Fine-needle aspiration of the thyroid: rate and causes of cytohistopathologic discordance

Fine-needle aspiration (FNA) of the thyroid gland is a widely utilized, sensitive, specific, and cost-effective method for the evaluation of thyroid nodules. The purpose of this study was to evaluate the accuracy of thyroid FNA and causes of cytohistological discordance in our institution. Six hundred twenty-five thyroid FNAs obtained from 503 females (mean age, 54) and 122 males (mean age, 51) in whom histopathologic follow-up material was available for review, were analyzed. FNAs were classified as: nondiagnostic, negative, intermediate, and positive for malignancy, and the histopathologic material was categorized as benign or malignant. The review revealed 93% sensitivity and 96% specificity for the FNA diagnoses. The FNA results were diagnostic in 87%, indeterminate in 6%, and nondiagnostic in 7% of the cases. Cytohistologic correlation was achieved in 88% of the cases. The false-negative rate was 4% and the false-positive rate was 8%. The most common pitfalls for false-negative diagnoses consisted of suboptimal material and underdiagnosis of papillary carcinoma due to cystic degeneration. The most common pitfall for false-positive cases was overdiagnosis of follicular neoplasms. Our study confirmed that FNA of thyroid nodules can be performed with high sensitivity and specificity by experienced clinicians or pathologists. The application of strict specimen adequacy rules for FNA interpretation is likely to decrease the rate of false-negative and false-positive diagnoses.     

HBME-1 and CK19 are highly discriminatory in the cytological diagnosis of papillary thyroid carcinoma

The cytologic diagnosis of papillary thyroid carcinoma is straightforward in most instances. However, there are some mimics including goitrous nodules and Hurthle cell neoplasms. Many studies have shown the combination of HBME-1 and CK19 expression to be useful in reaching a correct histologic diagnosis on tissue sections. We aim to assess the value of these markers in the setting of cell blocks prepared from needle aspiration specimens. We performed immunohistochemical staining of HBME-1 and CK19 on cell block material from 22 thyroid nodules that also had follow-up histology. Both CK19 and HBME-1 were strongly positive in all nine cases of papillary thyroid carcinoma, the latter showing distinct luminal accentuation. In the non-papillary carcinomas, none showed positivity for both HBME-1 and CK19. Two of six Hurthle cell neoplasms were positive for CK19, however all were negative for HBME-1. One of nine goitrous nodules was strongly positive for HBME-1 with luminal/membranous staining, but this were negative for CK19. The sensitivity, specificity and positive predictive value of HBME-1 in distinguishing between papillary thyroid carcinoma and goitrous nodules/Hurthle cell neoplasms were found to be 100%, 92.9% and 0.9, respectively; and that of HBME-1 and CK19 combination was 100%, 100% and 1. We thus conclude that the combination of positive HBME-1 (luminal/membranous) and CK 19 (cytoplasmic) staining on cell blocks of thyroid cytologic specimens is highly discriminatory in the diagnostic workup for papillary thyroid carcinoma.     

Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma

AIMS: The purpose of this study was to investigate the significance of 'benign' encapsulated follicular thyroid nodules with papillary structures. METHODS AND RESULTS: Twenty-one cases of encapsulated neoplastic thyroid nodules with papillary structures and nuclear features not diagnostic of papillary thyroid carcinoma (PTC) were obtained. All cases were reviewed with particular attention to nuclear features (fine chromatin pattern, optical clearing, grooves and inclusions). Representative sections were submitted for measurement of the maximum diameter of 200 round or nearly round nuclei and for immunostaining for MIB1, CK19, HBME and Ret oncogene protein. Nine cases displayed scattered optically clear nuclei or nuclear grooves in less than 30% of total neoplastic cells. They were grouped in the category of thyroid nodules with limited nuclear features of papillary thyroid carcinoma (PTC), but not diagnostic of PTC. The other 12 cases had fine or coarse chromatin, but lacked other features of nuclei in PTC. The diameter of the nuclei ranged from 5.6 to 7.2 microm and were smaller than those of PTC (6.3-10.0 microm). Immunostaining revealed positive reactivity for MIB1 in the papillary structures. Immunostaining for CK19 and HBME varied from negative or focally weak to diffusely moderate reactivity. Ret oncogene protein immunostaining showed focal and weak reactivity in one case and was negative in other cases of the study. Clinical follow-up from 6 months to 15 years revealed no evidence of metastasis. CONCLUSIONS: The papillary structures in the study cases are unlikely to represent degenerative changes due to their proliferative activity. In view of (i) the encapsulation and the uniformity of the constituent cells, (ii) the varying degrees of immunoreactivity for CK19 and HBME and negative immunoreactivity for Ret oncogene protein, and (iii) the absence or insufficiency of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of follicular adenoma. Recognition of this pathological entity is important to avoid an over-diagnosis of PTC.     

