Material and Method: The present study included 291 consecutive patients who underwent FNAC, intraoperative section and subsequently surgery.
Results: Of 291 FNAC specimens, 213 were benign and 31 were suspicious, 25 were positive for malignancy, and 22 were nondiagnostic. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of FNAC in the diagnosis of malignancy were 43%, 68%, 80%, 72%, and 73%, respectively. No false positive results were noted. Of 291 patients analyzed by intraoperative section, the diagnosis was benign in 186 and positive for malignancy in 67 patients. Thirty-eight patients were diagnosed using permanent sections. Of these 38 patients, 21 had malignant tumors confirmed by the permanent sections. Falsepositive results were noted in only one case. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of intraoperative diagnosis were 76%, 82%, 82.8%, 85%, and 84.5%, respectively.
Conclusion: FNAC is a sensitive first diagnostic method in selecting patients who require surgery. Routine use of intraoperative section is specific and complementary in determining the extent of surgery in patients with suspicious or malignant cytology.
Our aim in this study was to determine the role, specificity and sensititivity of preoperative thyroid FNAC and intraoperative diagnosis for thyroid nodules by comparing the results of cases where these methods were used with histopathological diagnoses.
All thyroid FNAC material was obtained at the Radiology or Endocrinology Departments of our University and sent to our Department after being air-dried and fixated on slides with alcohol. The air-dried slides were stained with the May - Grünwald-Giemsa stain while the alcohol-fixated slides were stained with hematoxylin-eosin and the results were reported after screening by cytopathologists (AV, DN). FNAC material adequacy was accepted when at least 8-10 follicular epithelial cell clusters were found. The FNAC reports were as follows:
1. B enign cytology (colloid or adenomatous nodules,
hyperplastic nodules and thyroiditis)
2. Malignant cytology (papillary, medullary, anaplastic
carcinoma or unspecified type)
3. S uspicious cytology (smear contains atypical cells but
inadequate for diagnosis, cellular follicular nodule)
4. I nadequate cytology (material inadequate for
diagnosis, technical problems).
A sample was taken from the most macroscopically suspicious nodule among the thyroid surgery material for the intraoperative diagnostic sectioning. The number of samples was 2 for nodules 2 cm in size or smaller and 3 for larger nodules. The sectioning was from areas with possible macroscopic capsule invasion for encapsulated nodules as it would not be possible to evaluate the whole nodule during intraoperative diagnosis. Intraoperative sections were stained with hematoxylin-eosin and evaluated. Intraoperative diagnostic evaluation results were provided to surgery as follows:
1. B enign (colloid or adenomatous nodules, hyperplastic
nodules and thyroiditis)
2. Malignant (papillary, papillary–follicular variant,
medullary, anaplastic carcinomas)
3. S uspicious (follicular neoplasia where a definite
diagnosis could not be reached on capsule evaluation,
Hurthle-cell neoplasia).
The histopathological diagnosis was provided after the surgery material from thyroid was evaluated by two pathologists (MT, YE) following re-analysis and sampling.
The FNAC and intraoperative diagnosis results were compared with the histopathological diagnoses:
True positive: Positive for malignancy also proven
histologically
True negative: Negative for malignancy also proven
histologically
False positive: Positive for malignancy not proven
histologically
False negative: Negative for malignancy not proven
histologically
Sensitivity: True positive/True positive + False negative
Specificity: True negative/False negative + False positive
Estimated positive value: True positive/True positive +
False positive
Estimated negative value: True negative/True negative +
False negative
Diagnostic accuracy: True positive + True negative/True
positive + True negative + False positive + False negative
Analysis of statistical comparisons was performed by the
SPSS (Statistical Package for the Social Sciences, version
15.0) software.
Figure 1: Distribution of FNAC results.
Figure 2: Distribution of intraoperative results.
Figure 3: Distribution of histopathological results.
Correlation of FNAC and histopathological diagnosis
213 cases that had preoperatively received a diagnosis
of benign or malignant cytology with FNAC were
histopathologically also benign in 153 (72%) and malignant
in 60 (28%) cases. 31 cases that had received a diagnosis of
suspicious cytology were histopathologically benign in 11
(35.5%) and malignant in 20 (64.5%). None of the cases with
malignant FNAC diagnosis were benign histopathologically
(0%) and all 25 cases were found to be malignant (100%)
(Table I).
Table I: Correlation of FNAC and histopathological diagnosis
Of the 11 cases that had a suspicious cytology before surgery but received a diagnosis of benign histopathology, 6 were thyroiditis, 4 nodular goitre and 1 Hurthle-cell adenoma (Table II).
Table II: Correlation of FNAC and benign histopathological diagnosis
Of the 60 cases that had been evaluated as benign cytology before the surgery but the histopathological diagnosis was malignant, 15 were classic papillary carcinoma, 32 papillary microcarcinoma, 10 papillary carcinoma follicular variant, 1 follicular carcinoma and 2 medullary carcinoma (Table III). Of the 20 cases that had been evaluated as suspicious cytology but received a malignant histopathological diagnosis, 10 were classical papillary carcinoma, 5 papillary carcinoma follicular variant, 3 papillary microcarcinoma and 2 poorly differentiated thyroid carcinoma (Table III).
