Our study comprises one of the largest consecutive series of FNAC reports for parotid tumours and provides an insight into a common first line investigation for parotid masses in head and neck units in this country. The results demonstrate that free-hand or palpation-guided FNAC is acceptably accurate but has a higher inconclusive rate, therefore their usefulness remains questioned. The accuracy of parotid FNAC with or without US (without immediate cytology assessment) has been reported in single studies but not described separately within the same study; combining results from US-guided and free-hand techniques is a problem given the differences this study has shown [5, 13,14,15,16]. The difference in accuracy for free-hand versus ultrasound-guided FNAC of parotid masses has been documented in a previous meta-analysis . The meta-analysis results showed a sensitivity of 0.78 (95% CI, 0.74–0.78) for all FNAC groups that is comparable to sensitivity of 0.82 in the current study. The US group sensitivity 0.84 (95% CI, 0.76–0.91) also compares to 0.89. The meta-analysis specificities again were comparable and they are close to 1. In our study, we have failed to demonstrate a significant difference between the accuracy of US-guided and free-hand FNAC, although a trend can be seen in all measures. This is to be expected since the sample of 109 patients is too small to determine significance for small percentage differences.
The rate of inconclusive and repeat FNAC is significantly higher in free-hand FNAC than when it is performed under US guidance. The inconclusive percentage difference comparing free-hand versus US-guided FNAC, without immediate cytology assessment of the sample quality, has been previously documented in a single study for head and neck masses, but no specific studies were found in relation to parotid masses . The study showed similar percentage of inconclusive results with a 33.5% for free-hand versus 34.4% as noted in the present study and 15.3% for US-guided FNAC versus 12% as noted in the present study. In the comparing study, the percentage of free-hand inadequate specimens was 21.5% compared to 26% in the present study whereas the percentage of free-hand indeterminate samples was 12% compared to 7.9%. In the reference study, the US-guided FNAC inadequacy percentage was lower (3.4%) than in the current study (8.7%) whereas the indeterminate samples percentage was higher (11.9% versus 3.4%). The use of US reduced the inadequacy (21.5 to 3.4) whereas it did not affect the percentage of indeterminate samples (12 to 11.9) in the comparing study when using US-guided FNAC. Conversely, the present study showed both reduction in inadequacy (26.5 to 8.7) and indeterminate samples (7.9 to 3.4) when using US-guided FNAC. It is plausible that US use could improve both inadequacies and indeterminate samples in parotid masses.
The percentage of inadequacy and indeterminate samples has been documented recently in a study with immediate assessment of the FNAC sample. The percentage of inadequacy was similar in free-hand versus US-guided FNAC (11 to 12). Likewise, the percentage of indeterminate samples was similar as well (4 to 6). In this situation, using ultrasound with FNAC would become beneficial when there is no immediate assessment of the sample quality . Likewise, another recent study has shown that ultrasound-guided FNAC by the same surgeons without immediate cytology assessment had lower inadequacy rate than cytopathology free-hand FNAC with immediate sample assessment (3 to 7.2). In this last study, no information was provided regarding indeterminate samples . The current study supports this hypothesis. The rate of inadequacies has been reported in a previous meta-analysis for all but not specific for free-hand or US-guided FNAC. The overall results for this meta-analysis showed 5.3% percentage of non-diagnostic or indeterminate samples which is higher than US-guided FNAC (3.4%) and lower than free-hand FNAC (7.9%) in the current study. Likewise, inconclusive results account for 14.7% percentage of the meta-analysis which is higher than US-guided FNAC (12%) and lower that free-hand FNAC (34.4%). However, it needs to be considered that when doing meta-analysis there is a lack of good information about non-diagnostic and inconclusive reports as documented by the same meta-analysis which could be selecting the best studies and biasing the actual results .
The reasons for the difference between free-hand and US-guided FNAC are not well documented in the literature. They may include operator experience and pathologist experience (if it is not the operator) . It is known that the inadequacy percentage can be related to the presence of a one-stop service. A recent systematic review for head and neck FNAC has demonstrated the benefit of the service .
