Diagnostic Evaluation Of Thyroid Nodules Research Articles

Fine needle aspiration and the Bethesda system: Correlation with histopathology in 1,228 surgical patients

BackgroundFine-needle aspiration combined with the Bethesda System for Reporting Thyroid Cytopathology is indispensable in the diagnostic evaluation of thyroid nodules. Their increased detection over the last few decades mandates the determination of which thyroid nodules require surgical management for malignancy. This study examines the correlation of fine-needle aspiration to final histopathology of dominant thyroid nodules in a large series of surgical patients undergoing thyroidectomy at a single academic institution. MethodsA retrospective review of prospectively collected data of 1,228 patients who underwent fine-needle aspiration for a dominant thyroid nodule and thyroidectomy from a single institution between 2010 and 2019 was performed. The cases were stratified into all 6 Bethesda categories. Fine-needle aspiration results were compared to index thyroid nodule malignancy on final histopathology. ResultsOf 1,228 patients who underwent thyroidectomy, the overall malignancy rate was 53%. When fine-needle aspiration was stratified by the Bethesda System for Reporting Thyroid Cytopathology, malignancy rate was 29% for nondiagnostic; 11% for benign; 51% for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); 47% for follicular neoplasm/suspicious for follicular neoplasm (FN/SFN); 84% for suspicious for malignancy (SFM); and 98% for malignant results on final histopathology. There was a false positive rate of 1% and false negative rate ranging from 7 to 11%. ConclusionFine-needle aspiration of a dominant thyroid nodule in patients who underwent thyroidectomy had an overall malignancy rate of 53%. False negative and false positive rates are within the reported range in surgical patient populations. The majority of patients with AUS/FLUS, FN/SFN and SFM results with underlying malignancy received the appropriate surgical resection.

The value of routine measurement of serum calcitonin on insufficient, indeterminate, and suspicious thyroid nodule cytology.

Routine calcitonin measurement in patients with nodular thyroid disease is rather controversial. The aim of this study was to evaluate the contribution of serum calcitonin measurement in the diagnostic evaluation of thyroid nodules with insufficient, indeterminate, or suspicious cytology. Out of 1668 patients who underwent thyroidectomy with the diagnosis of nodular thyroid disease and were screened, 873 patients with insufficient, indeterminate, or suspicious fine-needle aspiration biopsy results were included in the study. From the total number of patients in this study, 10 (1.1%) were diagnosed as medullary thyroid cancer (MTC) using histopathology. The calcitonin level was detected to be above the assay-specific cutoff in 23 (2.6%) patients ranging between 6.5 and 4450 pg/mL. While hypercalcitoninemia was detected in all 10 MTC patients, a false positive elevation of serum calcitonin was detected in 13 patients (1.5%). Of the MTC group, seven patients had cytology results that were suspicious for malignancy (Bethesda V), one patient’s cytology showed atypia of undetermined significance (Bethesda III), and two patient’s cytology results were suspicious for follicular neoplasm (Bethesda IV). Among the cases with non-diagnostic cytology (Bethesda I), none of the patients were diagnosed with MTC. In conclusion, routine serum calcitonin measurement can be performed in selected cases rather than in all nodular thyroid patients. While it is reasonable to perform routine calcitonin measurement in patients with Bethesda IV and Bethesda V, this measurement was not useful in Bethesda I patients. In Bethesda III patients, patient-based decisions can be made according to their calcitonin measurement.

Correlation of Ultrasonography Guided Fine Needle Aspiration Cytology with Postoperative Histopathology in Diagnosis of Thyroid Nodule

