Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/ASO.2004.03.001
Annals of Surgical Oncology 11:94-98 (2004)
© 2004 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Callcut, R. A.
Right arrow Articles by Chen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Callcut, R. A.
Right arrow Articles by Chen, H.
Related Collections
Right arrow Surgery

ORIGINAL ARTICLES

The Utility of Frozen Section Evaluation for Follicular Thyroid Lesions

Rachael A. Callcut, MD, Suzanne M. Selvaggi, MD, Eberhard Mack, MD, Omer Ozgul, MD, Thomas Warner, MD and Herbert Chen, MD

From the Departments of Surgery (RAC, EM, OO, HC) and Pathology and Laboratory Medicine (SMS, TW), University of Wisconsin, Madison, Wisconsin.

Correspondence: Address correspondence and reprint requests to: Herbert Chen, MD, H4/750 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792; Fax: 608-263-7652; E-mail: chen{at}surgery.wisc.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background: Because fine-needle aspiration cannot reliably discriminate between benign and malignant follicular thyroid lesions, some surgeons use intraoperative frozen section (FS) to guide operative management. To determine the utility of FS for these lesions, we reviewed our institutional experience.

Methods: Between 1994 and 2001, 152 patients underwent surgical resection for follicular neoplasms.

Results: The mean age of the patients was 47 years, and 76% were female. Forty-one (32%) FSs were reported as benign, 5 (4%) as malignant, and 3 (2%) as indeterminate, and in 80 (62%), the diagnosis was "follicular lesion, deferred to permanent histology." On paraffin section, all patients with malignant FSs had thyroid cancer, and all 41 patients with benign FSs had benign lesions. Thus, FS for diagnosis of follicular thyroid cancer had a sensitivity, specificity, positive predictive value, and accuracy of 67%, 100%, 100%, and 96%, respectively. In most cases (64%), FS rendered no additional information at the time of operation. Therefore, the cost per useful FS was $7800, which is higher than the charge of a completion thyroidectomy (approximately $6000).

Conclusions: FS analysis for follicular lesions seems to be highly specific and accurate. However, because of the low sensitivity, routine use of FS is not cost-effective in patients with follicular thyroid lesions.

Key Words: Frozen section • Follicular thyroid lesions • Fine-needle aspiration • Thyroidectomy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Thyroid nodules occur in 4% to 7% of the general population, and 5% of these lesions are malignancies.1–4 Fine-needle aspiration cytology (FNA) has revolutionized the management of thyroid nodules by providing an accurate method for distinguishing benign from malignant disease to reduce the number and extent of operative interventions performed. Unlike other thyroid lesions, for which FNA is a helpful adjunct in diagnosing malignant lesions,5–7 FNA has proven significantly less useful for follicular lesions.3,4,8–14

The intraoperative distinction between follicular adenomas and carcinomas has remained a diagnostic dilemma for surgeons and pathologists. One modality that has received considerable attention is intraoperative frozen section (FS). A number of conclusions regarding the role of FS in follicular neoplasms have been extrapolated from studies designed to examine the diagnosis of thyroid nodules in general.8,10–12,15–18 Only a few studies have been performed to examine the role of FS for the specific diagnosis of follicular lesions.4,13,19,20 Despite the increased specificity (compared with FNA) reported, the utility and cost-effectiveness of FS remain controversial because of the reported low sensitivity of this technique in some studies.4,19 In an attempt to clarify the role of FS in the diagnosis and operative management of follicular thyroid lesions, we reviewed our institutional experience.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
One hundred fifty-two consecutive patients with follicular thyroid lesions diagnosed by intraoperative FS or final paraffin sections between January 1994 and December 2001 were identified from the University of Wisconsin–Madison pathology records. All patients had surgical resection performed at our institution, and FSs were performed at the discretion of the attending surgeon. Demographic data, operative indications, operative procedure, FNA results, FS data, and paraffin sections were reviewed. All pathologic diagnoses of malignancy were re-reviewed by a single pathologist.

