Thyroid Cancers with Benign-Looking Sonographic Features Have Different Lymph Node Metastatic Risk and Histologic Subtypes According to Nodule Size

A decision to perform fine needle aspiration (FNA) on thyroid nodules mainly depends on sonographic features. We investigated if lymph node metastasis (LNM) risk differed by tumor size of thyroid cancers without suspicious sonographic features. Three hundred sixty patients with thyroid cancers with benign looking sonographic features were grouped by nodule size on ultrasonography (US) (≤ or >1 cm). The clinicopathologic parameters were compared between the groups. A multivariate analysis was performed to discover the independent factors predicting the presence of LNM. The nodules greater than 10 mm on US (n?=?157) demonstrated a larger tumor size on histology (17.9?±?14.5 vs. 5.6?±?2.4 mm, P?P?P?P?=?0.007). A multivariate analysis revealed that classical PTC, extrathyroidal extension, and the US nodule size >10 mm were independent predictive factors of LNM after adjusting for age, sex, TSH level, and multifocality. Thyroid cancers larger than 10 mm with benign US features are more likely to be nonclassical PTC than those with smaller diameters. The larger ones also have an increased risk of LNM in classical PTC. These cases require a more aggressive approach to FNA.     

Clinical Utility of KAP-1 Expression in Thyroid Lesions

Although there are evidences of the involvement of KAP-1 in other tumors, data on differentiated thyroid carcinomas (DTC) are still lacking. We aimed to evaluate KAP-1 clinical utility in the diagnosis and prognosis of DTC. We used both visual immunohistochemistry and a semiquantitative analysis to evaluate KAP-1 expression in 230 thyroid carcinomas and 131 noncancerous thyroid nodules. There were 43 follicular carcinomas (FC) and 187 papillary thyroid carcinomas (PTC), including 130 classic (CPTC), 4 tall cells (TCPTC), and 53 follicular variants (FVPTC). Patients were followed up for 53.8?±?41 months. They were classified as free-of-disease (142 cases) or poor outcome (25 cases—10 deaths), according to their serum Tg levels and image evidences. KAP-1 was identified in 78 % PTC, 75 % TCPTC, 74 % FC, 72 % FVPTC, 55 % FA, 44 % hyperplasia, and 11 % normal thyroid tissues. A ROC analysis identified malignant nodules with 69 % sensitivity and 75 % specificity, using a cutoff of 73.19. In addition to distinguishing benign from malignant thyroid tissues (p?<?0.0001), KAP-1 expression differentiated CPTC from nodular hyperplasia (p?<?0.0001), CPTC from FA (p?=?0.0028), FVPTC from hyperplasia (p?=?0.0039), and FC from hyperplasia (p?=?0.0025). Furthermore, KAP-1 was more expressed in larger tumors (>4 cm; p?=?0.0038) and in individuals who presented recurrences/metastases (p?=?0.0130). We suggest that KAP-1 may help diagnose thyroid nodules, characterize follicular-patterned thyroid lesions, and identify individuals with poor prognosis.     

Predictive Factors of Malignancy in Thyroid Nodules with a Cytological Diagnosis of Follicular Neoplasm

In cases of follicular neoplasm identified by thyroid fine-needle aspiration (FNA), surgery is required to achieve a precise diagnosis. We investigated potential clinical factors for the preoperative prediction of malignancy in thyroid nodules with a cytological diagnosis of follicular neoplasm. We retrospectively reviewed the data of 97 patients who were diagnosed with follicular neoplasm by FNA and had undergone surgery at the Korea Cancer Center Hospital between April 2010 and April 2012. Age, sex, laboratory data (such as thyroid-stimulating hormone, free T4, thyroglobulin (Tg), and Tg antibody), and ultrasonographic findings were reviewed from the electronic medical records. Of 97 patients, 50 (51.5 %) were diagnosed with benign nodules, 16 (16.5 %) with follicular thyroid carcinoma (FTC), and 31 (32.0 %) with papillary thyroid carcinoma (PTC). In comparison with the features of benign nodules, FTC presented with a large nodule size, high serum Tg level, isoechogenicity, calcifications, and peripheral halo, whereas PTC exhibited traits similar to those of benign nodules, except for high serum Tg level and the presence of calcifications on ultrasonography. Therefore, a high serum Tg level (≥75 ng/mL) and calcification were the only significant predictive factors for malignancy in case of follicular neoplasm (p?<?0.01). Serum Tg levels and the presence of calcification on ultrasonography are important clinical features to predict malignancy in thyroid nodules with cytological diagnosis of follicular neoplasm.     

