AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Risk stratification based on thyroid cytology: Can we rely on national data?☆,☆☆ David S. Cohen, MD a , Zachary P. VandeGriend, MD a,⁎, George H. Yoo, MD a, b , Adam J. Folbe, MD a , Ho-Sheng Lin, MD a, b, c a b c
Wayne State University Department of Otolaryngology-Head and Neck Surgery, Detroit, MI Karmanos Cancer Institute, Detroit MI John D. Dingell VA Medical Center, Detroit, MI
ARTI CLE I NFO
A BS TRACT
Article history:
Purpose: Determine correlation of malignancy rates between fine needle aspiration (FNA)
Received 26 June 2013
biopsy and surgical specimen in an urban academic environment. Methods: Retrospective review at an academic medical center of fine needle aspiration biopsies and surgical specimens in a head and neck otolaryngology practice between 2000 and 2012. Results: Of the 74 biopsies diagnosed as follicular lesion, 34 (45.9%) were malignant. Of the 45 biopsies diagnosed as follicular neoplasm, 22 (48.9%) were malignant. These results are significantly higher than the average risk of malignancy cited by the American Thyroid Association of 5%–10% and 20%–30% for follicular lesions and neoplasms respectively. Conclusions: The rate of malignancy based on a FNA diagnosis of indeterminate cytology (follicular lesion or follicular neoplasm) can vary greatly among different institutions. Thyroid surgeons should be aware of their local pathology practices to better guide therapy and counsel patients. © 2014 Published by Elsevier Inc.
1.
Introduction
Increasing use of fine-needle aspiration (FNA) for diagnosis of thyroid nodules has become standard and often the primary diagnostic criterion for operative management. Although decisions for surgical resection are often clear, follicular patterned nodules cause a diagnostic dilemma and are risk stratified according to the likelihood of malignancy. Indeterminate nodules have commonly been divided into follicular lesions and follicular neoplasms. As there are controversies regarding the classification of follicular patterned lesions on
histologic specimens [1], this proves even more difficult with cytology. Diagnosis is based on findings such as high cellularity, lack of colloid, microfollicules, nuclear atypia or enlargement, and syncytial clusters [2]. Unfortunately none of these alone are very sensitive or specific and can be seen frequently with both benign non-neoplastic lesions and carcinoma [3]. Attempts have been made to standardize the classification and reporting of thyroid FNA to allow for effective risk stratification and communication between pathologists and clinicians. However, it has been shown that there is still a significant lack of inter- and intraobserver
☆ Financial Disclosure: Drs Cohen, VandeGriend, Yoo, Folbe and Lin have no financial interests related to the material in the manuscript. There was no financial support for this work. ☆☆ Material from this study was previously presented at the American Head and Neck Society Research Workshop by Dr. VandeGriend; October 29, 2010; Arlington, VA. ⁎ Corresponding author at: Department of Otolaryngology, Head and Neck Surgery, Wayne State University School of Medicine, 4201 St. Antoine St 5E-UHC, Detroit, MI 48201. Tel.: + 1 313 577 0804, +1 971 226 6078 (mobile); fax: +1 313 577 8555. E-mail address: [email protected] (Z.P. VandeGriend).
0196-0709/$ – see front matter © 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjoto.2013.12.014
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
reproducibility for thyroid FNA. One study found that over half of follicular lesions and neoplasms had discrepant cytologic diagnosis when compared among two pathologists [4]. The most commonly used current diagnostic classifications come from the 2007 National Cancer Institute (NCI) Bethesda System for Reporting Thyroid Cytopathology [5] and the 2009 American Thyroid Association (ATA) guidelines [6]. The Bethesda system classifies thyroid FNAs in one of six diagnostic categories: non-diagnostic, benign, follicular lesion of undetermined significance/atypia of undetermined significance (FLUS/ AUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy, and malignant [5]. The ATA guidelines use comparable diagnostic criteria as well. Accompanying these are accepted malignancy rates associated with each diagnosis which are used by surgeons for operative decision-making and preoperative counseling. The malignancy rates for indeterminate thyroid FNAs at our institution empirically seemed to be higher than these “accepted” values, and we sought to validate this hypothesis.
