Subclassification of atypical cells of undetermined significance in direct smears of fine-needle aspirations of the thyroid: distinct patterns and associated risk of malignancy

BACKGROUND:

Atypical cells of undetermined significance (AUS) in thyroid fine‐needle aspirates (FNAs) may have poor interobserver agreement. Some authors have suggested that “atrophic” microfollicles should be diagnosed as benign. This laboratory sought to determine whether criteria for this diagnosis could be improved by subcategorizing cases into specific patterns, including the atrophic pattern, and determining their risk of malignancy.

METHODS:

A series of 7089 FNAs were reviewed and correlated with subsequent resection specimens. Cases of AUS were reviewed and subclassified.

RESULTS:

Cases could be subcategorized into the following categories: 1) atypical, papillary carcinoma cannot be ruled out, 2) atypical, Hürthle cell neoplasm can not be ruled out, 3) cellular atrophic pattern, 4) scant atrophic pattern, and 5) cytologic atypia alone. Cytologic atypia alone (50%) and both atrophic patterns (21% and 34%) had a significant risk of malignancy.

CONCLUSIONS:

The majority of AUS cases in thyroid FNA can be subcategorized into 5 different patterns, all with associated significant risk of malignancy. “Atrophic” microfollicles are a significant risk factor for malignancy and should not be diagnosed as benign on the basis of lack of cytologic atypia. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.     

Thyroid fine‐needle aspiration with atypia of undetermined significance

BACKGROUND:

Atypia of undetermined significance is a controversial category in thyroid fine‐needle aspiration (FNA), not only for its questioned clinical utility, but also for its very existence as an expression of uncertainty. The current study was performed to investigate the potential impact of eliminating this category on the sensitivity and specificity for detecting thyroid neoplasms by FNA.

METHODS:

Forty cases originally diagnosed as atypia of undetermined significance with histologic follow‐up were selected for the present study. These cases were reinterpreted blindly by 2 experienced reviewers, who eliminated atypia of undetermined significance as a diagnostic possibility and reclassified these cases as either benign, follicular neoplasm, suspicious for malignancy, or malignant. Twenty‐six cases of atypia of undetermined significance were randomly selected and reevaluated 6 months later to study intraobserver variation.

RESULTS:

After eliminating the atypia of undetermined significance category, the sensitivity for detecting papillary thyroid carcinoma (PTC) was reduced from 100% to 27% (P = .04). In those atypia of undetermined significance cases that were reclassified as benign, 37% had PTC. In those reclassified as follicular neoplasm or suspicious for malignancy, 38% were histologically proven to be benign lesions. Unanimous interobserver and intraobserver agreement was observed in only 60% of cases.

CONCLUSIONS:

Eliminating the diagnosis of atypia of undetermined significance substantially decreases the sensitivity of thyroid FNAs and increases both false‐positive and false‐negative rates. In addition, it increases interobserver and intraobserver variability. Therefore, the atypia of undetermined significance category should not be eliminated; but we advocate minimizing its use. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Telomerase activity in "suspicious" thyroid cytology

BACKGROUND: Telomerase activity (TA) has been detected in most malignant neoplasms, including thyroid carcinomas. The authors studied the utility of TA detection as an ancillary tool to thyroid fine-needle aspiration (FNA) for patients with nonconclusive cytologic diagnoses. METHODS: Material obtained by FNA from palpable thyroid nodules in 167 consecutive patients was processed for conventional cytologic studies and simultaneously for TA study. Another 8 patients were excluded from TA because of the presence of lymphocytes. All patients with negative results cases were followed for > 1 year, and those who had tumors that were suspicious or positive by FNA or TA underwent resection for pathologic study of nodules. TA was analyzed by telomere repeat amplification protocol-polymerase chain reaction analysis. RESULTS: After excluding 20 patients because of insufficient material for cytologic study, 120 patients had negative results for malignant cells in cytology material, and the remaining 27 patients had results that were either suspicious (n = 21 patients) or positive (n = 6 patients). Histopathologic confirmation was obtained in 23 patients, including 18 with suspicious cytology (1 with scanty material) and 5 with positive FNA. The histopathologic diagnoses were nodular hyperplasia in 5 patients, follicular adenoma in 3 patients, papillary carcinoma in 11 patients, follicular carcinoma in 1 patient, medullary carcinoma in 2 patients, and lymphoma in 1 patient. TA was detected in 6 of 18 histologically confirmed thyroid neoplasms (1 of 3 follicular adenomas, 3 of 11 papillary carcinomas, 0 of 1 follicular carcinoma, 1 of 2 medullary carcinomas, and 1 of 1 lymphoma), including 1 neoplasm with scanty atypical cells. CONCLUSIONS: The detection of TA helped to confirm neoplasia in 6 of 23 suspicious thyroid nodules. Although it was less sensitive than FNA, TA specificity was 100% for neoplasia and 87.5% for malignancy. The sensitivity of thyroid FNA increased with the use of TA detection when cytology was nonconclusive for malignancy.     

