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Acta Cytologica 2011;55:499–506 DOI: 10.1159/000333234

The UK Royal College of Pathologists Thyroid Fine-Needle Aspiration Diagnostic Classification Is a Robust Tool for the Clinical Management of Abnormal Thyroid Nodules

Claudia Lobo a Andrew McQueen c Tim Beale c Gabrijela Kocjan b

a Department of Pathology, Portuguese Oncology Institute (IPOP), Porto , Portugal;Departments of b Cellular Pathology and c Radiology, University College London, London , UK

sion: The current thyroid FNA classification system used in the UK, which is comparable to TBSRTC, offers a sound basis for clear communication on which the management of pa-tients with abnormal thyroid FNA findings can be based. Cat-egories Thy3f, Thy4, and Thy5 carry a progressively rising risk of malignancy, justifying their continuing use. Diagnostic category Thy5 ‘malignant’ is robust and can be used as a sure indication of a definitive surgical management.

Copyright © 2011 S. Karger AG, Basel

Introduction

In recognition of the role that thyroid fine-needle aspi-ration (FNA) cytology has in the clinical management of patients with thyroid pathology, in the last few years there has been a surge of discussion on unifying the systems for reporting thyroid FNA, which in 2007 after the Thyroid FNA State of the Science Consensus Conference proposed by the National Cancer Institute (NCI) culminated in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) [1, 2] . Following the US example, the European Working Group reached a consensus to either adopt the TBSRTC in its original version or adapt their existing na-tional classifications to TBSRTC [3] . In the UK, the system currently in use is the British Thyroid Association/Royal

Key Words

Thyroid diagnosis � FNA cytology � Bethesda thyroid classification � Thyroid cancer � Risk of malignancy

Abstract

Objective: To compare the outcomes and evaluate the rela-tive risk of thyroid cancer by using the UK thyroid fine-nee-dle aspiration (FNA) cytological diagnostic categories, with the main objective being the clarity of patient management. Study Design: Results of thyroid FNA reported as Thy3a, Thy3f, Thy4, and Thy5 were correlated with histological out-comes. The specificity and positive predictive value (PPV; risk of malignancy) for each reporting category was assessed. Results: Of a total of 873 thyroid FNAs, 237 (27%) were re-ported as ‘abnormal’: 40 (4.6%) as Thy3a, 119 (13.6%) as Thy3f, 20 (2.2%) as Thy4, and 58 (6.6%) as Thy 5. The final outcomes were available in 136 (57%) cases which underwent surgical resection (25, 60, 55, and 74% of Thy3a, Thy3f, Thy4, and Thy5, respectively). The known outcomes of the Thy3a category were too low to be statistically significant. The specificity and PPV of the Thy3f, Thy4, and Thy5 (equivalent to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) IV, V, and VI) categories were 50, 50, and 100% and 28, 64, and 100%, respectively. The PPV of Thy3f for diagnosis of ‘neoplasms’ (benign and malignant) was 63%. Conclu-

Received: June 23, 2011 Accepted: September 9, 2011 Published online: December 9, 2011

Correspondence to: Dr. Claudia Lobo Department of Pathology, Portuguese Oncology Institute, Porto (IPOPFG, EPE) Rua Dr. Antonio Bernardino de Almeida PT–4200-072 Porto (Portugal) Tel. +351 22 508 4000, E-Mail cslobo_77 @ hotmail.com

© 2011 S. Karger AG, Basel0001–5547/11/0556–0499$38.00/0

Accessible online at:www.karger.com/acy

http://dx.doi.org/10.1159%2F000333234

Lobo /McQueen /Beale /Kocjan

Acta Cytologica 2011;55:499–506500

College of Pathologists (BTA/RCPath) terminology, first published in 2002 and modified in 2009 [4] .

We were interested in the robustness of the newclassification systems in determining clinical manage-ment, in particular in the outcomes of patients whose FNAs were reported as abnormal. These were classified as BTA/RCPath categories Thy3a, Thy3f, Thy4, and Thy5 (TBSRTC III, IV, V, and VI, respectively). We compared the outcomes and evaluated the relative risk of thyroid cancer for each cytological diagnostic category, with the main objective being the clarity of patient management.

Materials and Methods

In the period between January 2008 and August 2010, a total of 873 thyroid FNAs were performed at the Department of Cellular Pathology, University College London. The data was retrieved from the Department data base using the SNOMED codes.

The study group consisted of 232 patients comprising 176 fe-males and 56 males (female-to-male ratio = 3.14), with a mean age at diagnosis of 45.3 years and a median of 42 years (range 5–91) in which the FNA diagnosis was abnormal. This consisted of 237 FNA samples (29.3%) reported as Thy3a, Thy3f, Thy4, and Thy5 (TBSRTC III, IV, V, and VI, respectively).

