Neck Ultrasonography Research Articles

Focused Neck Ultrasound and Lymph Node Sampling by Respiratory Physicians in Suspected Lung Cancer

Background: Malignant cervical lymphadenopathy in the setting of lung cancer represents N3 disease, and neck ultrasound (NUS) with sampling is described in the Royal College of Radiologists ultrasound training curriculum for the non-radiologists. This study reviews the incorporation of NUS +/− biopsy in the routine practice of a lung cancer fast-track clinic in the UK. Methods: We retrospectively assessed 29 months of activity of a lung cancer fast-track clinic. Systematic focused NUS was conducted in suspected thoracic malignancy, sampling nodes with a ≥5-mm short axis, under real-time US using a linear probe (5–12 Mhz). Fine-needle aspirations (FNAs) with or without 18 Ga core biopsies were taken. Results: Between August 2017 and December 2019, of 152 peripheral lymph nodes (LNs)/deposits sampled, 98 (64.5%) were supraclavicular fossa LNs with median [IQR] size 12 [8–18] mm. Core biopsies were performed in 54/98 (55%) patients, while all patients had FNAs. No complications occurred. The representative yield was 90/95 (94.7%) in cases with suspected cancer. No difference was seen between FNA versus core biopsy (p = 0.44). Of the 5 non-diagnostic samples, one was FNA only. The commonest diagnosis was lung cancer in 66/98 (67.3%). PDL-1 was sufficient in 35/36 tested (97.2%). ALK-FISH was successful in 24/25 (96%) cases. EGFR mutation analysis was successful in 28/31 (90.3%) cases. Median time from clinic to initial diagnosis was 7 [5–10] days. Computed tomography (CT) scans reported no significant lymphadenopathy in 18/96 (18.7%) cases, yet 10/18 (55.5%) cases were positive for malignancy. Conclusion: Neck nodal sampling by respiratory physicians was safe, timely, with a high diagnostic yield and suitability for molecular testing. Neck US can provide a timely diagnosis in cases that may be missed by CT alone.

Outcomes after radioiodine ablation in patients with thyroid cancer: Long-term follow-up of a Chinese randomized clinicaltrial.

Two large randomized trials of patients with differentiated thyroid cancer (DTC) reported recently (HiLo and ESTIMABL1) found that the recurrence rate among patients who underwent 1.1 GBq radioactive iodine (RAI) ablation was not higher than that of patients who underwent 3.7 GBq radioactive iodine (RAI) ablation. However, no similar studies have been conducted in China. We aimed to report clinical outcomes in Chinese patients with low/intermediate risk of recurrence DTC after long-term follow-up, and evaluate the risk factors that influence the presence or absence of incomplete response at the final follow-up. A long-term follow-up of a Chinese randomized clinical trial (October 2014 and February 2021) was conducted. A total of 506 DTC patients at low/intermediate risk of recurrence who were randomized into two groups to receive 1.1(n = 251) or 3.7 GBq (n = 255) RAI ablation following thyroid hormone withdrawal were followed on levothyroxine treatment for a median of 4.5 years (range: 1.6-6.3). Suppressed serum thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) levels were determined, and neck ultrasonography was performed. At the final follow-up, 499 (98.6%) patients showed an excellent response. The other seven patients (two patients underwent 1.1 GBq and five patients underwent 3.7 GBq RAI ablation, respectively) showed either structural incomplete response (lymph node metastasis, n = 1), biochemical incomplete response (increased serum Tg ≥ 1 ng/ml, or increased positive TgAb levels, n = 5), or indeterminate response (stable positive TgAb levels, n = 1). The risk of incomplete response at the final follow-up was significantly increased in patients with stimulated serum Tg ≥ 10 ng/ml at ablation (p = .003) and in patients with unsuccessful ablation (p = .008). Our findings indicated that there was no difference in the long-term outcomes with RAI ablation using either 1.1or 3.7 GBq in patients with low/intermediate risk of recurrence DTC, and 1.1 GBq RAI might be suitable for patients who are recommended for ablation.

Indication for radioactive iodine in patients with papillary thyroid carcinoma without apparent disease after total thyroidectomy but with elevated antithyroglobulin antibodies.

To evaluate a criterion for the selective indication of radioactive iodine (RAI) based on the short-term behaviour of antithyroglobulin antibodies (TgAb) in patients with papillary thyroid carcinoma (PTC) who have negative thyroglobulin (Tg) and neck ultrasonography (US) without abnormalities after total thyroidectomy but elevated TgAb. This was a prospective study that evaluated 216 patients with low- or intermediate-risk PTC who had nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities but elevated TgAb 3 months after thyroidectomy. RAI was not indicated in patients with negative TgAb or a >50% reduction in TgAb concentrations 6 months after initial assessment followed by a negative test or an additional reduction (also >50%) after 12 months. Only two of the 114 patients who did not receive RAI developed recurrences; another 108 patients met the criterion of an excellent response to therapy in the last assessment and TgAb persisted in four patients but there was an additional reduction in their concentration during follow-up. Among the 102 patients who received RAI, post-therapy whole-body scanning (RxWBS) detected persistent disease in 8 (8%). Two of the 94 patients without persistent disease on RxWBS developed recurrences. In the last assessment, in the absence of additional treatment, 54/92 patients (58.7%) without structural recurrence had negative TgAb. The indication for RAI can be based on the short-term behaviour of TgAb in patients with PTC and elevated TgAb after thyroidectomy who are not high risk and who do not have apparent disease (nonstimulated Tg ≤ 0.2 ng/ml and no US abnormalities).

