Abstract
Introduction: Many surgeons use intraoperative frozen-section (FS) biopsy of thyroid nodules to predict malignant disease, but the findings are often not in agreement with those of fine-needle aspiration (FNA) biopsy. Our objective in this study was to assess the value of intraoperative FS biopsy in patients with nodular disease of the thyroid gland.
Methods: In this study, 203 patients underwent thyroid surgery at the Ankara Oncology Hospital. Nodules were assessed by FNA biopsy preoperatively, by FS intraoperatively and by histologic examination of the excised specimen. Sensitivity, specificity and accuracy were determined for FS and FNA with respect to the histologic findings.
Results: The sensitivity, specificity and accuracy rates for FNA, excluding occult cancers, were 74.1%, 100% and 95.2%, respectively, and for FS were 87.1%, 100% and 97.8%, respectively. FS influenced operative decisions in 0.6% of nodules found to be benign by FNA and in 20% of nodules found to be suspicious by FNA. FS contributed nothing for FNA-malignant disease since all the results in this group were true positive.
Conclusions: Intraoperative FS was most helpful when the FNA findings were suspicious for malignant disease. FS does not seem to be necessary when FNA indicates malignant or benign disease. Both FNA and FS failed to detect occult thyroid carcinomas.
Thyroid nodules, a feature of many thyroid disease processes, are mostly benign and are discovered by the patient or during a medical examination. Often these nodules can be managed conservatively. The clinical problem is to identify malignant lesions that require surgical excision. The most cost-effective test for evaluating thyroid masses is fine-needle aspiration (FNA) biopsy, the accuracy of which exceeds 80% in most series.1 Many surgeons use intraoperative frozen-section (FS) biopsy to confirm the FNA biopsy findings and to guide the extent of thyroidectomy. 2 Surgeons may be faced with a difficult decision when the FNA and FS diagnoses are discordant. The role of FS has been criticized by some authors who have found no or little difference in sensitivity, specificity and accuracy between FS and FNA biopsies, and some have recommended against the routine use of FS due to cost-ineffectiveness.3 The purpose of our study was to assess the value of FS in predicting malignancy in patients with nodular thyroid disease.
Patients and methods
Between July 1990 and December 2001, 203 patients underwent surgery for thyroid nodules at the Ankara Oncology Hospital. Most patients had thyroid goitre and were referred because malignant disease was suspected on clinical grounds. The diagnosis was made both by FNA preoperatively and by FS intraoperatively. FNA biopsies were obtained with the use of 24-gauge needles; the specimens were stained and interpreted in the conventional manner.4 The prominent nodule of multinodular goitre or a solitary nodule was sampled by FNA and FS. The final histopathological diagnosis of thyroidectomy specimens was available in all patients. The cytologic findings for FNA were classified as follows: 1, benign; 2, suspicious; 3, malignant; and 4, inadequate for evaluation. FS biopsy findings were categorized as 1, benign; 2, malignant; and 3, deferred. All FS and histologic diagnoses were from our laboratory; fine-needle aspirates were evaluated by several pathologists at our hospital and outside.
Sensitivity, specificity and diagnostic accuracy were assessed for FNA and FS procedures. The results were given as follows.
True positive: a result positive for malignancy with subsequent final histopathological confirmation
True negative: a result negative for malignancy with definitive histopathological confirmation
False positive: a result that was positive for malignancy but with no evidence of carcinoma on histopathological examination
False negative: a result that was negative for malignancy but with a diagnosis of malignant disease on histopathological assessment
Sensitivity was defined on the basis of thyroid cancer detected with FNA or FS technique: true positive/[true positive + false negative]. Specificity was defined on the basis of the detection of benign thyroid disease: true negative/[true negative + false positive]. Diagnostic accuracy represented the combination of sensitivity and specificity: [true positive + true negative]/[ true positive + false positive + true negative + false negative].
Minimal or occult microcarcinomas of the thyroid are defined as tumours 1 cm or smaller in dimension without evidence of capsular invasion and not associated with lymph-node metastases. They are nonpalpable and usually found incidentally at surgery or on pathological examination. There is controversy about their management and the importance of identifying them.5,6 Sensitivity, specificity and diagnostic accuracy of FNA and FS biopsies were assessed separately, including and excluding occult carcinomas.