A total of 209 thyroid FNAs were performed by a radiologist with ultrasound guidance and 23 FNAs were performed by a cy-topathologist using palpation only. The size of the nodules ranged from 1.0 cm onwards. Direct smears were prepared from each pass and were either air dried and stained with the May-Grün-wald Giemsa stain or fixed in alcohol and stained using the Papa-nicolaou method. On-site assessment of adequacy was performed routinely in 196 cases when a cytopathologist was present in the clinic. The remaining samples were received from outside hospi-tals as referral slides.

Cytological Diagnostic Terminology and Interpretation The UK BTA/RCPath Thyroid Classification [4] was used for

interpretation of the thyroid FNAs according to the definitions listed below. For comparison, the corresponding TBSRTC thyroid categories are shown in table 1 .

Thy3a (TBSRTC III equivalent) – atypia of undetermined sig-nificance (AUS): samples which exhibit cytological atypia or oth-er features which raise the possibility of neoplasia but which are insufficient to enable confident placing into any other category. Situations would include: (a) samples in which there is architec-tural ‘atypia’, in the form of a mixed micro and macrofollicular pattern (approximately equal proportions of each), where a defi-nite distinction between a follicular neoplasm (FON) and hyper-plastic nodule is difficult; (b) a specimen where only sparse colloid is evident and where a definite distinction between a FON and a hyperplastic nodule is difficult; (c) sparsely cellular samples containing predominantly microfollicles; (d) focal cytological changes which are most probably benign but where papillary car-cinoma cannot be confidently excluded; (e) a compromised spec-imen (e.g. obscured by blood, or a poorly spread smear) where some cells appear to be mildly abnormal but are not obviously

from a FON or suspicious of, or indicative of, malignancy, and (f) atypical ‘cyst lining cells’.

Thy3f (TBSRTC IV) – FON or suspicious for FON: samples suggesting FON. These are likely to form the majority of the Thy3 category. The histological possibilities therefore include hyper-plastic or other cellular but nonneoplastic nodules, as well as neo-plasms, including follicular adenomas and follicular carcinomas. Follicular variants of papillary thyroid carcinoma (PTC) without

Table 1. T he BTA/RCPath modified BTA nomenclature and com-parison with TBSRTC (modified from Redman et al. [21] and Yas-sa et al. [42]): recommended diagnostic categories

BTA/RCPath (UK) Bethesda (TBSRTC)

Nondiagnostic for cytological diagnosis (Thy1)

I. Nondiagnostic or unsatisfactory Virtually acellular specimen; other (obscuring blood, clotting artifact, etc.)

Nondiagnostic for cytological diagnosis – cystic lesion (Thy1c)

Cyst fluid only

Nonneoplastic (Thy2)

II. Benign Consistent with a benign follicular nodule (includes adenomatoid nodules, colloid nodules, etc);consistent with lymphocytic ( Hashimoto) thyroiditis in the proper clinical context

Nonneoplastic, cystic lesion (Thy2c)

Consistent with granulomatous (subacute) thyroiditis; other

Neoplasm possible – atypia/nondiagnostic (Thy3a)

III. AUS or FOL of undetermined significance

Neoplasm possible, suggesting FON (Thy3f)

IV. FON or suspicious for a FON Specify if Hürthle cell (oncocytic) type is present

Suspicious of malignancy (Thy4)

V. Suspicious for malignancy Suspicious for papillary carcinoma; suspicious for medullary carcinoma; suspicious for metastatic carcinoma; suspicious for lymphoma; other

Malignant (Thy5) VI. Malignant PTC; poorly differentiated carcinoma; MTC; undifferentiated (anaplastic) carcinoma; squamous cell carcinoma; carcinoma with mixed features (specify);metastatic carcinoma; non-Hodgkin’s lymphoma; other

The UK RCPath Thyroid FNA Diagnostic Classification

Acta Cytologica 2011;55:499–506 501

clear nuclear features of papillary thyroid cancer may fall in-to this category. These cannot be reliably distinguished on cytol-ogy alone. Samples consisting almost exclusively/exclusively of Hürthle cells are also included here.

Thy4 (TBSRTC V) – suspicious of malignancy: samples which are suspicious for malignancy but which do not allow a confident diagnosis of malignancy. This includes specimens of low cellular-ity and mixed cell types (normal and atypical). The tumor type suspected should be clearly stated and is often a papillary carci-noma.

