goiter (n = 164). Fisher's exact test, chi-square test, Wilcoxon rank sum, Kruskal-Wallis nonparametric t-tests, and multivariable logistic regression were used.
RESULTS: Overall, 238 (15.6%) cancers were recorded: Graves' disease (6.1%), nodular goiter (17.5%), and toxic nodular goiter (18.3%). Cancer rates were significantly different among these groups (p < 0.01) and significantly higher in nodular goiter and toxic nodular goiter vs Graves' disease (p < 0.01); no significant differences in cancer rates were noted among institutions. Overall, 275 patients had thyroiditis (18%). There was a significant association with younger age, male sex, nodular thyroids, and cancer (p < 0.05). Presence of thyroiditis or performance of preoperative fine-needle aspiration was not associated with cancer. Mean cancer size was 1.1 cm (46% >0.5 cm; 39% >1 cm). Most patients underwent total thyroidectomy (80%).
CONCLUSIONS: These data confirm higher than expected incidental thyroid cancer rates (15.6%) in the largest multi-institutional surgical series to date. Nodular thyroids, males, and young patients were more likely to harbor incidental carcinoma. These data support consideration of initial total thyroidectomy as the preferred approach for patients referred to the surgeon with bilateral nodular disease.


Candrlić B, Pusić M, Kukuljan M, et al.
Patient with lingual thyroid and squamous cell carcinoma of the tongue base--case report.
Coll Antropol. 2012; 36 Suppl 2:227-9 [PubMed]
We demonstrate a rare case of lingual thyroid together with squamous cell carcinoma of the base of tongue. 54-year-old patient presented with left sided lymph node enlargement in regions II, III and IV without any clinical symptoms. Physical examination revealed semicircular bulge at the base of tongue measuring 30 x 20 mm and tumorous lesion was suspected. Neck ultrasound showed pathological enlargement of lymph nodes and FNA of lymph node revealed squamous carcinoma cells in the smear. Further investigation included CT and MRI of the neck depicted ectopic thyroid tissue in base of tongue and enlarged and necrotic lymph nodes in regions II and III. Primary carcinoma could not be depicted. Biopsy of the lingual mass was performed and histology confirmed ectopic thyroid tissue. Physical examination of the oral cavity was repeated and suspicious area on the left side of the tongue base near ectopic thyroidal tissue was identified. Histology after biopsy confirmed squamous cell carcinoma with superficial growth. This case emphasizes the important role that collaboration of radiologist and otorhinolaryngologyst has in correctly diagnosing oropharyngeal pathology. Also, we underline the importance of careful oropharyngeal region screening in case of unknown pathologic lymphadenopathy, when the possibility of oropharyngeal cancer has to be considered.


Vukasović A, Kuna SK, Ostović KT, et al.
Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.
Coll Antropol. 2012; 36 Suppl 2:219-21 [PubMed]
The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.


Pauzar B, Karner I, Glavas-Obrovac L, et al.
PAX8-PPARgamma oncogene in follicular thyroid tumors: RT-PCR and immunohistochemical analyses.
Coll Antropol. 2012; 36 Suppl 2:79-82 [PubMed]
US-guided fine needle aspiration cytology is currently the best diagnostic tool for thyroid nodules. However, it is not sensitive and specific enough for differentiating between benign and malignant follicular tumors. A potentially useful marker for this differentiation is the PAX8-PPARgamma rearrangement, identified in follicular thyroid carcinomas, but not in follicular adenomas or other types of thyroid tumors. The aim of this research was to determine the clinical significance of the PAX8-PPARgamma oncogene in diagnostics follicular thyroid tumors. The study included 62 patients with follicular or Hürthle cell tumors. Gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) from paraffin embedded tissues, and PCR products were checked using the agarose gel electrophoresis. The immunohistochemical analysis was performed on archive paraffin embedded tissues with the monoclonal PPARgamma antibody. The statistical analysis has indicated that neither the expression of PAX8-PPARgamma mRNA, nor the immunohystochemical analysis with the PPARgamma antibody correlate with the patohystological diagnosis. The oncogene, PAX8-PPARgamma has not met the expectations as a reliable tumor marker for differentiation between benign and malignant thyroid tumors, which makes the only reliable histological criteria--capsular and vascular invasion.


