Diagnostic performance of RCPath Thy
grading system (Table 4 and supplementary Table
B)
We measured the diagnostic
performance of our FNAC categories and compared the results with the
most up-to-date figures published in the latest RCPath guidelines in
20161, and the latest meta-analyses published by
Poller et al. 5,6 for the RCPath Thy system (13
articles, 3911 nodules), and Bongiovanni et
al. 9 for TBSRTC (8 articles, 6362 nodules),Table 4 .
35% of the samples in our series were categorised as Thy1, which is
higher than previously published figures (18-27%).1,6There were also some minor differences in the utilisation of Thy1 and
Thy2 categories between the RCPath system and TBSRTC (Grade I, II),
where the later system identifying fewer grade I and more grade II
samples (Table 4 ).
While the risk of malignancy (ROM or PPV) in our Thy5 category (100%)
was comparable to published literature for the RCPath system
(98-100%)1,5 and TBSRTC (99%)9,
our malignancy rates were higher for all other categories (Table
4 ). ROM was higher for Thy2 grade in our study (15%) compared to
RCPath system rates (1.4-5%), and TBSRTC (4%). ROM was also
surprisingly much higher for our Thy 4 patients (90%) compared to the
RCPath figures (up to 68%)1, the meta-analysis of
results using the Thy system by Poller et al. 5(79%), or the TBSRTC system meta-analysis by Bongiovanni et
al. 9 (75.2%). Combining Thy4 and Thy5 groups
together (suspicious or malignant FNAC) demonstrated a high specificity,
PLR and PPV for malignancy (99.1%, 30.1, and 92.3% respectively), with
low sensitivity (27.6%), and moderate NPV (77.4%) and accuracy
(78.7%) (Table 4 and supplementary Table B). Combining Thy3-5
groups together (any abnormal FNAC) improved the sensitivity and the NPV
(67.8% and 85.3% respectively) at the expense of reducing the
specificity, PPV and the overall accuracy (74.3%, 51.3%, 72.5%
respectively).
Discussion
FNAC plays an important role in the initial evaluation and decision
planning for patients with thyroid nodules. However, FNAC has drawbacks
especially with its relatively high rate of inadequate or unsatisfactory
samples, necessitating repeat testing, and its inability to distinguish
between benign and malignant lesions in some
situations.8,10-12 Moreover, false positive diagnosis
of malignancy can sometimes occur, which can lead to unnecessary thyroid
surgery with a 2-10% risk for long-term postoperative
morbidity.13,14 As the decision to pursue surgery as
opposed to conservative management is greatly influenced by the FNAC
results, there is a need for a consistent reporting process and rigorous
evaluation of the diagnostic utility of thyroid
FNAC.1,13,15,16
The RCPath Thy grading system was designed to refine and improve the
reporting process, and to provide clarity for patient
management.1 It can provide consistent, reproducible
and auditable thyroid cytopathological reports, improve the
communication process between clinicians and patients, and give figures
for the predicted risk of malignancy with each cytological
diagnosis.8,9
This study builds on the growing body of literature to validate the
diagnostic utility of the RCPath Thy system in guiding the day-to-day
clinical management.1,5,6 While the validity of using
six-tiered systems (like the RCPath system or TBSRTC) is justifiable by
the strong reported cyto-histological correlation, there was a notable
variability in the implied risk of malignancy for different DCs and
subsequently the percentage of patients undergoing
surgery.1,5,6,9 As standards for FNAC reporting
outcomes are not universally set, quality assurance at individual
institutions by undertaking regular audit is paramount to maintaining
accuracy.1,6,17
Our results demonstrate higher rates of malignancy and utilisation of
the Thy1 non-diagnostic category in our cohort. This can be partially
explained by sampling error from using the less-precise PGFNAC technique
in cases from the early years of the study, and possibly poor operator
techniques. 19 In addition, unsatisfactory sample
preparation and preservation, especially from cystic lesions, are well
recognised factors leading to higher rates of non-diagnostic
aspirates.5,8 The Thy2 category also had a higher rate
of malignancy in our cohort. Interestingly, 40% of the false negative
Thy2 cases had PTMC (<1cm), which can further explain the
sampling challenges of smaller lesions, especially with PGFNAC
technique. In the meta-analysis performed by Wang et
al. 20, the authors noted a significant difference
between the FN rates for benign FNAC between academic (2%) and
community hospitals (10%). The authors attributed this difference to
higher sampling error with PGFNA and differences in cytological
interpretation.20 Moreover, selection bias for
treatment may also skew the ROM figures, as patients with Thy1 or Thy2
results will only undergo surgery if they show suspicious clinical or
radiological features.5,7
Cystic changes and degenerative processes in thyroid nodules can often
cause florid atypia, with a considerable potential for FN results and
malignancy in around 14-17% of Thy1c and 4-33% of Thy2c
nodules.13,21-24 Interestingly, our results when
compared to the published figures, showed a higher ROM in Thy1c (19%)
and Thy2c (50%), which can only be partially explained by treatment
selection bias. However, we agree with the BTA guidelines that FNAC
should be repeated for all Thy1 and Thy2 cases with suspicious clinical
or sonographic features.8 Table 5 summarises
the recommended clinical actions
for each RCPath FNAC category.
