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.     

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.     

The use of the Bethesda terminology in thyroid fine-needle aspiration results in a lower rate of surgery for nonmalignant nodules: a report from a reference center in Turkey

The Bethesda system (BS) for reporting thyroid fine-needle aspiration (FNA), which classifies nodules as nondiagnostic (ND), benign (B), atypia/follicular lesion of undetermined significance (AUS/FLUS), suspicious for follicular neoplasm (SFN/FN), suspicious for malignancy (SFM), or malignant (M), uses clinically valuable management guidelines. The authors employed a similar in-house classification system (IS) for thyroid FNAs, using the categories of ND, B, suspicious follicular cells (SFC), follicular lesion/neoplasm (FL/FN), SFM, and M. The authors compared IS and BS, and assessed the utility of BS in clinical practice. A total of 581 nodules with cytological/histological follow-up were examined and indeterminate lesions by BS were reclassified. The sensitivity and specificity for malignancy using IS were similar to that of BS (77% vs 99%). However, when SFN/FN and SFM were both considered positive, the results for IS and BS were as follows: sensitivity, 85% versus 85%; specificity, 87% versus 94%; and diagnostic accuracy, 86% versus 90%, respectively. Discrepancies between cytological and histological data were evident in 35 cases among all categories of BS except AUS/FLUS. The rate of surgery for nonmalignant nodules was lesser (20% vs 9%) by BS. Among 34 AUS/FLUS cases with follow-up data, hypocellularity was the case in 11 (46%) nonneoplastic and 10 (100%) neoplastic nodules. The use of BS results in a lower rate of surgery for nonmalignant nodules even though patients with borderline cytopathologic features are still encountered. AUS/FLUS category can be separated into subgroups according to the factors causing difficulties in the interpretation. There is a need of accumulation of AUS/FLUS cases to do further evaluations and studies.     

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.     

Implications of the proposed thyroid fine‐needle aspiration category of “follicular lesion of undetermined significance”: A five‐year multi‐institutional analysis

National Cancer Institute State of the Science Conference on thyroid fine‐needle aspiration (FNA) summarized diagnostic terminology. Six diagnostic categories were proposed including “follicular lesion of undetermined significance” (FLUS). FLUS was defined as findings neither convincingly benign nor sufficiently atypical for a diagnosis of “follicular neoplasm” or “suspicious for malignancy.” It was proposed that this category represent less than 7% of thyroid FNAs. A search of the cytology records at three University Hospitals was performed for the term FLUS or older equivalent terms. Usage of FLUS was compared between institutions and among pathologists. Surgical pathology outcome for FLUS cases was determined. Twenty‐eight pathologists evaluated 6,872 cases at the three institutions. Use of FLUS varied among pathologists (2.5 to 28.6%). Frequency of use of FLUS among institutions varied from 3.3 to 14.9%. FLUS cases [127 of 673 (18.9%)] underwent surgical exploration with malignancy identified in 36 cases (28.3%) undergoing resection. Use of FLUS varied substantially among pathologists and institutions. FLUS category requires more rigorously defined morphologic criteria for it to become a useful guide in clinical management. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of the diagnostic accuracy of thyroid fine‐needle aspiration in follicular‐patterned lesions using a 5‐tiered and a 6‐tiered diagnostic system: A double‐blind study of 140 cases with histological confirmation

Five‐tiered and 6‐tiered systems for reporting thyroid fine‐needle aspiration (FNA) results are used widely throughout the world. In this study, we present a double‐blind study of histologically confirmed follicular‐patterned neoplasms and evaluate the cytological classification of the same lesions according to both systems. One hundred and forty consecutive surgically resected thyroid follicular‐patterned lesions with a diagnostic preoperative FNA were retrieved from our archive. Two cytopathologists, who were blinded to all clinical information, classified each FNA case according to their respective routine diagnostic reporting system (5‐tiered or 6‐tiered). Interobserver variability was assessed using Cohen's Kappa (K) coefficient. Diagnostic accuracy was determined by measuring sensitivity and specificity. Receiver operator characteristic (ROC) curves were calculated for each cytopathologist. The 140 thyroid FNAs included histologically confirmed nodular hyperplasia, follicular adenomas, follicular carcinomas, and papillary carcinomas, follicular variant (35 cases for each) obtained from 104 females and 36 males with a mean age of 48.8 years and a mean tumor diameter of 27.8 mm. Negative predictive values (PV) for benign cases were 72.2% and 68.8% in the 5‐tiered and 6‐tiered systems, respectively (P = 0.7009). Positive PV were 100% for malignant cases in both systems. The sensitivity (78.6% vs. 72.9%, P = 0.4305), specificity (55.7% vs. 47.1%, P = 0.3103), and diagnostic accuracy (67.1% vs. 60.0%, P =0.2143) were similar between the systems. ROC curves almost entirely overlapped (P = 0.8937). Both the 5‐tiered and 6‐tiered systems show similar diagnostic accuracy in follicular‐patterned lesions, further supporting the adoption of a common reporting system for thyroid cytopathology. Diagn. Cytopathol. 2014;42:744–750. © 2014 Wiley Periodicals, Inc.     

Diagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytology.

The thyroid fine-needle aspiration (FNA) diagnosis of "follicular neoplasm" does not differentiate between a benign and malignant tumor. Often cases diagnosed as "follicular or Hürthle-cell neoplasm" undergo surgical excision for further characterization. The aim of this study was to identify clinical features that may help in predicting malignancy in patients with an FNA diagnosis of follicular neoplasm. One hundred eighty-four cases in 167 patients were diagnosed as "follicular neoplasm" among 1,024 thyroid FNA evaluated with on-site interpretation from 1998-2000. The cases were evaluated for the following variables: histologic diagnosis, age, sex, and size of the nodule. One hundred thirty-nine patients were female, and 28 were male (age range, 23-80 yr). Among 122 patients (67%) undergoing surgical excision (lobectomy, 96; total thyroidectomy, 26), malignancy was identified in 37 cases (31%). Nonpapillary (follicular/Hürthle) carcinoma was diagnosed in 11 (9%), follicular variant of papillary carcinoma in 25, and medullary carcinoma in 1 case. The risk of malignancy was greater in males (47% vs. 29%, P < 0.0004) than females, in nodules measuring 3 cm or more (55% vs. 23%, P < 0.0001), than in nodules measuring less than 3 cm, and in patients 40 or more yr old (20% vs. 10%, P = 0.0001) than in patients younger than 40 years. The diagnosis "follicular neoplasm" is indeterminate, and the majority of cases (70% in the current study) are benign. However, clinical features, including gender, nodule size, and age, can be a part of the decision analysis in selecting patients for surgery.     

“Cellular adenomatoid nodules” of the thyroid: Review of 219 fine-needle aspirates

We reviewed 219 consecutive thyroid aspirates previously diagnosed as “cellular adenomatoid nodule.” applying the criteria presented in this paper and reclassifying them as 146 adenomatoid nodules (AN), 31 cellular adenomatoid nodules (CELL-AN), 29 cellular adenomatoid nodules vs. follicular neoplasms (CELL-AN vs. FN), 5 follicular neoplasms (FN), 2 FN of oxyphilic cell type, 4 papillary carcinomas, and 2 chronic lymphocytic (Hashimoto's) thyroiditis. Of the 146 adenomatoid nodules, 14 occurred in multinodular goiters on histologic examination. Of the 31 CELL-AN, five had surgery: two were follicular adenomas, one was papillary carcinoma, and two were multinodular goiters. Of the 29 CELL-AN vs. FN, 11 had surgery: six were follicular adenomas, two were follicular carcinomas, two were multinodular goiters, and one was Hashimoto's thyroiditis. Surgery on four FN showed follicular adenomas (a fifth patient was lost to follow-up). Of the two FN of oxyphilic cell type, one was a multinodular goiter and the other a follicular adenoma with oxyphilic cells. Three of the four papillary carcinomas were confirmed histologically (one patient was lost to follow-up). Of the two cases showing Hashimoto's thyroiditis, one was diagnosed as FN on repeat aspiration and follicular carcinoma at surgery. After review, we identified 40 patients at higher risk of harboring a neoplasm and 31 with cellular adenomatoid nodules. Twenty-five underwent surgery with the above results. In the classification of follicular lesions of the thyroid by FNA, adherence to strict cytologic criteria helps identify those patients who will benefit most from surgery.     

