A rare case of subclinical hyperthyroidism due to Graves’ disease with papillary thyroid carcinoma in a young female

Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations.

Fine needle aspiration (FNA) biopsy is an established procedure by which to sample thyroid nodules to ascertain etiology and produce a diagnosis conveying risk of malignancy with recommended patient follow-up. This procedure is well-tolerated and endorsed given the accessibility and vascularity of the thyroid gland. FNA cytopathology has proven efficacious for the primary assessment of thyroid nodules. Well-differentiated papillary thyroid carcinoma (PTC) and benign lymphocytic (Hashimoto) thyroiditis (HT) are distinct thyroid lesions that may be reported with diagnostic confidence based on their characteristic cytomorphologic features. However depending on the adequacy of FNA sampling and the morphology of aspirated cellular material, thyroid nodules with coexisting PTC and HT may pose diagnostic pitfalls. This may be dependent upon: (a) the architectural nature of the coexisting lesions in-vivo; (b) whether both lesions are adequately sampled through FNA; and (c) which of the cell types and cytomorpholo...

The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives.

Introduction: Cervical lymphadenopathy can be caused by various factors, including infections and malignancies. Papillary thyroid carcinoma (PTC) is a type of thyroid cancer that can lead to metastasis in the cervical neck lymph nodes. Ultrasound is recommended for preoperative lymph node evaluation, and preventive central lymph node dissection is advised for moderate- and high-risk PTC patients. This case study describes a young patient who was diagnosed with PTC through cervical ultrasound and biopsy of the cervical adenopathy. Case Presentation: A 27-year-old patient with no significant medical history presented with a left jugulo-carotid lymph node of about 1 cm. A cervical ultrasound showed three suspicious lymph nodes with a left thyroid nodule. An excision biopsy of the largest lymph node revealed thyroid tissue with abnormalities suggesting papillary carcinoma with nodal metastasis. A total thyroidectomy was performed with central and homolateral lymph node dissection, revealing an encapsulated papillary carcinoma with nodal metastasis. The patient received radioactive iodine therapy and was placed on L-thyroxine for substitution and suppression. Regular follow-up is assured. Discussion: Lymphadenopathy can result from regional or systemic disease and may indicate an underlying condition. PTC should be considered in any patient with cervical adenopathy, even if the thyroid is normal in size. The combination of radiology and fine-needle aspiration cytology (FNAC) is essential for diagnosing cervical masses and their metastatic origin. Total thyroidectomy with ipsilateral and/or contralateral cervical lymph node dissection is the best treatment for lymph nodes revealing PTC, followed by post-surgical radiation therapy. The prognosis remains favorable, although lymph node metastases are a predictor of recurrence. Conclusion: PTC, which mainly presents as cervical lymphadenopathy, is rare. Early detection and proper management of PTC are crucial for the patient's long-term outcome. With careful monitoring and regular follow-up, patients with PTC can achieve a favorable prognosis and quality of life. Keywords: Papillary thyroid carcinoma, Cervical lymphadenopathy, fine-needle aspiration cytology, Total thyroidectomy, lymph node dissection, radioactive iodine therapy.