2.
Materials and methods
After IRB approval was obtained from Wayne State University, patients were identified by using CPT codes for any type of thyroidectomy performed by Wayne State University head and neck otolaryngology faculty from 2000 to 2012. Of the 570 patients who underwent thyroidectomy, 362 were identified who had an accompanying preoperative thyroid FNA report. Exclusion criteria included a lack of adequate documentation from either cytology or final histopathology, outside pathology which was not internally reviewed, other non-thyroid pathologies such as squamous cell carcinoma, and FNA on the opposite lobe of surgical resection. Cytology reports were categorized into the most appropriate diagnostic criteria. Reports with unclear or conflicting terminology were not used. For our purposes we regarded “follicular lesion of undetermined significance”, “atypia of undetermined significance”, “suspicious for follicular lesion”, “cellular follicular lesion” and “Hurthle cell lesion” to be regarded as “follicular lesion”. Diagnoses of “suspicious for follicular neoplasm”, “suspicious for neoplasm”, and “Hurthle cell neoplasm” were regarded as “follicular neoplasm”. Both Hurthle cell lesions
363
and neoplasms were included since they carry a similar malignancy rate as those without Hurthle cell features in the literature [6] and in our series.
3.
Results
Charts from 570 patients who underwent thyroidectomy were reviewed. Of these, 362 were identified who also had an FNA report associated with the site of resection. The malignancy rates for lesions that were rated as benign, atypical follicular lesions, follicular neoplasm, suspicious for malignancy, and malignant were 13%, 46%, 49%, 83% and 97%, respectively. Additionally, the rate of malignancy for indeterminate nodules (those of atypical follicular lesion or follicular neoplasm) was 47%. These findings are much higher than the ATA and NCI quoted risk of malignancy. When micro-carcinomas were excluded, the malignancy rates were 3%, 38%, 40%, 80% and 97% respectively. Additionally, the rate of malignancy for indeterminate nodules when micro-carcinomas were excluded was 38%. These rates are still significantly higher for the atypical follicular lesions and follicular neoplasms, but they are similar to ATA and NCI criteria for suspicious for malignancy and malignancy categories (Table 1). Associated final pathology is shown in Table 2. Follicular variant of papillary thyroid carcinoma (FVPTC) was the most common pathology for follicular lesions/neoplasms and suspicious for malignancy categories while papillary carcinoma was more common for benign and malignant FNAs. Pure follicular carcinomas were rare accounting for only 6/164 (3.7%) malignancies. Of the Hurthle cell lesion and neoplasms, 6/13 (46%) were malignant and their inclusion did not change malignancy rates for follicular lesions and neoplasms. Nodules which were suspicious for malignancy and malignant carried similar rates as national data. Data from other authors comparing final histopathologic diagnoses to FNA are shown in Table 3. Recent series published after the Bethesda reporting system in 2007 still show significant variation. These were most consistent for suspicious for malignancy and malignant diagnoses. There is a wide range of reported malignancy rates after surgical resection for benign and indeterminate FNA diagnoses.
Table 1 – Comparison of thyroid FNA to rate of thyroid malignancy.
FNA Diagnosis Benign Follicular lesion Follicular neoplasm Indeterminate (Follicular lesion/ Neoplasm) Suspicious for malignancy Malignant
Malignancy Rate Excluding Microcarcinoma a
Microcarcinoma a
ATA Risk of Malignancy
NCI Risk of Malignancy
WSU Malignancy Rate
95%
97%–99%
69/71 (97.2%)
47/69 (96.8%)
9/69 (13.0%)
4/133 23/61 15/38 38/99
(3.0%) (37.7%) (39.5%) (38.4%)
Abbreviations: ATA, American Thyroid Association; NCI, National Cancer Institute; WSU, Wayne State University. a Percent of malignancies identified with no focus >1 cm on final pathology.
