The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma.

BACKGROUND: Encapsulated angioinvasive follicular thyroid carcinoma (EAFTC) is associated with an increased risk of distant metastasis and reduced survival compared to minimally invasive follicular thyroid carcinoma (MIFTC). There is controversy regarding the extent of surgery and adjuvant radioactive iodine therapy for angioinvasive follicular thyroid carcinoma when stratified by number of foci of angioinvasion. METHODS: All follicular thyroid carcinoma cases from 1990-2018 were identified from a thyroid cancer database. Primary outcomes were distant metastasis-free survival (DMFS) and disease-specific survival (DSS) with factors of interest being age, gender, tumour size, treatment, foci of angioinvasion and histological subtype. RESULTS: A total of 292 cases were identified; 139 MIFTC, 141 EAFTC and 12 widely invasive follicular thyroid carcinoma (WIFTC). Over a follow-up period of 6.25 years, DMFS was significantly reduced (p < 0.001) with 14.2% (EAFTC) and 50% of WIFTC developing metastasis. The risk of metastasis in EAFTC with ≥ 4 foci of angioinvasion was 31.7% (HR = 5.89, p = 0.004), 6.3% for EAFTC with < 4 foci of angioinvasion (HR = 1.74, p = 0.47), compared to 3.6% MIFTC. Age ≥ 50 years (HR = 4.24, p = 0.005) and tumour size (HR = 1.27, p = 0.014) were significantly associated with increased risk of distant metastasis. DSS was reduced significantly (p < 0.001), with 7.8% EAFTC patients dying of disease. For EAFTC patients, DSS was 96.8% for < 4 foci and 82.6% for ≥ 4 foci of angioinvasion (p = 0.003). CONCLUSION: EAFTC is at increased risk of distant metastasis related to the extent of angioinvasion. Tumours with < 4 foci of angioinvasion should be considered for a total thyroidectomy, particularly in older patients.

Outcomes of Papillary Thyroid Microcarcinoma Presenting with Palpable Lateral Lymphadenopathy.

Purpose: Papillary thyroid microcarcinoma (PTMC) is typically indolent in nature, allowing management with active surveillance protocols. Occasionally, a more aggressive phenotype can present and may lead to poor outcomes such as patients presenting with clinically significant lateral lymphadenopathy (cN1b). Prior analysis of the outcomes of this cohort is largely from papillary thyroid cancer (PTC) (>1 cm) or from institutions where use of radioactive iodine (RAI) is limited. Hence, we aim to describe the outcomes of patients with PTMC who presented with palpable cN1b disease, treated with total thyroidectomy and RAI. Methodology: We performed a retrospective cohort study. Outcomes of patients with PTMC who presented with palpable lateral lymph node (LN) metastases (microPTC cN1b) treated between 1997 and 2020 at Royal North Shore Hospital were compared with two control groups' outcomes: patients with clinically detected PTMC without evidence of involved LNs (microPTC cN0) and with larger PTC (>10 mm) who presented with palpable lateral lymphadenopathy (larger PTC cN1b). We assessed clinicopathological variables, postoperative risk stratification, rates of disease recurrence, reoperative surgery, and structural disease-free survival (DFS). Results: In total, 1534 PTMCs were diagnosed following thyroid surgery in the study period; of these, 157 (10%) were clinically detected microPTC cN0 and 26 microPTC cN1b (1.7%). There were 138 patients in the larger PTC cN1b control group. All cN1b patients were treated with total thyroidectomy and adjuvant RAI. Mean size of the largest LN deposit was similar between the microPTC cN1b and larger PTC cN1b groups (23 vs. 27 mm, p = 0.11). Patients with microPTC cN1b were more likely to have biochemical or structural persistence or recurrence compared with microPTC cN0 (19%, 5/26 vs. 3.8%, 6/157, p = 0.002) but less likely than larger PTC cN1b patients (19%, 5/26 vs. 42%, 58/138, p = 0.04). All patients in the microPTC cN1b group who had an excellent response to initial therapy (85%, 22/26) were disease free at last follow-up. The rate of reoperation was similar for the microPTC cN1b and microPTC cN0 groups (4%, 1/26 vs. 2%, 3/157, p = 0.461) and significantly lower than the larger PTC cN1b group (4%, 1/26 vs. 26%, 36/138, p = 0.002). Five-year DFS estimates were significantly better for microPTC cN1b patients than for larger PTC cN1b patients (94% vs. 59%, p = 0.001). Conclusions: MicroPTC cN1b patients treated with thyroidectomy and adjuvant RAI have inferior clinical outcomes compared with microPTC cN0 patients but have better outcomes than their larger PTC cN1b counterparts with respect to disease persistence and recurrence. Response to initial therapy provides valuable prognostication in microPTC cN1b patients: if these patients had an excellent response to initial treatment, they achieved long-term DFS in this series.

Change in Practice of Radioactive Iodine Administration in Differentiated Thyroid Cancer: A Single-Centre Experience.

OBJECTIVE: Our study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade; to analyse key factors associated with clinical decisions in RAI dosing; and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence. METHODS: Retrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively. RESULTS: The median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008-2016 to 2.0 GBq (54 mCi) in 2017-2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008-2011 to 18.5% in 2017-2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi). CONCLUSIONS: Our data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.

Decreasing the dose of radioiodine for remnant ablation does not increase structural recurrence rates in papillary thyroid carcinoma.