One of the main aims of the RCPath Thy nomenclature, is to reduce the
cytological reporting variability for the indeterminate thyroid nodules.
These are often challenging for clinicians and pathologists because of
their heterogenous morphology, and the difficulty to establish
cytologically any invasive characteristics without thorough
histopathological examination.6 Our malignancy rates
for Thy3a and Thy3f categories are notably higher as shown inTable 4. It is well recognised that Thy3a category can often be
conceived by cytopathologists as a ‘haven of safety’, avoiding false
negatives when assigned instead of Thy2, and potentially unnecessary
surgery when assigned instead of Thy3f, and avoiding false positives
when assigned instead of Thy4.7
In our cohort, Thy4 patients also had a higher malignancy rate (90%)
compared to the published figures. The BTA recommendation of diagnostic
hemithyroidectomy for Thy4 lesions is based on the RCPath guidelines
which quotes a 30-35% possibility of benign disease in this cohort and
hence avoiding the potential long-term morbidity of total
thyroidectomy8. However, In centres with a malignancy
rate of >90% for Thy4 cytology, an argument could be made
for offering total thyroidectomy in patients with larger
nodules(>4cm) to avoid a second procedure of completion
hemithyroidectomy.8 Malignancy is almost always
histologically confirmed in Thy5 patients, justifying our standard
practice of therapeutic hemi- or total thyroidectomy ± central
compartment neck dissection guided by the MDT
decision.1,8
In our cohort, Thy4 patients also had higher malignancy rates compared
to the published figures. In keeping with the BTA recommendations
(Table 5) , our results confirm that total thyroidectomy should
not be offered to Thy4 lesions as this would put at least one in ten
patients at risk of unnecessary surgery with its potential long-term
morbidity.8 However, malignancy is almost always
histologically confirmed in Thy5 patients, justifying our standard
practice of therapeutic hemi- or total thyroidectomy ± central
compartment neck dissection guided by the MDT
decision.1,8
The limitations of our study include a possibly heterogenous population,
inclusion of samples taken using PGFNAC techniques, and our study period
crosses multiple revisions of the Thy system nomenclature. Since this
was a retrospective study, it is sometimes difficult to ascertain that a
histologically diagnosed malignant nodule is the same one aspirated for
FNAC preoperatively. Moreover, we only included
histologically-correlated FNAC samples, which likely skewed our
malignancy rates in the lower risk categories when cancer is not
frequently encountered. While using a tiered classification nomenclature
like the Thy or TBSRTC systems may improve comparability of results
between various institutions, these comparisons must be taken with
caution as the results are often influenced by multiple factors. These
factors include differences in thyroid cancer prevalence, variations in
nodule selection for aspiration, the skill of the aspirators, the
aspiration techniques, the experience of the cytopathologists, and the
percentage of cases progressing to have surgery.6,7Moreover, the methods of calculating the ROMs and PPVs rates are widely
variable in the literature, making it incredibly difficult to compare
different studies.6,7,16
The other issue limiting the generalisability of the FNAC outcomes is
the inherent inter- and intraobserver variability of thyroid cytology
reporting.6,13,15,25 In a large multi-centre
prospective study by Cibas et al. 16 that
assessed the reporting variability of the TBSRTC system, concordance
level between the local cytopathologists and a central review panel was
only 64%, with 74.7% intraobserver concordance. The false positive
rate of category VI (Thy5) was 6%, and these patients could potentially
have undergone unnecessary surgery if they were not downgraded by the
central review panel.15 Studies on the RCPath Thy
system show very similar pattern with highest concordance for Thy1 and
Thy5, moderate concordance for Thy2 and Thy3f, and lowest concordance
for Thy3a and Thy4 categories.25
Conclusion
The use of tiered classification nomenclature, such as the RCPath Thy
system, have paved the way to standardized thyroid FNAC reporting.
However, diagnostic performance can be variable between different
institutions. Our results demonstrate generally higher rates of
malignancy compared to other published series. Each individual centre
should be able to discuss suspicious cytology results in a
multidisciplinary team setting, and to be able to quote local malignancy
rates during patient counselling. It is prudent for all units performing
thyroid diagnostics to control the factors that might lead to reporting
variability, and to undertake regular audit of their performance.
Adjunct immunohistochemical and molecular testing is promising, and may
in future provide a route to improve thyroid cytology outcomes and so
help in standardising the reporting outcomes.