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The Value of Frozen Section Examinations in Determining the Extent of Thyroid Surgery in Patients With Indeterminate Fine-Needle Aspiration Cytology
Jeffrey C. Roach, MD;
Keith S. Heller, MD;
Sanford Dubner, MD;
Laura A. Sznyter, MD
Arch Otolaryngol Head Neck Surg. 2002;128:263-267.
ABSTRACT
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Objectives To determine the usefulness of intraoperative frozen section (FS) examinations
in establishing the diagnosis of thyroid cancer in patients undergoing thyroidectomy
for nodules with indeterminate cytological features and to determine the cost-effectiveness
of FS examinations in this situation.
Design Retrospective medical record review. The results of fine-needle aspiration
biopsies (FNABs), FS examinations, and final pathologic examinations are compared.
A cost-effectiveness analysis of routine FS examinations compared with the
cost of additional surgical procedures is performed.
Setting A private surgical practice in a medical school–affiliated teaching
hospital.
Patients The records of all 480 patients undergoing thyroidectomy between January
1, 1998, and September 30, 2000, were reviewed. All 199 patients with a dominant
thyroid nodule and FNAB results either highly suggestive of papillary cancer
or indeterminate were studied.
Results Of the patients with FNAB results highly suggestive of papillary cancer,
95% had cancer according to the final pathologic examination results. The
diagnosis of cancer was made by FS examination results in 67% of these patients.
Of the remaining 178 patients whose FNAB result was indeterminate, 64 (36%)
had thyroid cancer. Malignancy was diagnosed by FS examination results in
30 (47%) of these patients. If FS examinations had not been performed, these
30 patients would have required a second operation to complete a total thyroidectomy.
The cost savings of routine FS examinations in patients with indeterminate
FNAB results is $1298 per patient.
Conclusions The routine performance of FS examinations in patients with thyroid
nodules with indeterminate cytological features is a cost-effective way of
avoiding a second surgical procedure if a total thyroidectomy is indicated.
In patients with FNAB results highly suggestive of papillary cancer, FS examinations
are not useful. In these patients, the definitive operation can be based on
the results of the FNAB.
INTRODUCTION
SINCE ITS INTRODUCTION by Martin and Ellis1
more than 70 years ago, fine-needle aspiration biopsy (FNAB) of the thyroid
has become the single most useful test for determining the likelihood of malignancy
in patients with thyroid nodules.2-3
The results of FNAB are generally accurate when interpreted as benign or malignant.2, 4-5 In these situations,
the results of FNAB can be used to determine whether surgery is required and
what the extent of surgery should be. In the 10% to 25% of nodules considered
indeterminate by FNAB results, the incidence of malignancy is approximately
30%.2, 5-6 Because
of this, most surgeons recommend thyroidectomy for patients with nodules with
indeterminate cytological features.2, 6-7
The extent of thyroidectomy for patients with well-differentiated thyroid
cancer (papillary, follicular, and Hürthle cell) is controversial. Some
researchers8-9 recommend total
thyroidectomy for virtually all patients. Others10-11
suggest that unilateral thyroid lobectomy is appropriate for patients with
low-risk cancers. In patients whose indication for surgery is an indeterminate
FNAB result and in whom total thyroidectomy would be recommended if the nodule
were a well-differentiated cancer, the intraoperative diagnosis of malignancy
by frozen section (FS) examination permits the performance of the definitive
operation at the initial surgery, avoiding the need for a second completion
thyroidectomy.
Some researchers4, 7, 12-14
question the necessity of an intraoperative FS examination because this test
is difficult to interpret and can be inaccurate. This article determines the
usefulness and cost-effectiveness of intraoperative FS examinations in patients
with solitary thyroid nodules with indeterminate FNAB cytological features.