To determine current patterns of care and disease characteristics for patients with thyroid carcinoma, a Patient Care Evaluation Study was initiated in 1996 in the U.S. and Germany. This project addresses ongoing concerns with respect to the diagnostic evaluation and treatment of patients diagnosed with thyroid carcinoma and raises questions concerning how physicians are interpreting current standards and acting on the basis of these recommendations. Patients with primary thyroid carcinoma were entered into a prospective multicenter observational study with free choice of treatment (no control group) between January 1, 1996 and December 31, 1996 in Germany. This resulted in a total of 2537 cases under observation and analysis; 1685 patients had papillary carcinoma (66.4%), 691 had follicular carcinoma (27.2%), 70 had medullary carcinoma (2.8%), and 91 had anaplastic carcinoma (3.6%). The 2376 patients with carcinoma of either papillary or follicular histology were included in the current analysis. The major symptoms reported for patients with papillary and follicular thyroid carcinoma was neck mass (reported in 76% and 79%, respectively) followed by dysphagia (reported in 25% and 27%, respectively), stridor (reported in 9% and 14%, respectively), and neck pain (reported in 7% and 8%, respectively). Greater than 50% of the patients with papillary thyroid carcinoma were reported to have American Joint Committee on Cancer/International Union Against Cancer Stage I disease. Between 37-39% of the follicular carcinoma patients had Stage I and Stage II disease. Only slight differences in the diagnostic approach to patients with papillary or follicular carcinoma were noted. The majority of patients underwent an ultrasound of the thyroid region (78.1%), which was suggestive of carcinoma in only 39% of the cases. A thyroid scan was performed on 76.6% of patients, and the results were suggestive of carcinoma in 44.8% of the individuals. In contrast, fine-needle aspiration biopsy of the thyroid is highly recommended in the current Clinical Practice Guidelines (CPG) but results were obtained in only 27.4% of the patients. Total thyroidectomy without lymph node dissection was the most commonly used surgical procedure in the treatment of patients with papillary and follicular thyroid carcinoma. Only approximately 2% of patients at low risk in the group with Stage I disease were treated with a lobectomy. In 80% of the patients with Stage I papillary thyroid carcinoma and approximately 90% of those patients diagnosed with Stage II, III, and IV disease treating physicians chose to utilize radioiodine as adjuvant treatment after disease-directed surgery. External beam radiation was added to the treatment regimen for many patients diagnosed with Stage III and IV disease (30% in patients with papillary thyroid carcinoma and 33% in patients with follicular thyroid carcinoma). To the authors' knowledge no single effective diagnostic test for thyroid carcinoma currently is available and in the majority of cases a combination of ultrasound, thyroid scan, or fine-needle aspiration biopsy together with the clinical findings (e.g., thyroid mass) led to a diagnosis of carcinoma. The authors suspect that the high prevalence of concomitant pathologic findings such as goiter, even in the healthy population in Germany, reduces the accuracy of all diagnostic test methods and may account for the frequent use of imaging techniques. The majority of patients underwent a total or near-total thyroidectomy. Total thyroidectomy with radical lymph node dissection was used very frequently in those patients with papillary thyroid carcinoma (22%). German physicians tend to surgically treat early stage thyroid carcinoma somewhat more radically than recommended in the CPG. With respect to other treatment options employed as part of the first course of treatment, radioiodine appears to play the most important role. [See commentary o

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

To determine the frequency of tuberculous cervical lymphadenopathy mimicking metastasis from papillary thyroid cancer. Case series. Surgical Unit-I, Ward-3 of Jinnah Postgraduate Medical Centre, Karachi, from March 2005 to March 2010. All patients above 12 years of age of either gender diagnosed on investigations as papillary thyroid cancer (PTC) were included in the study. Ultrasound and fine needle aspiration cytology (FNAC), neck of solitary thyroid nodules (STN) and cervical lymph nodes were done. Total thyroidectomy and excision biopsy of cervical lymph nodes was performed, histopathological results were recorded and patients were managed accordingly. A total of 55 patients had PTC and 25 had cervical lymphadenopathy. Eighteen patients of PTC with cervical lymphadenopathy were diagnosed after investigations as cases of tuberculous cervical lymphadenopathy (TCL) initially considered as metastasis from PTC; 5 patients had metastasis from PTC. Two patients proved to be of reactive hyperplasia which initially showed tuberculous cervical lymphadenopathy on FNAC. So 80% patients of cervical lymphadenopathy with PTC were due to benign disease and 20% had metastasis in lymph node due to PTC. PTC with cervical lymphadenopathy due to co-existent tuberculosis is common. Metastasis from PTC in lymph nodes were less common than tuberculous lymphodenitis in this study. Tuberculosis should be considered before deciding for neck dissection in cases of PTC.

Molecular Rearrangements and Morphology in Thyroid Cancer

Iodine or Not (IoN) for Low-risk Differentiated Thyroid Cancer: The Next UK National Cancer Research Network Randomised Trial following HiLo

We here report on two cases of suspicious cytological findings upon ultrasound (US)-guided fine-needle aspiration (US-FNA) in patients with subacute thyroiditis (SAT). A 46-year-old woman who underwent US-FNA for a suspicious thyroid nodule in the right lobe at a local clinic was referred to our hospital for surgical treatment. Based on the cytology results, total thyroidectomy was performed. The histopathology findings confirmed the presence of SAT in the right lobe and absence of thyroid malignancy. A 40-year-old woman with a thyroid nodule in the left lobe with suspicious cytological findings upon US-FNA was referred to our hospital for surgical treatment. However, neck US revealed typical sonographic findings of SAT. On follow-up US 3 months later, near complete disappearance of the typical sonographic findings of SAT was observed, while a hypoechoic solid thyroid nodule in the left upper lobe was clearly visualized. Accordingly, US-FNA was performed for the hypoechoic thyroid nodule. Papillary thyroid carcinoma was suspected on the basis of the cytology findings; histopathologically, SAT was confirmed in both thyroid lobes and a papillary thyroid carcinoma was confirmed in the left lobe.

AIUM-ACR-SPR-SRU Practice Parameter for the Performance and Interpretation of a Diagnostic Ultrasound Examination of the Extracranial Head and Neck.

Disclosure: M. Ahmad: None. A.P. Calimag: None. B. Arshad: None. J.T. Chaiban: None. Introduction: Thyroglobulin (Tg) is standard practice for follow-up of differentiated thyroid cancer (TC). Due to existence of thyroglobulin antibodies (Tg Ab) and Heterophile antibodies, Tg immunometric assays may be subject to interference. We present 2 challenging cases of TC with elevated Tg with absence of structural disease. Both tested positive for Epstein-Barr virus antibodies to viral capsid antigen (EBV anti VCA ab). DESCRIPTION: Case 1: 70 y.o Pt found to have calcified thyroid nodule on CT cervical spine. Thyroid ultrasound (U/S) revealed a left thyroid nodule- FNA being papillary thyroid cancer (PTC) with Bethesda 6. She had total thyroidectomy and central left lateral neck dissection. Pathology revealed PTC with 3/14 l.nodes +ve for cancer. Her Tg was 40.5 (1.2 - 35.0 ng/mL) 6 days after surgery, she received 100 mCi of radioactive Iodine (RAI). Subsequent WBS showed uptake in thyroid bed only. On follow ups, Tg started to rise persistently. PET CT unremarkable and her commensurate unstimulated Tg was 12. PET CT with interval development of a hypermetabolic focus in the postsurgical bed of thyroid and hypermetabolic cervical l.nodes. She received 100 mCi RAI + WBS that was negative for recurrence. Her Tg transiently improved but then was persistently elevated in the range 8.1-11.6 ng/ml on multiple checks. Repeat thyroid U/S did not show residual disease. Her Tg antibodies (Tg Ab) as well as Heterophile Antibody and HAMA were negative. Tg by LC-MS, was elevated in the range of 7.5 to 10.8 ng/ml. EBV anti VCA ab, IgG were positive. Case 2: 76 y.o lady initially diagnosed with toxic compressive goiter, found to have follicular thyroid cancer (FTC) after total thyroidectomy: a 5.5 cm FTC with minimal capsular/lymphatic invasion, no extrathyroidal extension, and negative margins. She received 103.7 mCi RAI after surgery. Subsequent WBS showed uptake only in the thyroid bed. Postoperatively Tg levels decreased to the range 1.6 to 5.1 ng/ml. Follow-up WBS a year later was unremarkable, and the Tg started to rise. CT scan of the chest and neck were negative. Tg by LC-MS was elevated in the range 1.6-9.2 ng/ml. PET CT was negative. Tg Ab as well as Heterophile Antibody and HAMA were negative. She tested positive for EBV anti VCA ab, IgG as well. Conclusion: Both case were elderly females- almost similar age, one with PTC and one with FTC- that had excellent structural response, but incomplete biochemical response. Measurement of Tg by LC-MS is recognized as an accurate method for Tg quantification. LC-MS assays are based on peptide quantitation after tryptic digestion which itself can have limitations due to existence of abnormal polymorphic tumor thyroglobulin (for which not much literature is available). The elevated Tg could be related to assay interference from EBV anti VCA ab (a cause or coincidence!?) or a possibility of persistent microscopic disease, hence longitudinal follow up of patients is important. Presentation: 6/2/2024