A simplified Bethesda System for reporting thyroid cytopathology using only four categories improves intra- and inter-observer diagnostic agreement and provides non-overlapping estimates of malignancy risks

Our previous study utilizing the 2008 NCI six-category system (also known as The Bethesda System) for reporting thyroid fine-needle aspirations (FNA) identified considerable overlap in diagnosis and in assigned malignancy risk estimates for the "follicular lesion of undetermined significance (FLUS)" and "follicular neoplasm (FN)" categories and for the "suspicious for malignancy (Susp)" and "malignant" categories. We proposed a simplified Bethesda System for reporting thyroid FNAs that provided four non-overlapping, statistically significant, and more clinically relevant diagnostic categories: unsatisfactory, benign, FLUS/FN, and Susp/malignant. In the current study, six cytopathologists participated in a blinded retrospective review of 60 thyroid FNAs and kappa statistics were utilized to compare the intra- and inter-observer diagnostic agreements obtained using the six-category and the simplified four-category schemes. Surgical follow-up was used to determine which scheme provided more discrete malignancy risk estimates. Use of the simplified four-category scheme significantly improved intra- and inter-observer diagnostic agreement levels, significantly increased the sensitivity of FNA for a diagnosis of carcinoma in the subsequently resected thyroid glands, and provided non-overlapping malignancy risk estimates for each diagnostic category.     

Thyroid bed fine needle aspiration in patients after thyroidectomy—a useful follow-up tool with proposed diagnostic categories

After thyroidectomy for primary thyroid malignancies, patients are closely monitored for recurrence or metastasis. Fine needle aspiration (FNA) has been used as the appropriate diagnostic modality for occult masses identified radiographically in the thyroid bed. In this study, we report our institutional experience with FNA of the thyroid bed and propose practical diagnostic categories. A retrospective chart review of all thyroid bed FNAs between April 2008 and January 2013 was performed, and a cohort of 39 patients was retrieved. The cytology diagnoses were divided into 5 categories including nondiagnostic, inflammatory/reactive, bland follicular cells, suspicious for neoplasm/malignancy, and malignant. The follow-up histologic and/or clinical findings were collected for each category. The 39 patients included 9 males and 30 females (ages 15-79 years). Prior thyroidectomies were due to papillary thyroid carcinoma (31 cases), follicular carcinoma (3 cases), medullary carcinoma (1 case), Hürthle cell carcinoma (1 case), malignancy unspecified (1 case), follicular adenoma (1 case), and multinodular goiter (1 case). Overall, 33% (13 cases) of thyroid bed FNAs were nondiagnostic, and 10% (4 cases) were categorized as “inflammatory/reactive.” None of the patients in these 2 categories demonstrated evidence of clinical recurrence. One patient with a “bland follicular cells” thyroid bed FNA diagnosis had metastatic papillary thyroid carcinoma on follow-up histology. Of 14 patients in the “suspicious” and “malignant” categories, 10 had malignant follow-up diagnosis on histology. In conclusion, thyroid bed FNA with standardized diagnostic categories is a useful modality for follow-up in patients who have undergone thyroidectomy.     

Immunohistochemical expression of HBME-1 and galectin-3 in the differential diagnosis of follicular-derived thyroid nodules

BackgroundThyroid nodules are common among adults with only a small percentage being malignant and histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management. The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histological findings. Therefore, affected patients are referred for surgery, although only 10% will have a final diagnosis of malignancy. The aim of this study was to investigate the ability of two immunohistochemical (IHC) markers; galectin-3 and Hector Battifora mesothelial-1 (HBME-1) individually or in combination, to distinguish between benign (non-neoplastic and neoplastic) and malignant (follicular and papillary carcinomas) thyroid lesions removed by surgical resection.MethodsWe investigated the immunoexpression of galectin-3 and HBME-1 in 50 cases of benign and malignant thyroid nodules. The benign group included 13 cases of thyroid nodular goiter (NG) and 9 cases of follicular adenoma (FA). The malignant group included 5 cases of follicular thyroid carcinomas (FC), 18 cases of classic papillary thyroid carcinoma and 5 cases of follicular variant papillary carcinoma (FVPC).ResultsThe staining results showed that malignant tumors expressed galectin-3 and HBME-1 significantly more than benign nodules. The sensitivity of these markers for the distinction between benign and malignant lesions ranged from 89.3% to 92.9%. Co-expression of galectin-3 and HBME-1 was seen in 82.1% of carcinomas, but in none of the benign nodules. Immunoexpression was usually diffuse in malignant tumors, and focal in the benign lesions.ConclusionOur findings indicate that these immunohistochemical markers are significantly more expressed in malignant tumors compared to benign lesions and may be of additional diagnostic value when combined with routine histology. Galectin-3 has higher sensitivity and specificity of immunoexpression in thyroid malignancy than HBME-1, and the combined use of galectin-3 and HBME-1 can increase the specificity of immunoexpression in malignant tumors.     

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.     

Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy

Aims : To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of thyroid malignancy markers including HBME-1, cytokeratin (CK) 19 and galectin-3.
Methods and results : We evaluated 170 thyroid lesions including 148 neoplastic lesions [84 papillary carcinomas (PC), 38 follicular carcinomas (FC), 18 follicular adenomas, one hyalinizing trabecular tumour, five medullary carcinomas, two anaplastic carcinomas] and 22 non-neoplastic lesions (12 adenomatous nodules and 10 Hashimoto's thyroiditis). HBME-1, galectin-3 and CK19 were expressed in 94%, 72.6%, 72.6% of PCs and in 63%, 21%, 21% of FCs. The three markers were mostly negative in all normal tissues. Although the most helpful marker in terms of sensitivity and specificity for the follicular variant of PC and for FC diagnosis was HBME-1, when we consider the differentiation between cases of follicular variant of papillary carcinoma (FVPC) and FC or adenoma, in terms of percentage of positive cells, galectin-3 and CK19 were more relevant.
Conclusions : HBME-1 is the most sensitive marker for thyroid malignancy but the three markers may be useful in specific cases. This panel of markers is useful to differentiate the follicular patterned lesions, with special reference to the FVPC.     

Follicular lesion of undetermined significance in thyroid FNA revisited

Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5–15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P < 0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS. Diagn. Cytopathol. 2014;42:18–22. © 2013 Wiley Periodicals, Inc.     

Fine-needle aspiration in the evaluation of thyroid lesions in children

The role of fine-needle aspiration (FNA) cytology in the evaluation of thyroid lesions in not as well established in children when compared with adults. Hence we aimed to ascertain the utility and limitations of FNA in childhood thyroid lesions. This was a retrospective analysis of all thyroid FNA performed in children less than 14 years of age over a 4-year period (2005-2009). Histopathological follow-up was available in six cases. A total of 77 cases were included in the analysis. The most common cytological diagnosis was lymphocytic thyroiditis (49.3%), followed by colloid goiter (18.2%), hyperplasia (10.4%), and benign aspirate (7.8%); malignancy was identified in six cases (7.8%). Of these six cases, three were papillary thyroid carcinoma. There was one false-positive case reported as a Hurthle-cell neoplasm, which on histology showed Hashimoto's thyroiditis. One case each of rhabdomyosarcoma and spindle epithelial tumor with thymus like differentiation was wrongly diagnosed as thyroid neoplasm, NOS, and medullary carcinoma (spindle variant), respectively. The overall diagnostic accuracy was 98.6% with 100% sensitivity, 98.6% specificity, 80% positive predictive value, and 100% negative predictive value. FNA is extremely valuable in the initial evaluation of thyroid swelling in children. Rare neoplasms masquerading as thyroid nodules in children can pose difficulties in diagnosis; however, papillary carcinoma is easily recognized. In lymphocytic thyroiditis, it provides a tissue diagnosis, thereby avoiding more invasive procedure for merely diagnostic purposes.     

Nuclear crease as a cytodiagnostic feature of papillary thyroid carcinoma in fine-needle aspiration biopsies

Nuclear crease or grooving was found to be a diagnostic feature of papillary thyroid carcinoma (PTC) in fine-needle aspiration (FNA) biopsies. The FNA biopsies of 37 cases of PTC, 50 cases of multinodular goiter, and 50 cases of follicular neoplasms (45 follicular adenomas and five follicular carcinomas) were examined. The diagnosis was histologically verified in all the cases. The nuclear crease was found to be present in 34 of 37 cases of PTC and in two of five cases of follicular carcinoma. There was no nuclear crease in any of the other cases examined. Thus, it is concluded that the nuclear crease is a fairly constant and characteristic feature of PTC in FNA biopsies and can be used as a valuable diagnostic criterion.     

Cytopathologic analysis of thyroid lesions in the pediatric population

Fine-needle aspiration (FNA) of the thyroid is seldom performed in the pediatric population. Therefore, the clinical utility of thyroid FNA in this patient group has not been adequately addressed. A 15 yr retrospective review of the cytopathology archives at the participating institutions was performed to identify cases of thyroid FNA performed in pediatric patients. The medical records of these cases were reviewed, including the surgical pathology reports of those patients who had subsequently undergone surgical resection. One hundred one specimens from 82 patients were identified. Of these, 40 had a cytopathologic diagnosis of carcinoma, "suspicious" for carcinoma, neoplasm, or atypia, 48 were benign, and 13 were unsatisfactory. Of the 82 patients, 45 underwent partial or total thyroidectomy. Twenty-two (49%) of these were found to harbor a malignant neoplasm (18 papillary carcinomas). The diagnostic sensitivity for identifying a lesion was 87% (26/30) and the diagnostic specificity was 92% (47/51). There were four false-positives and four false-negatives in the review, yielding a positive predictive value of 87% and a negative predictive value of 92%. We conclude that FNA is a useful adjunct to the management of thyroid lesions in the pediatric population, with good diagnostic accuracy. Although thyroid neoplasms are relatively rare in children, our experience demonstrated that 40% of thyroid masses referred for FNA had an interpretation that caused concern, ranging from "atypical" to carcinoma. Additionally, a benign diagnosis by FNA may avoid unnecessary surgery with its potential complications, a significant consideration for this age group.     