Thy5 (TBSRTC VI) – malignant: samples that can be confi-dently diagnosed as malignant. The tumor type should be clearly stated, e.g. PTC, medullary thyroid carcinoma (MTC), anaplastic thyroid carcinoma, lymphoma, and other malignancy, including potentially nonthyroid/metastatic malignancy.

This five-tier numerical reporting system for thyroid FNA has been in use at University College London since 2005 and was adapted following the 2009 RCPath guidelines. [4] .

Histopathology of the 136 cases that underwent surgery was reported in line with RCPath guidance for the reporting of thy-roid histopathology [5, 6] and for the purposes of this study was divided into ‘benign, nonneoplastic’ lesions, including nodular/adenomatoid hyperplasia and multinodular goiter, and ‘neoplas-tic’ lesions which comprised benign (follicular adenoma) andmalignant neoplasms (PTC, follicular thyroid carcinoma, MTC, thyroid carcinoma nonspecified, anaplastic thyroid carcinoma, squamous cell carcinoma, and lymphoma).

Histological diagnosis of patients who had undergone surgery was used as the ‘gold standard’ for correlation with the cytologi-cal diagnosis. Surgery usually included either partial or total thy-roidectomy. In those cases where a histological report for direct correlation with the cytological diagnosis was not available be-cause they were either awaiting surgery or surgery was not planned were considered as ‘no follow-up available’ ( table 2 ). When more than one nodule in the same patient underwent FNA, the most abnormal FNA result was used for analysis. Spec-imens with discrepant cytological and histological diagnoses were reviewed to determine plausible explanations for the dis-crepancies.

The FNA and surgical pathological reports were correlated and the specificity and positive predictive value (PPV) were re-corded for each abnormal reporting category (Thy3a and above). Since the study does not include ‘ negative’ reports or their follow-up, we could not identify ‘false negatives’ and could therefore not calculate the sensitivity or negative predictive value.

Results

In the study period there were a total of 873 thyroid FNAs performed. Of these, there were 33 (3.7%) cases re-ported as Thy1 (TBSRTC I), 603 (69%) as Thy2 (TBSRTC II), 40 (4.6%) as Thy3a (TBSRTC III), 119 (13.6%) as Thy3f (TBSRTC IV), 20 (2.2%) as Thy4 (TBSRTC V), and 58 (6.6%) as Thy5 (TBSRTC VI). The study group comprised 237 (27.1%) cases reported as Thy3a (TBSRTC III), Thy3f (TBSRTC IV), Thy4 (TBSRTC V), and Thy5 (TBSRTC VI) ( fig.1 ; table 2 ). Of these, the final outcomes were avail-able in 136 (57.4%) cases which underwent surgical resec-tion ( table 3 ).

The Thy5 (TBSRTC VI) ‘malignant category’ com-prised 58 (24.5%) cases. Cytological diagnoses were the following: PTC in 55 cases, anaplastic thyroid carcinoma in 1 case, non-Hodgkin’s lymphoma in 1 case, and squa-mous cell thyroid carcinoma in 1 case. Forty-three (74.1%) of the 58 Thy5 (TBSRTC VI) cases underwent surgery and the original cytological diagnosis was con-firmed as malignant in all cases. In 1 case, the original cytological diagnosis of PTC turned out to be MTC on histology. The histological diagnosis of non-Hodgkin’s lymphoma was Burkitt’s lymphoma and the histological interpretation of the squamous cell thyroid carcinoma was a transformation from PTC. Since the Thy5 catego-ry did not have any false-positive (FP) cases, the specific-ity and PPV of Thy5 (TBSRTC VI) for diagnosis of ma-lignancy was 100%.

The cytological category Thy4 ( TBSRTC V), ‘suspi-cious for malignancy’, comprised 20 patients, with al-most all cases interpreted as ‘suspicious for PTC’ and only one reported as ‘suspicious for lymphoma’. Eleven of the 20 patients underwent surgery and malignancy was diag-nosed in 7 cases. The remaining 4 cases were found to be benign lesions. Of these, one was neoplastic (adenoma) and 3 were nonneoplastic (hyperplasia) on histology. Ac-cordingly, there were 7 TP, 4 FP, and 4 TN cases. The

Table 2. C omparison of the FNA diagnoses and follow-up data in the study population (Thy3a and above)

Thy TBSRTC n Malignant Benign Awaiting operation No surgery Unknown

3a III 40 4 6 (1 adenoma) 5 21 43f IV 119 20 52 (25 adenomas) 11 32 44 V 20 7 4 (1 adenoma) 3 3 35 VI 58 43 0 3 6 6

Total 237 74 62 22 62 17



specificity (TN/TN + FP) of Thy4 (TBSRTC V) for diag-nosis of malignancy was 50% and PPV (TP/TP + FP) 64%.