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Overtreatment of Transient Maternal Hyperthyroidism Resulting in Fetal Goiter.

Evaluation of the Reliability of US-based TI-RADS in Predicting Thyroid Malignancy

Thyroid nodules are a common and prevalent problem encountered in every day clinical practice. Ultrasound (US) is considered to be the initial imaging modality used in the evaluation of thyroid nodules. The TI-RADS (Thyroid Image Reporting and Data system) is an US-based system used to categorize thyroid nodules and stratify their malignant risk in the aim to standardize reporting and simplify communication among practitioners. The aim of this study is to compare the TI-RADS classification of thyroid nodules on ultrasound with the findings of fine-needle aspiration cytology (FNAC) reported using the Bethesda system. A retrospective study of 59 thyroid nodules that underwent single radiologist bedside neck and thyroid US over a period of one year between January 2020 – January 2021 was performed. The US findings were based on the TI-RADS and all the nodules were eventually subjected to US-guided FNAC. Clinico-pathological retrospective analysis was performed by comparing TI-RADS findings to the Bethesda FNAC classification. Comparing TI-RADS results with the Bethesda system of classification, the risk of malignancy for TI-RADS 2, TI-RADS 3, TI-RADS 4, and TI-RADS 5 were 0%, 10%, 50%, and 100%, respectively. A significant association was noted between the TI-RADS and Bethesda system of classification (P < 0.001). We derived 91.3% sensitivity, 88.9% specificity, 84% positive predictive value, and 94.1% negative predictive value for our study. There is a strong correlation between thyroid sonographic reporting using the TI-RADS and Bethesda cytological classification system for thyroid nodules. The TI-RADS classification is an effective method for risk stratification of thyroid nodules into categories predictive of their malignant potential. This aims to guide further management and facilitate the selection process for fine-needle aspiration biopsy, thus avoiding unnecessary procedures.

Primary Hyperparathyroidism – A Contemporary Picture Based on 100 Patients from the Last Decade

Abstract Primary hyperparathyroidism (PHPT) is an endocrine disease, the clinical picture of which has slowly shifted to milder and asymptomatic forms during the last decades. Objective to describe the clinical presentation and the main laboratory and imaging findings in a group of patients with PHPT diagnosed during the last 10 years. Materials and Methods This was a retrospective cross-sectional study with data review from the database of a tertiary endocrine clinic from the last 10 years. Secondary causes for elevated PTH were excluded. The major clinical symptoms and signs of hypercalcemia/HPT were reviewed as well as concomitant diseases and medications. Serum calcium (total, albumin-corrected and ionized; sCa, corrCa, iCa+), phosphates (P), magnesium, creatinine, alkaline phosphatase, beta-crosslinks were measured. The intact parathyroid hormone (iPTH) and 25(OH)-vitamin D were determined by electro-hemi-luminescence (Elecsys, Roche Diagnostics). 24-hour urinary probes for calcium and phosphate were collected. Neck ultrasound (US) was used as the localization study of choice. Almost half of the participants underwent fine-needle aspiration biopsy (FNAB) with cytology and needle-washouts for iPTH. One fourth of the patients were assessed by Single-Photon Emission Tomography (SPECT-CT). Data on bone density (from DXA), fractures and renal stones (from renal US) were collected. Results One hundred patients met the study criteria – 95 were women. Most of them were in their 5th and 6th decades. The median corrected sCa was 2.73 mmol/l, iCa+ – 1.39 mmol/l, P – 0.88 mmol/l, iPTH – 14.5 pmol/l and 25(OH)D – 54.0 nmol/l. Normal sCa was registered in 20 participants (20%), while normal sP – in 67.0%. The neck US located single lesions (parathyroid adenoma) in 81% – behind or below the left inferior pole of the thyroid gland in 33 cases (33%) and contra-laterally in another 33%. FNAB of the suspicious lesion had been performed in 51% of the study subjects. The cytology confirmed the presence of parathyroid cells in 22 cases (43.1%), Bethesda II thyroid nodules in 21 cases (41.2%), Bethesda III nodules in 2 cases (3.9%) and insufficient samples (Bethesda I) in 5 cases (9.8%). SPECT-CT from 27 patients identified a suspicious left parathyroid in 11 cases, a right one – in 6 cases, as well as three ectopic locations. BMD data were available in 66 female patients and showed a higher prevalence of osteoporosis than in the general age-matched population; fractures, however, were not more frequent. Data from renal ultrasound were available in 77% and revealed chronic pyelonephritis without stones in 8 patients and renal stone disease – in 37 patients. Conclusion To our knowledge, this study is the first of its kind in our country during the last two decades. Mild to moderate hypercalcemia was very common, although most patients were oligoor asymptomatic. Renal and bone involvement were surprisingly frequent, with reduced eGFR and low bone mass being more prevalent than in the general population. The most typical location was a single parathyroid lesion within the lower glands. The use of SPECT-CT seems to decline and is replaced by US-guided FNAB with needle washout measurements of iPTH and cytological examination. Although the general picture of PHPT is shifting towards milder and asymptomatic (and probably earlier) forms of the disease, the classical clinical presentation can still be found in everyday practice.

