The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine-needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The two-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding diagnostic terminology/classification scheme for thyroid FNA interpretation and cytomorphologic criteria for the diagnosis of various benign and malignant thyroid lesions. (http://thyroidfna.cancer.gov/pages/info/agenda/).

Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.

On October 22 and 23, 2007, the National Cancer Institute (NCI) hosted "The NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference," a two-day gathering in Bethesda, Maryland. Its mission was to establish a comprehensive interdisciplinary informational dialogue dedicated to thyroid FNA. Preparations for the conference began 18 months earlier with the designation of a steering committee, the appointment of nine working committees, coordination with co-sponsoring organizations, and the establishment of a dedicated permanent web site. The function of the website was to serve as a permanent educational tool for health care practitioners and patients alike, as well as to foster on-line dialogue.

Six committees were charged with preparing summary documents based on literature reviews on the following subjects: 1. Indications/Pre-FNA requirements; 2. Training and Credentialing; 3. Technique; 4. Terminology and Morphologic Criteria; 5. Ancillary Studies; and 6. Post-FNA Options for Testing and Treatment. Three additional committees were formed, one each to oversee the website, publications ensuing from the conference and the establishment of an on-line educational cytopathology atlas.

Literature reviews were limited to English language publications dating back to 1995, using PubMed as the search engine, with key words determined by the committee members. The first draft of the committees' summary documents ("Review and Conclusions") was posted on the web site and open for on-line forum discussion from May 1-June 30, 2007. There were several subsequent drafts and on-line discussion periods (Aug 15 – Sept. 30, 2007 and Nov. 30-Dec. 15, 2007). The documents underwent revision after each comment period prior to re-posting on the web. The two-day "live" conference in October, attended by 154 registrants, comprised of pathologists, endocrinologists, surgeons, and radiologists, gave the committees an in-depth opportunity to present their conclusions and debate controversial areas.

This is an abridged version of the topics reviewed at the conference and the website. This is not a "standards of practice" guideline, nor is it endorsed as such by the National Cancer Institute.

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The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation

The differential diagnosis of a follicular lesion/neoplasm in thyroid FNA specimens includes hyperplastic/adenomatoid nodule, follicular adenoma and carcinoma, and follicular variant of papillary thyroid carcinoma. In our laboratory we separate follicular lesions of thyroid into hyperplastic/adenomatoid nodule (HN), follicular neoplasm (FON) and follicular derived neoplasm with focal nuclear features suspicious for papillary thyroid carcinoma (FDN). This study reports our experience with 339 cases diagnosed as FON and 120 as FDN. All cases were evaluated for histologic diagnosis, age, sex and size of the nodule. Histopathologic follow-up was available in all cases. The malignancy rate was 22% (74/359) and 72% (86/120) for cases diagnosed as FON and FDN, respectively. In the FON category almost half of the malignant cases were papillary carcinoma. The risk of malignancy was higher in patients younger than 40 yr (53% vs. 30%) than in patients 40 year or more years old and greater in males (41% vs. 33%) than females. No statistically significant relationship was noted between the sizes of the nodules and benign vs. malignant diagnosis. According to this study it is important to divide follicular patterned lesions of thyroid into FON and FDN in the cytology specimens due to significantly different risk of malignancy (22% vs. 72%). In addition, clinical features, including gender and age can be part of the decision analysis in selecting patients for surgery.

Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow-Up

A National Cancer Institute (NCI) “Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference” recently proposed standardized nomenclature and “risks of malignancies” associated with various diagnostic categories. We evaluated the evidence levels of the data used by NCI to predict malignancy risks and whether those estimates had clinical validity in our patient population.



Eight hundred seventy-nine patients underwent thyroid FNA during 2006. FNA diagnoses were translated into NCI diagnostic categories, and 2-year follow-up retrospective information was obtained. Four percentages of malignancies were calculated for each diagnostic category using follow-up information from FNA, thyroidectomy, both, and all patients as denominators. 95% confidence intervals (CI) were estimated for all proportions, and results were analyzed with chi-square statistics. “Relative risk” calculations were performed using the percentage of malignancies in the entire population under study as a denominator.



Most of the studies cited by the NCI provided incomplete and variable level III evidence based mainly on surgical follow-up. Among our patients, the percentages of malignancies calculated with follow-up data from all patients as the denominator were similar to the “risk estimates” proposed by the NCI, but estimates based on surgical follow-up overestimated the probability of thyroid malignancy for patients with FNA diagnosis of “benign” and “follicular lesions of undetermined significance” (FLUS). Relative risk and 95% CI calculations suggested that the NCI classification could be simplified into three categories: “benign,” “FLUS + neoplasm,” and “suspicious + malignant.” Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc.

Evidence-based evaluation of the risks of malignancy predicted by thyroid fine-needle aspiration biopsies.

Immediate adequacy assessment (IADA) during fine-needle aspiration (FNA) is not universal and the optimal number of passes has not been well determined. The aim of this study was to evaluate the nondiagnostic rates (NDR) with and without the IADA forthyroid aspirates. Subsequent cytological and surgical follow-up were reviewed for non-diagnostic cases. In addition, we evaluated the number of passes performed in each FNA to determine the optimal number. Retrospective analysis of NDR was performed on 883 thyroid FNA specimens retrieved through a Computer SNOMED Search from our files between January 2001 to December 2003. For FNAs with IADA, one Diff-Quick and one fixed smear for each pass were prepared, and the needle was rinsed in CytoLyt solution for a ThinPrep and/or a cell-block. FNAs without IADAwere received in CytoLyt solution, from which a ThinPrep and a cell-block were prepared for each case. Of the total 883 cases, 443 were performed with IADA, of which 417 cases were diagnostic. The remaining 440 cases were performed without IADA, of which 300 cases were diagnostic.NDR for IADA was 5.9% (26 cases-group-I)compared to 31.8% (140 cases-group-II)without IADA. In group-I, 5 cases were followed-up by repeat FNA, 10 cases by surgical resection, and 11 cases received no tissue follow-up. In group-II, 23 cases were followed-up by repeat FNA, 36 by surgical resection, and 82 cases received no tissue follow-up. Interestingly, follow-up in group-I did not reveal any missed malignancy, while that in group-II resulted in a malignant diagnosis in 13.8% (8 cases). We also found that the optimal number of passes with least NDR was 4-6 passes.NDR was 25% for < 3 passes, 11% for 4 passes, 5.2% for 5 passes, 1.4% for 6 passes, and 2.5% for 7 passesor more. IADA significantly reduces the NDR and increases the sample adequacy for diagnosis. Optimal number of passes is 4-6 passes, and additional passes did not improve the diagnostic rate. Our study also emphasizes the significance of repeat FNA or histological follow-up for nondiagnostic cases, especially for those without IADA.

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How important is on‐site adequacy assessment for thyroid FNA? An evaluation of 883 cases

Thyroid nodules (TN) are a common clinical problem. Fine needle aspiration (FNA) of the thyroid now is practiced worldwide and proves to be the most economical and reliable diagnostic procedure to identify TNs that need surgical excision and TNs that can be managed conservatively. The key for the success of thyroid FNA consists of an adequate or representative cell sample and the expertise in thyroid cytology. The FNA cytologic manifestations of TNs may be classified into seven working cytodiagnostic groups consisting of a few heterogenous lesions each to facilitate the differential diagnosis. Recent application of diagnostic molecular techniques to aspirated thyroid cells proved to be useful in separating benign from malignant TNs in several cases of indeterminate lesions.

Darcy Bilodeau

Papers

Fine-needle aspiration of the thyroid: an overview