Electron Kebebew

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial.

American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer

BACKGROUND Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multidisciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC. METHODS Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop. RESULTS The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations. CONCLUSIONS These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.

Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors.

Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment outcomes in patients with ATC reported in the National Cancer Institutes Surveillance, Epidemiology, and End Results data base.

Somatic HIF2A Gain-of-Function Mutations in Paraganglioma with Polycythemia

Hypoxia-inducible factors are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. When these proteins are dysregulated, they contribute to tumorigenesis and cancer progression. However, mutations in genes encoding α subunits of hypoxia-inducible factors (HIF-α) have not previously been identified in any cancer. Here we report two novel somatic gain-of-function mutations in the gene encoding hypoxia-inducible factor 2α (HIF2A) in two patients, one presenting with paraganglioma and the other with paraganglioma and somatostatinoma, both of whom had polycythemia. The two mutations were associated with increased HIF-2α activity and increased protein half-life.

A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology

BACKGROUND Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed. METHODS Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies. RESULTS FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%). CONCLUSIONS Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.

Differentiated Thyroid Cancer: “Complete” Rational Approach

Controversy continues regarding the optimal management of patients with differentiated thyroid cancer because no prospective randomized studies evaluating the merits of (1) extent of thyroidectomy, (2) postoperative radioactive iodine ablation, or (3) thyroid-stimulating hormone (TSH) suppressive therapy exist. Patients with low risk differentiated thyroid cancer enjoy a relatively good prognosis with a mortality rate of about 2% to 5% and a recurrence rate of about 20%. Despite the excellent prognosis in patients considered to be at low risk, total or near-total thyroidectomy in patients with differentiated thyroid cancer has the advantages that: (1) postoperative radioactive iodine can be used to detect and treat residual normal thyroid tissue and local or distant metastases; (2) follow-up serum thyroglobulin levels are a more sensitive marker of persistent or recurrent disease when all thyroid tissue has been removed; and (3) total or near-total thyroidectomy with postoperative 131I ablation and TSH suppressive therapy is associated with better survival and lower recurrence rates. Patients with occult papillary thyroid cancer and minimally invasive follicular thyroid cancer can be treated by thyroid lobectomy because they have a near-normal life expectancy. Virtually all other patients with differentiated thyroid cancer appear to benefit from more extensive initial treatment.

Coexisting Chronic Lymphocytic Thyroiditis and Papillary Thyroid Cancer Revisited

Abstract. The effect of chronic lymphocytic thyroiditis (CLT) on the behavior of papillary thyroid cancer (PTC) remains unclear. In recent studies the presence of CLT in patients with PTC was reported to be associated with a lower recurrence rate and an improved survival rate. Furthermore, patients with PTC and tumor infiltrating lymphocytes (TILs) have been reported to have lower recurrence rates and a lower frequency of distant metastases. Because of these and other observations, a tumor immune response in PTC has been suggested. The aim of our study was to determine: (1) the relative frequency of CLT in PTC; (2) the prognostic significance of CLT in patients with PTC; and (3) if TIL occurs independently or in association with CLT. A 10-year retrospective study of patients who underwent initial thyroidectomy for PTC from 1986 to 1996 was completed. The extent of thyroid lymphocytic infiltration was determined within the tumor, surrounding the tumor, and in the distant parenchyma by two independent observers blinded to the clinical data. Dense focal/diffuse lymphoid aggregates throughout the thyroid gland were diagnostic of CLT and when present within or surrounding the tumor were designated TILs. A total of 136 patients with PTC (typical and follicular variant of PTC histologic subtypes) were identified with a mean follow-up of 4.4 years and a 8% mortality rate at 10 years. Thirty percent of the patients with PTC had coexisting CLT, and 65% of these patients with CLT had positive anti-thyroglobulin antibodies. Patients with coexisting CLT and PTC were younger (p < 0.05), more likely to be female (p < 0.05), and more likely to have multicentric tumors (p < 0.001) compared to patients without CLT. Only 5% of patients had TILs without CLT, but 82.5% of patients with CLT had TILs identified (p < 0.0001). By univariate analysis CLT, age, gender, stage of PTC, tumor multicentricity, and tumor size were significant prognostic factors. Only age and TNM stage of PTC remained independent prognostic factors by multivariate analysis. We found a similar frequency (30%) of coexisting CLT and PTC as reported by others; but, more importantly, the presence of TILs primarily occurred in association with CLT. The presence of CLT in patients with PTC correlated with an improved prognosis. It was not an independent prognostic factor, however, and was not associated with a lower recurrence rate or a lower frequency of distant metastasis.

Accuracy of preoperative localization studies and intraoperative parathyroid hormone assay in patients with primary hyperparathyroidism and double adenoma

BACKGROUND The purpose of this retrospective investigation was to evaluate the results of preoperative localization studies and intraoperative parathyroid hormone (IOPTH) assay in patients with primary hyperparathyroidism and double adenomas. STUDY DESIGN Twenty-one of 287 consecutive patients with primary hyperparathyroidism who had double adenomas identified during first-time parathyroid exploration between July 1999 and September 2002 were analyzed. Individual and combined accuracy of preoperative localization studies, and IOPTH assay and their influence on surgical strategy, were compared. RESULTS Seven percent of these 287 patients had double adenomas. Fifteen of the patients were female and six were male with a mean age of 59 years (range 17 to 76 years). The accuracy of ultrasonography (US) and technetium 99m sestamibi ((99m)TC-sestamibi) was 40% and 30%, respectively, in this select group. Combined accuracy of both tests reached 60% and guided the surgeon to select a bilateral approach. After removal of the first gland, IOPTH failed to decrease by 50% relative to the highest baseline value in 43% of the cases, indicating other hyperfunctioning parathyroid glands. These results prompted the surgeon to explore further after an initially planned focused approach. When the combination of three tests was analyzed, at least one test accurately suggested a double adenoma in 80% of the patients; in 15% of the patients, no test was suggestive of a double adenoma and in 5% the sestamibi scan was false positive. CONCLUSIONS This retrospective investigation documents that neither preoperative localization tests nor IOPTH assay accurately document double adenomas in patients with primary hyperparathyroidism. The combined accuracy of US, sestamibi, and IOPTH assay predicted a double adenoma in 80% of the patients.

MicroRNA profiling of adrenocortical tumors reveals miR‐483 as a marker of malignancy

The authors are interested in identifying molecular markers that can aid in the diagnosis of adrenocortical carcinoma (ACC). The aim of this study was to identify microRNAs (miRNAs or miRs) that are differentially expressed in malignant adrenocortical tumors as compared with benign tumors and assess their potential as diagnostic predictors.

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.