Absence of BRAF, NRAS, KRAS, HRAS Mutations, and RET/PTC Gene Rearrangements Distinguishes Dominant Nodules in Hashimoto Thyroiditis from Papillary Thyroid Carcinomas

Dominant nodules within Hashimoto thyroiditis (HT) may present with unique morphological features that overlap with but are not diagnostic of papillary thyroid carcinoma (PTC). Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT. We identified 28 cases of Hashimoto thyroiditis with a dominant nodule, from 345 consecutive HT thyroidectomies. Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on paraffin-embedded material from 17 of these dominant nodules. Patients ranged in age from 29 to 76 years and were predominantly female, and the nodules ranged from 1.5 to 6.2 cm. No BRAF or RAS mutations or RET-PTC rearrangements were identified in a dominant nodule, including those with atypical, worrisome histopathologic features. Of ten cases with diagnostic concomitant or incidental papillary carcinoma, three had a V600E point mutation in BRAF, and one case had a BRAF exon 15 deletion (600–604E), while the dominant nodules were negative for mutation, supporting the notion that dominant nodules are neither malignant nor precursor lesions, and strict histological, clinical, and molecular criteria must be met for the diagnosis of papillary thyroid carcinoma.     

Immune characterization of thyroid neoplasm's and its variants using immunohistochemical markers: CK-19, Galectin-3 and Hector Battifora mesothelial-1

BackgroundNodular lesions of the thyroid are amongst the common palpable lesions that are encountered by the pathologists in the fine needle aspiration clinics and not only aspiration smears, but even biopsy sections pose significant challenges in their characterization and further classification. Neoplastic lesions of the thyroid have shown a steady rise worldwide and are diagnosed at age younger than most other cancers. Histopathology remains the gold standard in diagnosis and classification of thyroid neoplasms, with variable sensitivity and specificity of immunohistochemical markers, also attributed to variation in the inclusion criteria. We classified the thyroid neoplasms based on WHO Classification (2017) and aimed to study the diagnostic utility of immunohistochemical markers - CK-19, Galectin-3 and Hector Battifora mesothelial-1 performed on manual tissue microarray sections to differentiate various variants of papillary carcinoma from its mimickers, specifically follicular patterned papillary neoplasms from other follicular patterned lesions.MethodProspective study of neoplastic lesions of thyroid from July 2018 to August 2020. Authors describe the clinico-radiological, cytological, histo-morphological and immunohistochemical features of neoplastic nodular lesions of the thyroid.ResultsProspective analysis of nodular thyroid lesions yielded 76 cases, of which 38 were neoplastic. Cytology showed discordance in 10/24 cases, amongst the discordant cases, 70% were confirmed as papillary carcinoma. CK-19 showed high expression in all variants of papillary carcinomas (24/24), low expression in well differentiated tumor of uncertain malignant potential (WD-TUMP) and medullary carcinoma. It was negative in follicular and Hurthle cell neoplasms. Galectin-3 showed 100% specificity and HBME-1 showed 100% sensitivity in diagnosis of papillary carcinoma and its variants. Adenomatoid nodules did not express Gal-3 which helped in their differentiation from FVPTC.ConclusionsGal-3 in combination either with CK-19 or HBME-1 improves the sensitivity and specificity of detection of papillary carcinoma, its variants and its differentiation from follicular patterned lesions to 100% with a significant p value.     

