BRAF mutation and thyroid cancer recurrence Yarchoan, Mark; LiVolsi, Virginia A; Brose, Marcia S
Journal of clinical oncology,
2015-Jan-01, Letnik:
33, Številka:
1
Journal Article
The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive ...follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing 'Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).' This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.
Formalin-fixed paraffin-embedded (FFPE) material presents a readily available resource in the study of various biomarkers. There has been interest in whether the storage period has significant effect ...on the extracted macromolecules. Thus, in this study, we investigated if the storage period had an effect on the quantity/quality of the extracted nucleic acids and proteins. We systematically examined the quality/quantity of genomic DNA, total RNA, and total protein in the FFPE blocks of malignant tumors of lung, thyroid, and salivary gland that had been stored over several years. We show that there is no significant difference between macromolecules extracted from blocks stored over 11-12 years, 5-7 years, or 1-2 years in comparison to the current year blocks.
The pathology of neoplasia tends to focus on the tumor that requires characterization, grading, and staging. However, nontumorous tissue surrounding the lesion can also provide information, ...particularly about pathogenetic mechanisms. In endocrine tissues, this takes the form of precursor lesions that characterize several genetic predisposition syndromes. In addition, because of the unique functional aspects of endocrine neoplasia, the nontumorous tissue provides evidence of hormone excess, with hyperplasia and/or atrophy and other involutional changes allowing the pathologist to confirm both hormone function by the tumor and the effects of medical therapies. In this article, we review the various clinically relevant features that should be assessed and reported to enhance clinical management of patients with endocrine neoplasms. For example, in thyroid there may be inflammatory thyroiditis or goiter of various etiologies; there may be C-cell hyperplasia either as a preneoplastic lesion in patients with genetic predisposition to medullary thyroid carcinoma or as a reactive phenomenon. Drug-induced changes can be seen in thyroid and adrenal cortex. In neuroendocrine tissues, the nontumorous tissues may show precursor lesions such as endocrine cell hyperplasia/dysplasia; there may be related or unrelated hyperplastic or neoplastic lesions. Some tissues, such as pituitary corticotrophs and adrenal cortex, develop changes that reflect feedback suppression by hormone excess that can serve as biomarkers of tumor functionality and provide enhanced clinicopathologic correlates.
Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional ...thyroid cancer.
To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median range, 13 10-26 years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.
Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and tumors of the pituitary and pancreatic ...islets. The mechanism by which MEN1 acts as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show that menin directly regulates expression of the cyclin-dependent kinase inhibitors p27Kip1and p18Ink4c. Menin activates transcription by means of a mechanism involving recruitment of MLL to the p27Kip1and p18Ink4cpromoters and coding regions. Loss of function of either MLL or menin results in down-regulation of p27Kip1and p18Ink4cexpression and deregulated cell growth. These findings suggest that regulation of cyclin-dependent kinase inhibitor transcription by cooperative interaction between menin and MLL plays a central role in menin's activity as a tumor suppressor.
Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is ...quite broad.
To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology.
A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma).
Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.
The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs ...produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia—changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.
Papillary thyroid microcarcinoma (PTMC) accounts for nearly 50% of newly diagnosed PTC cases. There is considerable debate in literature about the clinicopathologic features and prognostic ...significance of PTMC and whether it should be treated as a separate entity. Due to lack of agreement and supportive data, the consensus study group that established the criteria for non-invasive thyroid neoplasm with papillary-like features (NIFTP) kept its size above 1 cm i.e., excluding PTMC from this new group. As a result, to date, some patients diagnosed with PTMC get aggressive treatments such as partial or total thyroidectomy and even radioactive iodine ablation. We retrospectively studied clinicopathologic features and long-term follow-up of 48 cases of papillary thyroid microcarcinoma. Of these, 7 cases (15%) had capsular invasion, 2 cases (4%) had extrathyroidal extension, 1 case (2%) had lymphovascular invasion, 5 cases (25%) had lymph node metastases, no case (0%) had any distant metastases, and 1 case had recurrence after long-term follow-up (mean 13.7 years, range 1–21 years). Upon slide review, 8 cases fulfilled the criteria for NIFTP and were sub-classified under this new category. These 8 cases had no recurrence after long-term follow-up (mean 12.1 years, range 7–19 years). In this study, we confirmed the previous published reports exhibiting indolent nature of PTMC and also suggested that PTMC cases that fulfill all the criteria for NIFTP can be sub-classified under this term in order to avoid unnecessary aggressive treatment.
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