Background: Fine-needle aspiration cytology (FNAC) is recommended as a decisive diagnostic step in the workup of patients with nodular thyroid disease. Unfortunately, FNAC can miss malignancies in smaller and deeper nodule. Ultrasound guided FNAC (US-FNAC) can reduce this error in suspicious thyroid nodule.
 Objectives: To find out the correlation of USG guided FNAC with postoperative histopathology in diagnosis of thyroid nodule.
 Methods: After obtaining clearance and approval from Institutional Review Board, all 45 patients of thyroid nodule who were admitted in the Department of Otolaryngology – Head & Neck surgery of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from April 2017 to August 2018 and had fulfilled the inclusion and exclusion criteria were selected for the study. Each patient was assessed before surgery by USG guided FNAC and post operatively by histopathology.
 Results: In this study mean age of the respondents was 33.33 yearswith SD±10.84. Male female ration was 1:5.4. USG guided FNAC was reported by ‘The Bethesda System for Reporting Thyroid Cytopathology’ (TBS-RTC).Of the 45 specimens 2 samples were nondiagnostic or unsatisfactory (Class I), 26 samples were benign (Class II), 2 samples were showing Atypia of Undetermined Significance or Follicular lesion of Undetermined Significance (Class III), 6 were showing follicular neoplasm or suspicious for a follicular neoplasm (Class IV), 5 samples were suspicious for malignancy (Class V) and 4 samples were positive for malignancy (Class VI). On comparison of ultrasound guided FNAC with histopathology the sensitivity for correct diagnosis was 94%, specificity was 93%, positive predictive value was 88%, negative predictive value was 96% and accuracy was 93%. Pearson’s correlation coefficient was 0.85 which is very strong for positive relationship.
 Conclusion: USG guided FNAC is the most accurate method for diagnostic evaluation of thyroid nodules.
 Bangladesh J Otorhinolaryngol; April 2021; 27(1): 36-43

Ultrasound Elastography and TI- Rads (Thyroid Imaging Reporting and Data System) in the Diagnostic Evaluation of Thyroid Nodules

Abstract Background Thyroid nodules refers to an abnormal growth of thyroid cells that forms a lump within the thyroid gland. Although the vast majority of thyroid nodules are benign , a small percent is presenting as a thyroid cancer. Objective To quantify the sensitivity & the specifity of ultrasound elastography and TI-RAADS in evaluation of thyroid nodules among study population in Ain Shams university hospitals. Patients and Methods Type of study: cross sectional study. Study setting: it was conducted at Ain Shams University hospitals. Study period: March2018 to September 2018. Sample size: 41 patients were included in this study. Results There is a significant increase in the hyperechoic and isoechoic echogenicity in benign groups while no significant difference in hypoechogenicity and a significant difference in very hypoechogenicity in malignant group P- value=0.002. Conclusion Finally both the use of TI- RADS and elastography are methods to evaluate thyroids nodules according to US features and scoring systems that they are easy to perform, not invasive, informative, not costy and can be combined together to increase the accuracy of evaluation.

Efficacy of dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin scintigraphy for the assessment of thyroid nodules.

Radioisotope methods have shown to be useful in the non-invasive diagnosis of thyroid nodules over the past years. The present prospective study aims to evaluate the efficacy of gamma imaging using single and dual tracer using Tc-99m pertechnetate and Tc-99m tetrofosmin for evaluation and management of thyroid nodules. Dynamic (perfusion) imaging was performed after injecting 148-185MBq (4-5mCi) of Tc-99m pertechnetate followed by static imaging. A second, dynamic (perfusion) imaging study within same week was performed with 296-370MBq (8-10mCi) of Tc-99m tetrofosmin on same group of patients followed by early and delayed images. Results of radionuclide perfusion scan from both studies were compared qualitatively with postsurgical histopathology or fine needle aspiration cytology (FNAC). Total 65 nodules in 50 patients were included in the study. With single tracer, the specificity and accuracy of Tc-99m pertechnetate was 23% and 45% and for Tc-99m tetrofosmin scan was 40% and 49%. When dual tracers were evaluated for the same group of patients, the specificity was 56% and accuracy was 55%. Dual Tracer technique with Tc-99m pertechnetate and Tc-99m tetrofosmin could be helpful in selecting nodules need surgical intervention. This technique can be used for convenient and rapid diagnostic evaluation of thyroid nodules non-invasively. We suggest a combination of fine needle aspiration biopsy and dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin as a routine diagnostic approach to thyroid nodules.

Needle Biopsy of Routine Thyroid Nodules Should Be Performed Using a Capillary Action Technique with 24- to 27-Gauge Needles: A Systematic Review and Meta-Analysis.

