Acta chir belg, 2006, 106, 199-201
Frozen Section in Thyroid Surgery D. Giuliani, P. Willemsen, J. Verhelst*, M. Kockx**, M. Vanderveken Departments of General Surgery, Endocrinology* and Anatomopathology**, Middelheim General Hospital, Antwerp, Belgium.
Key words. Frozen section ; thyroid surgery. Abstract. Objective : We studied the use of frozen section in the detection of malignancy in thyroid surgery in a large teaching hospital. Materials and methods : We reviewed all case notes of patients operated on for thyroid disease between January 1st 1997 and December 31st 2004. We identified 420 operations in 408 patients. Data were available for 417 operations. Results : In patients with a solitary thyroid nodule, a frozen section is sometimes performed. Frozen section was done in 128 of 417 operations. The specificity for malignancy was 98.16%. The positive predictive value was 81.81% and the negative predictive value 93.85%. However the sensitivity was 56.25%. Frozen section is a time-consuming investigation. With follicular lesions it is very difficult to distinguish between benign disease and malignancy since the diagnosis of malignancy depends on capsular and/or blood vessel invasion. Also it costs about 100 Euro (approximately 125 dollars). Conclusion : This study confirms that adequate histopathologic diagnosis of thyroid disease is based on extensive subsampling of the specimen which is not possible during a peroperatory frozen section procedure.
Introduction There is an ongoing controversy regarding the use of frozen section (FS) in thyroid surgery for suspected malignancy. Those who support it, use it mainly to determine the extent of the operation, especially when fine needle aspiration biopsy is equivocal (1-7). They want to reduce the chance of a second operation with its own complications (higher risk of recurrent laryngeal nerve damage, parathyroid injury) (4). Those against, on the other hand, do not use it because it cannot reliably distinguish a benign follicular lesion from a malignant one and because it is time consuming (8-16). Because of this major point of discussion, we decided to review our own experience with frozen section. Material and methods We conducted a retrospective study of all patients who underwent thyroid surgery in the Department of General Surgery of the Middelheim General Hospital, Antwerp, Belgium between January 1st 1997 and December 31st 2004. We reviewed all case notes of these patients and collected the following data : age, sex, date and type of operation, result of FS (if performed) and the final anatomopathological result. Frozen section was performed at the discretion of the surgeon when malignancy was suspected. For frozen section one slice is taken in the most suspicious zone and then evaluated. It takes
about 25 minutes and costs 100 Euro (about 125 dollars). Results were classified as benign, malignant or inconclusive. The results of frozen section were compared with the results of the permanent section (gold standard). We calculated the sensitivity (true positive / true positive + false negative), specificity (true negative / true negative and false positive), positive predictive value (PPV) (true positive / true positive + false positive) and negative predictive value (NPV) (true negative / true negative and false negative) of frozen section. Results During this period 420 operations were performed on 408 patients. Due to insufficient data 3 patients were excluded. Data were collected for 417 operations on 405 patients. 12 patients underwent 2 operations. The median age was 48 years of age (range 15-95). There were 81 male patients and 324 female patients. Frozen section was performed in 128 operations when doubt existed about the presence of malignancy. The median age of these patients was 46 years of age (range : 16-75). There were 24 male patients and 104 female. Results are shown in table I. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) respectively were 56.25% ; 98.16% ; 81.81% and 93.85%. Due to positive frozen section the operative plan was changed to subtotal thyroidectomy in seven
200
D. Giuliani et al. Table I Results of frozen section. PS : permanent section. FS : frozen section
PS benign PS malignant Total
FS Benign
FS Malignant
FS Inconclusive
107
2
3
6
9
1
113
11
4