Ninety-eight patients with follicular thyroid lesions had preoperative FNAs performed, 129 patients underwent FS, and 83 patients had both diagnostic procedures performed. FNA results were reported as benign, malignant/suspicious for malignancy, follicular neoplasm, or indeterminate/inadequate. "Suspicious for malignancy" and "malignant" readings were treated as one category because of similar treatment algorithms. FS results were reported as benign, malignant, follicular neoplasm, or indeterminate. Intraoperative FS results reflected the reading of one or two representative sections from the area most likely to show capsular invasion. Paraffin section was reported as follicular adenoma or follicular cancer. Thirty-six patients had an additional incidental diagnosis including thyroiditis, goiter, or micropapillary cancer found on paraffin sections.

Sensitivity (true positives/true positives + false negatives), specificity (true negatives/true negatives + false positives), accuracy (true positives + true negatives/total evaluations), and positive predictive value (true positives/true positives + false positives) were calculated for FNA and FS data. Indeterminate and follicular neoplasm diagnoses were not included in these calculations.

Cost analysis was performed by using the charges billed to the patient by our institution. The cost of FS analysis was determined to be the charge for the preparation and interpretation of one representative sample by the staff pathologists. The operative charges for a bilateral thyroidectomy and unilateral thyroidectomy and reoperative charges were approximated from patient charges for 2001.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patient Data
During the 8-year study, 152 operative procedures for follicular thyroid lesions were performed. There has been a marked increase in the number of thyroidectomies performed for follicular neoplasms at our institution (Fig. 1). The mean age of patients undergoing thyroidectomy for follicular lesions in this study was 47 ± 1 years (range, 16–86 years), and 76% were female. The most common operative indications cited in preoperative data were symptomatic lesions (30%) or enlarging lesions (27%; Table 1). All operative procedures were performed by a total of five surgeons; 83% of procedures were performed by three surgeons. Follicular cancer was diagnosed by permanent histology in 6.6% of patients. Vascular invasion was present in 80% of follicular cancers on final histology. In all of these cases, thyroid tumor cells were present within the lumen of multiple vessels. All follicular carcinomas exhibited full capsular invasion. No lesions were partially or minimally invasive.



View larger version (20K):
[in this window]
[in a new window]
  		FIG. 1. Total operative case volumes per study year for thyroidectomies performed for follicular lesions between 1994 and 2001 at the University of Wisconsin–Madison. *Eleven months of data were available for 2001.

 

View this table:
[in this window]
[in a new window]
  		TABLE 1. Operative indications
 
FNA Results
Of the 98 (65%) patients who had preoperative FNAs performed, 15 (15%) were reported as indeterminate, 19 (19%) were read as benign, 16 (16%) were interpreted as malignant/suspicious, and 48 (49%) were categorized as follicular neoplasms (Table 2). For patients with an FNA of follicular neoplasm, 5% had a follicular cancer on paraffin section. One patient with a benign reading was found to have a malignancy on final histological interpretation. The sensitivity, specificity, and accuracy for diagnosis of follicular malignancy by FNA were 75%, 78%, and 78%, respectively.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Classification of FNA results
 
FS Results
One-hundred twenty-nine (85%) patients had FSs performed. Of those undergoing FS, a benign diagnosis was rendered on 41 (32%) specimens, a malignant diagnosis on 5 (4%), "follicular neoplasm, defer to permanent histology" on 80 (62%), and indeterminate on 3 (2%; Table 3). Thus, FS provided no definitive diagnostic information in 64% of cases. Final histological assessment was found to be a follicular thyroid malignancy in 2% of deferred cases. Overall, for each malignancy identified by FS, allowing an initial total thyroidectomy versus a second, completion thyroidectomy, 26 FS were performed at a cost of $300 per patient. Therefore, the cost per useful FS for the diagnosis of malignancy was $7800.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Classification of frozen section results
 
All samples read as benign or malignant on FS were confirmed as benign or malignant, respectively, on final histological study. Of note, one sample was read on FS to be a papillary cancer and was found to contain both a papillary cancer and a follicular adenoma on paraffin section. Thus, for detecting follicular malignancies or benign follicular pathology, there were no false positives and no false-negative results. The sensitivity, specificity, positive predictive value, and accuracy were 67%, 100%, 100%, and 96%, respectively.