Fine-needle biopsy is the international standard for diagnostic evaluation of thyroid nodules. There is a lack of consensus regarding the optimal needle biopsy technique. The implementation of capillary action versus aspiration and the optimal needle gauge remain topics of debate. A systematic review of the Medline, Embase, and Cochrane databases was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles evaluating the effects of capillary action versus aspiration and needle gauge on success rates of fine-needle biopsy of the thyroid were assessed for inclusion. The primary outcome of interest was the rate of non-diagnostic cytopathology. Twenty-four articles with a collective 4428 nodules were ultimately included in the review. Twenty articles evaluated capillary action versus aspiration, and six evaluated needle gauge. All but two studies were prospective, most of which were blinded trials with or without randomization. Using a random-effects model, capillary action was associated with a statistically significant reduction in the relative risk of non-diagnostic cytopathology (relative risk = 0.57 [confidence interval 0.34-0.92]; p = 0.02). There was a nonsignificant trend in favor of smaller needle gauges. Given the statistically significant deceased rate of non-diagnostic cytopathology with capillary action and the potential for increased pain and complications with larger needles without a proven benefit, needle biopsy of routine thyroid nodules should be performed without aspiration and with smaller needle gauges (24-27G).

Genomic Profiling of Thyroid Nodules: Current Role for ThyroSeq Next-Generation Sequencing on Clinical Decision-Making.

In recent years there has been an increased awareness of the genetic alterations underlying both benign and malignant neoplasms of the thyroid. Next-generation sequencing (NGS) is an emerging technology that allows for rapid detection of a large number of genetic mutations in thyroid fine-needle aspiration (FNA) specimens. NGS for targeted mutational analysis in thyroid tumors has been proposed as a tool to assist in the diagnosis of thyroid nodules with indeterminate FNA cytology. Results of genomic testing of thyroid nodules and thyroid cancers could also have prognostic implications and play a role in determining optimal treatment strategies including targeted therapies. We provide a critical review of existing studies assessing the performance of the ThyroSeq NGS test for the diagnosis and management of patients with thyroid nodules with indeterminate cytopathology and discuss the applicability of findings from these studies to clinical practice. While there are early indications to suggest a possible utility of data obtained from NGS to aid in prognostication and therapeutic decision-making in thyroid cancer, we recommend judicious use and cautious interpretation of such molecular testing until results of ongoing clinical trials become available. Lastly, we discuss recommendations provided from clinical practice guidelines regarding the use of mutation detection via NGS in the diagnostic evaluation of thyroid nodules.

Strain ultrasound elastography in the diagnostic evaluation of thyroid nodules

Strain ultrasound elastography in the diagnostic evaluation of thyroid nodules

Fine needle aspiration of thyroid nodules in the pediatric population: A 12‐year cyto‐histological correlation experience at north shore‐long island jewish health system

Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature. 13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology-surgical follow-up. Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U-category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy-four children had surgical follow-up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category. To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to "follow-up and repeat" may not apply to the pediatric population. Surgery may be reasonable in these categories instead.