16/20 13/34 7/22 20/56
(80%) (38.2%) (31.8%) (35.7%)
364
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
Table 2 – Comparison of thyroid FNA to malignant pathology subtype. Overall malignancy rate FNA Diagnosis Benign Follicular lesion Follicular neoplasm Indeterminate (Follicular lesion/ Neoplasm) Suspicious for malignancy Malignant
20/149 34/74 22/45 56/119
Papillary carcinoma
FVPTC
(13.4%) (45.9%) (48.9%) (47.1%)
10/20 (50%) 5/34 (14.7%) 2/22 (9.1%) 7/56 (12.5%)
9/20 23/34 16/22 39/56
(45%) (67.6%) (72.7%) (69.6%)
19/23 (82.6%) 69/71 (97.2%)
9/19 (47.4%) 47/69 (68.1%)
10/19 (52.6%) 17/69 (24.6%)
Follicular carcinoma a 1/20 4/34 4/22 8/56
(5%) (11.7%) (18.2%) (14.3%)
0 0
Other 0/20 0/34 0/22 0/56
b
(0%) (0%) (0%) (0%)
0 5/69 (7.2%)
Abbreviation: FVPTC, follicular variant of papillary thyroid carcinoma. Includes Hurthle cell carcinoma. b Includes medullary and poorly differentiated carcinomas. a
4.
Discussion
Our data clearly falls outside of the “accepted” rates for several categories, most notably for follicular lesions and neoplasms. Although a benign FNA diagnosis appeared to carry an unusually high malignancy rate, this may be partially explained by the fact that some of these were operated later due to continued growth despite initially negative biopsy. Similar rates have been seen by other authors, however (Table 3). Additionally, 80% of these thyroid cancers found on final pathology were 3 mm in only 6.4% of patients after 5 years [14]. Post-graduate training varies among institutions and regions of the country. It is not unexpected that thresholds for reporting atypical features would as well. Ohori acknowledged this variability, noting that after the Bethesda reporting system started to be implemented reported variations in malignancy rates for AUS/FLUS ranged from 15% to 46% [9]. They attributed this to potential diagnostic disagreements regarding delineation of these groups as well as shifts between categories particularly with nondiagnostic and AUS/FLUS diagnoses. Published malignancy rates for follicular lesions and neoplasms range from 3% to 48% and 4% to 36% respectively [13,15–21]. Some authors have advocated for repeat FNA for follicular lesions to improve on this accuracy [22]. Despite this, it is still
Table 3 – Probability of malignancy in recently reported series.
FNA diagnosis Benign Follicular lesion Follicular neoplasm Suspicious for malignancy Malignant
WSU
Marchevsky et al. [18].
Theoharis et al. [13].
13.40% 45.90% 48.90% 82.60% 97.20%
32.20% 37.90% 27.30% 100.00% 100.00%
9.80% 48.00% 34.00% 87.00% 100.00%
Abbreviations: WSU, Wayne State University; NR, not reported.
Lew et al. [19].
Williams et al. [17].
8.60% NR 36.00% 78.00% 98.00%
NR 7.00% 21.40% NR NR
Nayar and Ivanovic [21]
Jo et al. [20].
2.00% 6.00% 14.00% 53.00% 97.00%
1.10% 17.00% 25.40% 70.00% 98.10%
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
common to base the decision for surgical resection predominantly on cytology for indeterminate nodules. We discourage this practice unless the surgeon is familiar with the pathologic reporting at their institution. Recent advances in oncogene testing have shown promise in significantly improving the diagnostic accuracy of indeterminate thyroid aspirations [23]. Molecular and oncogenetic testing for BRAF, RET/PTC, RAS, PAX8-PPAR and other markers will likely have a prominent role in the future, improving the accuracy of these biopsies.
[10]
[11]
[12]
[13]
5.
Conclusions
Thyroid surgeons should be aware of their own institution’s pathology practices for indeterminate thyroid FNAs. Better diagnostic tests and more uniform reporting are necessary to improve this variability.