Features associated with locoregional spread of papillary carcinoma correlate with diagnostic category in the Bethesda System for reporting thyroid cytopathology

BACKGROUND:

Most malignancies identified by thyroid fine‐needle aspiration (FNA) are papillary thyroid carcinoma (PTC). This study sought to determine if clinically adverse features of PTC correlate with the preceding cytologic diagnosis.

METHODS:

Thyroid FNA diagnoses were correlated with subsequent histopathologic findings.

RESULTS:

From 6175 thyroid FNAs, histologic follow‐up confirmed PTC in 52 of 184 (28%) FNAs with atypia of undetermined significance (AUS), 52 of 190 (27%) FNAs suspicious for follicular neoplasm, 182 of 229 (79%) FNAs that were suspicious for malignancy, and 188 of 198 (95%) FNAs that were malignant (M). Sex, age, and disease multifocality did not differ among FNA diagnosis groups. However, PTCs following an M FNA were more likely to have a higher American Joint Committee on Cancer T and N stage, and have lymphovascular invasion and/or extrathyroidal extension. Two patients had distant metastasis at initial surgery, whereas 16 developed subsequent recurrence and/or metastasis; all had a preceding M FNA. High‐risk histologic subtypes of PTC also stratify to the M category, accounting at least partly for the association of cytologic diagnosis with adverse pathological parameters. Conversely, follicular variants of PTC predominate in non‐M categories.

CONCLUSIONS:

The Bethesda System for Reporting Thyroid Cytopathology conveys malignancy risk, but also predicts the presence of pathological risk factors and disease progression when the malignancy is PTC. M diagnoses identify higher risk PTCs, whereas AUS diagnoses identify low‐risk PTCs, mostly follicular variants. These findings support the concept of conservative clinical management for some patients with AUS, while suggesting that a central neck dissection may be routinely justified in some patients with a M FNA. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.     

Ultrasound‐guided fine‐needle aspiration biopsy of thyroid bed lesions from patients with thyroidectomy for thyroid carcinomas

BACKGROUND:

To evaluate the efficacy and the limitation of fine‐needle aspiration (FNA) biopsy in thyroid bed lesions, a retrospective review was performed of the medical records of thyroid cancer patients who underwent ultrasound‐guided FNA biopsy of the thyroid bed at The University of Texas MD Anderson Cancer Center over a 5‐year period.

METHODS:

Data were reviewed on 220 FNA biopsies taken from thyroid bed lesions in 195 patients who had undergone thyroidectomy for thyroid carcinoma. Thyroid bed FNA results were compared with clinical follow‐up, including neck dissection results.

RESULTS:

Recurrent carcinoma was diagnosed by FNA biopsy in 139 of 220 (63%) cases. Neck dissections were performed for 112 sites identified by FNA biopsies, and recurrent carcinoma was confirmed in 110 sites. The concordance between positive and/or suspicious FNA diagnosis and positive neck dissection results was 98% (118 of 120 cases). A false‐positive FNA occurred in one patient with follicular thyroid carcinoma. The other discrepancy was attributed to failure to remove the lesion by neck dissection. The diagnostic accuracy of thyroid bed FNA was 100% in papillary and medullary thyroid carcinoma and 93% in follicular thyroid carcinoma. Suspicious and rare false‐negative FNA results were attributed to low cellularity and lack of characteristic cytomorphologic features of thyroid carcinoma.

CONCLUSIONS:

Ultrasound‐guided thyroid bed FNA biopsy is accurate and efficient in triaging patients who require post‐thyroidectomy follow‐up for recurrent thyroid carcinoma. Caution should be taken in the interpretation of FNA specimens that have low cellularity and lack characteristic cytologic features of thyroid carcinoma. Cancer (Cancer Cytopathol) 2013. © 2012 American Cancer Society.     