The Management of Thyroid Nodules

In Germany, about 59 000 thyroid operations are performed each year for uni- or multinodular goiter, most of them for diagnostic purposes. The rate of detection of thyroid cancer in such operations is relatively low, at 1:15. Evidence suggests that the preoperative tests recommended in guidelines for estimating the risk of cancer are not being performed as often as they should. In the present study, we determined the measures that were actually taken to diagnose and treat thyroid nodules and compared the findings with the guideline recommendations. We retrospectively analyzed data from a single, large statutory healthinsurance carrier in Germany (AOK), determining the diagnostic and therapeutic measures that were reimbursed for 25 600 patients in whom a uni- or multinodular goiter was newly diagnosed in the second quarter of 2006 (none of these patients had carried such a diagnosis 1 year previously). We recorded the diagnostic measures performed in the preceding 9 months and all other tests and treatments, including surgery and radioactive iodine treatment, in the 2 years thereafter. Among patients who underwent surgery for uninodular goiter, the preoperative diagnostic studies included ultrasonography (in 100% of patients), scintigraphy (94%), measurement of thyroid-stimulating hormone (95%), measurement of calcitonin (9%), and fine-needle aspiration cytology (FNAC)(21%). An ultrasonographic examination was billed for only 28% of patients with uninodular goiter in the two years after the diagnosis was made. 13% of patients with uninodular goiter who were not operated on were given L-thyroxine, even though this is against guideline recommendations. Inadequate preoperative risk stratification of thyroid nodules may explain the large number of thyroid operations that are performed for diagnostic purposes, resulting in a low percentage of malignancies detected. Preoperative FNAC and calcitonin measurement should be used in the diagnostic evaluation of thyroid nodules far more often than this is now done. As a rule, follow-up ultrasonography should be performed for all thyroid nodules that are not operated on. Patients with non-operated thyroid nodules should not be given thyroxine. A limitation of this study is that diagnostic measures were only recorded if they were performed in the 9 months before surgery, with earlier diagnostic measures (if any) being missed.

Rapid Onsite Evaluation Improves the Adequacy of Fine-Needle Aspiration for Thyroid Lesions: A Systematic Review and Meta-Analysis

Fine-needle aspiration (FNA) with ultrasonography guidance is one of the optimal techniques for the diagnostic evaluation of thyroid nodules. A significant subset of thyroid FNAs continues to be inadequate for interpretation, which potentially leads to increased costs from repeat aspirations. Numerous studies have been published regarding the influence of rapid onsite evaluation (ROSE) by cytopathologists on thyroid FNAs, some indicating that FNA is more likely to be adequate for interpretation with ROSE, while others refute this idea. To our knowledge, no meta-analysis of the literature on this subject has been undertaken. We searched MEDLINE and EMBASE using the following search string: (needle biopsy) AND (assessment or onsite OR onsite or immediate or rapid)/title or abstract. There were no restrictions on study design, language, anatomic site, or time period. Only studies comparing two arms (with/without ROSE) at a single site were eligible for inclusion. Potentially relevant studies were subjected to a citation search (forward search) and reference search (backward search) using SCOPUS. Statistical calculations were performed using Stata Release 12. Meta-analysis was completed using a random-effect model as implemented in the metan routine in Stata. An initial search obtained 2179 studies from MEDLINE and EMBASE, and screening yielded 71 potentially relevant studies. A focused review of this subset resulted in seven full studies and one abstract that met our inclusion criteria. Our citation search using SCOPUS yielded no new studies. Overall, the average adequacy rate was 83% without ROSE compared to 92% with ROSE. Visual inspection of the data suggested that the improvement in adequacy due to ROSE may be related to the adequacy rate without ROSE. Metaregression analysis showed that the change in the adequacy rate was strongly correlated (t=-12.7, p<0.001) with the non-ROSE adequacy rate. In addition, the non-ROSE adequacy rate explained all, but 10% of the residual between study variability in the change in the adequacy rates due to ROSE. ROSE is generally associated with an improvement in adequacy, but the impact of ROSE depends heavily on the initial adequacy rate. Sites with lower initial adequacy rates can benefit the most from the implementation of ROSE.

Szintigraphisch mehranreichernde Schilddrüsenknoten gehen überwiegend mit normwertigem TSH einher

