Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up.

Objective: The objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up. Methods: A retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019. Results: In total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively). Conclusions: WDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Clinicopathological features and outcomes after radioactive iodine treatment of oncocytic well-differentiated thyroid carcinomas.

OBJECTIVE: The aim of this study was to compare the clinicopathological features of Hürthle cell carcinomas (HCC) and oncocytic papillary thyroid carcinomas (OPTC) and to evaluate their response to radioactive iodine (RAI) treatment. METHODS: We retrospectively reviewed the charts of patients with histopathologically verified OPTC (group 1) and HCC (group 2), during a 17-year period. All patients underwent total thyroidectomy and received RAI adjuvant therapy. Clinicopathological characteristics of the two groups were compared. Response to initial therapy was assessed 6 to 24 months after RAI ablation according to the American Thyroid Association dynamic risk reclassification. Clinical outcomes were evaluated. RESULTS: A total of 28 patients (8 OPTC and 20 HCC) were included. There was no significant difference in clinicopathological features including sex, age, tumour size and vascular invasion. Distant metastases were absent in both groups. OPTC, however, presented more features of local invasion (50% vs. 10%, P = 0.03), extrathyroidal extension (25% vs. 0%, P = 0.07) and lymph node involvement (37.5% vs. 0%, P = 0.01). Median cumulative RAI activity administered to both groups was 200 mCi (range: 100-300 mCi). Response to RAI therapy was excellent in all HCC and 87.5% of OPTC (P = 0.28). One patient with OPTC (12.5%) presented an indeterminate response. Clinical outcomes were favourable after a median follow-up of 87.5 and 49 months, respectively. CONCLUSION: Although OPTC presented more locoregional invasion, clinicopathological characteristics of OPTC and HCC were comparable. Both OPTC and HCC were iodine responsive. We suggest that adjuvant RAI therapy after total thyroidectomy is beneficial for OPTC and HCC and may improve disease-free survival.

Comparison of clinical characteristics of patients with follicular thyroid carcinoma and Hürthle cell carcinoma. / Comparación de las características clínicas en pacientes con carcinoma folicular de tiroides y carcinoma de células de Hürthle.

INTRODUCTION: Hürthle cell carcinoma (HCC) is an uncommon thyroid cancer historically considered to be a variant of follicular thyroid carcinoma (FTC). The aim of this study was to assess the differences between these groups in terms of clinical factors and prognoses. PATIENTS AND METHODS: A total of 230 patients (153 with FTC and 77 with HCC) with a median follow-up of 13.4 years were studied. The different characteristics were compared using SPSS version 20 statistical software. RESULTS: Patients with HCC were older (57.3±13.8 years vs. 44.6±15.2 years; P<.001). More advanced TNM stages were also seen in patients with HCC and a greater trend to distant metastases were also seen in patients with HCC (7.8% vs. 2.7%, P=.078). The persistence/recurrence rate at the end of follow-up was higher in patients with HCC (13% vs. 3.9%, P=.011). However, in a multivariate analysis, only age (hazard ratio [HR] 1.10, confidence interval [CI] 1.04-1.17; P=.001), size (HR 1.43, CI 1.05-1.94; P=.021), and histological subtype (HR 9.79, CI 2.35-40.81; P=.002), but not presence of HCC, were significantly associated to prognosis. CONCLUSION: HCC is diagnosed in older patients and in more advanced stages as compared to FTC. However, when age, size, and histological subtype are similar, disease-free survival is also similar in both groups.

Favorable Outcome of Hurthle Cell Carcinoma of the Thyroid Treated With Total Thyroidectomy, Radioiodine, and Selective Use of External-Beam Radiotherapy.

OBJECTIVES: There is controversy about the prognosis of Hurthle cell carcinoma of the thyroid. The purpose of this project is to report the outcome of a well-defined group of patients treated at a single institution in the modern era. METHODS: Sixteen patients met the following inclusion criteria: Treatment with curative intent at our institution between January 1, 1997, and December 31, 2010. Primary treatment with total thyroidectomy with or without neck dissection. Age >18 years at the time of thyroidectomy. Confirmation by a pathologist of the diagnosis of a primary Hurthle cell carcinoma of the thyroid based on ≥75% Hurthle cells with extension through the tumor capsule. No areas of poorly differentiated (insular) or undifferentiated (anaplastic) carcinoma. Stage T1-3, NX-1b, M0. All patients received radioiodine immediately after thyroidectomy (remnant ablation, n=14) or as adjuvant for a recurrence (n=2). External-beam radiotherapy to the neck as adjuvant therapy after thyroidectomy was used in 2 patients and after resection of a neck recurrence in 1 patient. RESULTS: Five-year actuarial rates with a median 6 years of follow up on surviving patients were as follows:Overall and cancer-specific survival: 92% (1 death from Hurthle cell carcinoma). Relapse-free survival (no visible tumor and unstimulated thyroglobulin ≤1.0): 65%. CONCLUSIONS: Our experience suggests that the outcome of Hurthle cell carcinoma of the thyroid is favorable in adults with stage T1-3 NX-1b M0 disease who are managed with total thyroidectomy, radioiodine, and-in selected cases-external-beam radiotherapy. We do not have the ability to compare our results to other management strategies.