Parathyroid proliferations

BACKGROUND.

With wide use of fine‐needle aspirates (FNA) for investigation of thyroid nodules, a growing number of parathyroid glands are being inadvertently aspirated for cytologic study. Aiming to determine the effectiveness of FNA to differentiate between parathyroid and thyroid lesions, all cases aspirated initially as thyroid nodules and that had a final histologic diagnosis of parathyroid lesion were retrieved from the authors' files and were systematically reviewed to delineate possible specific diagnostic criteria.

METHODS.

From a total of 90,000 FNA diagnoses of thyroid nodules, 4740 cases were isolated for which a final histologic diagnosis was available. Among these, 29 cases with a final histologic diagnosis of a parathyroid lesion were identified and reanalyzed according to the initial cytologic diagnoses. Furthermore, the FNA smears were reviewed, and specific features were recorded.

RESULTS.

FNA failed to recognize the parathyroid origin of the lesions in all but 2 cases with known hyperparathyroidism. Most aspirates were misinterpreted either as suspicious for or as thyroid neoplasms because of high cellularity and absence of colloid. Histologically, the lesions proved to be parathyroid hyperplasia, adenoma, or carcinoma. Specific cytologic features are discussed.

CONCLUSION.

A safe differential diagnosis between thyroid and parathyroid disease on morphological ground in cytologic smears is difficult due to overlapping features of these lesions. To avoid surgical mismanagement, it is essential, in every highly cellular lesion seen in the context of a colloid‐free background, to consider and report the possibility of a parathyroid lesion, thus enabling the clinician to proceed to a more detailed preoperative evaluation in this direction. Cancer (Cytopathol) 2007. © 2007 American Cancer Society.     

Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients

BACKGROUND: Nodular thyroid disease is a frequent occurrence in clinical practice. The numerous diagnostic procedures available make the diagnosis of thyroid carcinoma possible but, if not used rationally, may lead to an unjustified increase in cost with little practical gain. The aim of the current study was to evaluate the usefulness of fine-needle aspiration (FNA) of palpable thyroid nodules after functional evaluation by thyroid scintigraphy. METHODS: The authors retrospectively evaluated 37,895 FNAs performed between 1980-1997. FNAs were performed on palpable thyroid nodules, except unambiguously autonomous ("hot") nodules, at the time of thyroid scintigraphy. Cytologic and histologic diagnoses were compared in 4069 patients to estimate the accuracy of FNA. RESULTS: The sensitivity of FNA was 91.8% and the specificity was 75.5%. A pretest probability of thyroid carcinoma of 4% was reduced to 0.4% in the patients with a cytologic diagnosis of benign nodular goiter, whereas it was increased to 90.7% in those patients with a positive cytologic diagnosis. Only in the case of a cytologic diagnosis of "follicular neoplasm" was the probability of malignancy not changed significantly and histologic evaluation of the nodule was necessary. CONCLUSIONS: In the majority of cases, FNA of palpable thyroid nodules allows for the identification of thyroid carcinoma and the planning of subsequent appropriate therapy. This can be achieved by using simple and inexpensive procedures, if cooperation among clinicians, pathologists, and nuclear physicians is maximized.     

Should cytopathologists stop reporting follicular neoplasms on fine-needle aspiration of the thyroid?

BACKGROUND: As the consequence of the decreasing incidence of follicular thyroid carcinoma (FC), one wonders whether cytopathologists should stop reporting follicular neoplasms in fine-needle aspiration (FNA) of the thyroid to minimize unnecessary thyroidectomies, if the follicular variant of papillary carcinoma (FVPC) has been excluded. METHODS: Over a 6-year-period, 2667 ultrasound-guided FNAs of the thyroid were performed at our practice. A total of 246 nodules (9.2%) were reported as follicular neoplasms, using abundant blood as the diagnostic clue. All FNA specimens were prepared and reported by one cytopathologist and the final pathology was reported by surgical pathologists in various hospitals in New York City. RESULTS: The histologic follow-up was available for 147 cases and showed 5 cases of widely invasive FC (3.4%), 10 cases of minimally invasive FC (6.8%), 8 cases of FVPC (5.4%), 92 cases of follicular adenoma (62.6%), and 32 cases of nonneoplastic nodules (21.8%). CONCLUSIONS: FVPC cannot be excluded completely from follicular neoplasms by FNA because of the patchy distribution of papillary carcinoma nuclei in the encapsulated variant. Widely invasive FC still exists and may cause considerable morbidity in patients as young as the third decade of life. It is the opinion of the authors that cytopathologists should continue reporting follicular neoplasms in FNA of the thyroid.     