In recent years, various professional societies published guidelines for diagnostic evaluation of thyroid nodules, in which the indication for scintigraphy is restricted to patients with subnormal TSH values. It is seen controversial whether such recommendations should be transferred to Germany, partly because of lower iodine intake in this country and the consequent higher percentage of autonomous thyroid nodules, which are not accompanied by a measurable dysfunction. Since reliable data to this topic are scarce, we analyzed multicentrically the spectrum of scintigraphically "hot" and "warm" nodules under the current epidemiological conditions. In 10 German nuclear medicine out-patient institutions we evaluated the diagnostic data from a total of 514 patients, in whom unequivocally hyperfunctional nodules (focal increased uptake in comparison to perinodular tissue with a sonographically nodular correlative ≥1 cm) could be detected by (99m)Tc-pertechnetate scintigraphy. To minimize selection bias, the surveys were not carried out in hospitals.The recorded parameters included the thyroid hormone levels, the global (99m)Tc-uptake (TcTU), the size of each nodule and the total autonomous nodular volume (V(aut)). Only 20% of the patients with "hot" nodules had subnormal TSH levels (<0.1 to 0.33 mU / l), the remaining patients had TSH levels from 0.34 to 3.5 mU /l (in one third of the patients TSH levels even exceeded 1.0 mU/l). Moreover, we found no relevant correlation between TSH and TcTU or V(aut). In Germany, in at far the largest proportion of patients with autonomous thyroid nodules objectified by means of scintigraphy, TSH levels are within the normal range. Since such nodules with maximum safety can be classified as benign, a corresponding scintigraphic finding has a high priority for the patient. These current data support that it is not reasonable to restrict scintigraphy to patients with subnormal TSH values in this country.

99mTc‐sestamibi scanning in thyroid nodules with nondiagnostic cytology

Our aim in this study was to assess the relevance of (99m)Tc-sestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with nondiagnostic cytology. In all, 74 patients with a single nodule and repeatedly nondiagnostic ultrasound-guided fine-needle aspiration cytology (US-FNAC) were enrolled. In all cases thyroid nodules were cold in (99m)Tc-pertechnetate (Tc) scans. Thyroid scans were also acquired 30 and 120 minutes after intravenous administration of MIBI. Nodules that concentrate MIBI were considered as positive (ie, suspicious for malignancy). Histologic findings were obtained after surgery in all patients. No differences occurred in early and late MIBI images. None of 63 patients with a negative MIBI scan had a final histologic diagnosis of malignancy (ie, no false-negative results). Two patients with a final histologic diagnosis of papillary thyroid carcinoma (PTC) and 1 with follicular thyroid carcinoma (FTC) had a positive MIBI scan. Eight patients with a final histologic diagnosis of benign lesions (3 with follicular adenomas) also had MIBI-positive scans. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 100%, 88%, 89%, 27%, and 100%. A negative MIBI scan in a cold nodule accurately excludes malignancy when US-FNAC is reported as nondiagnostic. This avoids the need for more invasive diagnostic procedures (ie, surgery) and positively influences the cost-effectiveness profile. A MIBI scan may be performed by acquiring images 30 minutes after tracer administration alone. Histology is still necessary to distinguish benign from malignant disease in a MIBI-positive nodule but unnecessary surgery could have been reduced from 71 to 8 cases in our series.

Role of thyroid ultrasound in the diagnostic evaluation of thyroid nodules

Thyroid ultrasound (US) features associated with malignancy in thyroid nodules are microcalcifications, hypoechogenicity, irregular margins or absent halo sign, solid aspect, intranodular vascularization, and shape (taller than wide).These patterns, taken singly, are poorly predictive. When they are simultaneously present the specificity increases at the expense of sensitivity. US elastography (USE) is a powerful new diagnostic tool that assesses hardness as an indicator of malignancy in thyroid nodules. USE has high specificity and sensitivity independent of the nodule size, and this predictive value is maintained in follicular lesions. Available data suggest that USE is the best available non-invasive tool comparable to fine-needle aspiration (FNA) for the evaluation of thyroid nodules, provided that the nodule is solid and devoid of coarse calcifications. Thus, conventional US retains its importance for selecting nodules in which USE is predictive. In conclusion, USE has great potential as a new tool for the diagnosis of thyroid cancer, especially in nodules with indeterminate cytology.