In the 46 patients in whom FS provided definitive diagnostic information, the operative outcome was altered in 2 cases, representing only 1.6% of patients undergoing FS analysis. In the 41 cases in which a benign diagnosis was found, the patients would have undergone initial unilateral thyroidectomy anyway without an FS diagnosis. Sixty percent of the patients found to have a malignant diagnosis on FS analysis would have undergone an initial bilateral thyroidectomy because of the large size of their lesions regardless of FS diagnosis. Thus, the total cost to perform all FSs was $38,800, compared with the charge savings of $12,000 generated by avoiding the need for completion thyroidectomy without the guide of FS in those with malignant diagnosis on paraffin sections.

Patients With an FNA of Follicular Neoplasm
If FS had been used only in patients with FNA of follicular neoplasms, FS would have provided no additional diagnostic information in 70% (39 of 56) of cases. In 14 of these cases in which FS was useful, the FS diagnosis was interpreted as benign. However, at our institution, if FS had not been performed, the patients would still have undergone unilateral thyroidectomy only. In the three remaining specimens, the FS was identified as malignant, and the patients underwent a total thyroidectomy at the initial operative procedure. Follicular carcinoma was confirmed on paraffin section in all three specimens. When FS was used in this select group, the operative outcome was altered in only 5% (3 of 56) of cases. Therefore, for each FS that changed the operative outcome, 19 FSs were performed at a cost of $5700 per useful FS. The total cost to perform all FSs in this group was $16,800, compared with the total avoided charges of $18,000.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
FNA remains the standard preoperative method of choice in the evaluation of thyroid nodules. Before 1999 at our institution, FNA of all thyroid nodules was not routinely practiced, accounting for our relatively low utilization (65%) in this series. Some surgeons believed that if thyroidectomy was already planned for a patient with a thyroid nodule, preoperative FNA would not affect patient management. However, since 1999, we have made an effort to increase our utilization of FNA to approximately 90%. Despite the relative success in the technique for distinguishing most benign and malignant thyroid pathology, follicular neoplasms still prove to be a diagnostic dilemma. In fact, as in other similar studies,12,14,21 FNA is unable to reliably distinguish benign from malignant follicular lesions because of its inability to identify hallmark features of these malignancies, including capsular and vascular invasion.1,3,8,9 Thus, alternative techniques, including intraoperative FS, have been explored to guide operative management of suspected follicular thyroid lesions. Unfortunately, the role of FS in the diagnosis and management of follicular thyroid lesions remains controversial.

As illustrated in this study and several others specifically examining follicular thyroid lesions, there is little debate that FS is highly specific3,4,19; however, the reported sensitivity of the technique has been generally poor and widely variable (Table 4). Likewise, the diagnostic accuracy of the technique has also been debated, with studies reporting an accuracy as low as 50%4 and as high as 98%.13 Criticisms of the Mayo Clinic study, which reported both the highest sensitivity and accuracy, focused on the tremendous volume of follicular neoplasm operations performed at that institution and the inapplicability to the average institution performing thyroid surgery for follicular lesions.13 It is estimated that most tertiary institutions will encounter only approximately two follicular thyroid malignancies per year.3 In this study, we have demonstrated a similar accuracy and slightly lower diagnostic sensitivity at an institution with a significantly lower volume of such cases compared with the Mayo study. Thus, a high accuracy is still obtainable at institutions with less experience using this technique for follicular thyroid lesions.


View this table:
[in this window]
[in a new window]
  		TABLE 4. Frozen section for use in diagnosis of follicular thyroid lesions
 
Accuracy and sensitivity are significant factors when determining the overall cost savings benefit of this technique and its role for altering operative management. Paphavasit et al.13 have advocated the use of FS on the basis of their reported overall cost savings of $400,000 in hospital charges due to the avoidance of many two-stage operations. However, this study did not account for the cost to perform the FSs and the relatively low number of patients whose operative course was altered by this technique. It is reasonable to conclude that if this technique allowed surgeons to avoid unnecessary operative procedures, then there would be a reduction in operative charges; however, this cost savings must be balanced by the number of diagnostic procedures performed to achieve such an outcome. In an effort to account for this, we based our analysis on the cost to perform the total number of FSs versus the charge savings generated by the use of FS to avoid unnecessary operative and reoperative procedures.

