Diagnosis and Reporting of Follicular-Patterned Thyroid Lesions by Fine Needle Aspiration

Over the past 3 decades, fine needle aspiration (FNA) has developed as the most accurate and cost-effective initial method for guiding the clinical management of patients with thyroid nodules. Thyroid FNA specimens containing follicular-patterned lesions are the most commonly encountered and include various forms of benign thyroid nodules, follicular carcinomas, and the follicular variant of papillary thyroid carcinoma. Based primarily upon the cytoarchitectural pattern, FNA is used as a screening test for follicular-patterned lesions to identify the majority of patients with benign nodules who can be managed without surgical intervention. The terminology and reporting of thyroid FNA results have been problematic due to significant variation between laboratories, but the recent multidisciplinary NCI Thyroid FNA State of the Science Conference has provided a seven-tiered diagnostic solution. A key element of this approach is the category “atypical cells of undetermined significance” (ACUS) which is used for those aspirates which cannot be easily classified as benign, suspicious, or malignant. Lesions in this category represent approximately 3–6% of thyroid FNAs and have a risk of malignancy intermediate between the “benign” category and the “suspicious for a follicular neoplasm” category. The recommended follow-up for an ACUS diagnosis is clinical correlation and in most cases, repeat FNA sampling

Renal cell carcinoma metastasizing to solitary fibrous tumor of the pleura: a case report

<p>Abstract</p> <p>Introduction</p> <p>A tumor metastasizing to another malignancy is an uncommon phenomenon. Since it was first described in 1902, there have been fewer than 200 cases reported in the literature, with lung cancer metastasizing to renal cell carcinoma being the most frequently described pattern. Here we report a case of a solitary fibrous tumor of the lung acting as the recipient for a renal cell carcinoma. To our knowledge, this is the first reported case of such a combination and the second case involving a solitary fibrous tumor.</p> <p>Case presentation</p> <p>A 58-year-old Caucasian man who developed a persistent dry cough presented to our hospital. Imaging studies revealed a large pleural-based mass in the left lung. A biopsy of the mass showed a spindle-cell lesion consistent with a solitary fibrous tumor. The patient underwent surgical excision of the 13 cm mass. The pathological examination confirmed the diagnosis of a solitary fibrous tumor but also demonstrated discrete foci of metastatic renal cell carcinoma. Until that point, a primary renal cell carcinoma tissue diagnosis had not been made and the initial radiological work-up was inconclusive.</p> <p>Conclusion</p> <p>Awareness of the unusual phenomenon of tumor-to-tumor metastasis is important for practicing surgical pathologists, particularly in the evaluation of a mass lesion showing bimodal histology. This case also highlights the importance of careful examination of surgical specimens, as minute and unusual findings can direct patient care.</p

Development of a clinical decision model for thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10–18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20–30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70–80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery.</p> <p>Methods</p> <p>Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules.</p> <p>Results</p> <p>Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82–0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%–91%) and 79% (95%CI: 72%–86%), respectively.</p> <p>Conclusion</p> <p>An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials.</p

Update to the College of American Pathologists Reporting on Thyroid Carcinomas

Background The reporting of thyroid carcinomas follows the recommendations of the College of American Pathologists (CAP) protocols and includes papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma. Despite past and recent efforts, there are a number of controversial issues in the classification and diagnosis of thyroid carcinomas (TC) that, potentially impact on therapy and prognosis of patients with TC. Discussion The most updated version of the CAP thyroid cancer protocol incorporates recent changes in histologic classification as well as changes in the staging of thyroid cancers as per the updated American Joint Commission on Cancer staging manual. Among the more contentious issues in the pathology of thyroid carcinoma include the defining criteria for tumor invasiveness. While there are defined criteria for invasion, there is not universal agreement in what constitutes capsular invasion, angioinvasion and extrathyroidal invasion. Irrespective of the discrepant views on invasion, pathologists should report on the presence and extent (focal, widely) of capsular invasion, angioinvasion and extrathyroidal extension. These findings assist clinicians in their assessment of the recurrence risk and potential for metastatic disease. It is beyond the scope of this paper to detail the entire CAP protocol for thyroid carcinomas; rather, this paper addresses some of the more problematic issues confronting pathologists in their assessment and reporting of thyroid carcinomas. Conclusion The new CAP protocol for reporting of thyroid carcinomas is a step toward improving the clinical value of the histopathologic reporting of TC. Large meticulous clinico-pathologic and molecular studies with long term follow up are still needed in order to increase the impact of microscopic examination on the prognosis and management of TC