Estimation of Second Primary Cancer Risk After Treatment with Radioactive Iodine for Differentiated Thyroid Carcinoma.

BACKGROUND: An increase in the incidence of second primary cancers is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work was to adapt the risk-estimation models developed by the Biological Effects of Ionizing Radiation Committee to local epidemiological characteristics in order to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI. Absorbed radiation doses in critical organs were also estimated to determine whether they exceeded the thresholds for deterministic effects. METHODS: A total of 416 DTC patients treated with RAI were retrospectively studied. Four organs were selected for absorbed dose estimation and subsequent calculation of carcinogenic risk: the kidney, stomach, salivary glands, and bone marrow. Absorbed doses were calculated by dose factors (absorbed dose per unit activity administered) previously established and based on standard human models. The lifetime attributable risk (LAR) of incidence of cancer as a function of age, sex, and organ-specific dose was estimated, relating it to the activity of RAI administered in the initial treatment. RESULTS: The salivary glands received the greatest absorbed doses of radiation, followed by the stomach, kidney, and bone marrow. None of these, however, surpassed the threshold for deterministic effects for a single administration of RAI. Younger patients received the same level of absorbed dose in the critical organs as older patients did. The lifetime attributable risk for stomach cancer incidence was by far the highest, followed in descending order by salivary-gland cancer, leukemia, and kidney cancer. CONCLUSION: RAI in a single administration is safe in terms of deterministic effects because even high-administered activities do not result in absorbed doses that exceed the thresholds for significant tissue reactions. The Biological Effects of Ionizing Radiation Committee mathematical models are a practical method of quantifying the risks of a second primary cancer, demonstrating a marked decrease in risk for younger patients with the administration of lower RAI activities and suggesting that only the smallest activities necessary to promote an effective ablation should be administered in low-risk DTC patients.

Radioactive Iodine Treatment Is Associated with Improved Survival for Patients with Hürthle Cell Carcinoma.

BACKGROUND: Hürthle cell carcinoma (HCC) is not typically iodine avid, raising questions regarding postoperative use of radioactive iodine (RAI). The aims of this study were to describe current practice patterns regarding the use of RAI for HCC and to assess its association with survival. METHODS: The National Cancer Data Base 1998-2006 was queried for all patients with HCC who underwent total thyroidectomy. Inclusion was limited to T1 tumors with N1/M1 disease, and T2-4 tumors with any N/M disease. Patients were divided into two treatment groups based on receipt of RAI. Baseline patient characteristics were compared between the two groups. Survival was examined using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 1909 patients were included. Of these, 1162 (60.9%) received RAI, and 747 (39.1%) did not. Patients treated with RAI were younger (57 vs. 61 years for no RAI, p < 0.001), more often had private insurance (61.7% vs. 53.5% for no RAI, p < 0.003), and were more likely to be treated at an academic center (40.0% vs. 33.1% for no RAI, p < 0.001). Five- and 10-year survival rates were improved for patients who received RAI compared with those who did not (88.9 vs. 83.1% and 74.4 vs. 65.0%, respectively, p < 0.001). RAI administration was associated with a 30% reduction in mortality (hazard ratio = 0.703, p = 0.001). CONCLUSION: Present guidelines are inconsistent with regard to indications for using RAI for HCC. This could explain why nearly 40% of HCC patients did not receive RAI. RAI is associated with improved survival, suggesting that it should be advocated for HCC patients with tumors >2 cm and those with nodal and distant metastatic disease.

Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer.

Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time.

Oncocytic carcinoma of the parotid gland.

OBJECTIVES/HYPOTHESIS: The incidence of oncocytic carcinoma of the parotid gland is low, so a systematic evaluation of treatment strategies is lacking. We aimed to describe our experiences in treating this malignancy. STUDY DESIGN: Retrospective study. METHODS: We reviewed the files for 18 patients (14 males) of oncocytic carcinoma of the parotid gland in our institution from 1991 to 2011. Four patients underwent surgery alone, four surgery and postoperative radiotherapy, nine surgery and postoperative brachytherapy, and one radiotherapy alone. Median follow-up was 36 months (range 2-108 months). RESULTS: The 5-year local control rate was 66.9%, overall survival 68.6%, disease progression-free survival 46.2%, and 5-year freedom from distant metastasis 61.0%. Clinical N category, local recurrence, and distant metastasis significantly influenced overall survival. CONCLUSIONS: Conservative parotidectomy is not radical enough to treat oncocytic carcinoma of the parotid gland. Elective neck dissection is recommended for patients with cancer stage T2 to 4. Surgery with postoperative (125) I brachytherapy leads to good local control for patients with advanced disease or with positive or close resection margins.

Parathyroid carcinoma and oxyphil parathyroid adenoma: an uncommon case of misinterpretation in clinical practice.