Results
The series comprised 157 women (77.3%) and 46 men (22.7%); the mean (and standard deviation) age was 46.1 (13.5), ranging from 13 to 76 years. Malignant disease was encountered in 48 patients (23.6%). The final or definitive histopathological diagnoses are shown in Table 1.
Final Histopathological Diagnosis in 203 Patients With Thyroid Nodular Disease
Fine-needle aspiration biopsy
On the basis of the FNA biopsy, 23 (11.3%) patients had findings of malignant disease, 152 (74.9%) had a benign specimen, 20 (9.8%) had findings that suggested malignant disease, and 8 (3.9%) had inadequate findings. Table 2 shows FNA results and their correlation with the FS and histopathological diagnoses. In all 23 patients reported to have malignant disease by FNA, the malignancy was confirmed by final pathological examination (i.e., there was no false-positive FNA result). Their FS diagnoses were malignant for 22 patients and deferred for 1.
Results of Preoperative Fine-Needle Aspiration (FNA) Biopsy and Frozen-Section Biopsy in 203 Patients With Thyroid Nodular Disease and Correlation With the Final Histopathological Findings
Among the 152 patients classified as having benign nodules by FNA biopsy, the final histopathological examination diagnosed malignant disease in 13 (8.6%); of these, occult papillary carcinoma was diagnosed in 5, papillary carcinoma in 2, a follicular variant of papillary carcinoma in 5 and follicular carcinoma in 1. In the FNA-benign group, FS biopsy reported only 1 (0.6%) patient with malignant disease (a papillary carcinoma) out of the 13 patients. FS diagnosis was deferred for 6 patients. The final histopathological diagnosis was malignant disease in 5 of these of whom 1 had occult papillary carcinoma (Table 2).
FS biopsy of the 20 patients with FNA-suspicious nodules revealed 4 (20%) cases of malignant disease, which was confirmed by postoperative histopathological diagnosis (1 follicular, 1 medullary, 2 anaplastic carcinomas). In 11 patients whose specimen was reported as benign by FS, 1 had a papillary carcinoma. In 5 patients, the FS diagnosis was deferred, and the histopathological examination revealed that all had malignant disease (1 papillary carcinoma, 1 follicular carcinoma, 1 papillary carcinoma follicular variant, 1 medullary carcinoma, 1 Hürthle cell carcinoma) (Table 2).
Although we repeated the FNA, the biopsy specimen was inadequate for a diagnosis in 8 patients; 2 of them were found to have occult papillary carcinoma on histopathological examination. For these 8 patients, the FS biopsy specimen was reported as benign in 7, and the diagnosis was deferred for 1 patient, whose tissue was benign on histopathological examination.
Frozen-section biopsy
FS biopsy results showed malignant disease in 27 (13.3%) of the 203 patients (the diagnosis was confirmed by histopathological examination), as benign disease in 173 (85.2%), but in 10 (5.8%) of these histopathological examination diagnosed malignant disease (6 occult papillary carcinomas, 2 papillary carcinomas, 1 follicular variant of papillary carcinoma and 1 follicular carcinoma). When the occult cancers are excluded, the rate drops to 2.3%. The preoperative FNA results in these 4 patients reported benign disease in 3 patients and “suspicious” in 1.
FS biopsy recognized malignant disease in 22 (95.6%) of 23 patients reported to have malignant disease by FNA biopsy, in 1 (0.6%) of 152 with FNA-benign disease and in 4 (20%) of 20 patients with FNA-suspicious disease. In other words FS biopsy recognized 4 suspicious specimens and 1 false-negative FNA biopsy specimen as malignant. Seven patients in this series had occult papillary thyroid carcinomas, and neither FNA nor FS could reveal them.
Overall sensitivities for FNA and FS were 63.8% and 72.9% respectively; specificities were 100% for both and diagnostic accuracy was 92.5% and 94.4% respectively. When occult carcinomas were excluded, sensitivity, specificity and accuracy rates for FNA reached 74.1%, 100% and 95.2%, respectively and for FS 87.1%, 100% and 97.8%, respectively (Table 3).