PATIENTS AND METHODS
The medical records of all 480 consecutive patients who underwent thyroid
surgery by the members of a single group practice (K.S.H., S.D., and L.A.S.)
at a single institution from January 1, 1998, through September 30, 2000,
were reviewed. One hundred ninety-nine patients were identified in whom the
indication for surgery was a dominant thyroid nodule with indeterminate FNAB
cytological features. These patients were selected for further review. Patients
in whom the indication for surgery was thyrotoxicosis, local compression due
to a benign multinodular goiter, bilateral nodules, or a history of thyroid
surgery were excluded from this study. Patients who did not undergo an FNAB
or intraoperative FS examination, and those with benign, malignant, or nondiagnostic
FNAB cytological features, were also excluded. All patients were either euthyroid
or taking replacement doses of thyroid hormone when the FNAB was performed.
Serum thyrotropin levels, when available, were either in the normal range
or minimally suppressed.
Diagnoses made by FS examination results were categorized as benign,
malignant, or deferred for final pathologic examination. Indeterminate FNAB
diagnoses were subdivided into 4 categories: indeterminate, not otherwise
classified; follicular neoplasm; Hürthle cell neoplasm; and indeterminate
with papillary features. Patients whose FNAB result was highly suggestive
of papillary cancer, but which did not satisfy all the criteria for the diagnosis
of papillary cancer, were considered separately.
The cost-benefit analysis is based on Medicare reimbursement rates for
the New York City/suburban/Long Island region of New York. These costs are
summarized in Table 1. Statistical
significance was calculated using the Fisher exact test (2 x 2 table)
or the  2 test (4 x 2 table).
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Table 1. Medicare Reimbursement Rates*
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RESULTS
In this group of 199 patients, there were 155 females (78%) and 44 males
(22%). The median age of the females was 47 years (range, 13-82 years) and
of the males, 49 years (range, 20-71 years).
Twenty-one patients had FNAB results that were considered highly suggestive
of papillary cancer, and 20 (95%) of these were cancers (19 papillary and
1 Hürthle cell cancer). In these 21 patients, malignancy was diagnosed
by FS examination results in 14 (67%). In 6 patients (29%), the diagnosis
was deferred on FS examination. One FS examination result was interpreted
as benign. The difference in the incidence of malignancy between this group
and the remaining patients with indeterminate FNAB results is highly statistically
significant (P<.001).
Of the remaining 178 patients, 64 had well-differentiated thyroid cancers.
The details of the incidence and types of malignancy in each FNAB category
are summarized in Table 2. There
is no significant difference in the incidence of malignancy among the 4 different
indeterminate categories (P = .13). An additional
10 patients had microscopic foci of papillary cancer separate from the dominant
thyroid nodule.
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Table 2. Final Pathologic Examination Findings
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The diagnosis of cancer was established by intraoperative FS examination
results in 30 of these patients. This is 17% of the 178 patients in the 4
indeterminate FNAB categories and 47% of the 64 patients with well-differentiated
cancer on final pathologic examination findings. The percentage of patients
in whom cancer was diagnosed on FS examination is as follows (data in parentheses
indicate the number/total of patients in each category):
There was one false-positive result in the FNAB category indeterminate,
not otherwise classified. There were no false-negative results. Of the 121
FS examinations that were deferred, 42 (35%) were cancers. The likelihood
of making the diagnosis of well-differentiated thyroid cancer on FS examination
is related to the FNAB category and the final pathologic examination results
(Table 3).
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Table 3. Patients With Cancer in Each FNAB Category in Whom the Correct
Diagnosis Was Made on Frozen Section Examination*
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In the 178 patients previously considered, the FS examination result
permitted the performance of the definitive surgical procedure (total thyroidectomy)
in 30, avoiding the need for a second surgical procedure (completion thyroidectomy).
This cost savings is offset by the additional costs of performing FS examinations
in all 178 patients and the additional surgical and anesthesia costs of total
thyroidectomy compared with thyroid lobectomy (Table 4). The net savings per patient because of the routine performance
of intraoperative FS examinations in all patients with indeterminate cytological
features (excluding those highly suggestive of papillary cancer) is $1298.
COMMENT
Nodular thyroid disease is a common clinical condition that affects
4% to 7% of the US population. Only 5% of these nodules are malignant.15 Fine-needle aspiration biopsy has enabled surgeons
to be more selective in choosing patients with solitary thyroid nodules that
require surgery. Although we recognize that the choice of the definitive operation
for well-differentiated thyroid cancer is controversial,8-11
it is our practice to perform total thyroidectomies for almost all of these
patients. Therefore, the accurate diagnosis of malignancy intraoperatively
could avoid the need for a second operation in many patients.
