Tall cell variant papillary thyroid carcinoma impacts disease-free survival at the 10 % cut-point on multivariate analysis.

INTRODUCTION: The diagnosis of tall cell variant papillary thyroid carcinoma (TCV-PTC) corresponds to the feature of "aggressive histology" within the framework of the American Thyroid Association (ATA) Risk of Recurrence (ROR) guidelines. Using the current World Health Organization (WHO) definition for TCV-PTC (tall cells with height at least twice the width, distribution ≥ 30 %), we examined the impact of this diagnosis on disease-free survival (DFS). METHODS: The study cohort consisted of 347 patients treated for primary papillary thyroid carcinoma (PTC). Current ATA guidelines were followed for the extent of surgery and the administration of adjuvant radioiodine therapy. Clinical surveillance included ultrasound examination and biochemical parameters according to ATA standards. The outcome was measured as time from surgery to first disease recurrence (DR) versus time from surgery until the last documented disease-free encounter (no evidence of disease, NED). Disease-free patients with fewer than 6 months of follow-up were excluded from this cohort. Structural recurrences are documented by histology or cytology whereas biochemical recurrences are documented by rising serum thyroglobulin in the absence of structural disease. All slides on all patients were examined by two pathologists with the substantial interobserver agreement (Kappa = 73 %). The primary tumors are categorically classified either as (1) TCV-PTC (definition above), (2) Papillary thyroid carcinoma with tall cell features (PTC-TCF) (≥ 10 % < 30 % tall cells), or (3) Control (< 10 % tall cells). Tumor size is categorized as either (1) ≤ 10 mm, (2) 11-29 mm, or (3) ≥ 30 mm. Degree of ETE is categorized as either intrathyroidal, microscopic ETE, histologic spread to strap muscles, or pT4 disease. RESULTS: 185 patients are classified as TCV-PTC (≥ 30 % tall cells), 62 as PTC-TCF (≥ 10 % < 30 % tall cells), and 100 as control group (< 10 % tall cells). TCV-PTC is associated with ≥ 30 mm size (p = .0246) and invasion of strap muscles and/or pT4 (p = .0325). There was no relationship between TCV-PTC and aggressive lymph node (ALN) status defined by ATA. Overall follow-up ranged from two months (one patient death) to 203 months (mean 40.8, median 33.0). DR occurred in 61 patients (mean 31.4 months, range 0 -184, 59 structural recurrences, 2 biochemical recurrences). Three models for TCV-PTC were examined: Model 1 - Tall cells ≥ 10% versus control, Model 2 - TCV-PTC versus TCF-PTC versus control, and Model 3 - TCV-PTC versus control. Kaplan Meier curves demonstrated decreased DFS with ALN status (p = .0001), ETE (p = .0295), and TCV-PTC (Model 1, p = .041). On multivariate analysis, TCV-PTC (Model 1) remained significantly predictive when adjusted for ALN (p = .0059). ETE dropped out of the model. CONCLUSION: TCV-PTC is significantly associated with larger tumors and a greater degree of ETE. The diagnosis of TCV-PTC significantly impacts DFS at the 10 % cut-point on multivariate analysis.

The Ethical Implications of the Reclassification of Noninvasive Follicular Variant Papillary Thyroid Carcinoma.