Deep neck infections with mediastinum abscess and respiratory failure in a pediatric patient

Abstract Rationale: Deep neck infections are infections of the potential fascial planes and spaces of the head and neck. They can be life-threatening due to complications of upper airway compression or obstruction, sepsis or septic shock or acute respiratory syndrome. The most common pathogens are Streptococcus viridans and Staphylococcus aureus. Patient concerns: A one-year one-month-old girl was admitted to our pediatric emergency department due to fever, rhinorrhea, and erythematous swelling in the right preauricular area for 3 days. A day later, she had dyspnea, dysphagia, decreased activity, and the swelling extended to the right neck area. Diagnosis: The initial soft neck tissue radiograph showed prevertebral soft tissue thickening, and neck sonography revealed hypoechoic nodes, which were highly suggestive of a deep neck infection. Subsequent computed tomography of the neck and chest showed an abscess of the right deep neck spaces over the parapharyngeal, carotid, parotid, and submandibular areas with intrathoracic extension, as well as an abscess over the anterior mediastinum and bilateral empyema. Interventions: Drainage from deep neck incisions and thoracoscopic decortication of the right-side pleura were performed. Outcomes: After appropriate surgical interventions, critical care with antibiotics and ventilator support, the patient's condition stabilized and was discharged home. Lessons: Complications of deep neck infections are potentially fatal, especially in children. Clinicians should be aware of such infections in children and should not underestimate their potential severity. Children with deep neck infections should be more closely monitored throughout their hospitalization.

Papillary thyroid microcarcinoma with lung metastases: a case report and review of the literature

BackgroundDistant metastasis from papillary thyroid microcarcinoma (PTMC) is rare. Here we report a case of PTMC with multiple lung metastases.Case presentationA 64-year-old man presented to our hospital with abdominal pain. Computed tomography incidentally revealed multiple lung nodules. The lung tumor was histologically diagnosed as metastasis of papillary thyroid carcinoma (PTC) by core needle biopsy via thoracoscopy. The patient was referred to our department for further examination. Neck ultrasonography revealed a 0.9 cm hypoechoic nodule in the right lobe of the thyroid gland, which was diagnosed as PTC by fine-needle aspiration cytology. Subsequently, total thyroidectomy was performed, followed by radioiodine therapy. Iodine-131 (131-I) scintigraphy showed a strong accumulation in the lung metastasis. The patient presented no evidence of progression of lung metastasis for 25 months after the operation.ConclusionsLymph node metastasis or extraglandular extension has been reported in the few published cases of metastatic PTMC, including the present case, and the average age of these cases was 58.8 ± 12.0 years. Although active surveillance without surgical resection is expected to become a standard of care for PTMC, this case indicates that a subset of PTMC patients with risk factors may develop distant metastases. Hence, careful preoperative screening is required to avoid complications associated with completion thyroidectomy.

Residual Thyroid Tissue on Postoperative Diagnostic 131 I Radioactive Whole-Body Scan After Surgery in Differentiated Thyroid Cancer: A Tertiary Referral Centre Experience.

Residual thyroid tissue after total thyroidectomy in differentiated thyroid cancers is considered an independent risk factor for recurrence. Guidelines recommend following up patients after surgery with thyroglobulin (Tg), neck ultrasonography, and occasionally whole-body radioactive scan. However, the results of serum thyroglobulin and whole-body radioiodine scan are often discordant. The present study was undertaken to determine the levels of serum-stimulated thyroglobulin to complement the findings of residual thyroid tissue in the radioactive whole-body scan. One hundred twenty-six patients had undergone a radioiodine (131 I) whole-body scan (WBS) during the study duration, and 121 were available for analysis. The thyroglobulin level (measured by the CLIA method) was recorded at the time of these scans. The data was analysed to determine the level of stimulated thyroglobulin correlating with residual thyroid tissue, locoregional, and distant metastasis as assessed by WBS. The presence of residual thyroid tissue was noted in an overwhelmingly high 94% of cases. Twenty-four of the 28 patients with stimulated Tg < 2ng/dl had residual thyroid tissue on a WBS. The discordancy rate (positive moderate - large WBS and negative serum thyroglobulin) of 64.28% was seen. Using ROC the serum thyroglobulin cut-offs levels for the loco-regional disease were found to be 27.705ng/dl and 94.770ng/dl for distant metastasis. The results highlight the fact that serum Tg levels cannot be used as an accurate predictor of the extent of the remnant thyroid tissue. Irrespective of the quality of surgery, which was analysed based on the centre and surgical specialty, over 90% of cases had residual thyroid tissue on WBS. The use of only stimulated Tg levels for follow-up may be inaccurate. Serum Tg is a useful test along with radioactive whole-body scans to distinguish local disease, loco-regional disease, and distant metastasis.