Thyroid microcarcinoma: fine-needle aspiration diagnosis and histologic follow-up

The increased sensitivity of many imaging modalities (ultrasound, computed tomography scan, magnetic resonance imaging) has resulted in the identification of thyroid nodules, measuring 1 cm or less. Usually these small lesions are regarded as incidental and are not sampled by fine-needle aspiration (FNA). However, some of these lesions undergo FNA because of suspicious radiology findings (multifocality, calcification, etc) or in patients with a history of radiation to the head and neck region. We present FNA findings and histologic follow-up of 39 thyroid nodules that measured 1.0 cm or less. All FNAs were performed under ultrasound guidance. The lesions ranged in size from 0.2 to 1.0 cm. Twenty-two lesions were diagnosed as papillary carcinoma (PTC), 4 as medullary carcinoma (MC), and 13 as suspicious for PTC on FNA. Histologic follow-up showed PTC in 35 and MC in 4 cases; 11 PTC were multifocal (31%) and lymph node metastases were present in 8 (16%) cases. Ultrasound-guided FNA is effective in the sampling of thyroid cancers that are 1.0 cm or less. The present study shows that some of these lesions can be clinically significant.     

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.     

Pathology of Thyroglossal Duct: an Institutional Experience

Thyroglossal duct (TGD) is a developmental anomaly in which a remnant of the thyroid anlage is left in the neck during its descent from the foramen cecum of tongue to final pretracheal position. A persistent duct can lead to thyroglossal duct cyst (TGDC). Histologically, TGDC contains an epithelial lining of squamous or pseudostratified ciliated columnar epithelium and ectopic thyroid gland tissue in the duct wall. TGD-associated malignancy is rare, and the majority is papillary thyroid carcinoma (PTC). A total of 242 patients with a diagnosis of TGD-associated lesions were identified in our institute. Two hundred and seventeen cases were diagnosed as TGDC. Sixty-eight of 217 (31.3 %) cases of TGDC had ectopic thyroid tissue in the cystic wall. Thirty-nine cases had preoperative fine needle aspiration (FNA). Of these cases, 37 of 39 (94.9 %) demonstrated macrophages and 19 (48.7 %) also showed cells of squamous and/or columnar epithelial lining. Only two cases showed rare thyroid follicular cells. Thyroid carcinoma was identified in 18 of 242 (7.4 %) cases. All cases were diagnosed as PTC including 12 cases of classic PTC (66.7 %), 3 cases of follicular variant (16.7 %), 2 cases of tall cell variant (11.1 %), and 1 case of classic PTC with focal tall cell features (5.6 %). Nine cases had TGD component (either epithelial lining cysts or ectopic thyroid tissue). Ten patients also underwent total thyroidectomy (67 %). Of these patients, four had no tumor and one had an incidental medullary carcinoma. Five of 10 (50 %) cases had incidental PTC with a size range of 0.1–0.3 cm. Five patients had follow-up by imaging studies; no suspicious or nodular lesions were found in the thyroid. In conclusion, we report an institutional case cohort of 242 patients with TGD-associated lesions, including 217 TGDC and 18 cases of PTC. Only seven cases fulfilled the diagnostic criteria of TGD-associated PTC, i.e., the presence of components of TGD and a normal thyroid. In the remaining 11 cases, we could not differentiate with certainty between pyramidal primary thyroid PTC/Delphian node metastasis or TGD-associated PTC.     

Muc-1 Expression May Help Characterize Thyroid Nodules but Does Not Predict Patients’ Outcome

Our purpose was to evaluate MUC1 clinical utility in the diagnosis and prognosis of thyroid cancer patients. We studied the protein expression of MUC1 in 289 thyroid carcinomas and 121 noncancerous thyroid nodules. There were 41 follicular carcinomas (FC) and 248 papillary thyroid carcinomas (PTC) including 149 classic (CPTC), 20 tall cell (TCPTC) and 79 follicular variants (FVPTC). In addition, we used a quantitative real-time PCR (q-PCR) method to measure MUC1 mRNA expression levels in 108 carcinomas, 23 hyperplasias, and 19 FA. According to their serum Tg levels and other evidences of recurrence/metastasis, the patients were classified as free-of-disease (185 cases) or bad outcome (56 cases, 10 deaths). MUC1 protein was identified in 80.2% PTC; 48.8% FC; 68.3% FVPTC; 70% TCPTC; 21.8% FA; 30% hyperplasias and 6% normal thyroid tissues. MUC1 distinguished benign from malignant thyroid tissues (sensitivity?=?89%; specificity?=?53%). MUC1 also differentiated FC from FA (p?=?0.0083). q-PCR mRNA expression of MUC1 also distinguished malignant from benign nodules (Mann–Whitney test, p?MUC1 expression was associated with any clinical or pathological feature of aggressiveness or outcome. We suggest that MUC1 expression may help differentiate follicular patterned thyroid lesions.     

Cystic papillary thyroid carcinoma in fine needle aspiration may represent a subset of the encapsulated variant in WHO classification

This study audits the reliability of ultrasound‐guided fine needle aspiration (FNA) in excluding papillary thyroid carcinoma (PTC) in thyroid cysts containing mural nodules, and investigates the histological counterpart of cystic PTC diagnosed on FNA. Using a 10–5 MHz ultrasound probe and a 27‐gauge needle, solid portions of thyroid nodules were sampled and assessed immediately using both Diff‐Quik and Ultrafast Papanicolaou stains. Unlike usual PTCs that demonstrate hypercellularity, the aspirates of cystic PTC showed low cellularity and consisted of papillae with atypical nuclei scattered in abundant thin colloid. Over a period of 13 years, histological follow‐up was obtained from 11 women and 6 men in whom cystic PTC was reported on FNA. This represented 4.4% of 383 cases of PTC reported and 0.25% of all thyroid FNAs performed. In all 17 cases, histopathology showed encapsulated PTC in various stages of cystic degeneration. Sonography correlated well with histopathology, where findings ranged from cysts with small mural nodules to solid nodules with pockets of thin colloid. In 87 patients with thyroid cysts containing mural nodules, FNA findings were benign, as was clinical follow‐up that ranged from 1 to 12 years. In conclusion, ultrasound‐guided FNA, if performed in the manner described, can reliably distinguish cystic PTC from a benign cyst with a mural nodule. Cystic PTC on FNA in this series correlates to a subset of the encapsulated variant of PTC, an entity described in the 1988 WHO Histological Typing of Thyroid Tumours in the good prognostic category. Diagn. Cytopathol. 2010;38:721–726. © 2009 Wiley‐Liss, Inc.     

Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.     

Feinnadelaspiration (FNA) der Schilddrüse

Background

Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail.

Objectives

Investigation of causes and relevance of discrepant diagnoses.

Materials and method

The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined.

Results

Malignant tumors were found in 45 patients (15.1?%). In 5 patients the cytological diagnosis was “false negative”. Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis “suspicious of malignancy” or “malignant,” 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity.

Conclusions

Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

     

The Flip Side of NIFTP: an Increase in Rates of Unfavorable Histologic Parameters in the Remainder of Papillary Thyroid Carcinomas

The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed to replace noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) both to promote more conservative management of these tumors and spare patients the psychological burden of a cancer diagnosis. This reclassification will lower the incidence of papillary thyroid carcinoma (PTC). In addition, it could result in an increase in the rates of unfavorable histologic prognosticators for PTC overall because NIFTPs had previously accounted for many of the PTCs without these features. Our aim was to evaluate the potential impact of the reclassification of NIFTP on the rates of extrathyroidal extension, lymphovascular invasion, and lymph node metastases in PTC. We identified all PTCs clinically over 1 cm diagnosed on surgical resection between August 2010 and August 2012. The histopathologic characteristics, including PTC subtype, tumor size, presence of extrathyroidal extension and lymphovascular invasion, and surgical margin and lymph node status were all recorded. Based on these parameters, cases were classified according to the American Thyroid Association (ATA) risk stratification system for structural disease recurrence. Tumor slides for cases initially diagnosed as FVPTC were reviewed to identify tumors that would now be classified as NIFTPs. Our cohort included 348 cases of PTC, of which 94 (27%) would now be classified as NIFTPs. After excluding NIFTPs from the PTC category, there were increased rates of extrathyroidal extension (26% up from 19%, p = 0.046), lymphovascular invasion (37% up from 27%, p = 0.0099), and lymph node metastases (26% up from 19%, p = 0.045) among the remaining PTCs. Based on these changes in histologic features, 10% fewer cases were defined as ATA low risk (62% down from 72%, p = 0.0081). Our results indicate that the downgrading of some carcinomas to NIFTP will increase the rates of higher risk histologic parameters in the remaining PTCs by statistically significant margins. Although the overall survival for PTC is very high and would likely not be changed significantly by the introduction of NIFTP, additional studies evaluating the impact of the NIFTP shift are warranted.     