BACKGROUND: Several studies have highlighted the lack of consensus in the diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC). An international multidisciplinary panel to address the controversy was assembled at the annual meeting of the Endocrine Pathology Society in March of 2015, leading to the recent publication reclassifying encapsulated (or noninvasive) FVPTC (EFVPTC) as a benign neoplasm. Does this change in histologic taxonomy warrant a change in clinical practice, and how should it affect those who have been given this diagnosis in the past? We consider the financial and psychological impact of this reclassification and discuss the ethical, legal, and practical issues involved with sharing this information with the patients who are affected. SUMMARY: The total direct and indirect cost of thyroid cancer surveillance in patients is significant. High levels of clinically relevant distress affect up to 43% of patients with papillary thyroid carcinoma, as estimated by the Distress Thermometer developed by the National Comprehensive Cancer Network for detecting distress in cancer patients. Although there are currently no legal opinions that establish a precedent for recontacting patients whose clinical status is altered by a change in nomenclature, the prudent course would be to attend to the requirements of medical ethics. CONCLUSION: Informing patients with a previous diagnosis of EFVPTC that the disease has been reclassified as benign is expected to have a dramatic effect on their surveillance needs and to alleviate the psychological impact of living with a diagnosis of cancer. It is important to re-evaluate the pathologic slides of those patients at risk to ensure that the invasive nature of the tumor is comprehensively evaluated before notifying a patient of a change in diagnosis. The availability of the entire tumor for evaluation of the capsule may prove to be a challenge for a portion of the population at risk. We believe that it is the clinician's professional duty to make a sincere and reasonable effort to convey the information to the affected patients. We also believe that the cost savings with respect to the need for additional surgery, radioactive iodine, and rigorous surveillance associated with a misinterpretation of the biology of the diagnosis of EFVPTC in less experienced hands will likely more than offset the cost incurred in histologic review and patient notification.

Management of recurrent and persistent metastatic lymph nodes in well-differentiated thyroid cancer: a multifactorial decision-making guide for the Thyroid Cancer Care Collaborative.

BACKGROUND: Well-differentiated thyroid cancer (WDTC) recurs in up to 30% of patients. Guidelines from the American Thyroid Association (ATA) and the National Comprehensive Cancer Network (NCCN) provide valuable parameters for the management of recurrent disease, but fail to guide the clinician as to the multitude of factors that should be taken into account. The Thyroid Cancer Care Collaborative (TCCC) is a web-based repository of a patient's clinical information. Ten clinical decision-making modules (CDMMs) process this information and display individualized treatment recommendations. METHODS: We conducted a review of the literature and analysis of the management of patients with recurrent/persistent WDTC. RESULTS: Surgery remains the most common treatment in recurrent/persistent WDTC and can be performed with limited morbidity in experienced hands. However, careful observation may be the recommended course in select patients. Reoperation yields biochemical remission rates between 21% and 66%. There is a reported 1.2% incidence of permanent unexpected nerve paralysis and a 3.5% incidence of permanent hypoparathyroidism. External beam radiotherapy and percutaneous ethanol ablation have been reported as therapeutic alternatives. Radioactive iodine as a primary therapy has been reported previously for metastatic lymph nodes, but is currently advocated by the ATA as an adjuvant to surgery. CONCLUSION: The management of recurrent lymph nodes is a multifactorial decision and is best determined by a multidisciplinary team. The CDMMs allow for easy adoption of contemporary knowledge, making this information accessible to both patient and clinician.

The differential diagnosis of central compartment radioactive iodine uptake after thyroidectomy: anatomic and surgical considerations.

OBJECTIVE: Foci of increased radioactive iodine (RAI) uptake in the thyroid bed following total thyroidectomy (TT) indicate residual thyroid tissue that may be benign or malignant. The use of postoperative RAI therapy in the form of remnant ablation, adjuvant therapy, or therapeutic intervention is often followed by a posttherapy scan. Our objective is to improve the clinician's understanding of the anatomic complexity of this region and to enhance the interpretation of postoperative scans. METHODS: We conducted a comprehensive review of the literature evaluating RAI uptake in the central compartment following thyroid cancer treatment and literature related to anatomic nuances associated with this region. Thirty-eight articles were selected. RESULTS: Through extensive surgical experience and a literature review, we identified the 5 most important anatomic considerations for clinicians to understand in the interpretation of foci of increased RAI uptake in the thyroid bed on a diagnostic scan: 1) residual benign thyroid tissue at the level of the posterior thyroid ligament, 2) residual benign thyroid tissue at the superior portion of the pyramidal lobe and/or superior poles of the lateral thyroid lobes, 3) residual benign thyroid tissue that was left attached to a parathyroid gland in order to preserve its vascularity, 4) ectopic benign thyroid tissue, and 5) malignant thyroid tissue that has metastasized to central compartment nodes or invaded visceral structures. CONCLUSION: By correlating anatomic description, medical illustrations, surgical photos, and scans, we have attempted to clarify the reasons for foci of increased uptake following TT to improve the clinician's understanding of the anatomic complexity of this region.