Parathyroid proliferations: a source of diagnostic pitfalls in FNA of thyroid

BACKGROUND: With wide use of fine-needle aspirates (FNA) for investigation of thyroid nodules, a growing number of parathyroid glands are being inadvertently aspirated for cytologic study. Aiming to determine the effectiveness of FNA to differentiate between parathyroid and thyroid lesions, all cases aspirated initially as thyroid nodules and that had a final histologic diagnosis of parathyroid lesion were retrieved from the authors' files and were systematically reviewed to delineate possible specific diagnostic criteria. METHODS: From a total of 90,000 FNA diagnoses of thyroid nodules, 4740 cases were isolated for which a final histologic diagnosis was available. Among these, 29 cases with a final histologic diagnosis of a parathyroid lesion were identified and reanalyzed according to the initial cytologic diagnoses. Furthermore, the FNA smears were reviewed, and specific features were recorded. RESULTS: FNA failed to recognize the parathyroid origin of the lesions in all but 2 cases with known hyperparathyroidism. Most aspirates were misinterpreted either as suspicious for or as thyroid neoplasms because of high cellularity and absence of colloid. Histologically, the lesions proved to be parathyroid hyperplasia, adenoma, or carcinoma. Specific cytologic features are discussed. CONCLUSION: A safe differential diagnosis between thyroid and parathyroid disease on morphological ground in cytologic smears is difficult due to overlapping features of these lesions. To avoid surgical mismanagement, it is essential, in every highly cellular lesion seen in the context of a colloid-free background, to consider and report the possibility of a parathyroid lesion, thus enabling the clinician to proceed to a more detailed preoperative evaluation in this direction.     

Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study

BACKGROUND:

At present, thyroid fine‐needle aspiration (FNA) specimens are diagnosed using a tiered classification scheme, with the most popular of these being the 5‐tiered and 6‐tiered systems. In this study, the authors present their institutional experiences using these 2 different systems and evaluate their efficacy based on the surgical follow‐up.

METHODS:

Thyroid FNA specimens and their corresponding surgical resection specimens were collected between 2007 and 2009. The following diagnostic categories are used in both systems: unsatisfactory/nondiagnostic, benign, follicular neoplasm/suspicious for follicular neoplasm, suspicious for malignancy, and malignant. An additional category termed atypia of undetermined significance/follicular lesion of undetermined significance was used for atypical cases in the 6‐tiered system. Statistical analysis was performed by comparing the different diagnostic categories.

RESULTS:

The case cohort included a total of 7686 thyroid FNA specimens representing 3962 nodules and 3724 nodules, respectively, in the 5‐tiered and 6‐tiered systems. Negative predictive values for the benign categories (96.9% vs 97.5%; P = 1) and positive predictive values for both the follicular neoplasm categories (26.5% vs 32.1%; P = .2531) and the malignant categories (99.1% vs 99.4%; P = 1) were similar. The most significant differences between the 5‐tiered and 6‐tiered systems were the percentage of cases classified as benign (83.9% vs 55.4%; P < .0001) and as follicular neoplasms (4.6% vs 23.8%; P < .0001). It is interesting to note that fewer patients were referred for surgery in the 5‐tiered system compared with the 6‐tiered one (9.1% vs 36.5%; P < .0001).

CONCLUSIONS:

Use of either the 5‐tiered or 6‐tiered reporting systems for thyroid FNA specimens can potentially affect the clinical management of patients with thyroid nodules. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.     

Improved preoperative definitive diagnosis of papillary thyroid carcinoma in FNAs prepared with both ThinPrep and conventional smears compared with FNAs prepared with ThinPrep alone

BACKGROUND:

ThinPrep (TP) liquid‐based preparations are increasingly being used in nongynecologic specimens. Few studies have evaluated TP as a sole diagnostic modality in the setting of thyroid fine‐needle aspiration (T‐FNA). Herein, the authors evaluate the usefulness of TP as a sole diagnostic modality in a nonsplit sample.

METHODS:

Consecutive T‐FNAs were identified at 2 tertiary care institutions; 1 institution processed thyroid FNA entirely with TP, and the other used a combination of TP and conventional preparations (CP). Cytodiagnoses, surgical pathology, and/or clinical follow‐up were recorded. Performance parameters for the 2 settings were compared.