A valuable adjunct to FNA diagnosis of papillary thyroid carcinoma: In‐house PCR assay for BRAF T1799A (V600E)

The diagnostic approach to thyroid nodules generally starts with FNA cytology. However, approximately one‐fifth of cytologic evaluations yield indeterminate cytological findings but only 20% of cases with indeterminate thyroid nodule cytology have a cancer diagnosis, emphasizing the need for an effective ancillary test based on FNA material to help prevent unnecessary surgery. Detection of BRAFV600E mutation, the genetic signature of papillary thyroid carcinoma (PTC) in FNA material provides an invaluable diagnostic adjunct to overcome the limitations of FNA cytology. There are many ways to detect V600E, such as direct DNA sequencing, allele‐specific PCR and hybridization‐based colorimetric methods. In this study, a newer simple PCR method is presented that removes requirements for sequencing special equipment and commercial kits. Two forward primers including the mutant sequence specific (F2), and one common reverse (R) primer were optimized to generate a 241 bp fragment (F1R), an internal PCR control, and a 141 bp fragment (F2R) denoting the presence of V600E. Sensitivity studies revealed that the assay is capable of detecting V600E even in 1 ng of DNA. Direct sequencing data of 241 bp F1R fragment proved the specificity of the assay. For validation studies of the sequence specific multiplex PCR assay, archival FNA slides were used in a group of thyroid lesions including PTC, follicular carcinoma, follicular adenoma, Hashimoto thyroiditis, and benign thyroid nodules. The newer PCR‐based method presented in this study is a practical, inexpensive one‐step assay to detect the BRAF T1796A mutation on FNA samples. Diagn. Cytopathol. 2011;39:424–427. © 2010 Wiley‐Liss, Inc.     

Soft tissue invasion of papillary thyroid carcinoma

Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is common and clinical presentation can vary from minimal to extensive locoregional involvement. Although PTC is generally considered the most benign among all thyroid carcinomas, it may present with local invasion with poor prognosis. Our retrospective study involved 3267 PTC patients undergoing regular follow-up at Chang Gung Medical Center in Linkou, Taiwan. Among them, 269 were PTC cases with ETE, having tumors greater than 1 cm in size and treated with total or complete thyroidectomy with or without lymph node dissection for which the follow-up period was over 10 years. The mean age of 269 cases was 46.8 ± 15.1 (range 11–83 years) years. The number of females was 204 (75.8 %). Patients were categorized into minimal ETE (175 cases) and extensive ETE (94 cases) groups according to surgical findings and pathological reports. Mean follow-up period was 13.3 ± 5.5 (range 0.2–29.3) years, during which 28 (10.4 %) patients died of thyroid cancer; and 63 (23.4 %) of all-cause mortality. Multivariate analysis showed that age, gender, extensive ETE, and lymph node metastasis had a statistically significant effect on thyroid cancer mortality. Survival rates were significantly different between minimal ETE and extensive ETE groups (p < 0.0001). In conclusion, perithyroidal soft tissue involvement by PTC is an important factor that determines patient prognosis and a closer follow-up and more aggressive treatment is necessary for patients who are old, male, extensive ETE, and with lymph node involvement.     

Sensitivity of fine-needle aspiration for papillary carcinoma of the thyroid correlates with tumor size

Fine-needle aspiration (FNA) of the thyroid for papillary carcinomas is highly sensitive. We sought to determine if the sensitivity of FNA for papillary carcinoma is correlated with the size of the tumor. We reviewed the results of thyroid resections for the last 12 years and correlated the findings with clinical and cytologic information. During the time period, a total of 1,331 resections were performed, and a total of 501 papillary carcinomas were identified, including 291 classic tumors, 65 follicular variants, and 145 "incidental" tumors. Sensitivity for all tumors was strongly correlated with tumor size and ranged from a sensitivity of 0-3% for tumors 2 mm or less, 90% for tumors 1-3 cm (220/244, P < 0.001) and 83% for tumors above 3 cm (47/59, P = 0.02). Abnormal FNAs of classic tumors were always recognized as papillary (262/262) compared to only 49% of follicular variants (32/65, P < 0.001). The sensitivity of FNA for papillary thyroid carcinoma is strongly correlated with tumor size. Tumors smaller than 0.5 cm and tumors larger than 3 cm may be more difficult to successfully aspirate on FNA, and the follicular variant may be more difficult to recognize as papillary.     