Many researchers suggest that intraoperative FS examinations of thyroid
nodules are not useful and should not be performed routinely. McHenry et al13 report no difference in the accuracy of FNAB and
FS examination results. An FS examination resulted in a change in operative
management in only 3% of their patients. Lin et al12
concluded that the routine use of FS examinations is unnecessary, and changed
the operative procedure in only 1 of 82 patients. In a series of 100 patients,
Davoudi et al identified only 2 patients in whom the FS examination result
changed the extent of surgical resection and concluded that "overall, frozen
section does not contribute to the management of the thyroid lesion at the
time of surgery."16(p1084)
The studies by Bugis et al17 and Irish
et al18 are similar in that they compare the
overall sensitivity, specificity, and accuracy of FS examination and FNAB
results. Because the results with FNABs and FS examinations are similar, Irish
et al conclude that the FS examination adds little to the management of the
patient. Bugis et al, based on similar data, conclude that FNAB and FS examination
results are complementary. In both of these studies, most patients had an
FNAB result that was conclusively either benign or malignant, both categories
in which the FNAB result is accurate. It is only in those patients in whom
the FNAB result is indeterminate that an FS examination can be expected to
influence the choice of surgical procedure.
Other studies do confirm the value of an FS examination in intraoperative
decision making. Rosen et al,19 in a study
of 504 patients, report that 68% of papillary cancers were diagnosed by FS
examination results. No case of follicular cancer was correctly identified
by FS examination results. While this study suggests a relatively high sensitivity
for the FS examination diagnosis of papillary cancer, studies such as this
do not correlate the results of FS examinations with those of FNABs. The ability
to make a diagnosis by FS examination results that can be made as accurately
by FNAB results preoperatively adds nothing to the management of the patient.
A more important study is that of Gibb and Pasieka,20
who identified 71 patients with lesions that were suggestive of cancer by
FNAB results, 21 of which were malignant by final pathologic examination results.
In 9 (43%) of these patients, malignancy was determined by FS examination
results. Similarly, Sabel et al,21 in a series
of 561 patients, identified 44 with equivocal FNAB results who subsequently
underwent FS examination. In this small group, there were 2 false-negative
and 2 false-positive results. Of 7 cancers, 5 were correctly identified by
FS examination results.
In the series reported herein, an intraoperative FS examination permitted
the performance of a total thyroidectomy at the initial surgery in 17% of
the patients with indeterminate cytological features. More important, cancer
was diagnosed by FS examination results in 47% of those patients with cancer.
It is unclear why our results are different from those previously summarized.
The incidence of malignancy in our patients with indeterminate cytological
features is 36%, similar to that reported in many other articles.2, 5-6 This suggests that our
results with FS examinations are not due to differences in the definition
of indeterminate FNAB results. An additional 10 patients had microscopic foci
of papillary cancer. These patients were not included in the calculations
of the incidence of malignancy or in the cost analysis because we do not consider
these occult cancers to be clinically significant and do not perform more
extensive surgical procedures when they are discovered.
The results of FS examinations are particularly inaccurate in the evaluation
of follicular lesions. Chen et al14 include
in their study 73 patients with follicular lesions by FNAB results. In only
4 (5%) of the patients did the FS examination result correctly identify a
cancer. In another 4 (5%) of the patients, an incorrect FS examination result
caused the performance of an inappropriate operation. In these patients, 23
(32%) had cancer (12 follicular, 6 Hürthle cell, 2 papillary, and 3 follicular
variant of papillary cancers). Mulcahy et al,22
while observing that an FS examination result is complementary to an FNAB
result, confirm that, for follicular lesions on FNAB, the FS examination result
is unlikely to be diagnostic. Even in this group of patients (FNAB category
follicular neoplasm), we were able to detect 4 (29%) of 14 cancers by FS examination
results. However, only 3 of these cancers were follicular. Of the remaining
cancers, 2 were papillary and 9 were follicular variant of papillary. We include
in the category follicular neoplasm patients whose FNAB result is described
as follicular neoplasm with atypia. This may explain the relatively high percentage
of papillary cancers in this group.