Radivojević RC, Prgomet D, Markesić J, Ezgeta C
Hypocalcaemia after thyroid surgery for differentiated thyroid carcinoma: preliminary study report.
Coll Antropol. 2012; 36 Suppl 2:73-8 [PubMed]
Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first choice treatment for differentiated thyroid carcinoma (DTC). The study comprised 46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.


Kucukalić-Selimović E, Alagić J, Valjevac A, et al.
The value of serum thyreoglobulin levels and whole body (I-131) scintigraphy in the follow-up of the thyroid cancer patients after thyroidectomy.
Coll Antropol. 2012; 36 Suppl 2:67-71 [PubMed]
Serum thyreoglobulin (Tg) and whole body scintigraphy (I-131 WBS) have been used to detect recurrent and metastatic thyroid cancers postoperatively. However, discordant results of Tg measurement and 131I WBS have been reported. Negative 131I WBS and a positive Tg test are usually found, but less common occurrence of positive 131I WBS and a negative Tg test has also been demonstrated in a small but significant number of cases. Therefore, the aim of the study was to retrospectively analyse patients with positive 131I WBS after total thyreoidectomy and again 1 year after the radioactive iodine. There were 52 patients included in the study. Four weeks after surgery, during which thyroid hormone treatment was not introduced, each patient received an ablative dose of 131I. The evaluation of the WBS was qualitative and considered positive if thyroid remnant, lymphatic node or metastasis were detected. WBS and serum Tg was measured 12 months after 131I ablation with thyroid hormone suppression. We considered positive any Tg level above the sensitivity values and negative if lower than this level. Tg levels were related to the existence of a positive scan or a negative one. In our 52 WBS positive patients concordant positive Tg levels were observed in 42 patients while in 10 patients we found a negative Tg levels after the surgery. After 1-year follow-up, out of initially 42 concordant patients 8 patients showed remaining concordant positive Tg and WBS values. Discordant results were observed in 13 patients (4 patients were Tg- and WBS+ while 9 patients were Tg+ and WBS-). In the majority of patients (50%) remained with concordant results but changed from Tg+ and WBS+ to Tg- and WBS-. Diagnostic WBS is an additional valuable tool, besides Tg levels, in the follow up of patients after total thyreoidectomy.


Slipac J, Janjanin S, Ljepava D, et al.
Thyroid metastasis from breast carcinoma resembling medullary thyroid carcinoma.
Coll Antropol. 2012; 36 Suppl 2:63-6 [PubMed]
We are reporting a case of a 42-yr-old female with a history of right breast carcinoma. She was surgically treated (breast quadrantectomy with axillary dissection) and receiving a third cycle of adjuvant chemotherapy when a feeling of a constant pressure in the front of the neck and lack of air occurred. Subsequent work-up revealed a node in the right thyroid lobe with enlarged paratracheal bilateral and right mid and lower jugular lymph nodes. Fine-needle aspiration cytology, repeated within a 20 days window and analyzed by two different cytologists, showed a medullary thyroid carcinoma with a cervical lymph nodes metastasis so the patient underwent total thyroidectomy with selective and paratracheal neck dissection. Histology and immunohistochemistry revealed the specimen to be metastasis of breast carcinoma. During regular follow-up of our patient, eighteen months after initial diagnosis, no new metastases were found. To our best knowledge, this is the first described case of a thyroid metastasis of breast carcinoma that was cytologically misdiagnosed as a medullary thyroid carcinoma.


Kliseska E, Makovac I
Skip metastases in papillary thyroid cancer.
Coll Antropol. 2012; 36 Suppl 2:59-62 [PubMed]
Papillary thyroid carcinoma (PTC) is the most common malignant thyroid disease characterized by a high rate of cervical metastases (30-80%), especially due to paratracheal lymph node involvement. "Skip metastasis" are defined as a lateral lymph node metastasis without central lymph node involvement. The aim of this prospective study was to establish the lateral nodal metastasis pattern according to neck level, general occurrence and significance of skip metastasis in PTC. Forty-two previously untreated patients who presented between 2007 and 2011 with concomitant diagnosis of papillary thyroid cancer and metastatic disease of the lateral neck, underwent total thyroidectomy and central and lateral neck dissection. Skip metastases were encountered in 8 (19.5%) patients, four female and four male, with a mean age of 43.3 years. In all patients with lateral skip metastasis, level III nodes were most frequently involved (75%) followed by level IV (50%), while no metastatic disease was found in level IIb. Based on our research, skip metastasis are not uncommon (a lateral lymph node metastasis without central lymph node involvement) and present in approximately 1/5 of PTC patients with cervical lymph node metastasis.


Salkić A, Brkić F, Cickusić A, et al.
Thyroid cancer in Tuzla region of Bosnia and Herzegovina: a 10-year study (1999-2008).
Coll Antropol. 2012; 36 Suppl 2:53-7 [PubMed]
Bosnia and Herzegovina (B&H) is one of the Eastern European countries with lacking data on thyroid cancer (TC) epidemiology. We aimed to assess the incidence of TC in Tuzla Canton of B&H during a 10-year period (1999-2008). We retrospectively evaluated 65000 hospital records of both inpatients and outpatients with possible thyroid symptoms residing in Tuzla Canton of B&H (total of 496280 inhabitants) between 1999 and 2008. Patients with histological proof of TC were included in study. Incidence rates were calculated with age standardisation using European standard population. Trends in incidence were evaluated as moving three-year averages. During observed period 117 patients met the diagnostic criteria for TC with male to female ratio of 1:4.85. Median age of all cases was 51 years (interquartile range: 41 to 60) with men in average 9 years older than women at the time of diagnosis. The mean annual standardized incidence was found to be 2.30/10(5) (% 95 CI = 1.38-3.22) inhabitants ranging from 1.0 to 3.2 per 10(5). The average crude incidence in men was 0.82/10(5) and 3.83/10(5) in women. The prevalence of TC, at the end of the observed period was found to be 23.58/10(5) (% 95 CI = 19.3-27.58). There is a slight decline of incidence in our region during the observed period, but with the increase in the latest years of the study. This increase is probably the result of combination of various factors, mainly the better detection of new cases due to wider availability of diagnostics. Based on depicted trends, we believe that in the future years, TC incidence in our region will continue to rise.


Dzepina D, Bedeković V, Cupić H, Kruslin B
Papillary thyroid microcarcinoma: clinical and pathological study of 321 cases.
Coll Antropol. 2012; 36 Suppl 2:39-45 [PubMed]
The primary aim of the study was to investigate microcarcinoma characteristics of aggressivity, multicentricity and metastasis. Though its features are not significantly different from those of other papillary carcinomas, the optimal therapeutic approach continues to be an issue of controversy, most notably appropriate surgical approach and indications for neck dissection. The study is retrospective analysis of 321 microcarcinoma cases, operated upon with total thyroidectomy, with or without neck dissection. These cases were compared to larger papillary cancers. We found that 35.1% tumors were aggressive; 25.2% were multicentric, with foci in the contralateral lobe nearly twice as often as in the ipsilateral lobe; and 18.2% were metastatic. In comparison to groups of < or = 2 cm and < or = 3 cm, microcarcinomas were less aggressive, multicentric and metastatic. Male gender and age < 45 were unfavorable parameters. Multivariate analysis revealed contralateral lobe multicentricity and male gender as risk factors for metastasis. Although microcarcinoma demonstrated better characteristics than larger tumors, this subgroup behaves aggressively and should be approached cautiously.


Alagić-Smailbegović J, Kucukalić-Selimović E, Setić I, et al.
Importance of measurement of thyroglobulin and anti-thyroglobulin antibodies in differentiated thyroid cancer.
Coll Antropol. 2012; 36 Suppl 2:33-8 [PubMed]
Differentiated thyroid cancers include papillary and follicular carcinomas, both originating from follicular epithelium. Treatment of choice is usually total or near total thyroidectomy, followed by ablative radioiodine 131I treatment, and by the long-term administration of thyroid hormone. Despite its excellent prognosis, recurrent disease does occur in approximately 20-40% of patients. Guidelines for the follow-up management of differentiated thyroid cancer are commonly based on circulating thyrogobulin measurement in the complete absence of eutopic thyroid tissue. A retrospective review was conducted on 116 patients (66 papillary and 50 follicular carcinoma, mean age 51.2 years) who had undergone total or near total thyroidectomy and radioactive iodine remnant ablation. Serum thyroglobulin (Tg) and anti-thyroglobulin antibodies (TgAb) levels were measured preoperatively, 1 month after thyroidectomy (before 131I treatment) and 6 and 12 months after ablation therapy (Tg1, TgAb1 and Tg2, TgAb2, respectively). During one year of follow-up, in a total of 24 patients (21%) recurrent disease were confirmed by ultrasonography and whole-body-scanning, mostly. It was found significant correlation between serum Tg levels (measured preoperatively and postoperatively) and recurrent diseases (p < 0.05), while serum TgAb levels did not have any statistical significance. However, in multivariate regression analysis only Tg levels measured 12 months after the therapy (Tg2) remained a significant predictor of recurrent disease (p = 0.008). Although a high Tg level before surgery does not indicate that tumor is present, in the postoperative period and after ablative therapy Tg has proven predictive value because stimulated Tg levels above 10 ng/ml confirmed that indicate residual or recurrent cancer, and its periodically measurements is recommended.


Moon JH, Kim YI, Lim JA, et al.
Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results.
J Clin Endocrinol Metab. 2013; 98(3):1061-8 [PubMed]
CONTEXT: There are still some controversies regarding the cutoff value and the influential factors of thyroglobulin (Tg) concentration in washout fluid from fine-needle aspiration (FNA) biopsy (FNA-Tg) on cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC).
OBJECTIVE: Our aims were to validate the cutoff value of FNA-Tg in diagnosing malignant LNs on a large scale and to investigate the influential factors that could result in the discrepancy between the final diagnosis and FNA-Tg.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study based on hospital records with 528 cases of FNA-Tg measurement from 419 PTC patients.
MAIN OUTCOME MEASURE: The cutoff value of FNA-Tg was obtained from receiver operating characteristic analysis with final diagnosis. Binary logistic regression analysis was performed to investigate the influential factors.
RESULTS: In the final diagnosis, 190 LNs were malignant, and 338 LNs were benign. The median FNA-Tg was 521.2 (3676.8) ng/mL in malignant LNs, and 0.1 (0.2) ng/mL in benign LNs. The optimal cutoff value of FNA-Tg in distinguishing malignant LNs from benign LNs was 1.0 ng/mL (sensitivity, 93.2%; specificity, 95.9%) in all cases. Combining FNA-Tg and FNA cytology showed superior diagnostic power (sensitivity, 98.4%; specificity, 94.4%) when compared with diagnostic strategy using either FNA cytology or FNA-Tg alone. FNA-Tg, serum TSH, and serum Tg were higher in nonthyroidectomized patients than in thyroidectomized patients (P < .001, respectively). FNA-Tg was correlated with serum TSH and Tg levels (P < .001, respectively), and binary logistic regression analysis showed that serum TSH suppression and serum Tg presence independently affected the diagnosis made by FNA-Tg.
CONCLUSIONS: Our results validated 1.0 ng/mL of FNA-Tg as a cutoff value for diagnosing LN metastasis of PTC and suggested that serum TSH suppression and serum Tg presence should be considered in diagnosing LN malignancy with FNA-Tg in PTC patients.


Rahbari R, Kitano M, Zhang L, et al.
RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function.
J Clin Endocrinol Metab. 2013; 98(3):E446-54 [PubMed] Article available free on PMC after 01/03/2014
CONTEXT: Previously we identified RTN4IP1 to be differentially expressed in thyroid cancer by sex and the gene is located on chromosome 6q21, a chromosomal region frequently deleted or with loss of heterozygosity in a variety of human malignancies including thyroid cancer.
OBJECTIVE: Because the expression and function of this gene is unknown, we sought to characterize its expression in normal, hyperplastic, and benign and malignant thyroid tissue samples and to evaluate its function in cancer cells.
DESIGN: RTN4IP1 expression was analyzed in normal and hyperplastic thyroid tissue and benign and malignant thyroid tissue samples. In 3 thyroid cancer cell lines (TPC1 from a papillary thyroid cancer, FTC133 from a follicular thyroid cancer, XTC1 from a Hürthle cell carcinoma), small interfering RNA knockdown of RTN4IP1 was used to determine its role in regulating the hallmarks of malignant cell phenotype (cellular proliferation, migration, apoptosis, invasion, tumor spheroid formation, anchorage independent growth).
RESULTS: We found RTN4IP1 mRNA expression was significantly down-regulated in follicular and papillary thyroid cancer as compared with normal, hyperplastic, and benign thyroid neoplasms (P < .05). Moreover, RTN4IP1 mRNA expression was significantly lower in larger papillary thyroid cancers (P < .05). Small interfering RNA knockdown of RTN4IP1 expression increased cellular proliferation (2- to 4-fold) in all 3 of the cell lines tested and increased cellular invasion (1.5- to 3-fold) and migration (2- to 7.5-fold), colony formation (3- to 6-fold), and tumor spheroid formation (P < .05) in 2 of the 3 cell lines tested (FTC-133 and XTC1).
CONCLUSIONS: This is the first study to characterize the expression and function of RTN4IP1 in cancer. Our results demonstrate RTN4IP1 is down-regulated in thyroid cancer and is associated with larger papillary thyroid cancer and that it regulates malignant cell phenotype. These findings, taken together, suggest that RTN4IP1 has a tumor-suppressive function and may regulate thyroid cancer progression.


Strosberg JR
Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.
Semin Oncol. 2013; 40(1):120-33 [PubMed]
Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms.


Okere PC, Olusina DB, Shamim SA, et al.
Pattern of second primary malignancies in thyroid cancer patients.
Niger J Clin Pract. 2013 Jan-Mar; 16(1):96-9 [PubMed]
Many factors, including relatively young age of thyroid cancer diagnoses and improved survival, have led to increased concerns about the occurrence of second primary malignancies. This paper describes the pattern of occurrence of second primary malignancies in patients who were treated for malignant thyroid neoplasms in an Indian hospital. There were 21 affected patients of the approximately 4500 seen over 25 years. Most of the second primary cancers are solid tumors, and when nonthyroid cancers are the second tumors, ductal carcinoma of the female breast is the most common. Most of these tumors have very short detection intervals (including synchronous occurrences), suggesting that therapy with internal radiation was not contributory to the tumor development. When thyroid malignancies were the second primary cancers, they usually follow radiotherapy to the head and neck region for treatment of the first primary tumor and tend to be of aggressive histologic types than the common well differentiated thyroid carcinomas.


Faquin WC
Can a gene-expression classifier with high negative predictive value solve the indeterminate thyroid fine-needle aspiration dilemma?
Cancer Cytopathol. 2013; 121(3):116-9 [PubMed]
The recent study by Alexander et al validates the effectiveness of the Afirma test, and suggests a potential ancillary role for this unique test when appropriately applied in the evaluation of thyroid nodules classified by fine-needle aspiration as indeterminate.


Pellegriti G, Mannarino C, Russo M, et al.
Increased mortality in patients with differentiated thyroid cancer associated with Graves' disease.
J Clin Endocrinol Metab. 2013; 98(3):1014-21 [PubMed]
CONTEXT: We previously reported that differentiated thyroid cancer (DTC) has higher aggressiveness and poorer prognosis in patients with Graves' disease (GD) than DTC in euthyroid control patients. Subsequent studies on this issue reached controversial conclusions. Genetic and environmental factors, as well as the lack of appropriate control subjects and/or inadequate patient follow-up, may account for these discrepancies.
OBJECTIVE: The aim of this study was to investigate the long-term disease-specific mortality of nonoccult DTCs occurring in patients with GD compared with DTCs in matched euthyroid control patients.
PATIENTS AND DESIGN: The previously described cohorts of nonoccult DTCs occurring in either patients with GD (DTC-GD, n = 21) or matched euthyroid DTC control patients (n = 70) were compared again after a longer follow-up (50-363.6 months; median, 165.6 months) to compare the major clinical endpoints of persistent/recurrent disease and overall survival. Both cohorts were recruited in 1982-1994 at a single institution. All patients had undergone total thyroidectomy and were followed up according to a standardized protocol.
RESULTS: Persistent/recurrent disease was more frequent in DTC-GD patients than in control patients (P = .0119). Disease-specific mortality was also significantly higher in DTC-GD patients (6 of 21, 28.6%) than in euthyroid control patients (2 of 70, 2.9%) (P = .0001). At the last visit, the percentage of disease-free patients was 57.1% (12 of 21) in the DTC-GD group vs 87.1% (61 of 70) in the control group (P = .0025).
CONCLUSIONS: Nonoccult DTCs occurring in patients with GD cause increased disease-specific mortality compared with DTCs in matched euthyroid control patients. These findings emphasize the need for early diagnosis and aggressive treatment of nonoccult DTCs in patients with GD.