Expression of hypoxia-inducible factor 1 alpha in papillary thyroid carcinoma is associated with desmoplastic stromal reaction and lymph node metastasis

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, and it early metastasizes into regional lymph nodes. We evaluated immunohistochemically the expression of the hypoxia marker hypoxia-inducible factor 1α (HIF-1α) as well as extracellular matrix protein tenascin C as a marker of stroma remodelling in a cohort of 160 PTCs. Expression of HIF-1α was seen focally accentuated in 100 of the 160 tumours (62.5 %) including 16 cases with equivocal staining (faint staining or only single-cell staining) and 84 cases with unequivocal staining. HIF-1α expression correlated with the degree of desmoplastic stromal reaction as well as with the expression of tenascin C (p?<?0.001, Kruskal–Wallis test, respectively). Moreover, expression of HIF-1α was significantly associated with the presence of lymph node metastases (p?<?0.001, Mann–Whitney test) as well as signs of invasion, namely, peritumoural and extrathyroidal invasion as well as angioinvasion (p?=?0.024, p?<?0.001, p?=?0.017, Mann–Whitney test, respectively). Additionally, PTC with unequivocal HIF-1α nuclear staining was a larger tumour than PTC with negative (?) or equivocal HIF-1α expression (p?<?0.001, Kruskal–Wallis test). Interestingly, the expression of HIF-1α was not significantly associated with BRAF V600E status (p?>?0.05, Mann–Whitney test). Our data show that the expression of HIF-1α is associated with stroma remodelling processes within the tumour and, thus, may play an important role in an invasive behaviour of these tumours independent of BRAF mutation status.     

Diagnosing atypia of undetermined significance in thyroid fine needle aspiration samples using nuclear scoring

BackgroundAtypia of undetermined significance (AUS) is an indeterminate category in the Bethesda system for reporting thyroid cytopathology. Cytological features described as atypia are not always observed in every case, and it is difficult to determine how the small population of cells with enlarged nuclei, a few grooves, and rare elongated nuclei should be classified. Therefore, there is inter-intra observer variability considering these cell types, even though the cytological criteria are well defined. Therefore, this study aimed to establish a nuclear scoring system to help in the differential diagnosis of AUS.MethodsFine needle aspiration (FNA) samples that showed AUS and had surgical follow-up were included in this study. The aspirate was scored for the presence of intanuclear cytoplasmic inclusions, nuclear grooves, overlapping, enlargement, and elongation individually. The total nuclear score for each case was calculated. Statistical analysis of the association between each nuclear feature and the presence of papillary thyroid cancer (PTC) in the surgical specimens was performed. Cut-off points from the total score of these nuclear features were also calculated.ResultsNuclear grooves and overlapping were more common in malignant cases (p < 0.001 and p = 0.048, respectively). A cut-off point of ≥5.5 for the total score was sensitive and specific for defining malignancy.ConclusionThe risk of PTC was higher in nodules with more prominent nuclear overlapping or nuclear groove in their FNA samples. In order to achieve a more confident AUS diagnosis, our scoring system can be helpful for thyroid FNA samples.     

Follicular Variant of Papillary Thyroid Carcinoma: Accuracy of FNA Diagnosis and Implications for Patient Management