The importance of an abnormal rate of inconclusive FNAC results is that it seems to be related to an increased risk of malignancy as documented in previous studies [8, 21]. In this study, there was an incidence of 11% in malignant tumours after an inconclusive FNAC report and as such it is recommend all inconclusive FNAC reports be treated with an appropriate index of suspicion.
The use of US-guided core needle biopsy is an alternative technique to consider since it can increase the sensitivity to 0.96 with specificity of 1. However, it comes with increased risk of facial hematoma (1.6%), facial nerve weakness (0.2%) and a possibility of seeding [22, 23].
To define the limits of the present study, STARD recommendations have been followed. QUADAS assessment guidelines have been helpful as well [12, 24, 25].
The description of FNAC process can introduce bias to the study since more than 10 surgical clinician and 3 radiologists have been involved with FNAC over the studied period. This problem, undoubtedly, increases variability of the described FNAC procedure [12, 19, 26].
Selection bias is likely to have happened when referring patient for US-guided FNAC. It is expected that patients with difficult clinical assessment or consultants with less experience in FNAC have referred more patients for US-guided FNAC while patients with suspected malignancy have had clinical FNAC to reduce time to get final diagnosis. Malignancy rate provides some light to the possible bias. In the study, 12.7% US-guided cases were positive for malignancy and 17.0% free-hand FNAC were malignant. According to these results, some bias can be expected that could minimise the difference found [12, 19, 26].
Selection bias could have happened as well since only 45.2% (139/307) of patients with FNAC eventually had available histology results by the first half of 2017. Some of these patients may have had some contraindications for surgery and others may have wished to have further radiological and clinical follow up instead of having the excision. That seems to be a common situation in parotid and head and neck studies including large series of around one thousand FNAC ranging from 28.6 to 52.8% [27,28,29,30]. Moreover, it is common not to report the amount of total FNAC performed or to include only the patients that have undergone surgery, excluding those that had the FNAC without surgery [4, 10, 14,15,16, 18]. This situation seems to be critical since there is rarely documentation regarding what were the results of the FNAC that did not have surgery or histology. In the present study, all FNAC have been documented to compensate for this bias (Table 1). It would be recommended that parotid cytology studies include any results of FNAC without histology as a quality marker.
Finally, this study was retrospective which could have introduced some bias by not selecting cases that had US and the US was enough to reduce need for FNAC whereas in the clinical setting this information may be missing unless there is a previous US report available. Verification bias affects the current study as with all, particularly retrospective FNAC studies since malignancies have more confirmed histology available than benign neoplasms. Review bias affects the study since it was not blinded. Misclassification bias is expected at a rate of 3% [12, 19, 26].
The median time to obtain the confirmed histological diagnosis was 55 days faster (78 vs 132.5) for the free-hand group compared to the US group. Since most parotid masses turn out to be benign the referral pathway preferring urgent, rather than suspected cancer might explain this delay. The increased percentage of malignancy within free-hand group (17 vs 12.7) and the increased inconclusive rate (34.4 vs 12) could have prompted histology being available more readily in the free-hand group [12, 19, 26].
Although it is not recommended free-hand FNAC for parotid lesions based on these results, US-guided FNAC may not be readily available in some clinics. In these examples, the benefit of free-hand FNAC is to reduce the time to obtain the cytology. The knowledge of FNAC technique whether US-guided or not is a valuable skill for the head and neck specialist, and it should be a standard for trainees . The recent proliferation of US FNAC instructional courses aimed at non-radiology trained practitioners suggest that in the future it may be more common for US FNAC to be performed by the surgeon in the head and neck clinic, should a designated head and neck radiologist not be available. However, the expert head and neck radiologist is invaluable in describing the mass features such as suspicious malignancy and probable diagnosis that are relevant to the management of the patient independently from FNAC outcome. Clearly, the gold standard would be a one stop US FNAC neck lump clinic and option to core biopsy with both radiologist and cytologist in attendance, but such clinics are unfortunately not the norm in most national centres. We hope this study helps the planification of equipment in geographic area where there is more prevalence of parotid pathology [7, 31, 32].