RESULTS:

A cytologic diagnosis of positive for malignancy was correct in 98.8% of TP + CP cases and in 100% of TP cases. Papillary thyroid carcinoma cases were definitively diagnosed in 53.1% of T‐FNAs prepared by TP + CP compared with 34.4% of T‐FNAs prepared with TP alone (P = .0015 by Fisher 2‐tailed exact test). Of patients ultimately diagnosed with papillary thyroid carcinoma, 89% were initially treated by total thyroidectomy in the TP + CP group compared with 79.5% in the TP‐only group (P = .027 by Fisher exact test).

CONCLUSIONS:

TP as a sole preparatory technique does not improve the usefulness of T‐FNA as a screening test. However, combining CP and TP increases the rate of definitive cytologic diagnosis of malignancy in papillary thyroid carcinoma. Thus, combining TP and CP enhances the diagnostic component of T‐FNA. Cancer (Cancer Cytopathol) 2011. © 2010 American Cancer Society.     

Contribution of molecular testing to thyroid fine‐needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”

BACKGROUND:

“Follicular lesion of undetermined significance/atypia of undetermined significance” is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis.

METHODS:

All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARγ gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome.

RESULTS:

From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic‐histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false‐positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001).

CONCLUSIONS:

By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and “suspicious for follicular neoplasm” categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high‐risk and low‐risk categories. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Breast fine‐needle aspiration samples reported as “proliferative breast lesion”: Clinical utility of the subcategory “proliferative breast lesion with atypia”

BACKGROUND:

The fine‐needle aspiration (FNA) diagnosis of proliferative breast lesion is an indeterminate category. The aim of this correlative study was to determine whether a subcategory of “proliferative breast lesion with atypia” was achievable and whether this subcategory has management utility.

METHODS:

Breast FNA cases from 2000 through 2005 diagnosed as proliferative breast lesion and proliferative breast lesion with atypia were retrieved. Both cytologic and surgical slides of these cases were reviewed blindly. A cytologic diagnosis of proliferative breast lesion (without atypia) or proliferative breast lesion with atypia was used if the findings of the proliferative breast lesion did not fit a more specific category.

RESULTS:

Of the 3934 breast FNAs performed on palpable breast masses from January 2000 to December 2005 at the LAC + USC Medical Center, 317 (8.1%) were diagnosed cytologically as proliferative breast lesion with atypia, without atypia or without mention of atypia. There was subsequent histopathology on 201 of these cases. After the cytologic smears were reviewed, 29 cases were excluded from this study. Of the 172 remaining cases, 21 (12.2%) were found to be malignant and the remaining 151 (87.8%) were found to be benign on histology. Of the malignant cases, 90% had an FNA diagnosis of proliferative breast lesion with atypia; of the benign cases, 78% were interpreted as proliferative breast lesion without atypia.

CONCLUSIONS:

Proliferative breast lesion with atypia was clinically significant because it was associated with a significantly increased likelihood of malignancy compared with proliferative breast lesion without atypia. Most of the malignancies had hypocellularity or low nuclear grade on the FNA smears. Fibroadenoma accounted for most of the benign lesions in both proliferative breast lesion and proliferative breast lesion with atypia. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Fine-needle aspiration of the thyroid