Retrospective evaluation of instituted standard adequacy criteria for on-site adequacy assessment of thyroid fine-needle aspiration

This retrospective study was conducted to investigate the impact of using instituted standard criteria for on-site assessment of specimen adequacy on fine-needle aspiration (FNA) diagnosis of thyroid nodules. The study included a total of 1,031 thyroid FNAs that were performed and assisted with on-site adequacy assessment using instituted standard criteria from July 2006 to March 2009. Adequate specimens require the presence of at least six groups of follicular cells in total on Diff-Quik stained smears with a minimum of 10 cells in each group. Agreement on specimen adequacy between on-site and final assessment, nondiagnostic rate, distribution of cytologic diagnoses, and cytohistologic concordance for cases with surgical follow-up was evaluated. Implementing the instituted standard criteria resulted in 93% level of agreement on specimen adequacy between on-site and final assessment. Nondiagnostic rate upon final assessment was 10.7%. Cytohistologic concordant rate reached 93.9% and 82.3% for nonneoplastic and neoplastic lesions, respectively. Most importantly, this approach to standardization not only provided diagnostic consistency among cytopathologists, but also minimized confusions and enhanced effective communication. Thus, high satisfactions have been achieved from endocrinologists/radiologists who utilized our on-site assessment service and/or participated in the management of thyroid nodules.     

Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion.

No single cytologic feature is specifically diagnostic for papillary thyroid carcinoma. We report herein the presence of swirl-like cellular aggregates in fine needle aspirates of papillary thyroid carcinoma but not in other thyroid entities. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid diagnosed as papillary carcinoma, including seven fine needle aspirates of cervical lymph nodes showing metastatic papillary carcinoma, with or without cell blocks, were reviewed for the presence of cellular swirls. An additional 100 thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter, Hashimoto's thyroiditis and follicular neoplasm were also reviewed for the presence of cellular swirls. Cellular swirls were easily observed at screening magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of papillary carcinoma contained cellular swirls. No cases diagnosed as nodular goiter, Hashimoto's thyroiditis or follicular neoplasm contained these structures. Thirteen cases with swirls had histologic follow-up. These comprised seven papillary carcinomas with classical histopathology, two designated 'differentiated papillary carcinoma,' two with follicular variant histopathology; one with a minor component of follicular variant histopathology; one papillary carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls occurred in cases with relatively little pleomorphism, or in well-differentiated regions of papillary carcinoma that also displayed less well-differentiated components. Cellular swirls are a finding that is highly specific to papillary thyroid carcinoma. They are easily seen at screening magnification. Their presence in a FNA specimen may be helpful in cases where classic criteria for papillary thyroid carcinoma are scarce, particularly in well-differentiated papillary thyroid carcinoma. While the size and scope of this study are insufficient to conclude that cellular swirls alone are diagnostic of papillary thyroid carcinoma in the absence of other criteria, we believe these structures should be added to the list of diagnostic criteria.     

Ultrasonography-guided fine-needle aspiration cytology for thyroid nodules: an emphasis on one-sampling and biopsy techniques

The aim of this study was to assess the adequacy and efficacy of ultrasonography (US)-guided fine-needle aspiration cytology (US-FNAC) with one-sampling technique (only one specimen through a single needle pass was obtained during the procedure on each thyroid nodule in each study patient) for the cytological diagnosis of thyroid nodules. In this study, US-FNAC techniques, including "free two-hand," "mixed sampling," "flipping-extraction," and "single-needle-pass" procedures were used to collect thyroid cells from July 2007 to June 2009. The cytopathology results and patients' complications were reviewed retrospectively. Of the 1456 thyroid-nodule samples obtained from 977 patients (1.49 per patient), the incidence of adequate and inadequate samplings was 88.5% (1289/1456) and 11.5% (167/1456), respectively. After thyroid surgery in 396 patients, 568 nodules were confirmed as 353 papillary thyroid carcinomas including one diffuse sclerosing variant, five follicular thyroid carcinomas, three medullary thyroid carcinomas, one anaplastic thyroid carcinoma, one metastatic renal cell carcinoma, two poorly differentiated carcinomas, 17 follicular adenomas, two nodular thyroiditis, two pseudonodules related to thyroiditis, and 182 cases of nodular hyperplasia. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false-negative rate, and false-positive rate for the US-FNAC were 94.3%, 91.9%, 96.2%, 88.3%, 93.6%, 3.9%, and 2.6%, respectively. There were no significant patients' complications, but 87 patients (8.9%) reported mild pain during or after the procedure. This study showed a good adequacy and efficacy of US-FNAC for thyroid nodules despite one-sampling.     

Fine-needle aspiration and intraoperative consultation in thyroid pathology: when and how?