[14]
[15]
[16] REFERENCES
[1] LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol 2004;11: 279–85. [2] Faquin WC. Diagnosis and reporting of follicular-patterened thyroid lesions by fine needle aspiration. Head Neck Pathol 2009;3:82–5. [3] Layfield LJ, Glasgow BJ, Cramer H, editors. Cytopathology of the head and neck. 1st ed. Chicago: American Society for Clinical Pathology; 1997. [4] Gerhard R, da Cunha Santos G. Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases. Cytopathology 2007;18:105–11. [5] Layfield LJ, Cibas ES, Baloch Z. Thyroid fine needle aspiration cytology: a review of the National cancer Institute state of the science symposium. Cytopathology 2010;21:75–85. [6] Pu RT, Yang J, Wasserman PG, et al. Does Hurthle cell lesion/ neoplasm predict malignancy more than follicular lesion/ neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol 2006;34:330–4. [7] Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–214. [8] Baloch ZW, LiVolsi VA. Follicular-patterned lesion of the thyroid: the bane of the pathologist. Am J Clin Pathol 2002;117:143–50. [9] Ohori NP, Schoedel KE. Variability in the atypia of undetermined significance/follicular lesion of undetermined significance diagnosis in the Bethesda system for reporting
[17]
[18]
[19]
[20]
[21]
[22]
[23]
365
thyroid cytopathology: sources and recommendations. Acta Cytol 2011;55:492–8. Redman R, Yoder BJ, Massoll NA. Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists. Thyroid 2006;16:1003–8. Sakorafas GH, Giotakis J, Stafyla V. Papillary thyroid microcarcinoma: a surgical perspective. Cancer Treat Rev 2005;31:423–38. Roti E, Rossi R, Trasforini G, et al. Clinical and histological characteristics of papillary thyroid microcarcinoma: results of a retrospective study in 243 patients. J Clin Endocrinol Metab 2006;91:2171–8. Theoharis CG, Schofield KM, Hammers L, et al. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid 2009;19:1215–23. Ito Y, Miyauchi A, Inoue H, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 2010;34:28–35. Matesa N, Tabain I, Dabelic N, et al. Diagnostic relevance of fine needle aspiration cytology for follicular lesion of the thyroid: retrospective study. Croat Med J 2002;43:606–9. Goldstein RE, Netterville JL, Burkey B, et al. Implications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodules. Ann Surg 2002;235:656–62. Williams MD, Suliburk JW, Staerkel GA, et al. Clinical significance of distinguishing between follicular lesion and follicular neoplasm in thyroid fine-needle aspiration biopsy. Ann Surg Oncol 2009;16:3146–53. Marchevsky AM, Walts AE, Bose S, et al. Evidence-based evaluation of the risks of malignancy predicted by thyroid fine-needle aspiration biopsies. Diagn Cytopathol 2010;38: 252–9. Lew JI, Snyder RA, Sanchez YM, et al. Fina needle aspiration of the thyroid: correlation with final histopathology in a surgical series of 797 patients. J Am Coll Surg 2011;213:188–94. Jo VY, Stelow EB, Dustin SM, et al. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2010;134:450–6. Nayar R, Ivanovic M. The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. Cancer Cytopathol 2009;19: 1215–23. Faquin WC, Baloch ZW. Fine-needle aspiration of follicular patterned lesions of the thyroid: diagnosis, management, and follow-up according to the National Cancer Institute (NCI) recommendations. Diagn Cytopathol 2010;38:731–9. Sapio MR, Posca D, Raggioli A, et al. Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings. Clin Endocrinol 2007;66:678–83.
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Risk stratification based on thyroid cytology: Can we rely on national data?☆,☆☆ David S. Cohen, MD a , Zachary P. VandeGriend, MD a,⁎, George H. Yoo, MD a, b , Adam J. Folbe, MD a , Ho-Sheng Lin, MD a, b, c a b c
Wayne State University Department of Otolaryngology-Head and Neck Surgery, Detroit, MI Karmanos Cancer Institute, Detroit MI John D. Dingell VA Medical Center, Detroit, MI
ARTI CLE I NFO
A BS TRACT
Article history:
Purpose: Determine correlation of malignancy rates between fine needle aspiration (FNA)
Received 26 June 2013
biopsy and surgical specimen in an urban academic environment. Methods: Retrospective review at an academic medical center of fine needle aspiration biopsies and surgical specimens in a head and neck otolaryngology practice between 2000 and 2012. Results: Of the 74 biopsies diagnosed as follicular lesion, 34 (45.9%) were malignant. Of the 45 biopsies diagnosed as follicular neoplasm, 22 (48.9%) were malignant. These results are significantly higher than the average risk of malignancy cited by the American Thyroid Association of 5%–10% and 20%–30% for follicular lesions and neoplasms respectively. Conclusions: The rate of malignancy based on a FNA diagnosis of indeterminate cytology (follicular lesion or follicular neoplasm) can vary greatly among different institutions. Thyroid surgeons should be aware of their local pathology practices to better guide therapy and counsel patients. © 2014 Published by Elsevier Inc.