Despite the high accuracy and specificity of FS, we have been unable to demonstrate that routine use produces a charge savings benefit by altering operative management. In examining all patients who underwent an FS, 26 FSs were needed to achieve 1 useful FS for the diagnosis of malignancy, at a charge of $7800 per useful FS. This cost is nearly $2000 more than the performance of a second completion thyroidectomy at our institution. In addition, because operative outcome was altered in only 1.6% of cases, the total charge for all FSs performed was $26,800 more than the charge savings generated by avoiding unnecessary operations. Thus, even with a higher accuracy and similar sensitivity compared with other studies that concluded that FS is not cost-effective,4,9,10 we are still unable to support its routine use for the diagnosis of and operative planning for follicular thyroid lesions.

Furthermore, many have advocated the selective use of FS when the FNA diagnosis is a follicular neoplasm.1,10,11,16,17 Subset analysis of our data found that in nearly 70% of patients with follicular neoplasms by FNA, FS provided no additional useful diagnostic information. It is important to note that operative outcome was altered in only 5% of these cases. Thus, the cost of performing FSs to generate 1 useful FS for the diagnosis of malignancy was nearly equivalent to the charge to perform a second completion thyroidectomy. In addition, when the total cost to perform all FSs in this group was balanced with the potential avoided charges by eliminating reoperative procedures, the overall savings would have been just $1200. This suggests that this technique has minimal to no cost savings benefit for this specific clinical population.

Because FNA is highly specific for papillary thyroid cancers, medullary thyroid cancers, lymphomas, and anaplastic thyroid cancers, FS is uncommonly used for these lesions, as well as for follicular neoplasms. However, in patients with FNA results "suspicious for," but not diagnostic of, papillary cancer, FS has been shown to provide additional diagnostic information.2,5 Thus, we would continue to advocate the use of FS in this select clinical scenario.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Intraoperative FS for follicular thyroid lesions can be performed with a high degree of accuracy and specificity at institutions with low operative volumes for follicular thyroid lesions; however, routine use of FS has not proven to result in a charge savings benefit for detecting malignancy, because of its low sensitivity. Selective use of FS when FNA is nondiagnostic provides additional relevant clinical information in only a low percentage of cases. Thus, widespread application is not likely to have a charge savings benefit.


   FOOTNOTES
 
Intraoperative frozen section has been used to guide operative management of follicular thyroid lesions. We found frozen section for follicular lesions to be highly specific and accurate. However, because of low sensitivity, routine use is not likely to be cost-effective.