Background: ATA guidelines recommend evaluation of hyperthyroidism with radioiodine scan and consideration of FNA for non-toxic nodules with suspicious sonographic features. However, there is no standard evidence-based approach to performing ultrasound in patients with toxic nodules. Recent studies have shown increased rates of thyroid cancer in patients with hyperthyroidism and has been shown to demonstrate aggressive histologic features. Clinical Case: A 41-year-old female presented to primary care provider for annual physical exam, found to have intermittent bigeminy and enlarged thyroid on exam. EKG notable for multiple premature ventricular complexes. Evaluation revealed suppressed TSH <0.01 µIU/mL (0.27-4.20), normal free T4 1.27 ng/dL (0.80-1.80), slightly elevated free T3 4.84 pg/mL (2.57-4.43) and elevated TSI 238% (<122). Methimazole was started for treatment of hyperthyroidism. Thyroid sonogram was ordered for abnormal exam, that showed 2.7 cm TIRADS 4 left thyroid nodule with microcalcifications. I-131 uptake values were 20% and 49% at 4-hours and 24-hours, respectively. Technetium-99M scan showed toxic autonomous nodule in the left thyroid lobe corresponding to the one seen on sonogram. The remainder of the thyroid gland showed heterogeneously suppressed uptake. FNA of the thyroid nodule was done due to the presence of microcalcifications and the cytopathology was suspicious for papillary carcinoma. She underwent total thyroidectomy with central neck dissection involving pre-tracheal and paratracheal lymph nodes (level VI). Pathology showed 1.4 cm papillary carcinoma with lymphovascular space invasion and multifocal papillary microcarcinomas in the left thyroid lobe, 0.2 cm papillary microcarcinoma in right thyroid lobe, metastatic papillary carcinoma in 2 out of 5 lymph nodes, largest metastatic deposit 0.1 cm in the largest dimension with no extra nodal extension. There was also follicular hyperplasia noted consistent with Graves’ disease. Post-operatively, she had thyrogen-stimulated adjuvant RAI treatment, dose 107.4 mCi. Post therapy scan did not show evidence of distant metastases. Conclusion: This case demonstrates the identification of a metastatic papillary thyroid carcinoma based on suspicious ultrasound features requiring total thyroidectomy, central neck dissection and adjunct radioactive iodine in a patient with hyperthyroidism from co-existent toxic thyroid nodule and Graves’ disease.

Introduction: Differentiated thyroid cancers such as papillary and follicular thyroid cancer make up more than 90% of all thyroid cancers. The presence of thyroglobulin autoantibodies makes interpretation of the thyroglobulin level unreliable, as it could be falsely low or falsely high. Studies have shown that rising thyroglobulin antibody levels, could be used to monitor for disease recurrence in patients with negative thyroglobulin and imaging studies. However, there are challenges in detecting recurrence in patients with normal thyroglobulin level and thyroid imaging studies, who are on lifelong immunoglobulin therapy and who have increasing thyroglobulin antibody levels.Clinical case: A 63 yr old female was found to have an incidental left thyroid nodule at age 48yrs from a carotid ultrasound. She underwent US guided FNA of the thyroid nodule and was found to have papillary thyroid cancer. She had total thyroidectomy a month later, with removal of a 1.4cm primary, with no evidence of extrathyroidal extension, clear margins and no evidence of lymphovascular invasion – Stage T1bN0M0. There was left level 6 neck dissection with no carcinoma identified in the 2 lymph nodes removed. She received 105.3 mCi radioactive iodine (RAI) and whole body thyroid scan done 7 days later revealed, increased uptake involving the thyroid bed likely residual thyroid tissue. Activity was noted inferolateral to the right thyroid bed which most likely represents a lymph node. There was no evidence of distant metastasis.She was commenced on levothyroxine post operatively. Her other past medical history is significant for idiopathic urticaria and angioedema, immune deficiency disorder with low IgG and IgM and asthma. She was commenced on monthly IV immunoglobulins 5yrs post RAI therapy, due to recurrent sinusitis, rhinitis and chronic diarrhea. She was later transitioned to weekly SQ immune globulin – Hizentra which she is on till date.Over the past 15 years, serial neck ultrasounds post radioiodine ablation have been negative for recurrence. Her TSH ranged 14.91 to 0.04 (ref 0.27-4.2 uiu/ml) and thyroglobulin (Tg) titer remains <0.1 (ref <0.1). Her thyroglobulin antibody titers have trended up from <0.2 (ref <2.0) 5yrs post RAI therapy to 49 (ref <4 iu/ml)) on her most recent test this year. She is currently undergoing further work up to rule out recurrence of her cancer. In our review of the literature we found one report that showed use of Liquid Chromatography–Mass Spectrometry (LC-MS) was able to differentiate thyroid cancer recurrence in an individual with positive antithyroglobulin antibody receiving immunoglobulin therapy.Conclusion: In patients with negative Tg levels, but elevated thyroglobulin antibody while receiving immune globulin therapy, thyroglobulin antibody levels may not be a reliable indicator of thyroid cancer recurrence. Measurement of Tg levels using a LC-MS may provide some clarity.

Introduction Papillary thyroid carcinomas are one of the most common endocrine neoplasms. It is well known for its low malignant potential. Papillary carcinomas mostly metastases to lymph nodes of level six. Recent advances in the pathology that is with proper ultra sound guided FNAC, early diagnosis can be made. Here we are presenting a patient with a huge neck mass that presented to our medical college hospital and how we managed the same. Case Blog 53 years old male patient, presented to a tertiary hospital with complaints of swelling in front of neck for the past 7 years. The patient was having a progressive swelling, it started as a small pea shaped swelling and it slowly progressed and has reached the present size (Figure 1). The patient was having no difficulty in respiration. CT scan of the neck region with chest was taken as the lower extent was not palpable and the FNAC of the swelling was taken. FNAC revealed papillary thyroid carcinoma. CT scan showed a huge soft tissue mass over left supra clavicular region with solid and cystic attenuation extending to the superior aspect of the thoracic inlet. The mass was shifting trachea to the right side (Figure 2). There were no palpable neck nodes. The patient was planned for surgical exploration of the tumour with sternotomy as the tumour was extending in to the thoracic inlet. A total thyroidectomy with central compartment neck dissection was done. The mass was proved to be papillary thyroid carcinoma of intra cystic variant. Discussion Papillary thyroid carcinoma is the most common thyroid cancer. Papillary thyroid cancer also has an excellent prognosis. Total thyroidectomy is done once histo pathological diagnosis is established [1]. This patient to begin with presented with a small pea shaped swelling on front of left side of neck and it started slowly progressing in size. Once the size of the tumour is more than 10 mm, total thyroidectomy is indicated. These papillary carcinomas mostly metastases to central neck nodes [2]. Hence for a better outcome it is always mandatory to go for central neck node dissection for proven cases of lymphatic spread. Biochemical analysis of free T4 and TSH is necessary before surgery. This patient was euthyroid before surgery was planned. Surgery of total thyroidectomy and neck dissection of central compartment was done [3]. Recurrent laryngeal nerve was identified during the procedure. Parathyroid glads were identified and preserved on the right side. The patient was kept on regular followup. Histopathological diagnosis confirmed it to be a papillary thyroid carcinoma. Conclusion Total thyroidectomy with central compartment dissection appears to be adequate treatment even for masses that are extending upto supra clavicle also with extension to thoracic inlet. CT scan plays a very important role in pre-operative planning for huge neck mass. Preservation of recurrent laryngeal nerve and parathyroid glands are very important in this surgery. Though it is controversial in the absence of neck node one should go for central node dissection, from our institutional experience, it is always safer to go for central node dissection, so that recurrence of the tumour can be avoided.