Reduction of overtreatment without reduction of overdiagnosis in patients with differentiated thyroid cancer: mission impossible

PurposeLateral neck nodal metastases are common in patients with differentiated thyroid cancer (DTC) and usually have an indolent nature. They may be detected via neck palpation or preoperative ultrasound (US) of the neck. We hypothesized that preoperative neck metastases detected with US did not affect regional recurrence or long-term survival.MethodsA retrospective analysis of patients’ records treated for DTC at our institution between January 2006 and December 2016 was performed. Information about preoperative US of the neck, treatment, demographics, staging, and histopathology was obtained. The endpoints for the study were nodal recurrence and survival. Differences in survival were analyzed between three groups of patients divided by presence or lack of preoperative US and/or palpable cervical lymph nodes (PLN). Furthermore, the prognostic value of multiple variables was tested by univariate and multivariate analysis.ResultsThere were 1108 patients with DTC, 221 males and 887 females. The median age was 48.3 years (range 3 to 86), the median time of observation was 68 months (range 0 to 142). Eight hundred sixty-two patients without PLN or preoperative US represented group 1, 112 patients with PLN were in group 2, and 134 patients without PLN and with preoperative US were in group 3. Only five patients had a regional recurrence, one died due to distant metastases. There was no statistically significant difference in survival between the groups (p = 0.841) and neck US was not significantly associated with overall survival neither in univariate nor in multivariate analysis.ConclusionIn patients with DTC, the benefits of preoperative US of cervical lymph nodes are probably limited and “less is more” approach is advised.

Is common carotid artery intima-media thickness (cIMT) a risk assessment marker in children with attention deficit/hyperactivity disorder?

Objective Attention deficit/hyperactivity disorder (ADHD) is associated with impairment in social, academic and job-related functioning in both children and adults. The purpose of this study is to investigate the susceptibility to cardiovascular risk factors in children with ADHD diagnosis through common carotid artery intima-media thickness (cIMT) measurement, to compare cIMT in ADHD and control groups and to evaluate the association between cIMT and ADHD symptom severity. Methods The mean cIMT of 42 children with ADHD, ADHD symptom scales and a semi-structured psychiatric interview, and 42 age and sex matched healthy controls were measured with B-mode Doppler neck ultrasonography. Results The median cIMT was significantly higher for the ADHD group compared to the healthy controls. There was a statistically significant, negative, moderate correlation between cIMT and Conners ADHD index score, hyperactivity score, oppositional score and the presence of ODD comorbidity. Conclusions In this study, we found significantly higher cIMT in children with ADHD when compared to healthy controls. Considering that increased cIMT is a sign of atherosclerosis and it can be used as a marker of cardiovascular risk factors, our finding may indicate that children with ADHD are at increased risk for cardiovascular diseases. Keypoints cIMT was significantly higher in children with ADHD when compared to healthy controls. Higher cIMT in children with ADHD may indicate that children with ADHD are at increased risk for cardiovascular diseases. cIMT measurement may be studied as a potential tool for risk assessment before a child with ADHD is started on psychostimulant medications.

Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors

BackgroundAlthough the incidence of thyroid cancer had been increasing until a few years ago, a decrease has been observed in the last years, probably due to the reduction of the screening tests in Korea. Childhood thyroid cancer has been increasing in the past with the same trend as in adults, but there have been few reports on recent trends. We analyzed the trends of thyroid cancer in Korean children and related factors.MethodsFrom national statistics and cancer register database, the data of age-specific incidence rate in Korean childhood thyroid cancer from 1999 to 2017 was obtained, and levels of seaweed intake, the number of computed tomography (CT) and neck ultrasonography (US), obesity prevalence rate, and smoking and alcohol consumption rates in children were analyzed.ResultsThe age-specific incidence of thyroid cancer in Korean children has increased in both genders between 1999 and 2017 (2.0 in 1999 vs. 7.2 in 2017, per population of 100,000), especially in the age group of 14-18 years (1.5 in 1999 vs. 5.5 in 2017, per population of 100,000). During the same period, levels of seaweed intake, number of CT scans and neck US, and prevalence of obesity in children increased significantly, while childhood smoking and alcohol consumption rates decreased.ConclusionUnlike the adult thyroid cancer in Korea, childhood thyroid cancer continues to increase, and the cause might be accompanied by actual increases due to the environmental factors such as excessive iodine intake, exposure to medical radiation, and increased obesity prevalence as well as the screening effect.