Liu Y, Cope L, Sun W, et al.
DNA copy number variations characterize benign and malignant thyroid tumors.
J Clin Endocrinol Metab. 2013; 98(3):E558-66 [PubMed] Article available free on PMC after 01/03/2014
CONTEXT: Fine-needle aspiration (FNA) is the best diagnostic tool for preoperative evaluation of thyroid nodules but is often inconclusive as a guide for surgical management.
OBJECTIVE: Our hypothesis was that thyroid tumor subtypes may show characteristic DNA copy number variation (CNV) patterns, which may further improve the preoperative classification.
DESIGN: Our study cohorts included benign follicular adenomas (FAs), classic papillary thyroid carcinomas (PTCs), and follicular variant PTCs (FVPTCs), the three subtypes most commonly associated with inconclusive preoperative cytopathology.
SETTING: Tissue and FNA samples were obtained at an academic tertiary referral center.
PATIENTS: Cases were identified that underwent partial or complete thyroidectomy for malignant or indeterminate thyroid lesions between 2000 and 2008 and had adequate snap-frozen tissue.
INTERVENTIONS: Pairs of tumor tissue and matching normal thyroid tissue-derived DNA were compared using 550K single-nucleotide polymorphism arrays.
MAIN OUTCOME MEASURE: Statistically significant differences in CNV patterns between tumor subtypes were identified.
RESULTS: Segmental amplifications in chromosomes (Ch) 7 and 12 were more common in FAs than in PTCs or FVPTCs. Additionally, a subset of FAs and FVPTCs showed deletions in Ch22. We identified the 5 CNV-associated genes best at discriminating between FAs and PTCs/FVPTCs, which correctly classified 90% of cases. These 5 Ch12 genes were validated by quantitative genomic PCR and gene expression array analyses on the same patient cohort. The 5-gene signature was then successfully validated against an independent test cohort of benign and malignant tumor samples. Finally, we performed a feasibility study on matched FA-derived intraoperative FNA samples and were able to correctly identify FAs harboring the Ch12 amplification signature, whereas FAs without amplification showed a normal Ch12 signature.
CONCLUSIONS: Thyroid tumor subtypes possess characteristic genomic profiles that may further our understanding of structural genetic changes in thyroid tumor subtypes and may lead to the development of new diagnostic biomarkers in FNA samples.


Ciabatti PG, Burali G, D'Ascanio L
Single-incision robot-assisted transaxillary surgery for early-stage papillary thyroid cancer.
Ann Otol Rhinol Laryngol. 2012; 121(12):811-5 [PubMed]
OBJECTIVES: We describe the surgical details, results, and learning curve of a proposed technique for single-incision transaxillary robot-assisted thyroid surgery for early-stage thyroid cancer.
METHODS: We performed single-incision transaxillary robot-assisted total thyroidectomy with the da Vinci surgical system in 29 patients (5 male, 24 female; median age, 45 years; age range, 19 to 69 years) with papillary thyroid cancer (cT1 NO) using our proposed technique with selected instrumentation. Preoperative ultrasound examination, fine-needle aspiration cytology, and contrast computed tomographic scanning were performed in all subjects. Ultrasound examination was carried out 1 month after surgery to assess the amount of residual thyroid tissue.
RESULTS: No procedure was converted to conventional open surgery. The mean total operation time was 178.51 +/- 24.18 minutes, and the mean console time was 126.10 +/- 14.47 minutes. A progressive reduction of console time was noted (160 minutes for the first procedure versus 102 minutes for the last one). No cases of permanent hypocalcemia, recurrent laryngeal nerve palsy, or postoperative bleeding occurred. The mean amount of postoperative residual thyroid tissue on ultrasound examination was 8.93 +/- 2.15 mm.
CONCLUSIONS: The single-incision transaxillary robot-assisted total thyroidectomy we propose is a feasible and relatively safe procedure in selected patients with early-stage thyroid cancer.


This page last updated: 22nd May 2013
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