Paradigm shifts in the management of osteoradionecrosis of the mandible.

Osteoradionecrosis (ORN) of the mandible is a significant complication of radiation therapy for head and neck cancer. In this condition, bone within the radiation field becomes devitalized and exposed through the overlying skin or mucosa, persisting as a non-healing wound for three months or more. In 1926, Ewing first recognized the bone changes associated with radiation therapy and described them as "radiation osteitis". In 1983, Marx proposed the first staging system for ORN that also served as a treatment protocol. This protocol advocated that patients whose disease progressed following conservative therapy (hyperbaric oxygen (HBO), local wound care, debridement) were advanced to a radical resection with a staged reconstruction utilizing a non-vascularized bone graft. Since the introduction of Marx's protocol, there have been advances in surgical techniques (i.e. microvascular surgery), as well as in imaging techniques, which have significantly impacted on the diagnosis and management of ORN. High resolution CT scans and orthopantamograms have become a key component in evaluating and staging ORN, prior to formulating a treatment plan. Patients can now be stratified based on imaging and clinical findings, and treatment can be determined based on the stage of disease, rather than determining the stage of disease based on a patient's response to a standardized treatment protocol. Reconstructions are now routinely performed immediately after resection of the diseased tissue rather than in a staged fashion. Furthermore, the transfer of well-vascularized hard and soft tissue using microvascular surgery have brought the utility of HBO treatment in advanced ORN into question.

The role of intraoperative rapid parathyroid hormone monitoring for predicting thyroidectomy-related hypocalcemia.

OBJECTIVE: To determine if the intraoperative rapid parathyroid hormone (PTH) assay can be used to accurately predict postoperative calcium levels following total or completion thyroidectomy. DESIGN: A prospective study. SETTING: Tertiary care referral center. PATIENTS: One hundred four patients following a total or completion thyroidectomy.Intervention Intraoperative rapid plasma PTH levels were determined for patients undergoing a total or completion thyroidectomy. MAIN OUTCOME MEASURES: Parathyroid hormone levels were recorded after the induction of anesthesia, before excision, and 5, 10, and 20 minutes after thyroidectomy. Postoperative calcium levels were monitored every 6 hours until hospital discharge. Intraoperative PTH levels were correlated with postoperative calcium levels and clinical symptoms of hypocalcemia. RESULTS: Twenty-two patients (21.2%) required short-term postoperative calcium supplementation, and 2 (1.9%) required long-term calcium replacement. There was a statistically significant difference between those patients requiring calcium replacement and those who did not require calcium supplementation, for postoperative total calcium level (7.2 vs 8.1 mg/dL [1.8 vs 2.0 mmol/L]; P<.001) and ionized calcium level (3.76 vs 4.36 mg/dL [0.94 vs 1.09 mmol/L]; P<.001). In addition, the PTH changes from baseline demonstrated statistically significant differences at 5, 10, and 20 minutes after the excision between the 2 groups (P<.005). In those patients requiring calcium supplementation, 14 (64%) of 22 demonstrated a change in PTH level at 20 minutes of greater than 75% from baseline, and in those patients who did not require postoperative calcium supplementation, 61 (74%) of 82 demonstrated a change in PTH level of less than 75% from baseline (P<.005). CONCLUSION: Intraoperative PTH monitoring may be a useful tool in identifying patients who will not require postoperative calcium supplementation following total or completion thyroidectomy.