BACKGROUND: Although fine-needle aspiration (FNA) of the thyroid is the key preoperative investigation of thyroid lesions, there are overlaps in the criteria for diagnosis of certain lesions, particularly important among which are those for follicular neoplasms. A proposal for a 5-category working system for thyroid FNA diagnosis is presented, devised using clearly defined diagnostic guidelines with a prospective 2-year evaluation in 1 center. METHODS: The results of FNA of 156 patients with nodular thyroid lesions are presented. All patients were observed over a 2-year period in a multidisciplinary thyroid clinic. In some cases, the aspirates were repeated before excision of the lesion. The results of the FNA are classified by worst category for each patient, according to a 5-category scheme: THY1: inadequate; THY2: benign; THY3: indeterminate; THY4: suspicious lesion; THY5: malignant. RESULTS: Seventy-five of the 156 patients (48.1%) proceeded to excision, of these 50 (67%) showed multinodular goiter or adenomatoid nodule within a goiter, 7 (9.3%) showed evidence of Hashimoto thyroiditis or lymphocytic thyroiditis alone, 1 (1.3%) showed evidence of Reidel thyroiditis, and 1 (1.3%) showed evidence of a parathyroid cyst. Eight patients (11%) showed evidence of follicular adenoma, and 5 patients (6.6%) showed papillary carcinoma; 1 (1.3%) showed follicular carcinoma, and 2 (2.7%) showed lymphoproliferative disease. There was a significant difference in the number of benign as compared with neoplastic thyroid lesions excised in the indeterminate (THY3) (2 of 13 [15%]) as compared with the suspicious categories (THY4) (10 of 24 [42%]), (P = 0.05). Although no false-negative FNAs were identified in this series, there was 1 false-positive (THY5) FNA. CONCLUSIONS: The use of an indeterminate (THY3) category is helpful because it improves the diagnostic efficacy of thyroid FNA. The indeterminate (THY3) category is clinically useful and may markedly reduce or eliminate false-negative FNA in many patients with thyroid nodules. Cancer (Cancer Cytopathol) Copyright 2000 American Cancer Society.     

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident

BACKGROUND:

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to ¹³¹I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine‐needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.

METHODS:

During the first screening cycle (1998‐2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

RESULTS:

All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered “positive” or “negative,” the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.

CONCLUSIONS:

Among children and adolescents who were exposed to ¹³¹I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. Cancer (Cancer Cytopathol) 2009. Published 2009 by the American Cancer Society.     

Potential pitfalls of needle tract effects on repeat thyroid fine‐needle aspiration

BACKGROUND:

Fine‐needle aspiration (FNA) is a screening and diagnostic tool used in the evaluation of thyroid nodules. Its use has resulted in an increase in the ratio of malignant versus benign thyroid nodules undergoing surgical excision. However, the FNA procedure produces some histological and cytologic alterations, which may lead to misinterpretation on repeat FNA. The goal of the current study was to characterize FNA‐induced morphological alterations and their potential influence on interpretations in repeat FNA specimens.

METHOD:

Thyroidectomy specimens that had benign histological diagnoses and for which previous FNA specimens were available were retrieved. The FNA‐induced histological alterations were evaluated and grouped based on the interval between the FNA procedure and surgical excision. Repeat thyroid FNA specimens with a cytologic diagnosis of “atypical cells/follicular lesion” were reviewed. Worrisome cytologic features that might occur after the previous FNA procedure were discussed.

RESULTS:

Needle tracts were identified in 68 of the 96 thyroidectomy specimens studied. FNA‐induced histological alterations included hemorrhage, granulation, exuberant fibroblastic reaction, reactive follicular cells, infarction, and scarring. The presence of plump endothelial cells, myofibroblasts, and, particularly, reactive follicular cells with nuclear grooving and nuclear clearing are potential pitfalls in repeat FNA and these changes are reported to peak within 20 to 40 days after the FNA procedure. Sixteen of 152 repeat FNA cases were diagnosed as atypical cells/follicular lesion, and FNA‐induced changes might have contributed to the diagnosis in 2 of these 16 cases.

CONCLUSIONS:

Cytologists should be aware of atypical cellular changes caused by previous FNA procedures. Although uncommon, these changes may become potential pitfalls in the cytologic diagnosis of repeat thyroid FNA specimens. Cancer (Cancer Cytopathol) 2013. © 2012 American Cancer Society.     

Cytomorphological and molecular genetic findings in pediatric thyroid fine‐needle aspiration

BACKGROUND:

The Bethesda System for Reporting Thyroid Cytopathology is largely based on data from adult studies. Although thyroid nodules in children are rare, the rate of malignancy is high. The authors' aim was to analyze the cytomorphology and mutational profiles in pediatric thyroid fine‐needle aspirations (FNAs).

METHODS:

Thyroid FNAs from patients 21 years old or younger were identified from the authors' pathology archive, categorized using the Bethesda System for Reporting Thyroid Cytopathology, and correlated with histological and molecular follow‐up.

RESULTS:

A total of 179 samples from 142 patients were identified, including 96 cases (54%) with histological follow‐up and 66 cases (37%) with molecular data. The diagnoses included 21 (12%) unsatisfactory, 82 (46%) negative, 43 (24%) atypia or follicular lesion of undetermined significance, 19 (11%) suspicious for follicular neoplasm, 6 (3%) suspicious for malignancy, and 8 (4%) positive for malignancy. The rate of malignancy in each category was 0%, 7%, 28%, 58%, 100%, and 100%, respectively. Of the 66 FNAs with molecular data, there were 11 (17%) positive for mutations. All mutation‐positive FNAs were papillary thyroid carcinomas (PTCs) on resection. The overall sensitivity and specificity in this population were 80% and 100%, respectively.