Inmunohistochemical Profile of Solid Cell Nest of Thyroid Gland

It is widely held that solid cell nests (SCN) of the thyroid are ultimobranchial body remnants. SCNs are composed of main cells and C cells. It has been suggested that main cells might be pluripotent cells contributing to the histogenesis of C cells and follicular cells, as well as to the formation of certain thyroid tumors. The present study sought to analyze the immunohistochemical profile of SCN and to investigate the potential stem cell role of SCN main cells. Tissue sections from ten cases of nodular hyperplasia (non-tumor goiter) with SCNs were retrieved from the files of the Hospital Infanta Luisa (Seville, Spain). Parathormone (PTH), calcitonin (CT), thyroglobulin (TG), thyroid transcription factor (TTF-1), galectin 3 (GAL3), cytokeratin 19 (CK 19), p63, bcl-2, OCT4, and SALL4 expression were evaluated by immunohistochemistry. Patient clinical data were collected, and tissue sections were stained with hematoxylin–eosin for histological examination. Most cells stained negative for PTH, CT, TG, and TTF-1. Some cells staining positive for TTF-1 and CT required discussion. However, bcl-2, p63, GAL3, and CK 19 protein expression was detected in main cells. OCT4 protein expression was detected in only two cases, and SALL4 expression in none. Positive staining for bcl-2 and p63, and negative staining for PTH, CT, and TG in SCN main cells are both consistent with the widely accepted minimalist definition of stem cells, thus supporting the hypothesis that they may play a stem cell role in the thyroid gland, although further research will be required into stem cell markers. Furthermore, p63 and GAL-3 staining provides a much more sensitive means of detecting SCNs than staining for carcinoembryonic antigen, calcitonin, or other markers; this may help to distinguish SCNs from their mimics

Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples

Fine-needle aspiration cytology, which is well established to be accurate for the diagnosis of thyroid cancer, may be inconclusive for the follicular thyroid neoplasms. As galectin-3 was suggested to be a marker of malignant thyrocytes, we investigated whether this protein might be helpful in the diagnosis of aspirates classified as undeterminate by cytology. After establishing an easy processing of aspirates for galectin-3 immunodetection, a series of aspirates categorised as benign (n=63), malignant (n=17) or undeterminate (n=34) was prospectively analysed for galectin-3. Only the patients with malignant or undeterminate lesions underwent surgery. Most lesions (86%) diagnosed as malignant by cytology or after surgery were positive for galectin-3. The majority of lesions (94%) classified as benign by cytology or after surgery was negative for galectin-3. The positive and negative predictive values were 83 and 95%, respectively. When focusing on the undeterminate lesions, the sensitivity and specificity were 75 and 90%, respectively, while the positive and negative predictive values were 82 and 87%, respectively. The specificity and the positive predictive value were higher (100%) when considering the percentage of stained cells. Altogether these results show that galectin-3 constitutes a useful marker in the diagnosis of thyroid lesions classified as undeterminate by conventional cytology

Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC

<p>Abstract</p> <p>Background</p> <p>RET/PTC (rearranged in transformation/papillary thyroid carcinomas) gene rearrangements are the most frequent genetic alterations identified in papillary thyroid carcinoma. Although it has been established that RET/PTC kinase plays a crucial role in intracellular signaling pathways that regulate cellular transformation, growth, and proliferation in thyroid epithelial cells, the upstream signaling that leads to the activation of RET/PTC is largely unknown. Based on the observation of high levels of PLD expression in human papillary thyroid cancer tissues, we investigated whether PLD plays a role in the regulating the RET/PTC-induced STAT3 activation.</p> <p>Methods</p> <p>Cancer tissue samples were obtained from papillary thyroid cancer patients (n = 6). The expression level of PLD was examined using immunohistochemistry and western blotting. Direct interaction between RET/PTC and PLD was analyzed by co-immunoprecipitation assay. PLD activity was assessed by measuring the formation of [³H]phosphatidylbutanol, the product of PLD-mediated transphosphatidylation, in the presence of <it>n</it>-butanol. The transcriptional activity of STAT3 was assessed by m67 luciferase reporter assay.</p> <p>Results</p> <p>In human papillary thyroid cancer, the expression levels of PLD2 protein were higher than those in the corresponding paired normal tissues. PLD and RET/PTC could be co-immunoprecipitated from cells where each protein was over-expressed. In addition, the activation of PLD by pervanadate triggered phosphorylation of tyrosine 705 residue on STAT-3, and its phosphorylation was dramatically higher in TPC-1 cells (from papillary carcinoma) that have an endogenous RET/PTC1 than in ARO cells (from anaplastic carcinoma) without alteration of total STAT-3 expression. Moreover, the RET/PTC-mediated transcriptional activation of STAT-3 was synergistically increased by over-expression of PLD, whereas the PLD activity as a lipid hydrolyzing enzyme was not affected by RET/PTC.</p> <p>Conclusion</p> <p>These findings led us to suggest that the PLD synergistically functions to activate the STAT3 signaling by interacting directly with the thyroid oncogenic kinase RET/PTC.</p