Thy3f (TBSRTC IV) was the most frequent abnormal diagnosis, corresponding to 50.2% (119 cases) of our study population. Seventy-two (60.5%) of the 119 patients underwent surgery. Of these, 45 were found on histology to be ‘neoplastic’ lesions, including 25 benign (follicular adenoma) and 20 malignant neoplasms (13 follicular car-cinomas, 6 PTC, and 1 MTC). In 27 cases, the histological findings were ‘benign, nonneoplastic lesions’ (20 hyper-plastic nodules and 7 cases of multinodular goiter), which were considered FP. The specificity (TN/TN + FP) of

Thy3f (TBSRTC IV) for diagnosing ‘neoplasms’ includ-ing malignancy of the thyroid is 50%. When calculating the PPV of Thy3f, we made separate calculations for the Thy3f category as a predictor of ‘neoplastic’ (including adenomas) and ‘malignant’ outcomes. The PPV (TP/TP +FP) of Thy3f for the diagnosis of thyroid ‘neoplasms’ is 63% (45/45 + 27). The PPV of Thy3f for the diagnosis of malignancy is 28% (20/20 + 52).

The Thy3a (TBSRTC III) ‘atypical category’ com-prised 40 of the 237 patients of the study population. Ten cases (25%) underwent surgery, with the histological out-come being a ‘benign, nonneoplastic’ lesion in 5 cases and a ‘neoplasm’ in 5 cases (1 follicular adenoma, 3 PTC, and 1 follicular carcinoma). Eighteen patients had a negative repeat FNA as part of a follow-up procedure. Thirty pa-tients did not have a cytohistological correlation at the time of the present study and consequently we consider the number of cases in this group to be too small to be statistically significant.

Discussion

FNA cytology has been widely accepted as the diag-nostic procedure of choice in the evaluation of patients presenting with nontoxic nodules [7, 8] . Thyroid cytology can provide a definite diagnosis of malignancy, often specifying the tumor type, enabling appropriate thera-peutic surgery in one stage. The primary objective is both to triage patients, that is, to determine whether or not

Table 3. D etailed breakdown of the cytohistological correlation in the 136 patients who underwent surgery

Benign M alignant

Thy n CN HN/MNG FA PTC SCC FTC MTC ATC NHL

3a 10 1 4 1 3 13f 72 27f 25 6g 13d, e 14 11 3 1 5 1b 1c

5 43 39a 1 1 1 1

Total 136 1 34 27 53 1 15 2 1 2

Thy2

Thy3a

Thy3f

Thy4

Thy5

Thy1

69%

3%

873 thyroid FNA cases in a 20-month period

4%

13%

7% 4%

Fig. 1. Relative proportions of thyroid FNA reporting categories at University College London from January 2009 to August 2010.

CN = Colloid nodule; HN/MNG = hyperplastic nodule/mul-tinodular goiter; FA = follicular adenoma; SCC = squamous cell carcinoma; FTC = follicular thyroid carcinoma; NHL = non-Hodgkin’s lymphoma.

a Thirty-four classical variants, 2 follicular variants, 2 micro-carcinomas, and 1 solid variant. b Minimally invasive follicular carcinoma + PTC. c High-grade non-Hodgkin’s lymphoma with

morphological, immunocytochemical, and genetic features of Bur kitt’s lymphoma. d Seven minimally invasive: 1 associated mi-cropapillary carcinoma and 1 associated follicular adenoma. e Six widely invasive: 4 oncocytic variants. f One case with incidental micropapillary carcinoma. g One case with the classical variant, encapsulated type, 1 case with the mixed follicular and papillary pattern, and 1 case with the follicular variant.