CONCLUSIONS:

This study demonstrates that thyroid FNA in children is a sensitive and highly specific tool. There was a 17% positivity rate for a genetic mutation, which correlated with malignancy in all cases. In comparison to adults, there was a higher prevalence of RET/PTC mutations and lower prevalence of BRAF mutations, which may in part explain the less aggressive nature of PTCs reported in children. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.     

Malignant solitary fibrous tumor

BACKGROUND:

Malignant solitary fibrous tumors (SFTs) are extremely uncommon and poorly understood mesenchymal neoplasms. There are only rare published accounts of the cytopathologic features of these tumors, prompting the current study.

DESIGN:

All cases of malignant SFT with preoperative fine‐needle aspirations (FNAs) from 1999 to 2008 were retrieved from the archives of 3 large teaching hospitals. FNA smears and cell block material including immunoperoxidase stains were reviewed, and the cytologic characteristics were described.

RESULTS:

Thirteen cases of malignant SFT were identified in 11 patients. Mean age was 58 years, with a men:women ratio of 1:2.6. The tumors were generally large, with a mean size of 13.4 cm. Cytomorphologic features included mostly hypercellular smears with tissue fragments of monotonous, plump spindled cells with blunt‐ended and indented nuclei and fragile, wispy cytoplasm. Also seen were bare nuclei, occasional mitoses, and rare necrosis. Some cases showed a predominance of epithelioid cells, whereas others displayed a loose myxomatous matrix. There was a general lack of single cells. None of the cases was diagnosed accurately as malignant SFT on FNA, and only 6 cases were called malignant or suspicious for malignancy.

CONCLUSIONS:

The FNA diagnosis of malignant SFT is extremely difficult and needs histologic material for accurate interpretation. Predominant FNA diagnoses were SFT or spindle cell neoplasm. Malignant SFT must be included in the differential diagnosis of a spindle cell neoplasm of any anatomic site, particularly if it displays features not typical of benign SFT. Immunoperoxidase staining has some utility, mainly in ruling out other neoplasms in the differential diagnosis. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

The indeterminate thyroid fine‐needle aspiration

BACKGROUND:

To date, thyroid fine‐needle aspiration (FNA) has been used by clinicians as the screening test of choice to determine whether surgery is required and this is what the pathology report should communicate. Standard terminology for reporting thyroid FNA has not been implemented yet, and pathologists have used various reporting systems to communicate results. A significant source of confusion among both pathologists and clinicians has been the use of the indeterminate category. On the basis of an analysis of 1150 thyroid FNAs in 2000, this institution modified the reporting of thyroid biopsy results into 6 categories, including unsatisfactory. The indeterminate category was separated into 3 subroups: 1) indeterminate for neoplasia (IND), 2) follicular neoplasm (FN), and 3) suspicious for malignancy (SUSP). Repeat FNA in 6 months to 12 months was recommended for IND and surgery for FN and SUSP categories.

METHODS:

To determine the validity of this approach, the outcomes of this reporting system from July of 2000 to December of 2006 were analyzed. The IND category was used for 2 subsets of cases: (a) those that morphologically fall into the gray zone between adenomatoid nodule (AN) and FN, for Hurthle cell nodule (hyperplasia vs neoplasm), and chronic lymphocytic thyroiditis with concern for neoplasia; and (b) for suboptimal specimens due to low epithelial cellularity or collection artifacts.

RESULTS:

Among 5194 thyroid nodules, the IND category comprised 18%. FNA follow‐up was done in 21% of IND cases: 58% were benign/negative and did not require surgery based on cytology alone. Surgical follow‐up in 46% of IND showed 52% were benign/negative, and 42% were follicular/Hurthle cell adenomas. The surgical yield of malignancy in IND was low (6%) when compared with the FN category, which was 14% (more than 2× that of the IND category), and the SUSP category, which was 53% (almost 9× that of the IND category).

CONCLUSIONS:

A 6‐tier reporting system for thyroid FNA was effective for determining which patients needed surgery versus follow‐up FNA and also guided the clinician on the extent of surgery. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.