Value of accurate diagnosis for metastatic supraclavicular lymph nodes in breast cancer: assessment with neck US, CT, and 18F-FDG PET/CT

Purpose Neck ultrasonography (US), computed tomography (CT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are all known to be useful imaging modalities for detecting supraclavicular lymph node (SCN) metastasis in breast cancer. The authors compared the diagnostic values of neck US, CT, and PET/CT in the detection of SCN metastasis in breast cancer. Methods SCN metastases identified in neck US, CT, or PET/CT during follow-up visits of patients with breast cancer were pathologically confirmed with the use of US-guided fine-needle aspiration cytology. The clinicopathological factors of the patients were analyzed, and the statistical parameters including sensitivity, specificity, positive and negative predictive values, false-positive and false-negative rates, and accuracy of neck US, CT, and PET/CT were compared. Results Among 32 cases of suspicious SCNs, 24 were pathologically confirmed as metastasis of breast cancer. The sensitivity of US + CT was 91.7%, which was the same as that of PET/CT, while the sensitivity rates of US alone and CT alone were 87.5% and 83.3%, respectively. Accuracy was 99.8% in PET/CT alone and 98.1% in US + CT. The false-negative rate was 0.1% in US + PET/CT, while it was 0.2% in PET/CT and US + CT, 0.3% in US alone and 0.4% in CT alone. Conclusion PET/CT can be the first choice for detecting SCN metastases in breast cancer. However, if PET/CT is unavailable for any reason, US + CT could be a good second option to avoid false-negative results.

Regrowth of Thyroid Gland: Is This Possible????

Abstract Introduction: Adult Thyroid gland which derived from primitive pharynx and neural crest is considered a non-regenerative organ. In this nature, partial or total thyroidectomy is considered a curative treatment for compressive non-malignant goiter. While there is a potential regrowth from stimulating by pituitary thyroid stimulating hormone (TSH), such growth is rarely significant and suppressive TSH therapy is currently indicated only for thyroid malignancy. We present an unusual case of rapid regrowth of normal thyroid tissue that expanded both of the lobes from a single unilateral remnant. Case: 58-year-old male with prior history of multinodular goiter status post subtotal thyroidectomy due to compressive symptoms in 2006 present to our clinic for follow up. Post-operatively, case was complicated with Iatrogenic Hypoparathyroidism thus on replacement of calcium and calcitriol. Follow up neck ultrasound (US), showed no thyroid gland with minimal residual tissue in the right fossa and pathology was benign. In 2011, patient complained of new onset globus sensation, and voice changes which initially concern for gastroenterology issue as the etiology. A neck US unexpectedly revealed normal right thyroid lobe of 5.7 cm without any tissue on the left and no nodule. FNA subsequently performed which was benign tissue. Due to high risk of complication for repeat surgery, annual US was planned for monitoring. In 2013 there was a significant new growth of left thyroid of 1.7 cm in size, no nodules. A repeat US six months later revealed an increase in size in the right from 5.7 to 6.1 cm as well as 1.7 to 2.1cm on the left. Patient denied any compressive symptoms, so we continue with neck US surveillance. By 2020, the right lobe was 6.4 cm and left lobe at 2.4 cm. Within both lobes, now multiple nodules start appearing. FNA were performed on several of those nodules with a benign cytopathology in all of them. Of note, other than regrowth of his thyroid, it is also physiologically functional as patient is euthyroid without levothyroxine replacement since 2013. Discussion: When patient underwent thyroidectomy for benign multinodular goiter, thyroid function test is the only routine test for follow up without additional further images. While it is considered a curative treatment, some regeneration or recurrence is still a possibility which is shown in our case. This is one of the few cases in the literature that we could found about normal thyroid tissue regrowth. It is still unclear how the mechanism for this phenomenon occurs. Further studies may need to be pursued with regards to suppressive TSH therapy or even radioactive iodine ablation for benign goiter that have regrowth potential. It is crucial that physicians become aware of such occurrence may happen since new thyroid nodules can also develop in the new thyroid tissue and fine needle aspiration should be performed accordingly.

Hurthle Cells Adenoma With Distant Metastases Refractory to Radioiodine

Introduction: Adenoma of the thyroid is defined as an encapsulated follicular tumor that is well delimited in relation to the adjacent parenchyma and whose cells do not exhibit the nuclear alterations of papillary thyroid carcinoma (PTC), and in the absence of capsular and vascular invasion. Adenoma, including the of Hurthle cells, is considered a benign tumor. No additional treatment is recommended after resection of the tumor. Case: A 64-year-old man was submitted to total thyroidectomy because of a nodule measuring 3.5 cm with indeterminate cytology (predominance of Hurthle cells). Histology revealed an Hurthle cells adenoma of 3.2 cm. The tumor did not exhibit vascular or capsular invasion, the cells did not contain nuclei of PTC, and no necrosis or mitoses were observed. Five years after surgery, serum thyroglobulin (Tg) was elevated (25 ng/ml) during euthyroidism (TSH 0.6 mUI/l) and in the absence of anti-Tg antibodies. Serum calcitonin was undetectable. The patient developed a progressive increase in Tg and neck ultrasonography (US), chest computed tomography (CT), and FDG-PET/CT were performed. US revealed atypical lymph nodes (the largest with 12 mm) and cytology showed abundance of Hurthle cells. Chest CT detected multiple nodules, the largest measuring 15 mm, and FDG-PET/CT revealed areas of cervical and pulmonary uptake corresponding to the lesions seen on US and CT. The patient received 100 mCi radioactive iodine and post-therapy whole-body scanning showed mild uptake only in the thyroid bed. The patient continues to show progressive increase in Tg (last measurement > 1,000 ng/ml), as well as progression of metastases. He remains under follow-up and on therapy with tyrosine kinase inhibitor. The histology result was revised by two pathologists with broad experience in thyroid pathology who confirmed the initial findings compatible with adenoma. Conclusion: The present case shows that, although rare, Huthle cells tumors can develop metastases even when the tumor is < 4 cm and unequivocally without nuclei of PTC or capsular and vascular invasion, thus considered benign (adenoma). As observed in this case, these metastases can be macrometastases, distant, and refractory to radioiodine. Reference: Lloyd RV, Osamura RY, Klöppel G, Rosai J, ed. WHO Classification of Tumours of Endocrine Organs. 4th edition Lyon: IARC; 2017