Received for publication March 6, 2003. Accepted for publication August 25, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Boyd LA, Earnhardt RC, Dunn JT, Frierson HF, Hanks JB. Preoperative evaluation and predictive value of fine-needle aspiration and frozen section of thyroid nodules. J Am Coll Surg 1998; 187: 494–502.[CrossRef][Medline]
  2. Udelsman R, Chen H. The current management of thyroid cancer (review). Adv Surg 1999; 33: 1–27.[Medline]
  3. Grant CS. Operative and postoperative management of the patient with follicular and Hurthle cell carcinoma. Do they differ (review)? Surg Clin North Am 1995; 75: 395–403.[Medline]
  4. Chen H, Nicol TL, Udelsman R. Follicular lesions of the thyroid. Does frozen section evaluation alter operative management? Ann Surg 1995; 222: 101–6.[Medline]
  5. Chen H, Zeiger MA, Clark DP, Westra WH, Udelsman R. Papillary carcinoma of the thyroid: can operative management be based solely on fine-needle aspiration? J Am Coll Surg 1997; 184: 605–10.[Medline]
  6. Chen H, Udelsman R. Papillary thyroid carcinoma: justification for total thyroidectomy and management of lymph node metastases (review). Surg Oncol Clin North Am 1998; 7: 645–63.[Medline]
  7. Cha C, Chen H, Westra WH, Udelsman R. Primary thyroid lymphoma: can the diagnosis be made solely by fine-needle aspiration? Ann Surg Oncol 2002; 9: 298–302.[Abstract/Free Full Text]
  8. Mandell DL, Genden EM, Mechanick JI, Bergman DA, Biller HF, Urken ML. Diagnostic accuracy of fine-needle aspiration and frozen section in nodular thyroid disease. Otolaryngol Head Neck Surg 2001; 124: 531–6.[Medline]
  9. Udelsman R, Westra WH, Donovan PI, Sohn TA, Cameron JL. Randomized prospective evaluation of frozen-section analysis for follicular neoplasms of the thyroid. Ann Surg 2001; 233: 716–22.[CrossRef][Medline]
  10. McHenry CR, Raeburn C, Strickland T, Marty JJ. The utility of routine frozen section examination for intraoperative diagnosis of thyroid cancer. Am J Surg 1996; 172: 658–61.[CrossRef][Medline]
  11. McHenry CR, Rosen IB, Walfish PG, Bedard Y. Influence of fine-needle aspiration biopsy and frozen section examination on the management of thyroid cancer. Am J Surg 1993; 166: 353–6.[Medline]
  12. Brooks AD, Shaha AR, DuMornay W, et al. Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors. Ann Surg Oncol 2001; 8: 92–100.[Abstract/Free Full Text]
  13. Paphavasit A, Thompson GB, Hay ID, et al. Follicular and Hurthle cell thyroid neoplasms. Is frozen-section evaluation worthwhile? Arch Surg 1997; 132: 674–8.[Abstract]
  14. Emerick GT, Duh QY, Siperstein AE, Burrow GN, Clark OH. Diagnosis, treatment, and outcome of follicular thyroid carcinoma. Cancer 1993; 72: 3287–95.[CrossRef][Medline]
  15. Morosini PP, Mancini V, Filipponi S, et al. Comparison between the diagnostic accuracy in diagnosis of thyroid nodules with fine needle biopsy: an intraoperative histological evaluation of frozen tissue (in Italian). Minerva Endocrinol 1997; 22: 1–5.[Medline]
  16. Aguilar-Diosdado M, Contreras A, Gavilan I, et al. Thyroid nodules. Role of fine needle aspiration and intraoperative frozen section examination. Acta Cytol 1997; 41: 677–82.[Medline]
  17. Shaha AR, DiMaio T, Webber C, Jaffe BM. Intraoperative decision making during thyroid surgery based on the results of preoperative needle biopsy and frozen section. Surgery 1990; 108: 964–7.[Medline]
  18. Shaha A, Gleich L, Di Maio T, Jaffe BM. Accuracy and pitfalls of frozen section during thyroid surgery. J Surg Oncol Suppl 1990; 44: 84–92.
  19. Kingston GW, Bugis SP, Davis N. Role of frozen section and clinical parameters in distinguishing benign from malignant follicular neoplasms of the thyroid. Am J Surg 1992; 164: 603–5.[Medline]
  20. Leteurtre E, Leroy X, Pattou F, et al. Why do frozen sections have limited value in encapsulated or minimally invasive follicular carcinoma of the thyroid? Am J Clin Pathol 2001; 115: 370–4.[Medline]
  21. McHenry CR, Thomas SR, Slusarczyk SJ, Khiyami A. Follicular or Hurthle cell neoplasm of the thyroid: can clinical factors be used to predict carcinoma and determine extent of thyroidectomy? Surgery 1999; 126: 798–802.[Medline]



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
Y. W. Zhang, D. Y. Greenblatt, D. Repplinger, A. Bargren, J. T. Adler, R. S. Sippel, and H. Chen
Older Age and Larger Tumor Size Predict Malignancy in Hurthle Cell Neoplasms of the Thyroid
Ann. Surg. Oncol., October 1, 2008; 15(10): 2842 - 2846.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. R. Haymart, D. J. Repplinger, G. E. Leverson, D. F. Elson, R. S. Sippel, J. C. Jaume, and H. Chen
Higher Serum Thyroid Stimulating Hormone Level in Thyroid Nodule Patients Is Associated with Greater Risks of Differentiated Thyroid Cancer and Advanced Tumor Stage
J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 809 - 814.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
T.-C. Chao, J.-D. Lin, H.-H. Chao, C. Hsueh, and M.-F. Chen
Surgical Treatment of Solitary Thyroid Nodules Via Fine-Needle Aspiration Biopsy and Frozen-Section Analysis
Ann. Surg. Oncol., February 1, 2007; 14(2): 712 - 718.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
P. W. S. Rosario, J. S. Reis, E. L. Padrao, L. L. Rezende, T. A. Fagundes, and A. L. Barroso
The Utility of Frozen Section Evaluation for Follicular Thyroid Lesions
Ann. Surg. Oncol., September 1, 2004; 11(9): 879 - 879.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Callcut, R. A.
Right arrow Articles by Chen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Callcut, R. A.
Right arrow Articles by Chen, H.
Related Collections
Right arrow Surgery

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS