Secondary Logo

Journal Logo

Approach to thyroid cytology: rationale for standardisation

Kumarasinghe, M. P.1; Cummings, M. C.2; Raymond, W.3; Shield, P.4; Judge, M.5; Beaty, A.6; Bethwaite, P.7; Braye, S.8; Carter, C. D.9; Chong, G.10; Downey, P.11; Frost, F.12; Loo, C.13; Nga, M. E.14; Nguyen, H.15; Panicker, V.16; Parker, A. J. C.17; Phillips, G.18; Salisbury, E.19; Twin, J.20; Papadimos, D.21

Pathology - Journal of the RCPA: June 2015 - Volume 47 - Issue 4 - p 285–288
doi: 10.1097/PAT.0000000000000268
EDITORIAL
Free

1PathWest, Queen Elizabeth II Medical Centre, Nedlands and University of Western Australia, WA

2RCPAQAP Cytopathology, St Leonards, Sydney, NSW

3Clinpath Laboratories and Flinders Medical Centre, SA

4School of Biomedical Sciences, Queensland University of Technology and Department of Cytology, Sullivan Nicolaides Pathology, Qld

5Royal College of Pathologists of Australasia

6Royal Melbourne Hospital, Parkville, Vic, Australia

7Aotea Pathology Ltd, Wellington, New Zealand

8Pathology North, c/o John Hunter Hospital, NSW

9SA Pathology and Flinders University, Adelaide, SA

10Academic Unit of Surgery, ANU Medical School, ACT

11Medical Imaging, Flinders Medical Centre, Bedford Park, SA

12PathWest, Queen Elizabeth II Medical Centre, Nedlands, WA

13Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, and Southern IML Pathology, Wollongong, NSW, Australia

14Department of Pathology, National University Hospital, Singapore

15Perth Endocrine Surgery, Leederville, WA

16Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands WA

17Department of Anatomical Pathology, St Vincent's Hospital, Darlinghurst, NSW

18Australian Society of Cytology, Brooklyn Park, SA

19Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, NSW

20Capital Pathology, Deakin, ACT

21Histology and Cytology Departments, Sullivan Nicolaides Pathology, Indooroopilly, Qld, Australia

Address for correspondence: Prof Marian Priyanthi Kumarasinghe, PathWest, QE11, J Block, Hospital Avenue, Nedlands, WA 6009, Australia. E-mail: Priyanthi.Kumarasinghe@health.wa.gov.au

Back to Top | Article Outline

INTRODUCTION

A standardised approach to thyroid cytology handling and reporting was recently endorsed by the Royal College of Pathologists of Australasia (RCPA), and a comprehensive document, encompassing all aspects of thyroid cytology, is available from the websites of the RCPA1 and the Australian Society of Cytology (ASC).2 This editorial provides the background and rationale for this standardised approach.

Back to Top | Article Outline

BACKGROUND

Institutions in Australasia maintain a very high standard of cytology practice with strict approaches to accreditation, quality control and quality assurance exercises, due to the efforts of individuals, organisations and professional bodies. Thyroid cytology practice has been part of this quality service; however, the approaches used have not been uniform and significant variability of practice exists, both in thyroid cytology and in other areas of non-gynaecological cytology. Creating a standardised approach, addressing all aspects of thyroid cytology practice, is one means of attempting to create greater uniformity.

In Australasia, pathology services are delivered through public and private sector pathology laboratories. These include large public sector academic and semi-academic institutions, small regional and peripheral public pathology practices and large and small private pathology services. All of these institutions are very likely to encounter requests to handle various aspects of thyroid cytology which may include performing direct fine needle aspirations (FNAs), reporting of received smears and rapid on site evaluation (ROSE) for radiologically-guided FNAs. A survey undertaken by the RCPA Cytopathology Quality Assurance Programs (QAP) showed that thyroid FNAs constitute between 0 and 62% of the total workload of cytology laboratories. It was found that radiologists perform approximately 65% of aspirations while pathologists perform only 11%. There was significant variability noted in the techniques and practices in use for the collection, ROSE, ancillary testing, reporting terminology and quality control and improvement measures. Of 143 laboratories surveyed, 60 used no defined classification system for the reporting of thyroid FNAs, 53 used the Bethesda system, and 14 used other systems. Participants in the survey indicated an overwhelming consensus in favour of the use of a uniform reporting system suitable for Australasia.

