Manuscript:
Introduction
Thyroid nodules represent a common problem for surgeons as well as a
diagnostic challenge for pathologists. These can be detected in more
than 60% of the general population, with incidence of malignancy found
to be around 5%, and 3254 new cases diagnosed in the United Kingdom
(UK) in 2017.1-4 The challenge facing clinicians
dealing with thyroid nodules is to achieve an accurate preoperative
diagnosis of malignancy, and therefore fine needle aspiration cytology
(FNAC) can play an important role in the diagnostic workup. It is a
relatively safe, cost effective and simple procedure. Although it is
less precise than standard histological assessment, it may help avoid
invasive and potentially unnecessary surgery.1
In current UK practice, FNAC specimens are reported according to the
Royal College of Pathologists (RCPath) Thy grading system, first
published in 2009 and revised in 2016 (Table 1) . In its latest
version, the RCPath Thy system had six diagnostic categories (DCs), as
it divided the neoplasm possible category (Thy3) into Thy3a (neoplasm
possible-atypia/nondiagnostic) and Thy3f (neoplasm possible, suggestive
of follicular
neoplasm).1 Thyroid cysts were also subcategorised
within Thy1 and Thy2 grades as Thy1c and Thy2c respectively. The RCPath
system is well aligned and largely comparable with the six-tiered
Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and other
internationally recognised reporting terminologies for thyroid FNAC
(Table 1 ).5
Regardless of the terminology used, approximately 20-25% of all thyroid
cytology is classified as indeterminate (Thy3a and Thy3f), in which it
is not possible to differentiate between benign, malignant, or
suspicious nodules.5,6,7 For some of these
indeterminate lesions the current UK management guidelines recommend
diagnostic removal of the affected lobe, guided by the decision of
multidisciplinary team (MDT), with potential progression to completion
thyroidectomy following review of the post-operative
histology.8 This will inevitably lead to some benign
lesions labelled as Thy3 or Thy4 being overtreated with
hemithyroidectomy unnecessarily, with all the associated risks.
Conversely, a high false negative rate with Thy2 cytology could lead to
missed cancers and potential progression of disease. Therefore,
optimising the diagnostic performance of the grading systems used in
individual centres is of the utmost importance.7,8
The aim of this retrospective study was threefold. 1) to correlate
pre-operative FNAC results with subsequent histology findings as the
gold standard. 2) to audit the utilisation and the diagnostic
performance of each category of the RCPath Thy system, including the
sensitivity, specificity, accuracy and positive predictive values for
malignancy within the patient population in our locality. 3) to compare
our diagnostic performance results to previously published literature.
Materials and Methods
Study subjects and data
Acquisition
We conducted a retrospective single-centre observational study in a UK
district general hospital. As we used deidentified routinely collected
data, this was not classified as research using the NHS health research
authority online decision tool (accessible from
www.hra-decisiontools.org.uk/research),
and therefore IRB approval was not required, supplementary
material, Figure . We included all patients who had thyroid resection
(total or hemithyroidectomy) performed over a ten-year period, between
January 2006 and December 2015. Eligible thyroid histology data was
extracted from our digital pathology database and was correlated with
FNAC where available. Data collected included age, gender, indication
for surgery, details of FNAC, and the final histological diagnosis. If a
patient had abnormal aspirate results taken from more than one nodule,
the most abnormal result was used for analysis. If final histology
reported incidental malignant lesions that were not sampled during the
FNAC, these reports were excluded from the analysis.
Fine needle aspiration sample processing
In our institution, FNAC samples are routinely aspirated using
ultrasound guidance (UGFNAC), with a minority obtained by
palpation-guidance (PGFNAC), generally from the early years of the
study. Each specimen contains at least an air-dried slide and an alcohol
fixed slide. Samples were prepared by the conventional methods using
Papanicolaou Romanowsky-type stains. The department uses a ‘Quick Dip’
Rapid Romanowsky staining kit for air-dried slides. Samples are
distributed for reporting among eight general histopathologists in the
department.
Data Management
All FNAC data was sorted in to six cytopathological groups according to
the RCPath Thy grading system. For those cytology results from the
earlier years of the study, reports were ‘translated’ into Thy
categories and slides were reviewed if needed. Incidence rates of
malignancy for each Thy grading and other diagnostic performance
indicators were calculated and compared with figures from previously
published literature and guidelines.
Statistical analysis
The performance of thyroid
cytology was assessed for its sensitivity, specificity, diagnostic
accuracy, positive predictive value (PPV), negative predictive value
(NPV), positive likelihood ratio (PLR), and negative likelihood ratio
(NLR). These parameters were calculated according to the statistical
equations described in the supplementary material, Table A . For
the purpose of yielding accurate results, patients with Thy1 results
have been excluded when measuring the diagnostic performance of other
categories, and were reported separately.