In commenting on the accuracy of FNABs, Hamburger and Hamburger4 note that FNAB results are more accurate than FS examination
results in correctly predicting malignancy in patients whose FNAB result is
consistent with a high risk of cancer. We make the same observation in our
category highly suggestive of papillary cancer. This group has such a high
likelihood of malignancy that the patients must be considered separately from
other patients with indeterminate cytological features. Because 95% of these
patients had cancers and only 67% were diagnosed by FS examination results,
we recommend that FS examinations not be performed in this group and that
the definitive procedure be performed based on the FNAB results alone.
Although there is a trend suggesting a higher incidence of cancer in
the category indeterminate with papillary features, this category is not significantly
different from the other categories. Because 50% of the nodules in this group
are benign, we are reluctant to perform total thyroidectomies unless cancer
is confirmed by FS examination results.
Only 1 patient in this series underwent a total thyroidectomy inappropriately
based on a false-positive FS examination result. This low rate of false-positive
FS examination results is similar to that reported in many other series.19 The risk of a false-positive FS examination result
is so low that it should not be used as an argument against the routine use
of an FS examination.
Because we do not recommend FS examinations for nodules in the highly
suggestive of papillary cancer category, only the remaining 4 categories were
used in the cost analysis. In this analysis, we chose to use reimbursement
rather than charges. Hospital and physician charges vary greatly and frequently
bear little relation to actual payments, which almost all come from insurance
companies. Medicare reimbursement rates were chosen because in our geographic
area they are the standard on which private insurance companies base their
payment schedules. The routine performance of FS examinations on all patients
with indeterminate cytological features in this series resulted in a savings
of $1298 per patient. Even if the costs of FS examinations were substantially
higher, the cost benefit would still be substantial.
Our data are in disagreement with those of McHenry et al13
and Chen et al,14 who concluded that routine
FS examinations are not cost-effective. Their calculations, however, were
based on charges, not reimbursement. In addition, both series noted that the
routine performance of FS examinations rarely resulted in a change in the
surgical procedure performed at the initial operation.
This study does not consider the additional risks of a second operation.
It does not address the intangibles, such as pain and anxiety, or the real
cost of lost wages resulting from a second operation. Hamburger and Husain
recognize that "most patients prefer a cancer operation as the initial procedure
rather than take a chance of having to undergo a second surgical procedure
if a diagnosis of cancer is established by permanent sections."23(p521)
CONCLUSIONS
Intraoperative FS examination results can accurately establish the diagnosis
of cancer in 17% of patients undergoing thyroid lobectomy for thyroid nodules
with indeterminate cytological features. If a surgical procedure more extensive
than a thyroid lobectomy is recommended for a well-differentiated cancer,
the routine performance of FS examinations avoids the need for a second surgical
procedure in those patients in whom the diagnosis can be established intraoperatively.
Because of the high cost of a second surgical procedure, the routine performance
of FS examinations is cost-effective. In those whose FNAB results are highly
suggestive of papillary cancer, the likelihood of malignancy is so high that
the FS examination adds nothing to the management of these patients and should
not be performed.
AUTHOR INFORMATION
Accepted for publication October 2, 2001.
This study was presented at the annual meeting of the American Head
and Neck Society, Palm Desert, Calif, May 16, 2001.
Corresponding author and reprints: Keith S. Heller, MD, Long Island
Surgical Specialists, PC, 410 Lakeville Rd, Suite 310, Lake Success, NY 11042
(e-mail: kheller{at}lisurg.com).
From the Head and Neck Services, Departments of Surgery and Otolaryngology,
Long Island Jewish Medical Center–Long Island Campus of the Albert Einstein
College of Medicine, New Hyde Park, NY.
REFERENCES
| |
1. Martin HE, Ellis EB. Biopsy by needle puncture and aspiration. Ann Surg. 1930;92:169-181.
ISI
| PUBMED
2. Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med. 1993;118:282-289.
FREE FULL TEXT
3. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med. 1993;328:553-559.