Sensitivity, Specificity and Diagnostic Accuracy of Fine-Needle Aspiration Biopsy and Frozen-Section Biopsy in Patients With Thyroid Nodular Disease Compared With That in the Literature
Discussion
FNA cytology of thyroid nodules has been shown to be safe, accurate and superior to clinical assessment in cases of malignant thyroid disease.2,7 Many surgeons prefer to confirm all diagnoses of neoplasia made by FNA biopsy by intraoperative FS examination, 8 but the role of FS has been debated in the literature; some authors have found no or little difference in sensitivity, specificity or accuracy between the 2 techniques3,6 (Table 3). FS increases operating time and expenditure, and its necessity is still uncertain. 9 The surgeon may be faced with a difficult decision when the results of FNA and FS biopsies are discordant.8
In this study, FNA biopsy results in 23 (11.3%) patients were reported to be malignant and malignancy was confirmed by final pathological examination in all; FS reported 22 of them as malignant. FS sensitivity for the FNA-malignant group was 100%, but FNA was always correct and FS contributed nothing and did not alter surgical decisions in this group.
Thirteen of 152 patients who were reported to have benign disease by FNA were confirmed to have malignant disease by histopathological examination. FS reported only 1 patient with malignant disease out of these 13 patients and diagnosis was deferred for 6 cases. The sensitivity of FS for the FNA-benign group was 25% even when 5 occult cancers were excluded, so the contribution of FS in this group was also small. This could be explained by the fact that in follicular neoplasms and Hürthle cell neoplasms diagnosis depends on demonstrating capsular or vascular invasion, which is not possible by FNA and FS.10–12 There is also difficulty in diagnosing the follicular variants of papillary carcinoma by FNA and FS biopsy because its cytomorphologic features overlap with those of benign and neoplastic follicular lesions; the follicular variant contains very few of the nuclear features characteristic of papillary carcinoma and may be missed by both techniques.13 Freezing may induce cellular distortion making differentiation even more difficult.12
FNA biopsy findings showed that 20 patients had specimens that were suspicious for malignant disease, and 4 of these were reported to be malignant by FS. FS sensitivity for the FNA-suspicious group was 80%, which was parallel to that reported in the medical literature3 (Table 3 and Table 4). For the present series FS influenced the operative decision in 20% of cases. From these results we concluded that FS was most helpful in recognizing malignancy when the FNA results were suggestive of malignancy.
Sensitivity, Specificity and Diagnostic Accuracy of Frozen-Section Biopsy in Patients With Thyroid Nodular Disease Relative to Fine-Needle Aspiration Biopsy
In the inadequate FNA group of 8 patients, in which 2 were eventually found to have occult papillary carcinoma, FS biopsy reported 7 benign results and 1 deferred result. The small group size and lack of invasive cancer prevented any conclusion as to the need for FS biopsy. Most authors recommend either FS or touch imprint cytology if FNA is inadequate. 14–16
In this series, neither FNA nor FS demonstrated the 7 cases of occult thyroid carcinoma. Occult carcinomas are difficult to diagnose by cytologic methods and some recommend ultrasound-guided FNA biopsy.17
Overall FNA sensitivity in our series was lower than that reported in the literature (63.8%), whereas FS sensitivity (72.9%) was within the reported range3 (Table 3 and Table 4). In the present study, suspicious findings were considered separately from clearly malignant and benign FNA findings, and when occult carcinomas were excluded, sensitivity rates for FNA reached 74.1% and FS, 87.1%.
Many recent papers report results similar to ours; i.e., when FNA was sufficient (benign or malignant), FS did not contribute more.18,19 Some prefer to add intraoperative touch imprint cytology to FS; others suggest imprint cytology as an alternative to FS and recommend it especially for small hospitals lacking the facilities for FS examination.15
Conclusions
FNA and FS were found to be specific, accurate and sensitive diagnostic procedures in evaluating thyroid nodules. Intraoperative FS biopsy was most helpful for patients with suspicious FNA biopsy findings. Present data also suggest that FS biopsy is not necessary when FNA biopsy gives a malignant or benign diagnosis. Both techniques fail to reveal occult carcinomas of the thyroid.
Footnotes
Competing interests: None declared.
- Accepted November 3, 2003.