Table III: Correlation of FNAC and malignant histopathological diagnosis
The group with suspicious cytology was included in the malignant group for statistical analysis due to the effect on surgical decision stage and the higher number of malignant results (64.5%) from histopathological diagnosis. This gives the following values for preoperative FNAC in the diagnosis of thyroid nodules: sensitivity 43%, specificity 68%, positive predictive value 80%, negative predictive value 72% and diagnostic accuracy rate 73%. The false negative rate was 28% while the false positive rate was 0%.
Correlation of intraoperative diagnosis and
histopathological diagnosis
The histopathological diagnosis was benign in 159 of the 186
cases with a benign diagnosis on intraoperative diagnosis
while 27 were malignant. Of the 38 paraffin-embedded
tissues, 17 were histopathologically benign and 21 were
malignant. Only one of the 67 cases reported malignant was
histopathologically benign while 66 were malignant (Table IV).
Table IV: Correlation of Intraoperative diagnosis and histopathological diagnosis
Nine of the 17 cases that had been embedded in paraffin and received a benign histopathological diagnosis had thyroiditis, 7 had nodular goitre and 1 was diffuse hyperplasia. A case reported as false positive received a diagnosis of lymphocytic thyroiditis on histopathology (Table V). Of the 21 paraffin-embedded cases, 10 were diagnosed as papillary carcinoma follicular variant while 6 had papillary carcinoma and 5 classic papillary carcinoma (Table VI).
Table V: Correlation of intraoperative diagnosis and benign histopathological diagnosis
Table VI: Correlation of intraoperative and malignant histopathological diagnosis
There were 26 cases evaluated as benign with intraoperative diagnosis but found to be malignant on histopathology and 16 were papillary microcarcinoma, 6 classic papillary carcinoma, 3 papillary carcinoma follicular variant and 1 medullary carcinoma (Table VI).
We performed a statistical evaluation by including the paraffin-embedded group in the malignant group for the intraoperative diagnosis method, due to the same reasons with suspicious FNAC. We found the sensitivity of intraoperative diagnosis method for the diagnosis of thyroid nodules as 76%, with specificity 82%, positive predictive value 82.8%, negative predictive value 85% and diagnostic accuracy rate of 84.5%.
False negativity rate in FNAC is 0% to 29% in the literature[3,13,19,23-25]. Morgan et al.[26] have reported a false negativity rate of 46% in their 253-case study. Our false negativity rate was 28%. Errors in sampling and interpreting nodules are the most important causes of false negative FNAC results[27-29]. Repeated FNAC will increase diagnostic accuracy if suspicion continues with a solitary nodule or dominant nodule interpreted as benign cytology. Some investigators prefer routinely using the intraoperative diagnosis methods[30].
The intraoperative diagnosis method is generally thought to have higher specificity in the diagnosis of thyroid nodules[13,20,24,31,32]. The reported sensitivity for intraoperative diagnosis is 57-80% while the specificity is 90-99%, positive predictive value is 95-97%, negative predictive value is 74-95% and the diagnostic accuracy rate is 77-96%[13,20,24,31]. We found the sensitivity of the intraoperative diagosis method to be 76% for the diagnosis of thyroid nodules while the specificity was 82%, positive predictive value 82.8%, negative predictive value 85% and diagnostic accuracy 84.5%. The higher values of FNAC results indicate that the intraoperative diagnosis procedure is a very specific diagnostic method for the diagnosis of thyroid nodules and for planning the surgery. The changes in follicular epithelial cells in cases accompanied by thyroiditis can lead to interpretation errors. These cellular changes must therefore be considered before making a diagnosis of malignancy during the intraoperative evaluation of cases with thyroiditis. The false positive rate in our series was 0.87% and only one lymphocytic thyroiditis case received a malignant diagnosis with the intraoperative diagnosis method. Nine of the 17 cases embedded in paraffin received a histopathological diagnosis of thyroiditis.
There were one Hurthle-cell follicular adenoma, one follicular carcinoma and 17 papillary carcinoma follicular variant in the group defined as “follicular neoplasia” in our series. This difference in distribution is due to our inclusion of cases with all three materials. The diagnosis of follicular carcinomas is based on capsule and/or vascular invasion[33]. FNAC is not suitable for the differential diagnosis of follicular adenoma/carcinoma due to these diagnostic criteria. Some studies suggest not using the intraoperative diagnosis method for these lesions due to its low diagnostic value[19,34,35]. However, some investigators suggest imprint analysis as well so that the nuclear details can be better imaged without freezing artifact during intraoperative diagnosis for these lesions[21,36-38].
FNAC is an excellent method in selecting cases that need surgery but it may not be adequate by itself in planning the extent of surgery for some lesions due to its low sensitivity and specificity. The higher specificity of the intraoperative diagnosis method decreases the rate of secondary surgical intervention. The reasons for the low FNAC sensitivity in our series are:
• Different physicians (endocrinologist and radiologist)
performing FNAC
• I nclusion of cases with FNAC, intraoperative diagnosis
and surgical material
• Presence of microcarcinomas and especially
microscopic tumor foci found by chance in our case
group.
However, the lack of a false positive result in FNAC and a 0.87% rate for the intraoperative diagnosis method increases our diagnostic accuracy.
In conclusion, each institution should evaluate procedures regarding the preoperative and peroperative approaches to thyroid nodules according to its own technical capacity. We use FNAC preoperatively as the primary method to diagnose thyroid nodules and the intraoperative diagnosis method is always used as a complementary method especially for cases that receive a diagnosis of suspicious cytology.
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