patients. Afterwards, on permanent section there was no malignancy present in one of these patients, who is currently on thyroid substitution. Twelve patients underwent two operations. Seven patients had a completion thyroidectomy for malignancy. Of these patients four had undergone frozen section : three showed benign pathology, one was inconclusive. One patient who was originally operated upon for a metastasis of a renal cell cancer, developed a recurrence. Another patient developed a recurrence of a Hürthle cell carcinoma in the thyroid remnant. Two patients were operated upon twice for benign pathology (follicular adenoma), and one patient developed a papillary cancer (follicular variant) after left hemithyroidectomy for multinodular goitre. Discussion As is known from the literature, frozen section has its limitations in detecting malignancy in thyroid surgery. Firstly, it is difficult to distinguish benign from malignant pathology, especially in follicular and/or Hürthle cell lesions (1-5, 8-12, 14-16). The same applies to the follicular variant of papillary carcinoma (1, 3, 5, 9-15). This is because the diagnosis of malignancy depends on finding capsular and/or vascular invasion (1, 3, 5, 9-15). To assure its presence or absence one must evaluate the entire capsule (11, 12), which brings us to the second point. Secondly, is the problem of sampling error (1-3, 5, 7, 9, 11-13, 17). Due to the limited number of slices available with frozen section it is difficult to find capsular and/or vascular invasion. But micro-carcinomas with a diameter of less than 1 cm are also difficult to find (9, 13). In a study in small hospitals in the USA, frozen sections in thyroid and/or parathyroid tissue were the third most frequent cause of discordant diagnosis with the permanent section, mainly because of sampling error (17). Thirdly, the interpretation of frozen sections is made more difficult by freezing artefacts that cause cellular distortion, blood vessel distortion and collapse (3, 1113, 15). For instance, it is more difficult to see the ground glass appearance of the nuclei in follicular variants of papillary cancer (11, 13, 15).
Fourthly, frozen section is a time-consuming investigation. In our centre it takes about 25 minutes which is well within the range reported in the literature (1548 minutes) (2, 5, 7, 11-14, 16, 18). We use only one slice, but the more slices that are made, the more time is spent. These factors limit the usability of frozen section in thyroid surgery. Our sensitivity is on the lower end of the range reported in the literature (53-93%) (1-4, 6, 11, 12, 14-16, 18, 19). The same applies regarding the specificity (range 98-100%) (1-4, 6, 11, 12, 14-16, 18, 19), and negative predictive value (74-97.8%) (1, 4, 6, 11, 14, 16, 18, 19). Our positive predictive value is lower than reported in the literature (75-100%) (1, 3, 6, 11, 14, 16, 18, 19), mainly because of our low sensitivity. However, we must consider that these results are not entirely comparable. This is for three reasons. Firstly, different centres use a different number of slices to evaluate a lesion. This ranges from 1 slice (as in our centre) to as many as 10 slices (1, 5, 6, 12-14, 18). The more slices that are taken, the higher is the chance of finding capsular and/or vascular invasion or microcarcinomas. This can be attributed to the better result of FS in these centres. A drawback is that there is less tissue available for permanent section. It also takes more time (2, 5, 7, 11-14, 16, 18). Secondly, we must consider the differences between experienced (third line/referral) centres and smaller centres (17). Referral centres have a large, somewhat selected, population and therefore a greater workload. They can develop a higher level of experience in interpreting a frozen section. Thirdly, some authors have studied selected populations, e.g. only follicular lesions, patients with fine needle aspiration biopsy and frozen section, etc (4, 8-13, 15, 19). Therefore their results cannot be completely extrapolated to every institution. The cost of one frozen section in Belgium is 100 Euro (approximately 125 dollars). Of course, due to differences in social security systems, the costs between countries are not comparable. E.g. in Turkey it costs 12 dollars (18) compared with 246 to 600 dollars in the USA (12, 15). We do recognize the limitations of our study. It is a retrospective study, not randomised, and we did not compare fine needle aspiration biopsy with frozen section. Also frozen section was used at the discretion of the surgeon without a clear protocol. However, in our experience we cannot recommend the use of frozen section for thyroid surgery in cases of suspected malignancy. This study therefore confirms that adequate histopathologic diagnosis of thyroid disease is based on extensive subsampling of the specimen which is not possible during a peroperatory frozen section procedure. Frozen section can be useful for the
Frozen Section in Thyroid Surgery evaluation of nodal involvement to assess the need for nodal dissection. If frozen section is used, its limitations must be recognised, preferably based on first hand data.
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