Follicular variant of papillary thyroid carcinoma (FVPTC) creates a continuous diagnostic dilemma among pathologists because of the paucity of nuclear changes of papillary carcinoma and overlapping features with benign and other neoplastic follicular lesions. Current guidelines for the management of thyroid nodules recommend surgery for confirmed PTC, suspicious for PTC, and follicular neoplasm cases, while further immediate diagnostic studies or treatment are not routinely required if the nodule is benign on cytology. This study is designed to determine the accuracy of cytology in the diagnosis of FVPTC, based on the Bethesda classification system, and determine the implications for patient management based on the current recommendation. Based on a retrospective review of cytologic diagnoses between January 2008 and December 2011, thyroid fine needle aspiration (FNA) cytology specimens with subsequent surgical intervention and a final diagnosis of FVPTC were selected. The cytologic diagnoses were compared with the final diagnoses, and the percentage of cases contributing to the final diagnosis of FVPTC was calculated for each diagnostic category. Triage efficiency and diagnostic accuracy were calculated. One hundred and fifty-two cases with histologic confirmation of FVPTC were identified (representing 128 patients—101 female, 27 male). All patients had undergone either lobectomy with completion thyroidectomy or total thyroidectomy. The cytologic diagnosis of “positive for malignancy” accounted for only 27 % of the final histologic diagnosis of FVPTC, while suspicious for carcinoma, follicular neoplasm, follicular lesion of undetermined significance, and benign accounted for 11, 23, 23, and 16 % of the final diagnosis of FVPTC, respectively. Only 18 % of the 55 cases tested were positive for BRAF mutation. The subtle nuclear features of FVPTC pose challenges for an accurate diagnosis. Therefore, a better approach is to triage these cases for surgical intervention and/or further evaluation of the particular nodule. Our triage efficacy for FVPTC was 84 %; however, the diagnostic accuracy of PTC was 38 %. A negative diagnosis on FNA has diagnostic and management implications for up to 16 % of cases because they may have no further immediate diagnostic studies or treatment. BRAF mutation analysis provides minimal effect on diagnostic accuracy.     

Comparison of diagnostic values of thyroid aspiration samples using liquid‐based preparation and conventional smear: one‐year experience in a single institution

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Fine‐needle aspiration (FNA) is the most useful tool in the diagnosis of thyroid nodules. Liquid‐based preparation (LBP) in FNA of thyroid nodules is now widely used and is replacing the conventional smear (CS). We compared the diagnostic value of the LBP method with that of CS in thyroid lesions. A total of 1767 CS FNA samples and 2523 LBP FNA samples were included in this comparison of diagnostic values. We also assessed the differences in cytomorphologic features in 41 randomly selected cases of PTC. The measured sensitivities of CS and LBP were 78.9% and 76.3%, respectively, and the specificities were 64.2% and 54.9%, respectively, whereas the positive predictive values were 92.3% and 94.3%, respectively, and the negative predictive values were 89.5% and 81.8%, respectively. The cytomorphological features of LBP showed better‐preserved nuclear details, cleaner background and fewer large papillae than were evident in CS. The results indicate that LBP reduces the diagnosis of non‐diagnostic or unsatisfactory/atypia of undetermined significance or follicular lesion of undetermined significance, although the diagnostic values for CS and LBP are not appreciably different.     

Can cytomorphology differentiate between benign nodules and tumors arising in Graves' disease?

Fine-needle aspiration (FNA) specimens from thyroid nodules arising in Graves' disease (GD) can pose diagnostic difficulties because the cytomorphologic changes in GD may mimic nuclear features of papillary thyroid carcinoma (PTC). In addition, treatment of GD patients with radioactive iodine (RAI) may cause significant cytologic atypia, further increasing the diagnostic difficulty. From March 1999 to April 2002, a total of 14 hypofunctioning nodules in 9 patients with GD underwent FNA; 3 patients had received RAI treatment. Three cases were diagnosed as suspicious for PTC and 11 as benign. Three patients with the diagnosis of suspicious for PTC on FNA underwent surgery and were found to have papillary carcinoma. We assessed all cases to find key cytologic features that can differentiate between nodules with reactive/reparative nuclear atypia from PTC arising in GD. The cytologic features assessed included cellularity, amount of colloid, monotony of the cell population, oncocytic features, cell crowding, lymphocytic infiltration, nuclear elongation, nuclear grooves, pale powdery chromatin, presence of small eccentric nucleoli, and random nuclear atypia. Each feature was semiquantitatively graded on a sliding scale of 0 to 4, with 0 representing absence and 4 representing a predominance of the feature. The mean value of each feature was calculated and the benign and malignant lesions were compared using the unpaired t-test. Four features were found to be statistically significant in the diagnosis of PTC as compared to the benign nodules in GD. The nuclei of PTC in GD show prominent nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli. All other features studied were not found to be statistically significant. There does exist an overlap between the cytologic features of benign nodules and PTC arising in GD. However, adherence to strict diagnostic criteria (nuclear elongation, pale powdery chromatin, intranuclear grooves, and small eccentric nucleoli) can enable the diagnosis of PTC arising in GD.     

Differential Expression of a Set of Genes in Follicular and Classic Variants of Papillary Thyroid Carcinoma

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.