Retinoblastoma expression in thyroid neoplasms.

Retinoblastoma (Rb) mutation in thyroid neoplasia has been identified in a few molecular studies; however, the utility of Rb immunohistochemistry in distinguishing benign and malignant thyroid lesions has not been documented in formalin-fixed, paraffin-embedded tissues. The present study investigated Rb immunohistochemistry in a series of 111 formalin-fixed, paraffin-embedded benign and malignant thyroid lesions. All of the major histologic subtypes were included to detect any heterogeneity in Rb-1 expression that might influence the diagnostic utility of this technique or further elucidate the pathogenesis of thyroid neoplasia among the categories. Altogether, 34 follicular adenomas, 9 follicular carcinomas, 7 Hürthle cell adenomas, 5 Hürthle cell carcinomas, 23 papillary carcinomas (8 of which were follicular variants), 4 insular carcinomas, 4 anaplastic carcinomas, 6 medullary carcinomas, and 19 nodular goiters were analyzed. Avidinbiotin immunohistochemistry was performed using the Dako Rb-1 clone. Pronase digestion was introduced into the epitope retrieval protocol to eliminate false-positive cytoplasmic stainig. Nuclear immunoreactivity was assessed as positive if 10% or more of thyroid epithelial nuclei stained positively, and conversely as negative. The majority of benign non-Hürthle thyroid lesions, whether hyperplastic or neoplastic, retained Rb nuclear immunopositivity in most cells (51 of 53 cases [96%]). Conversely, malignant thyroid neoplasms lacked Rb immunoreactivity in the majority (42 of 51 cases [82%]), including all papillary carcinomas (23 of 23) and almost all follicular carcinomas (8 of 9 [89%]). Virtually all Hürthle cell neoplasms were negative (11 of 12 [92%]), whether benign or malignant. In conclusion, Rb immunohistochemistry can aid in the distinction between benign and malignant thyroid lesions in conjunction with morphology. This seems to be most applicable to the often problematic differentiation between follicular adenoma and the follicular variant of papillary carcinoma (P < .0001; sensitivity and specificity, 100%) or minimally invasive follicular carcinoma (P = .0007; sensitivity, 89%; specificity, 100%).     

Parathyroid hormone assay in fine-needle aspirate is useful in differentiating inadvertently sampled parathyroid tissue from thyroid lesions

To assess the utility of chemical analysis for parathyroid hormone in the rinse (PTH-r) obtained via fine-needle aspiration (FNA) in the setting of inadvertently sampled parathyroid tissue or lesions (PTL) during "thyroid" or "neck" FNA, the authors review their experience at a large, tertiary care academic medical center. All cases of inadvertent sampling of PTL during "thyroid" or "neck" FNA were identified by computer search. The cytologic and histologic material was reviewed and pertinent clinical data including patient demographics, serum calcium, intact serum PTH (PTH-s), and intact PTH-r was recorded. The cytologic interpretations and histologic diagnoses were also recorded. Of 3,521 cases of total thyroid and neck FNA during the study 21 (0.59%) cases of histologically confirmed sampling of PTL were identified. In all 10 cases with PTH-r the level was markedly elevated (range 248-240,075 pg/mL) and in every case PTH-r/PTH-s was elevated (range 3.67-458.3). In all 10 cases with PTH-r the cytologic diagnosis was PTL or included PTL in the differential. In 4/11 cases without PTL-r diagnoses of thyroid neoplasm or suspicious for thyroid neoplasm were rendered, each resulting in thyroidectomy. PTH-r has utility in differentiating PTL from thyroid lesions in the setting of inadvertent sampling of PTL during thyroid or neck FNA. Cellular specimens with features not typical for thyroid lesions should be triaged for PTL-r. Routine use of PTH-r will result in appropriate triage of patients to less aggressive excisional biopsies rather than unnecessary thyroidectomy.     

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.