FREE FULL TEXT
4. Hamburger JI, Hamburger SW. Declining role of frozen section in surgical planning for thyroid nodules. Surgery. 1985;98:307-312.
ISI
| PUBMED
5. Charles MA, Heller KS. Cytologic determinants of well-differentiated thyroid cancer. Am J Surg. 1997;174:545-547.
FULL TEXT
|
ISI
| PUBMED
6. Tyler DS, Winchester DJ, Caraway NP, Hickey RC, Evans DB. Indeterminate fine-needle aspiration biopsy of the thyroid: identification
of subgroups at high risk for invasive carcinoma. Surgery. 1994;116:1054-1060.
ISI
| PUBMED
7. 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.
FULL TEXT
|
ISI
| PUBMED
8. Degroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab. 1990;71:414-424.
ABSTRACT
9. Samaan NA, Schultz PN, Hickey RC, et al. The results of various modalities of treatment of well differentiated
thyroid carcinoma: a retrospective review of 1599 patients. J Clin Endocrinol Metab. 1992;75:714-720.
ABSTRACT
10. Shah JP, Loree TR, Dharker D, Strong EW. Lobectomy versus total thyroidectomy for differentiated carcinoma of
the thyroid: a matched pair analysis. Am J Surg. 1993;166:331-335.
FULL TEXT
|
ISI
| PUBMED
11. Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid
carcinoma. Surgery. 1988;104:947-953.
ISI
| PUBMED
12. Lin HS, Komisar A, Opher E, Blaugrund SM. Surgical management of thyroid masses: assessing the need for frozen
section. Laryngoscope. 1999;109:868-873.
FULL TEXT
|
ISI
| PUBMED
13. 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;172:658-661.
FULL TEXT
|
ISI
| PUBMED
14. Chen H, Nicol TL, Udelsman R. Follicular lesions of the thyroid: does frozen section evaluation alter
operative management? Ann Surg. 1995;222:101-106.
ISI
| PUBMED
15. Rojeski MT, Gharib H. Nodular thyroid disease: evaluation and management. N Engl J Med. 1985;313:428-436.
ISI
| PUBMED
16. Davoudi MM, Yeh KA, Wei JP. Utility of fine-needle aspiration cytology and frozen-section examination
in the operative management of thyroid nodules. Am Surg. 1997;63:1084-1089.
ISI
| PUBMED
17. Bugis SP, Young JEM, Archibald SD, Chen VSM. Diagnostic accuracy of fine-needle aspiration biopsy versus frozen
section in solitary thyroid nodules. Am J Surg. 1986;152:411-416.
FULL TEXT
|
ISI
| PUBMED
18. Irish JC, van Nostrand AWP, Asa SL, Gullane P, Rotstein L. Accuracy of pathologic diagnosis in thyroid lesions. Arch Otolaryngol Head Neck Surg. 1992;118:918-922.
FULL TEXT
|
ISI
| PUBMED
19. Rosen Y, Rosenblatt P, Saltzman E. Intraoperative pathologic diagnosis of thyroid neoplasms. Cancer. 1990;66:2001-2006.
FULL TEXT
|
ISI
| PUBMED
20. Gibb GK, Pasieka JL. Assessing the need for frozen sections: still a valuable tool in thyroid
surgery. Surgery. 1995;118:1005-1010.
FULL TEXT
|
ISI
| PUBMED
21. Sabel MS, Staren ED, Gianakakis LM, Dwarakanathan S, Prinz RA. Use of fine-needle aspiration biopsy and frozen section in the management
of the solitary thyroid nodule. Surgery. 1997;122:1021-1027.
FULL TEXT
|
ISI
| PUBMED
22. Mulcahy MM, Cohen JI, Anderson PE, Ditamasso J, Schmidt W. Relative accuracy of fine-needle aspiration and frozen section in the
diagnosis of well-differentiated thyroid cancer. Laryngoscope. 1998;108:494-496.
FULL TEXT
|
ISI
| PUBMED
23. Hamburger JI, Husain M. Contribution of intraoperative pathology evaluation to surgical management
of thyroid nodules. Endocrinol Metab Clin North Am. 1990;19:509-522.
ISI
| PUBMED
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