1.
Introduction
Increasing use of fine-needle aspiration (FNA) for diagnosis of thyroid nodules has become standard and often the primary diagnostic criterion for operative management. Although decisions for surgical resection are often clear, follicular patterned nodules cause a diagnostic dilemma and are risk stratified according to the likelihood of malignancy. Indeterminate nodules have commonly been divided into follicular lesions and follicular neoplasms. As there are controversies regarding the classification of follicular patterned lesions on
histologic specimens [1], this proves even more difficult with cytology. Diagnosis is based on findings such as high cellularity, lack of colloid, microfollicules, nuclear atypia or enlargement, and syncytial clusters [2]. Unfortunately none of these alone are very sensitive or specific and can be seen frequently with both benign non-neoplastic lesions and carcinoma [3]. Attempts have been made to standardize the classification and reporting of thyroid FNA to allow for effective risk stratification and communication between pathologists and clinicians. However, it has been shown that there is still a significant lack of inter- and intraobserver
☆ Financial Disclosure: Drs Cohen, VandeGriend, Yoo, Folbe and Lin have no financial interests related to the material in the manuscript. There was no financial support for this work. ☆☆ Material from this study was previously presented at the American Head and Neck Society Research Workshop by Dr. VandeGriend; October 29, 2010; Arlington, VA. ⁎ Corresponding author at: Department of Otolaryngology, Head and Neck Surgery, Wayne State University School of Medicine, 4201 St. Antoine St 5E-UHC, Detroit, MI 48201. Tel.: + 1 313 577 0804, +1 971 226 6078 (mobile); fax: +1 313 577 8555. E-mail address: [email protected] (Z.P. VandeGriend).
0196-0709/$ – see front matter © 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjoto.2013.12.014
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
reproducibility for thyroid FNA. One study found that over half of follicular lesions and neoplasms had discrepant cytologic diagnosis when compared among two pathologists [4]. The most commonly used current diagnostic classifications come from the 2007 National Cancer Institute (NCI) Bethesda System for Reporting Thyroid Cytopathology [5] and the 2009 American Thyroid Association (ATA) guidelines [6]. The Bethesda system classifies thyroid FNAs in one of six diagnostic categories: non-diagnostic, benign, follicular lesion of undetermined significance/atypia of undetermined significance (FLUS/ AUS), follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy, and malignant [5]. The ATA guidelines use comparable diagnostic criteria as well. Accompanying these are accepted malignancy rates associated with each diagnosis which are used by surgeons for operative decision-making and preoperative counseling. The malignancy rates for indeterminate thyroid FNAs at our institution empirically seemed to be higher than these “accepted” values, and we sought to validate this hypothesis.
2.
Materials and methods
After IRB approval was obtained from Wayne State University, patients were identified by using CPT codes for any type of thyroidectomy performed by Wayne State University head and neck otolaryngology faculty from 2000 to 2012. Of the 570 patients who underwent thyroidectomy, 362 were identified who had an accompanying preoperative thyroid FNA report. Exclusion criteria included a lack of adequate documentation from either cytology or final histopathology, outside pathology which was not internally reviewed, other non-thyroid pathologies such as squamous cell carcinoma, and FNA on the opposite lobe of surgical resection. Cytology reports were categorized into the most appropriate diagnostic criteria. Reports with unclear or conflicting terminology were not used. For our purposes we regarded “follicular lesion of undetermined significance”, “atypia of undetermined significance”, “suspicious for follicular lesion”, “cellular follicular lesion” and “Hurthle cell lesion” to be regarded as “follicular lesion”. Diagnoses of “suspicious for follicular neoplasm”, “suspicious for neoplasm”, and “Hurthle cell neoplasm” were regarded as “follicular neoplasm”. Both Hurthle cell lesions
363
and neoplasms were included since they carry a similar malignancy rate as those without Hurthle cell features in the literature [6] and in our series.