Fine-needle aspiration (FNA) and frozen section evaluation are traditional components of the management of thyroid lesions. Their role and usefulness are dictated by some basic facts about thyroid pathology: (a) nodules are very common; (b ) they are benign in the majority of cases; and (c) the diagnosis of malignancy is primarily based on cytologic features in the case of papillary carcinoma, and on the presence of invasion of the tumor capsule or of blood vessels in the case of follicular carcinoma. The common occurrence of benign thyroid nodules mandates a cost-effective effective method for preoperative screening. Since, as already stated, the diagnosis of papillary thyroid carcinoma (by far the most common thyroid malignancy) is based on the identification of characteristic cytologic features, FNA has easily emerged in the past 30 years as the most accurate and cost-effective tool-indeed a true cornerstone-for the preoperative management of thyroid nodules. Standardized terminology to report cytologic diagnoses is highly recommended and is being implemented worldwide. Conversely, the importance of intraoperative frozen section diagnosis has been constantly decreasing over the past years, as a direct consequence of the widespread application of FNA. It may, however, be very useful in cases that are suspicious for papillary carcinoma on FNA and in selected cases with an indeterminate cytologic diagnosis.     

Benign Hürthle cell adenoma with papillary architecture: a benign lesion mimicking oncocytic papillary carcinoma

We studied the significance of encapsulated Hürthle cell thyroid nodules with papillary structures lacking the nuclear features of papillary thyroid carcinoma (PTC); 19 cases fulfilling these criteria were encountered The patients' ages ranged from 22 to 40 years (32+/-6), and the F:M ratio was 3:1 The tumors measured from 0.5-5 cm (2+/-1.1). The diameter of the tumor cell nuclei ranged from 5.6 to 7.2 microns. Many nodules had nuclei displaying a fine chromatin pattern somewhat resembling those of PTC, but these were present in <20% of the tumor cells. Immunohistochemically, there was reactivity for MIB-1 in the papillary structures, negativity to focally weak reactivity for HBME and galectin-3, and negativity to moderate diffuse reactivity for CK19. Clinical follow-up from 1 to 19 years revealed no evidence of metastases in any of the cases. It is unlikely that the papillary structures in the study cases represent degenerative changes in view of the proliferative activity we have demonstrated in them. In view of (1) the encapsulation and the uniformity of the constituent cells, (2) the negative or weak immunoreactivity for galectin-3 and HBME and negative to moderate immunoreactivity for CK19, and (3) the absence or paucity of nuclear criteria for the diagnosis of PTC and the absence of lymph node metastasis in all study cases, we believe that these lesions represent the papillary variant of oncocytic follicular adenoma (Hürthle cell adenoma). Recognition of this entity is important to avoid an overdiagnosis of oncocytic PTC.     

Does Fine-Needle Aspiration Cytology Optimize the Surgical Management of Thyroid Disorders in Endemic Goiter Region?

Aim The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region. Methods One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups. 0, no thyroid cells; 1, normal thyroid cells; 2, degenerative thyroid cells without evidence of malignacy; 3, follicular or oncocytary neoplasia; and 4, malignant thyroid cells. FNAC was compared with postoperative histopathological diagnoses. Results Only 76% of the FNAC allowed an adequate cytological examination. In 15 patients (15%), carcinomas were found in the postoperative histopathological diagnosis (including four follicular carcinomas). In the 48 patients of FNAC groups 3 and 4, nine carcinomas (18.7%) were found (including four follicular carcinomas). In the 28 patients of groups 1 and 2, there was only one papillary carcinoma (3.5%). In the 24 patients of group 0, there were two papillary, two follicular, and one anaplastic carcinomas (total of 20.8%). The sensitivity, specificity, and likelihood ratio (LR) of the FNAC for benign nodules were 90%, 40.9%, 0.24, respectively. The LR for malignant nodules was 13.2, and that for follicular neoplasia was 0.55. Conclusions Despite the high prevalence of carcinoma in an endemic goiter region, FNAC disappointed its diagnostic expectation. The lower specificity of FNAC may be caused by a higher prevalence of thyroid nodules in an endemic goiter region or by the absence of a specialized cytopathologist. T. Osei-Agyemang and I. Hassan contributed equally to this work. Presented in part to Second Biennial Congress of the European Society for Endocrine Surgeons (ESES), May 18–20, 2006, Krakow (Poland)     

Fine‐needle aspiration of follicular patterned lesions of the thyroid: Diagnosis,management, and follow‐up according to National Cancer Institute (NCI) recommendations