Estimabl2: Is There a Need for Radioiodine Ablation in Low Risk Differentiated Thyroid Cancer (DTC) Patients?: Results From the French Randomized Phase III Prospective Trial on 776 Patients (NCT 01837745)

Background: The benefits of post-operative radioactive iodine (RAI) administration have not been demonstrated in patients with low risk differentiated thyroid cancer (DTC). The objective of this randomized phase III trial is to assess in low risk DTC patients the non-inferiority of a follow-up strategy as compared to a systematic adjuvant post-operative RAI administration. Methods: ESTIMABL2 is a French multicentric randomized phase III trial in patients with low-risk DTC treated with total thyroidectomy with or without prophylactic neck lymph node dissection (pT1am N0 or Nx with a sum of the diameters of tumor lesions ≥ 10mm, pT1b N0 or Nx). Two to five months after surgery, in the absence of suspicious lateral neck lymph node on ultrasonography (US), patients were randomized either to the follow-up group (FU, no RAI administration) or to the ablation group and received post-operative RAI (1.1 GBq following rhTSH stimulation). Yearly controls under levothyroxine treatment consisted in thyroglobulin (Tg) and Tg antibodies (TgAb) determinations and neck-US. The primary objective was to assess at 3 years after randomization the non-inferiority of the proportion of patients without tumor-related event in the FU group as compared to the ablation group. Non-inferiority is demonstrated if the rate of patients without event at 3 years does not differ by more than ΔL=-5%. A tumor-related event was defined by the occurrence of subsequent treatment (RAI administration or surgery) for abnormal RAI uptake on the post-therapeutic WBS or by elevated Tg or TgAb levels and/or abnormal neck US during controls. Tg levels on levothyroxine treatment were considered elevated if > 2ng/mL in the FU group and > 1ng/mL in the ablation group. TgAb were considered elevated if > the upper limit range with an increase above 50% on 2 consecutive determinations performed 6 months apart. Results: 776 low-risk DTC patients were included between 2013 and 2017 in 35 French centers within the TUTHYREF network; 83% females, mean age: 52 years, papillary TC: 96%, pT1bNx: 43.6%, pT1bN0: 37.5%, pT1amNx: 12.6%, pT1amN0: 6.3%. Among the 729 patients evaluable at 3 years after randomization, tumor-related events occurred in 18/367 patients (4.9% IC95%=[2.9; 7.6]) in the FU group and in 15/362 patients (4.1% IC95%=[2.3; 6.7]) in the ablation group. Thus, 95.1% of patients in the FU group had no event at 3 years and this percentage is not inferior from the 95.9% of patients observed in the ablation group (difference = -0.8% [95% CI:-3.3%; 1.8%]. The number of subsequent surgery and/or RAI administration was 6 (1.6% IC95%=[0.6; 3.5]) in the FU group and 9 (2.5% IC95%=[1.1; 4.7]) in the ablation group. Conclusion: this phase III trial demonstrates the non-inferiority of a follow-up strategy compared to a systematic adjuvant post-operative administration of RAI (1.1GBq following rhTSH) in low risk DTC patients (PHRC 2012; NCT01837745).

A Pediatric Patient With Papillary Thyroid Carcinoma With Local and Distant Metastases

