Ten percent tall cells confer the aggressive features of the tall cell variant of papillary thyroid carcinoma.

BACKGROUND: The tall cell (TC) variant of papillary thyroid carcinoma (PTC) is more aggressive than classic PTC, but the percentage of TC necessary to diagnose this variant has been debated. We aimed to better determine what percentage of TC correlates with a more aggressive phenotype. METHODS: Cases from 2005 to 2010 that were the TC variant of PTC or PTC with TC features were identified and compared with classic PTCs. All cases were reviewed to determine what percent, if any, of the tumors consisted of TC. RESULTS: One hundred forty-one cases of PTC were reviewed. Eighty-three cases had some TC component, and 58 cases had none. There were no differences in patient demographics. Tumors with ≥10% TC had more extrathyroidal extension, angiolymphatic invasion, positive surgical margin, and lymph node involvement than classic PTC. There were more recurrences in patients with ≥10% TC, but this was not significant. Similar findings were also observed with increasing percentages of TC. CONCLUSION: The aggressive features conferred by the presence of TC in PTCs occur with as little as 10% TC and are maintained with increasing percentages. Therefore, TC in a PTC should be reported if they comprise at least 10% of the tumor.

Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules: a prospective case series of 960 patients.

BACKGROUND: Preoperative B-type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules. METHODS: Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined. RESULTS: A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P = .030), pseudoinclusions (P < .001), and oval nuclei (P = .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively. CONCLUSIONS: Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules.

Infertility and pregnancy loss in euthyroid women with thyroid autoimmunity.

Thyroid autoimmunity is the most prevalent autoimmune state that affects up to 5-20% of women during the age of fertility. Prevalence of thyroid autoimmunity is significantly higher among infertile women, especially when the cause of infertility is endometriosis or polycystic ovary syndrome. Presence of thyroid autoimmunity does not interfere with normal embryo implantation and have been observed comparable pregnancy rates after assisted reproduction techniques in patients with or without thyroid autoimmunity. Instead, the risk of early miscarriage is substantially raised with the presence of thyroid autoimmunity, even if there was a condition of euthyroidism before pregnancy. Furthermore the controlled ovarian hyperstimulation, used as preparation for assisted reproduction techniques, can severely impair thyroid function increasing circulating estrogen levels. Systematic screening for thyroid disorders in women with a female cause of infertility is controversial but might be important to detect thyroid autoimmunity before to use assisted reproduction techniques and to follow-up these parameters in these patients after controlled ovarian hyperstimulation and during pregnancy.

Female infertility related to thyroid autoimmunity: the ovarian follicle hypothesis.

PROBLEM: The aim of this study was to verify whether anti-thyroid antibodies are present in the follicular milieu of euthyroid infertile women with thyroid autoimmunity undergoing in vitro fertilization (IVF) and whether IVF outcome is different in affected women with respect to negative controls. A secondary endpoint was to check whether there are changes in thyroid hormone levels during the IVF cycle. METHOD OF STUDY: Anti-thyroglobulin and anti-thyroperoxidase levels were measured in both follicular fluid and serum on the day of oocyte retrieval in women with thyroid autoimmunity. Serum TSH, FT3, and FT4 levels were measured in all patients before treatment initiation, on the day of oocyte retrieval and of pregnancy test. IVF outcome parameters were recorded in all women. RESULTS: Oocyte fertilization, grade A embryos, and pregnancy rates were lower in women with thyroid autoimmunity than in negative controls, while early miscarriage rate was higher. Anti-thyroid antibodies were measurable in follicular fluid in all affected women and were strongly correlated with serum levels. No significant changes in thyroid hormone levels were recorded in any women. CONCLUSION: The presence of anti-thyroid antibodies in ovarian follicles, as demonstrated for the first time in this study, may play a critical role in female infertility related to thyroid autoimmunity.

Chromosomal abnormalities in women with premature ovarian failure.

Premature ovarian failure is a complex disorder that results in the early loss of ovarian function; however this disease must be separated from early menopause because these patients can sporadically ovulate and in literature are described pregnancies. The aetiology and the patho-physiology of premature ovarian failure are still matter of debate, but is commonly accepted that genetic factors play an important role. This review is aimed to present an overview of known inherited factor implied in the pathogenesis of this disorder to help physician in the counselling of affected pregnant women.