surgical intervention is indicated, and to assist in decid-ing the appropriate surgical procedure when necessary [4, 9–14] . Despite a long history of clinical application of FNA in the diagnosis of thyroid nodules and attempts by several professional organizations to clarify appropriate utilization, terminology, diagnostic criteria, post-FNA follow-up, and therapeutic options, until relatively re-cently no universally accepted guidelines for reporting or recommendations for management existed. In the past few years, clinical practice guidelines and recommenda-tions have been developed by many, including the Papa-nicolaou Society, the American Thyroid Association of Clinical Endocrinologists, the Italian Association for Medical Endocrinology, and the BTA/RCPath [15] . In October 2007, the NCI sponsored a conference to review the state of the science for the use of FNA in the manage-ment of thyroid nodules. This conference included an in-terdisciplinary program with a permanent website and a 2-day meeting at Bethesda in an attempt to establish a standardized diagnostic terminology/classification sys-tem and morphological criteria for reporting thyroid FNA [15–21] . One of the recommendations endorsed by the conference and published in 2010 is the establishment of a six-tiered diagnostic classification system based on a probabilistic approach [22] . In the meantime, during 2008 and 2009, the UK RCPath adapted the existing BTA five-tier classification which was already in use since 2002 and, after a period of consultation, made it available in November 2009 [4] . A recently published interobserv-er reproducibility study for reporting thyroid FNA using this classification showed a good agreement between 6 experienced cytopathologists for diagnosing Thy1, Thy2, Thy3f, and Thy5 (TBSRTC I, II, IV, and VI) categories and no agreement for diagnosing TBSRTC categories Thy3a and Thy4 (TBSRTC III and V equivalents) [23] .

Since the incidence of thyroid malignancy is relatively low, with approximately 1 in 20 clinically identified nod-ules being malignant, thyroid FNA can help reduce the rate of surgery for benign thyroid disease. With increas-ing confidence in the use of thyroid FNA for the diagno-sis of benign disease, the importance of the accuracy of diagnosing ‘atypical’, ‘suspicious’, and malignant lesions is becoming greater.

In an average laboratory in a nonendemic area, such as ours, the majority of the thyroid nodules are classified cytologically as benign [24, 25] . The management of these lesions will, according to the current thinking, be clinical follow-up/discharge or surgery, i.e. either a hemithyroid-ectomy for Thy3f (TBSRTC IV) and Thy4 (TBSRTC V) or a total thyroidectomy for the malignant category

(Thy5, BTSRTC VI). Until recently, various diagnostic terminologies, including ‘atypical’, ‘indeterminate’, and ‘suspicious for malignancy’, were used to describe diag-nostically challenging cases [26, 27] . Furthermore, until recently there were no uniform criteria established for the specimen adequacy [28, 29] . This resulted in diagnostic inconsistencies and difficulties in conveying the clinical implications of the thyroid FNA result to the various clin-ical teams. In short, there was no clarity in communica-tion [30] . Universally acceptable diagnostic reporting cat-egories are an excellent tool for improving such commu-nication.

Following the US and UK examples, European coun-tries agreed to reach a consensus to either adopt theTBSRTC in its original version or adapt their existing na-tional classifications to it [3] .

When discussing thyroid FNA reporting categories, we are aware that any patient management decisions must be based on a multidisciplinary team (MDT) as-sessment of the patient. The MDT usually includes aradiologist, an endocrinologist, and a surgeon, as wellas a pathologist. In the UK, BTA/RCPath guidelinesrecommend that any thyroid cytology cases categorized as Thy3a (TBSRTC III), Thy3f (TBSRTC IV), Thy4(TBSRTC V), or Thy5 (TBSRTC VI) be reviewed by a thy-roid MDT and discussed by the MDT so that a correct management plan can be made.

To assess the diagnostic accuracy of thyroid FNA, it is essential that reporting categories and outcomes be au-dited. The likelihood of malignancy for each cytological reporting category should be known locally [9, 31, 32] . Recently published data regarding thyroid cancer detec-tion for thyroid FNA [33] indicate a sensitivity for diag-nosis of malignancy of between 65 and 98% and a speci-ficity of 76–100%, with a false-negative rate of 0–5%, a FP rate of 0–5.7%, and an overall accuracy of 69–97% [34, 35] .

One of the problems with comparisons of internation-al data is how the results are categorized and analyzed. The use of standardized, consensus-based reporting cat-egories should help make better comparisons between the studies and collect evidence on which management can be based ( table 1 ).

One of the advantages of the TBSRTC classification is that it is linked to a ‘risk of cancer’ for each category, with associated clinical management recommended for each category. Our results for risk of malignancy (PPV in ab-normal categories) using BTA/RCPath fall within the range adopted by TBSRTC ( table 4 ).



The management of patients with cytological results consistent with a ‘malignant’ diagnosis usually involves surgery. The high specificity and PPV of the Thy5(TBSRTC VI) diagnosis justify the use of this category for definitive patient management (usually a total thyroidec-tomy). However, there is no current consensus concern-ing the management of nodules classified as ‘atypical’ (Thy3a, TBSRTC III), ‘follicular’ (Thy3f, TBSRTC IV), and ‘suspicious’ (Thy4, TBSRTC V). The American Thy-roid Association and the American Association of Clini-cal Endocrinologists management guidelines (2006) have proposed the term ‘indeterminate for malignancy’ for all thyroid FNA specimens which could be diagnosed as ‘fol-licular lesions’ (FOL), ‘FON’, and ‘suspicious for malig-nancy’ and recommended surgery for all patients, quot-ing a malignancy rate of approximately 20% for an ‘inde-terminate’ FNA [36] . Since the NCI Thyroid State of the Science Conference, three categories have been used to report thyroid aspirates that fall between the negative/benign and positive/malignant diagnostic categories: ‘AUS’, ‘suspicious for follicular neoplasia’, and ‘suspicious for malignancy’ [37] . Based on malignancy outcomes, the management suggested by TBSRTC guidelines was: ‘re-peat FNA’ in TBSRTC III and surgery in TBSRTC IV, V, and VI. More recently, follow-up of ‘indeterminate’ le-sions has been increasingly used [36, 37] .

The TBSRTC III category ‘atypia of indeterminate sig-nificance’ comprises one of the grey zones in FOL, with the differential being between hyperplasia and neoplasm.

According to the BTA/RCPath classification, it is consid-ered a heterogeneous category that corresponds to sam-ples which exhibit cytological atypia or other features which raise the possibility of neoplasia but which are in-sufficient to enable confident placement into any other category. Contrary to what may have been expected from a ‘waste basket’ category, the Thy3a (TBSRTC III) catego-ry formed less than 5% of all thyroid FNAs. By showing that a repeat FNA as part of a follow-up procedure was negative in half of the cases, we support the conservative approach and avoiding overtreatment of patients [19, 38] . Nevertheless, the existence of rare malignant cases in this category justifies its existence.

The diagnostic category of ‘FON’ (Thy3f, TBSRTC IV) has a role in the detection and triage of ‘neoplastic’ FOL in which cytology is unable to distinguish between be-nign and malignant cases, which may have similar mor-phologies. Our results support this, showing that 27% of Thy3f patients had invasive cancer and therefore the ‘risk of cancer’ can be discussed with the patient. Currently, in the UK and in line with TBSRTC guidelines, manage-ment of Thy3f lesions, in the proper clinical setting, is a lobectomy/hemithyroidectomy. However, recent survey showed that only 40% of the institutions are currently aware of the subclassification of the Thy3 category into ‘Thy3a’ and ‘Thy3f’, each of which is associated with a different risk of malignancy, so that there is still consider-able confusion about their management [36] .

Table 4. T BSRTC and UK RCPath systems for reporting thyroid cytopathology (modified from Redman et al. [21] and Roh et al. [41]) with comparisons of the implied risk of malignancy and recommended clinical management

Terminology of TBSRTC andUK RCPath

Risk of cancer(TBSRTC), %

Risk of cancer(UK/RCPath), %

Clinical management

I. (Thy1) Nondiagnostic ? Solid nodule: repeat FNACystic nodule: correlate with USReaspirate suspicious areas under US guidance at least 3 months after initial FNA

II. (Thy2) Benign 0–3 Clinical follow-up at 6- to 8-month intervals for 3–5 years

III. (Thy3a) AUS or FOL ofundetermined significance

5–15 If TSH is low consider iodine 123 scanRepeat FNA in 3–6 months with US guidance

IV. (Thy3f) FON or suspicious for a FON 15–30 28 Surgical consultation

V. (Thy4) Suspicious of malignancy 60–75 64 Surgical consultation

VI. (Thy5) Malignant 97–100 100 Surgical consultation

US = Ultrasound.



Since the risk of malignancy for the ‘suspicious for ma-lignancy’/Thy4 reporting category is higher, this sub-group of ‘indeterminate’ FNAs should undergo surgical excision for histological characterization, usually a lobec-tomy. Our results were within the range of the risk of ma-lignancy reported by other authors [37–42] . An impor-tant point for discussion is the appropriate use of Thy4 since it has been shown to have a low interobserver agree-ment kappa value and, in addition, a low PPV, and there-fore potentially some patients may be over treated.

The UK RCPath system, as a recent modification ofan established terminology for the reporting of thyroid FNA, has strong parallels to the TBSRTC system. By showing that despite some differences in terminology the impact of the UK RCPath system on the management of thyroid nodules in our reported patient population, as reflected in the assessment of the risk of malignancy ( ta-ble 4 ), achieved results similar to those of TBSRTC con-firms that the UK RCPath system is a credible alternative method for guiding the management of thyroid nodules

in the UK population. Given that, according to a current report, only a third of all patients undergoing thyroid sur-gery have malignant disease, further work is needed to establish the impact of the use of such terminology in re-ducing surgery in patients with benign disease [43] .

Conclusion

Our study confirms that the current thyroid FNA clas-sification systems (TBSRTC and UK RCPath) offer a sound basis for clear communication on which the man-agement of patients with abnormal FNA findings can be based. Categories Thy3f (TBSRTC IV ‘follicular’) and Thy4 (TBSRTC V ‘suspicious’) carry a risk of malignancy of 28 and 64%, respectively, justifying their existence. The diagnostic category Thy5 (TBSRTC VI ‘malignant’) has a 100% risk of malignancy and as such is robust, so it can be used as a sure indication for a definitive surgical management.

References

1 Gray W, Kocjan G (eds): Diagnostic Cytopa-thology, ed 3. New York, Elsevier Science, 2010.

2 National Institute for Health and Clinical Excellence: Improving outcomes in head and neck cancers. 2004. http://www.nice.org.uk/guidance/csghn/guidance/pdf/English.

3 Kocjan G, Cochand-Priollet B, de Agustin PP, et al: Diagnostic terminology for report-ing thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009. Cytopathology 2010; 21: 86–89.

4 British Thyroid Association, Royal College of Pathologists: Guidelines for reporting of thyroid cytology specimens. 2009. http://www.rcpath.org/resources/pdf/g089guid-anceonthereportingofthyroidcytologyfinal.pdf.

5 Royal College of Pathologists: Dataset for thyroid cancer histopathology reports. 2006. http://www.rcpath.org/resources/pdf/Thy-roidDatasetFeb06.pdf (accessed May 24, 2009).

6 Royal College of Pathologists: Tissue path-ways for endocrine pathology. 2008. http://www.rcpath.org/resources/pdf/g078_tpendocrine_jul08.pdf.

7 Cooper DS, Doherty GM, Haugen BR, Kloss RT, et al: Management guidelines for pa-tients with thyroid nodules and differenti-ated thyroid cancer. Thyroid 2006; 16: 109–142.

8 Gharib H: Fine-needle aspiration biopsyof thyroid nodules: advantages, limitations, and effect. Mayo Clin Proc 1994; 69: 44–49.

9 British Association of Otorhinolaryngolo-gists – Head and Neck Surgeons: Effective Head and Neck Cancer Management: Third Consensus Document. London, Royal Col-lege of Surgeons, 2002.

10 Department of Health: Manual for cancer services: head and neck special measures. 2006. http://www.dh.gov.uk/en/Healthcare/NationalServiceFrameworks/Cancer/DH_4135595.

11 Kocjan G, Chandra A, Cross P, Denton K, Giles T, Herbert A, Smith P, Remedios D, Wilson P: BSCC Code of Practice – fine nee-dle aspiration cytology. Cytopathology 2009; 20: 283–296.

12 Layfield L, Cibas ES, Gharib H, Mandel S: Thyroid aspiration cytology: current status. CA Cancer J Clin 2009; 59: 99–110.

13 Zagorianakou P, Malamou-Mitsi V, et al: The role of FNA in the management of pa-tients with thyroid nodules. In Vivo 2005; 19: 605–609.

14 Kocjan G, Chandra A, Cross PA, et al: The interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists’ classification sys-tem. Am J Clin Pathol 2011; 135: 852–859.

15 Abati A: The National Cancer Institute Thy-roid FNA State of the Science Conference: ‘wrapped up’. Diagn Cytopathol 2008; 36: 388–389.

16 Cibas ES, Alexander EK, Benson CB, et al: Indications for thyroid FNA and pre-FNA requirements: a synopsis of the National Cancer Institute Thyroid FNA State of the Science Conference. Diagn Cytopathol 2008; 36: 390–399.

17 Baloch ZW, LiVolsi VA, Asa SL, et al: Diag-nostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 2008; 36: 425–437.

18 Layfield LJ, Abrams J, Cochand-Priollet B, at al: Post-thyroid FNA testing and treatment options: a synopsis of the National Cancer Institute Thyroid FNA State of the Science Conference. Diagn Cytopathol 2008; 36: 442–448.

19 Pitman MB, Abele J, Ali SZ, et al: Techniques for thyroid FNA: a synopsis of the National Cancer Institute Thyroid FNA State of the Science Conference. Diagn Cytopathol 2008; 36: 407–424.

20 Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A: The Nation-al Cancer Institute Thyroid Fine Needle As-piration State of the Science Conference: a summation. Cytojournal 2008; 5: 6.



21 Redman R, Yoder BJ, Massoll NA: Percep-tions of diagnostic terminology and cytopa-thologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clini-cians and pathologists. Thyroid 2006; 10: 1003–1008.

22 Mazzaferri EL: Management of a solitary thyroid nodule. N Engl J Med 1993; 328: 553–559.

23 Theoharis CG, Schofield KM, et al: The Bethesda Thyroid Fine Needle Aspiration Classification System: year 1 at an academic institution. Thyroid 2009; 19: 1215–1223.

24 Amrikachi M, Ramzy I, et al: Accuracy of FNA of thyroid. Arch Pathol Lab Med 2001; 125: 484–488.

25 Yang J, Schnadig V, et al: FNA of thyroid nodules: a study of 4,703 patients with histo-logic and clinical correlations. Cancer 2007; 11: 306–315.

26 Guidelines of the Papanicolaou Society of Cytopathology for fine needle aspiration procedure and reporting – the Papanicolaou Society of Cytopathology Taskforce on Stan-dards of Practice. Diagn Cytopathol 1997; 17: 239–247.

27 Baloch ZW, LiVolsi VA: FNA of thyroid nod-ules: past, present and future. Endoc Pract 2004; 10: 234–241.

28 Eedes CR, Wang HH: Cost-effectiveness of immediate specimen adequacy assessment of thyroid FNA. Am J Clin Pathol 2004; 121: 64–69.

29 Kelly NP, Lim JC, DeJong S, et al: Specimen adequacy and diagnostic specificity of thy-roid nodules. Diagn Cytopathol 2006; 34: 188–190.

30 Poller DN, Stelow EB, Yiangou C: Thyroid FNAC cytology: can we do it better? Cytopa-thology 2008; 19: 4–10.

31 Ali S, Cibas ES: The Bethesda System for Re-porting Thyroid Cytopathology. New York, Springer, 2010.

32 Mehrotra P, Viswanathan H, Johnson SJ, Wadehra V, Richardson DL, Lennard TWJ: Ultrasound guidance improves the adequa-cy of our pre-operative thyroid cytology but not its accuracy. Cytopathology 2006; 17: 137–144.

33 Bomeisl PE Jr, Alam S, Wakely PE Jr: Inter-institutional consultation in fine-needle as-piration cytopathology: a study of 742 cases. Cancer 2009; 117: 237–246.

34 Belfiore A, La Rosa GL: Fine-needle aspira-tion biopsy of the thyroid. Endocrinol Metab Clin North Am 2001; 30: 361–400.

35 Haberal AN, Toru S, Ozen O, Arat Z, Bilezik-ci: Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thy-roid: correlation with histopathology in 260 cases. Cytopathology 2009; 20: 103–108.

36 Lakhani R, Rourke T, Jefferis A, Perry L, Ghiacy S, Wood S: Thy3 cytology: what to do next? Ann R Coll Surg Engl 2011; 93: 225–228.

37 Faquin WC, Baloch ZW: Fine-needle aspira-tion of follicular patterned lesions of the thy-roid: diagnosis, management and follow-up according to National Cancer Institute rec-ommendations. Diagn Cytopathol 2010;38:731–739.

38 Nayar R, Ivanovic M: The indeterminate Thyroid Fine–Needle Aspiration. Cancer Cytopathology 2009; 117: 195–2002.

39 Layfield LJ, Morton MJ, Cramer HM: Impli-cations of the proposed thyroid fine-needle aspiration category of ‘follicular lesion of in-determinate significance’: a five-year multi-institutional analysis. Diagn Cytopathol 2009; 37: 710–714.

40 Agarwal A, Kocjan G: FNA thyroid report-ing categories: value of using the BritishThyroid Association (Thy1 to Thy5) thyroid FNA reporting guidelines. Cytopathology 2009; 20: 133–134.

41 Roh MH, Jo VY, Stelow EB, Faquin WC, Zou KH, Alexander EK, Larsen PR, Marqusee E, Benson CB, Frates MC, Gawande A, Moore FD Jr, Cibas ES: The predictive value of the fine-needle aspiration diagnosis ‘suspicious for a follicular neoplasm, Hürthle cell type’ in patients with Hashimoto thyroiditis. Am J Clin Pathol 2011; 135: 139–145.

42 Yassa L, Cibas ES, Benson CB, Frates MC, Doubilet PM, Gawande AA, Moore FD, Kim BW, Nosé V, Marqusee E, Reed Larsen P,Alexander EK: Long-term assessment of a multidisciplinary approach to thyroid nod-ule diagnostic evaluation. Cancer 2007; 111: 508–516.

43 Goldfarb M, Perry Z, A Hodin R, Parangi S: Medical, surgical risks in thyroid surgery: lessons from the NSQIP. Ann Surg Oncol 2011, E-pub ahead of print.

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