Introduction: Thyroid cancer is less common among children than adults, but the incidence has been increasing, especially in adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in pediatric patients representing more than 90% of all cases. Children with PTC are likely to present with regional lymph node metastases, but distant metastases are rare. We present a 12-year-old female patient who presented with a neck mass found to be PTC with neck and pulmonary metastases. Case Presentation: A 12-year-old girl previously healthy presented to her primary doctor with a neck mass for several months. The patient had no other complaints, and the physical exam was notable for a palpable right anterior neck mass measuring 3x4cm. Thyroid studies were remarkable for a thyroid-stimulating hormone (TSH) of 2.13 uIU/mL (0.350-4.94) and negative antithyroid antibodies. Initial neck ultrasound (US) showed a multilobulated right thyroid nodule with macrocalcifications. Fine needle aspiration (FNA) of the nodule revealed PTC. Patient underwent neck and chest computed tomography (CT) preoperatively, notable for cervical lymph nodes involvement and multiple bilateral lung nodes less than 1cm each. She underwent neck exploration and total thyroidectomy and was started on thyroid hormone replacement therapy afterwards. Pathology of the specimen revealed PTC with extension into the perithyroidal soft tissue and two out of five lymph nodes with metastatic PTC. She underwent I-123 whole-body scan (WBS) eight weeks later, followed by I-131 therapy. Interestingly, the pulmonary nodes did not demonstrate any uptake on the WBS before or after receiving I-131 therapy. Patient continues with no pulmonary symptoms and her thyroglobulin (Tg) level continues to be low. She underwent extensive workup that ruled out infections and other malignancy causing the pulmonary nodes. The most recent chest CT, six months after I-131 therapy, showed a slight decrease in the pulmonary nodes. She underwent repeat WBS, 10 months after I-131, notable for minimal uptake in the lungs. The patient is currently euthyroid on thyroid hormone replacement therapy, and she is undergoing surveillance with laboratory studies every three months, neck US and chest CT every six months. Conclusion: In children with PTC, the pulmonary metastases usually demonstrate radioactive iodine uptake, making them responsive to I-131 treatment. Even though the pulmonary nodes were not iodine avid for our patient based on the WBS, it seems like they are responding to the first dose of I-131 as they have decreased in size. Pulmonary metastases in children have different behavior than in adults, and studies have shown that clinical response to I-131 therapy may take several years to show a reduction in the size of nodes. Therefore, careful consideration should be made before giving another dose of I-131 to this group of patients.

Hypercalcemia in Pheochromocytoma: From MEN to VHL

Background: Co-occurrence of phaeochromocytoma and primary hyperparathyroidism is usually seen in patients of Multiple Endocrine neoplasia 2A(MEN2A) and is rare in Von Hippel Lindau disease (VHL). Parathyroid adenoma with pheochromocytoma in a genetically confirmed VHL has been reported only once till date (1). Clinical Case: A 30-year male was admitted for evaluation of hypertension and incidentally diagnosed adrenal mass on ultrasound. 9-years back, he was diagnosed as a case of VHL (right renal clear cell carcinoma, pancreatic cystadenoma, spinal hemangioblastoma and epididymal cysts). Right nephrectomy and pancreatic cyst excision had been done and past work-up for pheochromocytoma was normal. He also had been operated twice for recurrent renal calculi. Family history revealed surgery in mother for pancreatic mass. Current imaging revealed right adrenal mass (4.7*4.6 cm) with left renal cysts and calculi, pancreatic cysts and spinal- medullary hemangioblastoma and epididymal cysts. Fundus examination was normal. 24-hours urinary fractionated normetanephrines were elevated (2062 mcg/24 hours) and I131MIBG scan showed 4.7*4.6cm concentrating lesion in right renal fossa suggestive of right adrenal pheochromocytoma. However his biochemical evaluation revealed hypercalcemia (12.1 mg/dl), low phosphorus (3.2 mg/dl), low 25(OH) D (24.84 nmol/l), and raised PTH (121pg/ml). Ultrasound neck and Tc99m-Sestamibi localized left inferior parathyroid adenoma. DEXA scan showed severe osteoporosis. Genetic analysis confirmed VHL mutation in exon-1. Calcitonin and RET mutation were normal (ruled out MEN2A). Therapeutic approach was surgical excision of adrenal pheochromocytoma followed by parathyroidectomy. We report a case of pheochromocytoma with primary hyperparathyroidism (cause: left inferior parathyroid adenoma) in a patient of VHL (Renal clear cell carcinoma, pancreatic cystadenoma, epidydymal cysts and medullary and spinal hemangioblastoma). Hypercalcemia seen in patients of VHL is either due to bone metastasis/PTHrP/IL-6 secretion from RCC or due to PTHrP/PTH/calcitonin secretion from pheochromocytoma and rarely due to associated parathyroid adenoma. Literature search revealed four case reports of parathyroid adenoma with VHL. In only one of these, VHL had pheochromocytoma associated with parathyroid adenoma (1). Conclusion: Ours is the 2nd such case reported in literature of primary hyperparathyroidism in a genetically confirmed case of VHL with pheochromocytoma. This case highlights the overlap of tumorigenesis in two rare genetically divergent syndromes and importance of long-term follow-up for sequential development of new tumors. Reference: Arao T, Okada Yet al. A case of VHL disease with bilateral pheochromocytoma, renal cell carcinoma, pelvic tumor, spinal hemangioblastoma and primary hyperparathyroidism. Endocr J. 2002 Apr;49(2):181–8.