The National Cancer Institute (NCI) State of the Science Conference on thyroid fine‐needle aspiration (FNA) proposed that follicular patterned lesions can be divided into two diagnostic categories; follicular lesion of undetermined significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for follicular neoplasm/follicular neoplasm (SFON/FON). The former group can benefit from repeat FNA (RFNA) to achieve a more definitive diagnosis and the latter should undergo surgical excision for histologic characterization (adenoma vs. carcinoma). In this study, we report the combined experience from our institutions with thyroid FNA cases that can be placed into NCI‐designated thyroid FNA diagnostic categories for follicular patterned lesions. The case cohort comprised of 857 cases in 645 females and 212 males; 509 cases could be classified as FLUS/AUS and 348 as SFON/FON. Histologic follow‐up was available in 273/509 (54%) cases diagnosed as FLUS/AUS and 251/348 (72%) cases diagnosed as SFON/FON. RFNA was performed in 203/509 (40%) patients classified as FLUS/AUS. RFNA diagnoses were: benign (125 cases), FLUS (46 cases), SFON/FON (20 cases), suspicious for papillary carcinoma (7 cases), papillary carcinoma (3 cases) and non‐diagnostic (2 cases). The malignancy rate on surgical excision in the FLUS/AUS group was 27 and 15% with and without RFNA, respectively; and 25% in cases diagnosed as SFON/FON. RFNA is effective in managing thyroid nodules diagnosed as FLUS/AUS since the malignancy rates are different in cases with or without RFNA (27% vs. 15%). The malignancy rate (25%) in cases diagnosed as SFON/FON is similar to reported by other authors. Diagn. Cytopathol. 2010;38:731–739. © 2010 Wiley‐Liss, Inc.     

Evidence-based criteria for adequacy in thyroid fine-needle aspiration

To determine whether some thyroid fine-needle aspirates classified as nondiagnostic correlate with benign thyroid nodules and can be distinguished from other nondiagnostic aspirates, I reviewed (from a total of 1,581) 80 nondiagnostic cases, all of which were hypocellular and lacked colloid, and correlated the cytologic findings with the results of pathologic follow-up. Of the 80, 16 had carcinoma at follow-up and 64 were benign. The cellularity of the carcinoma cases ranged from 0 to 100 cells (mean, 20 cells), but every case with epithelial cells had Hürthle cell change or atypia suggestive of papillary carcinoma. The cellularity of the 64 benign cases ranged from 0 to 120 cells (mean, 40 cells), 17 of which had Hürthle cell change. There were 25 cases with at least 10 benign-appearing follicular cells without atypia or Hürthle cell change; all 25 cases were associated with benign follow-up. While these results need to be confirmed by others, the evidence suggests that a proportion of thyroid aspirates that do not meet traditional criteria for adequacy still may be associated strongly with a benign thyroid nodule and can be distinguished from other nondiagnostic aspirates.     

Accuracy of fine-needle aspiration of thyroid

CONTEXT: Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. OBJECTIVES: To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.-Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982-1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. RESULTS: The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. CONCLUSIONS: Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.     

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.     

Immunohistochemical study of papillary thyroid carcinoma and possible papillary thyroid carcinoma-related benign thyroid nodules

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.     

Dark and pale cerebriform nuclei in FNA smears of usual papillary thyroid carcinoma and its variants

The dark (hyperchromatic) cerebriform nucleus was recently described as a frequent finding in histopathology sections of papillary carcinoma of the thyroid. In the present study, we tried to determine the frequency of dark cerebriform nuclei in the fine-needle aspiration (FNA) smears of papillary thyroid carcinomas and compared it with those of other thyroid lesions, such as follicular neoplasms and benign hyperplastic lesions. In addition to the above-mentioned nuclear feature, pale (hypochromatic) cerebriform nucleus and other well-established cytomorphological criteria used in the diagnosis of papillary thyroid carcinomas were analyzed. FNA smears of a total of 102 cases comprising of 61 papillary carcinomas, 10 cases of suspicious papillary carcinomas, 12 follicular neoplasms, and 19 benign hyperplastic lesions were studied. Both the dark and pale cerebriform nuclei were found in a significantly higher number of cases of papillary thyroid carcinomas compared with follicular neoplasms (P = 0.0003 and P < 0.0001, respectively) or benign hyperplastic lesions (P = 0.0004 and P < 0.0001, respectively). Review sections available in 24 cases showed agreement between the cytopathological and the histopathological diagnoses in 18 (94.7%) of 19 papillary carcinomas. Thus, the dark and pale cerebriform nuclei can be regarded as useful cytomorphological parameters in the diagnosis of papillary thyroid carcinoma.     

Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms

AIMS: To determine whether galectin-3 is a sensitive indicator of thyroid malignancy. It has been suggested as a potential marker for differentiating thyroid carcinoma from benign or non-neoplastic lesions in preoperative fine-needle aspirates (FNAs). METHODS: Galectin-3 protein expression was assessed by immunohistochemistry in formalin-fixed thyroid tissues from 124 patients with histological diagnoses of papillary carcinoma (n = 38), follicular carcinoma (n = 19), follicular adenoma (n = 32) and dominant nodules of multinodular goitre (n = 35). Expression of galectin-3 was also assessed by Western blotting in 24 fresh thyroid tissues. RESULTS: Galectin-3 expression was observed in the majority of carcinomas (papillary 92%; follicular 74%). However, a large proportion of follicular adenomas (72%) and multinodular goitres (57%) also expressed galectin-3. In addition, galectin-3 expression was observed in epithelial cells of normal thyroid tissue and Hashimoto's thyroiditis. Galectin-3 immunopositivity was significantly greater in papillary carcinomas than in dominant nodules or follicular adenomas (P < 0.0001, P = 0.0005, respectively). However, galectin-3 expression was no greater in follicular carcinomas than in follicular adenomas (P = 0.8735). Western blotting analysis confirmed both the specificity of the antiserum and expression of galectin-3 in multinodular goitres, follicular adenomas/carcinomas and papillary carcinomas. CONCLUSION: The data demonstrate that galectin-3 is not a reliable immunohistochemical marker to distinguish benign from malignant thyroid follicular lesions.     

Fine needle aspiration cytology of the thyroid--a review of experience in 1853 cases

1853 thyroid lesions subjected to cytological sampling (either by the fine needle aspiration or fine needle capillary sampling technique) from January 1992 to December 1997 at the University Hospital, Kuala Lumpur, were reviewed. Nodular goitre was the most common thyroid lesion needled (67.35%). Among the neoplastic lesions, follicular neoplasms predominated (64%), followed by papillary carcinoma (29.4%). In 325 cases, partial or total thyroidectomy had been done, providing material for histological review and cyto-histological correlation. Cytological diagnosis was found to have high sensitivity and specificity rates of over 75%. Besides, most non-neoplastic thyroid lesions could be diagnosed on cytology. The scope of cytology in the diagnosis of lymphomas, anaplastic and metastatic tumours rendered diagnostic biopsies (or thyroidectomy) unnecessary in these cases. Being a cost-effective technique and having the capacity to provide exact morphological diagnosis in a large variety of thyroid lesions, cytology is obviously the method of choice in the assessment of thyroid nodules.     

Thyroid follicular neoplasm: Analysis by fine needle aspiration cytology,frozen section,and histopathology

We performed a retrospective analysis of follicular neoplasm data obtained from frozen section examinations of thyroid nodules. A total of 5,660 patients underwent preoperative neck ultrasonography and fine‐needle aspiration cytology (FNAC), surgical treatment, and follow‐up at a medical institute. Patients with papillary thyroid microcarcinoma were excluded from this study. In 971 cases, frozen section examination was performed during the surgical treatment of follicular neoplasm that was diagnosed via FNAC. Thyroid malignancies were histologically confirmed in 25.1% of cases (244/971). Among the patients with papillary thyroid carcinoma, 45 were diagnosed with the follicular variant of papillary thyroid carcinomas (27.4%). The diagnostic sensitivity of frozen section for the nonfollicular variant of papillary thyroid carcinoma was better than that for the follicular variant of papillary thyroid carcinoma (89.1% versus 78.9%; P = 0.1023). For 12 cases the diagnosis was atypical follicular adenomas. The diagnostic accuracy of frozen section in cases of follicular neoplasm was 76.9% with a sensitivity of 84.8% and a specificity of 98.9%. In conclusion, our analysis revealed high rates of accuracy when using frozen tissue sections for early diagnosis and treatment of follicular neoplasm; thus, an early decision to extent of surgery prevents a risky follow‐up surgery. Diagn. Cytopathol. 2010;38:801‐805. © 2009 Wiley‐Liss, Inc.