3.
Results
Charts from 570 patients who underwent thyroidectomy were reviewed. Of these, 362 were identified who also had an FNA report associated with the site of resection. The malignancy rates for lesions that were rated as benign, atypical follicular lesions, follicular neoplasm, suspicious for malignancy, and malignant were 13%, 46%, 49%, 83% and 97%, respectively. Additionally, the rate of malignancy for indeterminate nodules (those of atypical follicular lesion or follicular neoplasm) was 47%. These findings are much higher than the ATA and NCI quoted risk of malignancy. When micro-carcinomas were excluded, the malignancy rates were 3%, 38%, 40%, 80% and 97% respectively. Additionally, the rate of malignancy for indeterminate nodules when micro-carcinomas were excluded was 38%. These rates are still significantly higher for the atypical follicular lesions and follicular neoplasms, but they are similar to ATA and NCI criteria for suspicious for malignancy and malignancy categories (Table 1). Associated final pathology is shown in Table 2. Follicular variant of papillary thyroid carcinoma (FVPTC) was the most common pathology for follicular lesions/neoplasms and suspicious for malignancy categories while papillary carcinoma was more common for benign and malignant FNAs. Pure follicular carcinomas were rare accounting for only 6/164 (3.7%) malignancies. Of the Hurthle cell lesion and neoplasms, 6/13 (46%) were malignant and their inclusion did not change malignancy rates for follicular lesions and neoplasms. Nodules which were suspicious for malignancy and malignant carried similar rates as national data. Data from other authors comparing final histopathologic diagnoses to FNA are shown in Table 3. Recent series published after the Bethesda reporting system in 2007 still show significant variation. These were most consistent for suspicious for malignancy and malignant diagnoses. There is a wide range of reported malignancy rates after surgical resection for benign and indeterminate FNA diagnoses.
Table 1 – Comparison of thyroid FNA to rate of thyroid malignancy.
FNA Diagnosis Benign Follicular lesion Follicular neoplasm Indeterminate (Follicular lesion/ Neoplasm) Suspicious for malignancy Malignant
Malignancy Rate Excluding Microcarcinoma a
Microcarcinoma a
ATA Risk of Malignancy
NCI Risk of Malignancy
WSU Malignancy Rate
95%
97%–99%
69/71 (97.2%)
47/69 (96.8%)
9/69 (13.0%)
4/133 23/61 15/38 38/99
(3.0%) (37.7%) (39.5%) (38.4%)
Abbreviations: ATA, American Thyroid Association; NCI, National Cancer Institute; WSU, Wayne State University. a Percent of malignancies identified with no focus >1 cm on final pathology.
16/20 13/34 7/22 20/56
(80%) (38.2%) (31.8%) (35.7%)
364
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
Table 2 – Comparison of thyroid FNA to malignant pathology subtype. Overall malignancy rate FNA Diagnosis Benign Follicular lesion Follicular neoplasm Indeterminate (Follicular lesion/ Neoplasm) Suspicious for malignancy Malignant
20/149 34/74 22/45 56/119
Papillary carcinoma
FVPTC
(13.4%) (45.9%) (48.9%) (47.1%)
10/20 (50%) 5/34 (14.7%) 2/22 (9.1%) 7/56 (12.5%)
9/20 23/34 16/22 39/56
(45%) (67.6%) (72.7%) (69.6%)
19/23 (82.6%) 69/71 (97.2%)
9/19 (47.4%) 47/69 (68.1%)
10/19 (52.6%) 17/69 (24.6%)
Follicular carcinoma a 1/20 4/34 4/22 8/56
(5%) (11.7%) (18.2%) (14.3%)
0 0
Other 0/20 0/34 0/22 0/56
b
(0%) (0%) (0%) (0%)
0 5/69 (7.2%)
Abbreviation: FVPTC, follicular variant of papillary thyroid carcinoma. Includes Hurthle cell carcinoma. b Includes medullary and poorly differentiated carcinomas. a
4.