BACKGROUND: Our aim was to compare the rate of structural recurrence between patients who had lesser doses of radioactive iodine (RAI) and those who had traditional greater doses for remnant ablation after total thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: A retrospective cohort study of patients who had undergone thyroidectomy and RAI for PTC was undertaken. We divided the cohort into those who had < or =3 GBq (75 mCi) RAI (group A) and those who had >3 GBq (75 mCi) RAI (group B). The primary outcome measure was the rate of structural recurrence. RESULTS: Of 1,171 patients with PTC from 1990 to 2012 who were followed for a mean of 60 months, 970 with T1­T3 tumors underwent RAI in addition to thyroidectomy. The mean first dose of RAI was 2.5 GBq (68 mCi) for group A (n = 153) and 4.7 GBq (127 mCi) for group B (n = 817; P < .001). The overall rate of recurrence was 8%. When corrected for T stage, the recurrence rates were not different for T1 tumors (2% group A versus 4% group B; P = .54) nor for T2 and T3 tumors (P = .36 and .55, respectively). On multivariate analysis, the dose of RAI was not an independent predictor for structural recurrence. CONCLUSION: Decreasing the dose of RAI at initial ablation for patients with pT1­pT3 PTC does not seem to be associated with an increased risk of structural cancer recurrence.

Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis.

BACKGROUND: Primary mucoepidermoid carcinoma (MEC) of the thyroid is a rare clinical and pathological entity that accounts for <0.5% of all thyroid malignancies. Although the histogenesis has been controversial, most investigators now favor it as arising from either metaplasia of thyroid follicular epithelium or heterologous de-differentiation from papillary thyroid carcinoma (PTC). We report three cases of thyroid MEC found in continuity with, and clearly arising from de-differentiation of, well-differentiated thyroid carcinomas (WDTCs). PATIENT FINDINGS AND SUMMARY: The cases presented here included two women (aged 22 and 52) and one man (aged 58). One of these cases arose in conjunction with PTC, one with follicular thyroid carcinoma (FTC), and one with Hurthle cell carcinoma (HCC). In all three cases, there was a gradual transition in morphology between the areas of typical WDTC and the areas showing MEC differentiation. In addition, immunohistochemistry demonstrated a gradual loss of thyroid specific markers (thyroid transcription factor-1, thyroglobulin) mirroring the change in morphology. CONCLUSION: We conclude that thyroid MEC can arise from metaplastic de-differentiation of WDTC, including FTC or HCC in addition to PTC. Currently, we recommend that after excision, each of the WDTC and MEC components of these tumors be treated with targeted adjuvant therapies, which may involve radioactive-iodine ablation, thyrotropin suppression, and external beam radiotherapy.

Post-operative partial hypoparathyroidism: an under-recognized disorder.

BACKGROUND: Permanent hypoparathyroidism is a well-recognized complication of total thyroidectomy, and a commonly reported clinical indicator of that procedure. However, a small number of patients still require ongoing calcium supplementation post-operatively in order to avoid the symptoms of hypocalcaemia, despite a normal serum parathyroid hormone level. The aim of this study was to characterize this disorder of post-operative partial hypoparathyroidism and to identify any risk factors. METHODS: A retrospective study of patients undergoing a total thyroidectomy was performed. Patients with permanent hypoparathyroidism were excluded. Patients completed a telephone interview and had serum calcium and parathyroid hormone (PTH) measured. Patient demographics, operative indications and intervention, the number of parathyroid glands autotransplanted, the presence of ongoing symptoms and calcium requirements were documented. RESULTS: One hundred ninety-six patients participated. The overall rate of permanent hypoparathyroidism over the duration of the study was 0.77%. An additional 10 (5%) patients were identified with a normal PTH level but who were still requiring calcium supplementation to prevent the symptoms associated with hypocalcaemia and to maintain a normal serum calcium level. Nine patients were female with a mean age of 48.5 years. A mean of 1.4 parathyroid glands were autotransplanted and the mean PTH level was 3.95 pmol/L. CONCLUSION: This study demonstrates that in a small group of patients following total thyroidectomy, re-vascularization of parathyroid cells may be partial, with inadequate parathyroid reserve to avoid symptoms despite measurable PTH levels. This disorder of partial hypoparathyroidism has not been previously described and represents a small but important complication of total thyroidectomy.

The role of a more extensive surgical approach in the initial multimodality management of papillary thyroid cancer in children.

PURPOSE: Papillary thyroid cancer (PTC) in children is rare. The optimal initial surgical treatment remains controversial, given the generally favorable overall prognosis but high rate of cervical metastasis and local recurrence. Our objective was to examine the surgical outcomes of a policy of total thyroidectomy and routine selective lymph node dissection (SLND) as the initial surgical approach to children with PTC. METHODS: This is a retrospective cohort study comprising 14 children (age, < or =17 years) with PTC referred for thyroid surgery during the past 15 years. Clinical presentation, the surgical procedure, final pathology, lymph node involvement, complications, and recurrence rates are reported. RESULTS: There were 9 females and 5 males, with an average age of 12.5 years. Seven patients (50%) had clinically apparent cervical lymphadenopathy at the time of surgical referral. All subjects underwent total thyroidectomy, and 12 (86%) had SLND. Of the 12 who underwent SLND, 10 (83%) had nodal metastases. Temporary hypocalcemia was noted in 3 of the patients (21%), and 1 patient has required ongoing intermittent calcium supplementation. All patients are alive and well at follow-up with no clinical, biochemical, or radiological evidence of local recurrence. CONCLUSIONS: Total thyroidectomy with initial SLND is an appropriate surgical approach in children with PTC. It can be done without a significantly increased risk for permanent complications and may reduce the requirement for subsequent surgical intervention for local recurrence in this young population.