Detección de marcadores de malignidad en nódulos tiroideos por transcripción reversa y reacción en cadena de la polimerasa (RT-PCR)

Nodular thyroid disease is a very common disorder with a low frequency of malignancy. The most accurate diagnostic test is fine needle aspiration biopsy (FNAB) of nodules with cytological analysis of the sample. However, this procedure has some limitations in the diagnosis of follicular and papillary thyroid carcinoma. To detect mRNA from specific malignancy markers in thyroid nodules and to evaluate their potential correlation with cytological and pathological diagnosis. In 20 patients with thyroid nodules FNAB was performed prior to surgery. The main part of the FNAB sample was used to perform classical cytology. In the remaining of the sample were detected MUC-1, CD26, galectin-3 and TSH receptor mRNAs by RT-PCR technique. Eight patients had positive cytology for papillary cancer, which was confirmed by pathology. Nine had suspicious or non conclusive cytological findings and 3 were negative for neoplastic cells; all 12 were pathologically benign. We detected TSH receptor and galectin-3 mRNA in almost all benign and malignant nodules. MUC-1 was present in 5/8 papillary carcinoma (62.5%), and 1/12 benign nodules (8.3%). CD26 was detected in 7/8 papillary carcinomas but also in 8/12 benign nodules. RT-PCR can be performed in very small samples of thyroid tissue to detect several mRNA markers. MUC-1 can be a potentially useful marker of malignancy in thyroid nodules. It can be detected by RT-PCR as a complementary technique in the diagnostic evaluation of thyroid nodules.

Diagnosis and work-up of thyroid nodules

Thyroid nodularity is a common problem. The main indication for surgery is a fear of malignancy. A variety of diagnostic tests, including imaging studies, are available; of these, the best and most cost-effective diagnostic test is a fine-needle aspiration (FNA) biopsy. However, a variety of pitfalls of FNA need to be kept in mind before interpreting the information it provides. The FNA is helpful to decide the surgical versus nonsurgical approach. Recently, a large number of incidentalomas of thyroid have been noted during routine magnetic resonance imaging (MRI) or ultrasound of the neck. An ultrasound-guided fine-needle aspiration biopsy is helpful for further evaluation of these incidentalomas. When the fine-needle aspiration biopsy is reported as follicular neoplasm, generally a surgical intervention is considered, especially if the tumor is more than 3 cm because the fine-needle aspiration will not distinguish between benign follicular adenoma and minimally invasive follicular carcinoma, which requires complete evaluation of the capsule of the thyroid nodule. An algorithmic approach to the diagnostic evaluation of thyroid nodule is described.

The treatment of well-differentiated thyroid cancer

The management of well differentiated thyroid cancer continues to generate considerable debate and controversy regarding diagnostic evaluation, extent of surgery, and postoperative adjuvant therapy and follow-up. The fine-needle aspiration biopsy has been routinely used for diagnostic evaluation of thyroid nodule. Understanding prognostic factors and risk group analysis is extremely crucial in the overall management of thyroid cancer regarding the extent of thyroidectomy and adjuvant therapy. Patients in the low-risk group do extremely well and can be treated with lobectomy alone while those in the high-risk group invariably require total thyroidectomy due to the need of adjuvant radioactive iodine treatment. Thyroglobulin appears to be a good tumor marker in patients who have undergone total thyroidectomy during follow-up. One of the major nuances in the management of thyroid cancer is the availability of recombinant TSH which can be used for radioactive iodine dosimetry during the follow-up of patients with well differentiated thyroid cancer. This prevents patients from becoming hypothyroid for an extended period of time which directly affects their quality of life. Understanding poorly differentiated thyroid cancer is extremely crucial as an important histologic prognostic factor and generally being nonradioavid tumors. PET scan is useful in the follow-up of these patients to evaluate the extent of distant metastasis.

Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules.

The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied in patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels. A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied. In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery. All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive in the former patient but also in the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative in the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC. This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels.

475 FINE NEEDLE ASPIRATION BIOPSY OF THE THYROID NODULE IN CHILDHOOD AND ADOLESCENCE

Surgical biopsy has been recommended for all thyroid nodules in children because of the risk of thyroid cancer. Our 3-year experience with fine needle aspiration biopsy of the thyroid (FNA) was reviewed to determine whether some patients with thyroid nodule could be safely followed without surgical biopsy. 17 patients, ranging in age from 5-17 years, received FNA. Based on cytologic and clinical findings, it was determined whether surgery or observation was indicated. The following diagram illustrates the results. We conclude that FNA may be used for diagnostic evaluation of thyroid nodules in children and may reduce the number of patients requiring surgical biopsy.