There have been several systems of terminology and reporting of thyroid cytology3–5 in use in Australasia over the last decade, utilised in either their original format or modified to suit local needs. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC),6 which has gained wide acceptance in the United States and elsewhere, provided an ideal framework on which to build a standardised approach to thyroid cytology reporting for Australasia. However, any standardised approach to thyroid cytology must cover all integral parts of the process including FNA techniques, smear preparation, laboratory handling and laboratory techniques, as well as terminology, reporting, and management recommendations, incorporating available and relevant local and international evidence-based information. In addition, for any guidelines to be widely accepted across Australasia, due consideration must be given to existing local health care delivery structures, acknowledging past and current practices, in order to create a strong basis for the future of thyroid cytology.

Back to Top | Article Outline

PROCESS

This endeavour was undertaken by a working party comprising cytopathologists, cytologists and clinicians with an interest and expertise in this field, under the auspices of RCPA National Structured Reporting of Pathology Project (SPR) and the ASC, and aimed to address two main areas:

1. Provide a comprehensive description of appropriate collection and preparation of thyroid FNA material to optimise accurate assessment and reporting;

2. Develop an outline encompassing all elements needed for standardised reporting of FNA cytology of the thyroid, similar to the current published structured reporting protocols developed by the RCPA.1

Once the draft document was prepared in accordance with the SPR process, public consultation and comments were invited. Most comments received originated from tertiary care institutions and were in regard to reporting and terminology, and pertained to the impact of TBSRTC.

Back to Top | Article Outline

COLLECTION AND PREPARATION OF FNA MATERIAL

The technical aspects of performance of FNA of the thyroid and optimal slide preparation are provided with the aim of guiding the operator, most often a radiologist. ROSE is encouraged as this is a proven powerful tool to reduce the rate of non-diagnostic outcomes.7

The use of liquid based cytology (LBC) as a replacement for direct smears is discouraged until further validation is undertaken. There is no consistent evidence to support the use of LBC preparation methods alone for thyroid cytology samples. The data in this regard is variable in terms of adequacy rates and the accuracy of diagnosis.8,9 Direct smears provide important diagnostic information which can be lost in LBC material. Direct smears are essential for ROSE and air-dried preparations (Diff Quik or Giemsa stained) are not possible with LBC methods. The use of both alcohol-fixed and air-dried smears is optimal as the two techniques are complementary.

Back to Top | Article Outline

TERMINOLOGY RECOMMENDATIONS

The suggested terminology is based on the TBSRTC categories with some minor modifications and strong recommendations:

1. A general classification (category descriptor) of the aspirate must be recorded.

2. Following general categorisation, a specific diagnosis must be stated, favoured or suggested.

3. A category descriptor should always be stated in the report in conjunction with the category number when using the classification system in Table 1. The number should NOT be used without the descriptor, to avoid any potential miscommunication or confusion with numbered categories used for other sites, e.g., breast.

4. A standard comment or recommendation for follow-up may be used, particularly when referring clinicians are not specialists in the field.

Table 1 shows the Australasian nomenclature for thyroid cytology reporting based on TBSRTC categories. These recommendations are based on available, local and international evidence-based information and the experiences of the expert group.

Aspirates that are inadequate in cellularity according to accepted adequacy criteria, and unsatisfactory samples due to poor technique or poor preparation, are best referred to as ‘non-diagnostic’ with further explanation as to the reason. As defined in the TBSRTC, adequacy refers to: ‘greater than 6 groups of well-visualised follicular cells, with at least 10 cells per group, preferably on a single slide’.6 The rationale behind this definition is that a sheet of 10 cells is thought to be sufficient to exclude a microfollicular arrangement.