A 46 year-old male presented with persistently high level of serum parathyroid hormone (PTH), despite successful resection of an oxyphilic cell parathyroid adenoma of the left lower gland. Renal function and serum calcium were normal, leading to vitamin D deficiency being considered. Tc99m-sestamibi parathyroid scintigraphy showed no capitation, but a cervical ultrasound demonstrated an increase in the lower parathyroids. Surgery confirmed that the right gland was normal but the left corresponded to parathyroid carcinoma. The patient developed severe hypocalcemia, with PTH values being consistent with hypoparathyroidism for a few months. However, a progressive increase in calcium and PTH serum levels indicated recurrence of disease. Tc99m-sestamibi scintigraphy demonstrated hyperfixation in topography of the left inferior parathyroid and the patient was subjected to a third and more extensive surgery, with removal of lymph nodes and adjacent thyroid tissue. Serum calcium and PTH remained elevated, requiring loop diuretics and intravenous bisphosphonates to control hypercalcemia. Cervical radiotherapy was implemented as adjuvant therapy. After two months the patient complained of dyspnea, and a CT scan of the chest demonstrated areas of parenchymal condensation, suggestive of actinic pneumonitis. At the 2-year follow-up no major issues were evident.

Optimizing therapy for radioactive iodine-refractory differentiated thyroid cancer: current state of the art and future directions.

The majority of patients with differentiated thyroid cancer are cured with standard primary treatments including surgery, radioactive iodine and TSH suppression. A small proportion of patients who develop radioactive iodine-refractory metastatic disease have few treatment options. Recent discovery of the molecular mechanisms that contribute to thyroid cancer tumorigenesis and its progression have revealed key targets that are currently being evaluated in clinical trials. In the last decade several novel targeted therapies have shown encouraging results and have brought hope to patients with advanced disease. However, identifying the subpopulation of patients who may benefit from systemic therapies remains a challenge as the use of these therapeutic modalities is associated with high toxicity rates and most patients have a long indolent phase where the tumor is stable or slowly progressive and asymptomatic. The objective of this review is to summarize the management of patients with metastatic, radioactive iodine refractory differentiated thyroid cancer.

Spindle cell oncocytoma of the adenohypophysis with marked hypervascularity. Case report.

A 68-year-old male presented with a very rare case of spindle cell oncocytoma (SCO), a recently identified very rare neoplasm of the anterior pituitary, manifesting as panhypopituitarism and visual field defect. The pituitary tumor with suprasellar extension was only partially resected via transsphenoidal surgery because of the tumor consistency and bleeding. Histological diagnosis was consistent with schwannoma. The tumor regrew and angiography revealed hypervascularity, so a transcranial approach was employed for the re-operation which only achieved partial resection because of intraoperative extensive bleeding. The tumor cells showed similar histological and immunohistochemical profiles to the previous specimen, but electron microscopy demonstrated that cytoplasm abundantly filled with mitochondria. The final diagnosis of SCO was established and the patient received postoperative conventional radiation therapy of 50 Gy. Only 15 cases of SCO have been reported, and the diagnosis was mistaken in many cases as schwannoma, oncocytic pituitary adenoma, or craniopharyngioma, and multiple surgeries followed by radiation therapy were required.

The utility of I-123 pretherapy scan in I-131 radioiodine therapy for thyroid cancer.

BACKGROUND: There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. METHODS: We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I-123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. RESULTS: Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). CONCLUSIONS: Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or distant metastases, indicating the requirement for a significantly higher I-131 dose, and unexpected large thyroid remnants, suggesting the need for two-step ablation. We should take advantage of stimulated pretherapy scans and adjust the treatment dosing accordingly.

Poorly differentiated oncocytic thyroid carcinoma--diagnostic implications and outcome.

AIMS: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. METHODS AND RESULTS: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan-Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour-specific survival but no difference for relapse-free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. CONCLUSIONS: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

[Differentiated thyroid cancers]. / I carcinomi tiroidei differenziati.

The Authors, after a review of the topic of thyroid cancer, focus on the epidemiology, aetiology and diagnosis of well-differentiated thyroid cancers. They then describe their own case series and their many years' experience in treating the patients affected by this pathology, which is generally regarded as having low malignancy. Nowadays the Authors consider the treatment of choice the total thyroidectomy with central compartment lymphectomy, eventually associated with metabolic radiotherapy.

Parotid gland oncocytosis: CT findings with histopathologic correlation.

Oncocytic neoplasms result from metabolically altered cells that accumulate abundant mitochondria within their cytoplasm by oncocytic metaplasia. In this report, the CT findings are described and correlated with the histopathologic features of a case of oncocytoma involving the parotid gland that arose in a background of nodular oncocytic hyperplasia. When imaging demonstrates multiple small nodules in the parotid gland with a large, solid, or cystic mass, the diagnosis of oncocytic neoplasia should be considered.

Metastatic Hurthle cell carcinoma and medical certification.

Thyroid carcinoma is the most common malignancy of the endocrine system. Thyroid cancers generally have a favorable prognosis but require ongoing follow-up. Surgery is the treatment of choice. Thyroglobulin can be a useful tumor marker for disease surveillance. Disease impact on safety of flight is the primary aeromedical concern.