Zebra Case of Papillary Thyroid Cancer in MEN-2 Syndrome

Introduction: The occurrence of papillary thyroid cancer in patients with familial medullary thyroid cancer (FMTC) is extremely rare and underreported. Case Presentation: A 51-year-old caucasian female with no past medical history who presented to primary care physician for her annual visit. She denied any complaints. Vital signs were unremarkable. Physical examination was remarkable for large left thyroid nodule without cervical lymph nodes enlargements. Family history was significant for metastatic MTC of her two sisters (at the age of 55, 60) and her niece at age of 21. She previously declined genetic testing. Labs were unremarkable including serum calcium of 8.3 mg/dL. Thyroid function panel revealed a TSH of 2.1 μU/mL, Free T4 of 1.4 ng/dL, Thyroid peroxidase (TPO) antibody of <6 IU/mL. Neck ultrasonography revealed a mid-left thyroid hypoechoic nodule of 1.8 ×1.5 cm, without cervical lymph nodes enlargements. Fine needle biopsy revealed a papillary thyroid cancer, follicular variant. The diagnosis confirmed by two university pathologists, without any evidence of MTC. Genetic testing revealed a germline mutation in RET oncogene exons 13. Further labs revealed normal metanephrines of 12 pg/mL and normal normetanephrine of 31 pg/mL, normal serum calcitonin was less than 2 pg/mL (0-5), normal serum CEA was 2.5 ng/mL (0-5), elevated anti- thyroglobulin (anti-TG) antibodies of 1234 iu/mL (0-0.9), and elevated thyroglobulin of 50 ng/mL (1.5-38.5). The patient was referred to ENT for total thyroidectomy. Further, she was treated with radioactive iodine ablation by 155 mCi of iodine 131. Follow up whole body thyroid scan revealed no evidence of residual or recurrence. The patient was treated with 112 mcg levothyroxine with a target of TSH less than 0.1. On six months follow up, repeated neck ultrasonography revealed no remnant of thyroid tissue. Follow up Thyroglobulin (TG) was less than 0.1 ng/mL, TSH 0.05 μU/mL, FT4 of 1.98 ng/dL, and calcitonin was still less than 2 pg/ml. Genetic testing of her daughters (24, 31) revealed germline mutations in RET-oncogene exons 13 and was referred for prophylactic thyroidectomy. Discussion: FMTC is an inherited syndrome characterized by the presence of only MTC without hyperparathyroidism or pheochromocytoma and is considered a variant of MEN2A. Most cases of MEN2A have been attributed to mutations in the intracellular portion of RET, and somatic mutations in RET have been identified in 50% of cases of sporadic FMTC. We recommend in patients with germline RET mutations and a family history of MTC, the diagnosis of papillary thyroid cancer should be confirmed by two pathologists, and patients should be tested for serum calcitonin, serum calcium, and metanephrines/normetanephrine levels. Genetic testing of first-degree relatives of FMTC at an early age is essential in guiding major management decisions such as the timing of prophylactic thyroidectomy.

Primary Thyroid Lymphoma: Maintaining Diagnostic Scrutiny

Background: Primary thyroid lymphoma (PTL) is a rare condition representing <5% of thyroid malignancies with diffuse large B-cell lymphoma (DLBCL) as the most common subtype (1). Although not commonly managed in the endocrine sphere, identification is paramount to prognosis and treatment. We present a case of PTL to highlight the importance of diagnostic scrutiny and clinical follow up. Clinical Case: A 69-year-old man with a history of Hashimoto’s thyroiditis presented with an enlarging neck mass. The patient noted development of a left-sided anterior neck mass 3 days prior to seeking care. He denied compressive symptoms and B symptoms (weight loss, fevers, and night sweats). Physical exam revealed a large, firm left-sided thyroid nodule. Serum studies were notable for TSH 39.1 mcIU/mL (0.30-4.7 mcIU/mL), FT4 0.9 ng/dL (0.80-1.70 ng/dL), and TPO Ab 127 IU/mL (<=20 IU/mL). Levothyroxine 100 mcg daily was started. Neck ultrasonography showed a 54 mm hypoechoic, solid left thyroid nodule without calcifications. No abnormal cervical lymph nodes were present. FNA revealed a mixed population of small lymphocytes with no monoclonal B cell population or T cell aberrancies on flow cytometry. In the setting of ongoing nodular growth, the patient underwent core needle biopsy which revealed DLBCL (Ki67 proliferation index >80%, EBV-EBER negative). For diagnostic confirmation and staging, a whole-body FDG-PET scan was performed with an intensely FDG-avid left thyroid mass and no metabolic evidence of additional lymphoproliferative disease. Bone marrow biopsy did not show lymphomatous involvement. The patient was diagnosed with primary thyroid lymphoma and started on chemotherapy with R-CHOP. Conclusion: PTL commonly presents as a rapidly enlarging, painless neck mass that may be accompanied by B symptoms. Hashimoto’s thyroiditis is a known risk factor. Our case in particular required more diligence in the setting of an FNA with mixed lymphoid cells and negative flow cytometry. Initial differential diagnosis included intrathyroidal lymph node, Hashimoto’s thyroiditis, thyroid adenoma/malignancy with a false FNA, and lymphoma. Notably, FNA biopsy is only associated with 71% sensitivity in diagnosing PTL, whereas core biopsy has a 93% sensitivity rate (2). Upon histopathologic disease diagnosis, collaboration with oncology is needed for further staging and initiation of chemotherapy +/- radiation.