A standardised approach to reporting cystic lesions is recommended with strong emphasis on collaborative clinical and radiological information and whether the cyst could be completely emptied.

For those aspirates which fall short of fulfilling all criteria to be diagnosed as either a specific benign process, or suggestive of a neoplasm, the preferred terminology is ‘Indeterminate’ or ‘Follicular lesion of undetermined significance’ (FLUS). The use of the term ‘atypia’ for these lesions in the general diagnostic category is strongly discouraged. The term ‘atypical’ as a category for these lesions would convey a greater degree of concern for neoplasia and therefore could trigger surgery which, in many cases, may be inappropriate for the patient. The term ‘atypia’ may be used to describe a cellular or architectural feature in the microscopic description as appropriate. The descriptors ‘indeterminate’ and ‘follicular lesion of undetermined significance’ are equally acceptable and can be used interchangeably. Many of these cases have a benign outcome.4,5 The terms atypia or atypical have been used with different implications over at least the last decade in Australasian cytology practices.3–5 Recently TBSTCR subcategory of ‘nuclear atypia’ within AUS/FLUS has been shown to indicate a higher risk of malignancy than other subcategories of AUS.10–12 These findings support the recommendation to avoid the nomenclature ‘atypia’ in the ‘Indeterminate’ category (category 3).

Any aspirate in which the cytological features strongly suggest a neoplasm should not be categorised as ‘indeterminate’ or ‘FLUS’. For aspirates that do not show features suspicious of malignancy, but raise the possibility of a neoplasm, the term ‘suggestive’ is recommended in preference to ‘suspicious’. The term ‘suspicious’ indicates a reasonable possibility of malignancy and use of this term in the ‘suggestive of follicular neoplasm’ category may lead to over-treatment. Surgical management of category 4 lesions is usually conservative unless there are specific clinical reasons to advocate a more aggressive approach. The most common neoplasm in the thyroid gland is a follicular adenoma (benign). Only 5% of thyroid nodules are likely to be malignant.13,14 Therefore use of the term ‘suspicious’ is best reserved for those aspirates which show features strongly indicating malignancy but in which an unequivocal malignant diagnosis is not possible. Restricting the term ‘suspicious’ to cases which show abnormal cytological features, but which fall short of ‘full house’ criteria for malignancy (for example some but not all nuclear features of papillary carcinoma), will lead to a higher predictive value for the ‘suspicious of malignancy’ category (category 5).

Avoiding terms which have been used with variable connotations in the past will potentially prevent over-interpretation and over-treatment. Although it can be argued that the above guidelines are self explanatory, a national standard regarding thyroid cytology terminology will provide uniformity between highly specialised thyroid practices and general clinical pathology services.

Management recommendations for each terminology category are based on the available scientific evidence which correlates described cytological patterns with outcomes, as well as the opinions and experiences of the members of the multidisciplinary committee.4,5 These recommendations are described in detail in the document that is available from the websites of the RCPA and ASC.1,2 TBSRTC categories and recommendations were formulated following both assessment of available evidence and consensus opinion at the National Cancer Institute conference in 2007.15 The framework for the Australasian guidelines follows these basic principles.

Back to Top | Article Outline

ANCILLARY TESTING

An evolving area in thyroid cytology is the use of ancillary testing. Ancillary stains are valuable and in specific instances may lead to a specific diagnosis. The value of molecular cytology in the diagnostic algorithm in thyroid cytology needs careful evaluation before it can be introduced into routine practice and recommended for health care reimbursements. While it is acknowledged that the field of molecular diagnostics is rapidly progressing, there are conflicting data on its value and cost-effectiveness in current routine practice of thyroid cytology.16–18

Back to Top | Article Outline

CONCLUSION

The joint effort by the RCPA and ASC provides a standardised approach to all aspects of thyroid cytology, and can be adopted by specialist and non-specialist pathology practices. This approach will ensure that the aspirated material is optimally prepared and that key features are observed, interpreted and translated into the report to guide clinicians in the optimal management of their patients. Its adoption will also facilitate laboratory quality control and allow for the future development of appropriate performance measures, as well as being of educational and research value. It is hoped that these Australasian Recommendations, covering all aspects of thyroid cytology, will evolve with the modification of other classification systems, including TBSRTC.19,20 This model is strongly recommended for other areas of non-gynaecological cytology assessment in Australasia.