Discussion
Our data clearly falls outside of the “accepted” rates for several categories, most notably for follicular lesions and neoplasms. Although a benign FNA diagnosis appeared to carry an unusually high malignancy rate, this may be partially explained by the fact that some of these were operated later due to continued growth despite initially negative biopsy. Similar rates have been seen by other authors, however (Table 3). Additionally, 80% of these thyroid cancers found on final pathology were 3 mm in only 6.4% of patients after 5 years [14]. Post-graduate training varies among institutions and regions of the country. It is not unexpected that thresholds for reporting atypical features would as well. Ohori acknowledged this variability, noting that after the Bethesda reporting system started to be implemented reported variations in malignancy rates for AUS/FLUS ranged from 15% to 46% [9]. They attributed this to potential diagnostic disagreements regarding delineation of these groups as well as shifts between categories particularly with nondiagnostic and AUS/FLUS diagnoses. Published malignancy rates for follicular lesions and neoplasms range from 3% to 48% and 4% to 36% respectively [13,15–21]. Some authors have advocated for repeat FNA for follicular lesions to improve on this accuracy [22]. Despite this, it is still
Table 3 – Probability of malignancy in recently reported series.
FNA diagnosis Benign Follicular lesion Follicular neoplasm Suspicious for malignancy Malignant
WSU
Marchevsky et al. [18].
Theoharis et al. [13].
13.40% 45.90% 48.90% 82.60% 97.20%
32.20% 37.90% 27.30% 100.00% 100.00%
9.80% 48.00% 34.00% 87.00% 100.00%
Abbreviations: WSU, Wayne State University; NR, not reported.
Lew et al. [19].
Williams et al. [17].
8.60% NR 36.00% 78.00% 98.00%
NR 7.00% 21.40% NR NR
Nayar and Ivanovic [21]
Jo et al. [20].
2.00% 6.00% 14.00% 53.00% 97.00%
1.10% 17.00% 25.40% 70.00% 98.10%
AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y –H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 36 2–3 6 5
common to base the decision for surgical resection predominantly on cytology for indeterminate nodules. We discourage this practice unless the surgeon is familiar with the pathologic reporting at their institution. Recent advances in oncogene testing have shown promise in significantly improving the diagnostic accuracy of indeterminate thyroid aspirations [23]. Molecular and oncogenetic testing for BRAF, RET/PTC, RAS, PAX8-PPAR and other markers will likely have a prominent role in the future, improving the accuracy of these biopsies.
[10]
[11]
[12]
[13]
5.
Conclusions
Thyroid surgeons should be aware of their own institution’s pathology practices for indeterminate thyroid FNAs. Better diagnostic tests and more uniform reporting are necessary to improve this variability.
[14]
[15]
[16] REFERENCES
[1] LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol 2004;11: 279–85. [2] Faquin WC. Diagnosis and reporting of follicular-patterened thyroid lesions by fine needle aspiration. Head Neck Pathol 2009;3:82–5. [3] Layfield LJ, Glasgow BJ, Cramer H, editors. Cytopathology of the head and neck. 1st ed. Chicago: American Society for Clinical Pathology; 1997. [4] Gerhard R, da Cunha Santos G. Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases. Cytopathology 2007;18:105–11. [5] Layfield LJ, Cibas ES, Baloch Z. Thyroid fine needle aspiration cytology: a review of the National cancer Institute state of the science symposium. Cytopathology 2010;21:75–85. [6] Pu RT, Yang J, Wasserman PG, et al. Does Hurthle cell lesion/ neoplasm predict malignancy more than follicular lesion/ neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol 2006;34:330–4. [7] Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167–214. [8] Baloch ZW, LiVolsi VA. Follicular-patterned lesion of the thyroid: the bane of the pathologist. Am J Clin Pathol 2002;117:143–50. [9] Ohori NP, Schoedel KE. Variability in the atypia of undetermined significance/follicular lesion of undetermined significance diagnosis in the Bethesda system for reporting
[17]
[18]
[19]
[20]
[21]
[22]
[23]
365
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