Back to Top | Article Outline

Acknowledgements

We wish to thank all those who provided feedback during the guideline development process and in particular Greg Sterrett, Andrew Field, Peter Earls and Jason Stone for their valuable contributions.

Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose.

Back to Top | Article Outline

References

1. RCPA (Royal College of Pathologists of Australasia). Structured Pathology Reporting of Cancer Protocols. 2014; cited Jan 2015. www.rcpa.edu.au/Library/Practising-Pathology/Structured-Pathology-Reporting-of-Cancer/Cancer-Protocols.
2. Australian Society of Cytology (ASC). 2014; cited Jan 2015. http://www.cytology-asc.com/.
3. Orell SR, Philips J. Broadsheet number 57: Problems in fine needle biopsy of the thyroid. Pathology 2000; 32:191–198.
4. Nga ME, Kumarasinghe MP, Tie B, et al. Experience with standardized thyroid fine-needle aspiration reporting categories. Cancer Cytopathol 2010; 118:423–433.
5. Tsan CJ, Serpell JW, Poh YY. The impact of synoptic cytology reporting on fine-needle aspiration cytology of thyroid nodules. ANZ J Surg 2007; 77:991–995.
6. Ali S, Cibas ES, et al. The Bethesda System for Reporting Thyroid Cytopathology. Definitions, Criteria and Explanatory Notes. New York: Springer, 2010.
7. Schmidt RL, Witt BL, Lopez-Calderon LE, et al. The influence of rapid onsite evaluation on the adequacy rate of fine-needle aspiration cytology: a systematic review and meta-analysis. Am Clin Pathol 2013; 139:300–308.
8. Saleh H, Bassily N, Hammoud MJ. Utility of a liquid-based, monolayer preparation in the evaluation of thyroid lesions by fine needle aspiration biopsy: comparison with the conventional smear method. Acta Cytol 2009; 53:130–136.
9. Fischer AH, Clayton AC, Bentz JS, et al. Performance differences between conventional smears and liquid-based preparations of thyroid fine-needle aspiration samples: analysis of 47,076 responses in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Arch Pathol Lab Med 2013; 137:26–31.
10. Olson MT, Clark DP, Erozan YS, et al. Spectrum of risk of malignancy in subcategories of ’atypia of undetermined significance’. Acta Cytol 2011; 55:518–525.
11. Renshaw AA. Should ’atypical follicular cells’ in thyroid fine-needle aspirates be subclassified? Cancer Cytopathol 2010; 118:186–189.
12. Park HJ, Moon JH, Yom CK, et al. Thyroid ’atypia of undetermined significance’ with nuclear atypia has high rates of malignancy and BRAF mutation. Cancer Cytopathol 2014; 122:512–520.
13. Tan H, Gharib H, Reading CC. Solitary thyroid nodule. Comparison between palpation and ultrasonography. Arch Intern Med 1995; 155:2418–2423.
14. Mackenzie EJ, Mortimer RH. Thyroid nodules and thyroid cancer. Med J Aust 2004; 180:242–247.
15. Baloch ZW, Cibas ES, Clark DP, et al. The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Cytojournal 2008; 5:6.
16. Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012; 367:705–715.
17. McIver B, Castro MR, Morris JC, et al. An independent study of a gene expression classifier (Afirma) in the evaluation of cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab 2014; 99:4069–4077.
18. Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab 2011; 96:3390–3397.
19. Cibas E. Bethesda and beyond. Cancer Cytopathol 2010; 118:184–185.
20. Kocjan G, Chandra A, Cross PA, et al. The interobserver reproducibility of thyroid fine-needle aspiration using the UK Royal College of Pathologists’ classification system. Am J Clin Pathol 2011; 135:852–859.
© 2015 Royal College of Pathologists of Australasia