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The Utility of the Atypia of Undetermined Significance: Malignant (AUS:M) Ratio as a Performance Measure in The Bethesda System for Reporting Thyroid Cytopathology
Abstracts
S77
among individuals, we propose that review of atypical cases to reach a consensus may be a good exercise to improve the intrainstitutional reporting of thyroid FNAs.
Table 1 Non diagnostic Benign AUS/FLUS Suspicious for follicular neoplasm (SFFN) Suspicious for malignancy(SM) Malignant
C1
C2
C3
6.6% 70% 11.4% 4.4% 1.8% 5.14%
3.9% 66.3% 15.8% 4.9% 2.4% 6.67%
1.9% 68% 16.8% 1.9% 6.4% 5.09%
Table Correlation of FNA thyroid nodule cytology to surgical pathology specimens Ultrasound FNA Cytology Diagnosis
No. (n Z 63) (%)
Surgical Pathology Specimens Benign (%)
Malignant (%)
Malignancy Rate (%)
Suspicious for Follicular Neoplasm
25 (40)
24 (96) Multinodular hyperplasia (n Z 2) Adenomatoid nodule (n Z 2) Follicular adenoma (n Z13) Adenomatoid hyperplasia (n Z7) 7 (37) Hyperplastic Nodule (n Z 3) Follicular Adenoma (n Z 4)
1 (25) Hurthle cell carcinoma (n Z 1)
4% (1 / 25)
12 (63) PTC (n Z 9) PTC Follicular Variant (n Z 2) Anaplastic Carcinoma (n Z 1) 18 (95) PTC (n Z 17) Medullary Carcinoma (n Z 1)
63% (12 / 19)
Table 2 Artifact (blood, clot) Architectural atypia Cellular atypia (a, b) some features of PTC (papillary thyroid carcinoma)
C1
C2
C3
19.3% 35.5% a-25.8% b-3.2% 16%
20% 46.6% a-15.5% b-6.5% 19.3%
0% 4% a-4% b-0% 92%
19 (30) Suspicious for Papillary Carcinoma
Malignant
179 Correlation of Thyroid Nodule Fine Needle Aspiration with Thyroidectomy Histology: An Institutional Experience at the University of Florida Jennifer Loch, DO, Larry J. Fowler, MD, Michael Black, MD University of Florida, Gainesville, Florida Introduction: Thyroid nodules are a common clinical finding and appropriate management relies heavily on fine-needle aspiration (FNA). The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has standardized the diagnostic terminology for thyroid FNA, allowing appropriate triage of those patients at risk for malignancy. This study correlates these ultrasound-guided FNA diagnoses with the subsequent thyroidectomy or lobectomy specimens in order to analyze the appropriate triage for these patients. Materials and Methods: A retrospective quality assurance review of ultrasound-guided FNA cases performed between July 2009 to January 2013 at Shands Hospital. Only the cytology cases diagnosed as suspicious for follicular neoplasm, suspicious for malignancy, or malignant were selected. Moreover, only those cases which had subsequent thyroidectomy or lobectomy available for review were chosen. Results: The distribution of specimens over the three thyroid FNA categories examined were as follows: suspicious for follicular neoplasm, 25 (40%), suspicious for papillary carcinoma, 19 (30%), and malignant 19 (30%). The subsequent malignant histology for these three FNA categories ranged as follows: suspicious for follicular neoplasm, 1 (4%), suspicious for papillary carcinoma, 12 (63%), and malignant 18 (95%). In regards to the diagnostic category of suspicious for follicular adenoma; 52% and 44% proved to be a follicular adenoma or hyperplastic nodule respectively. And only one case out of twenty-five cytology cases diagnosed as suspicious for follicular neoplasms (4%), was shown to be malignant (Hurthle Cell Carcinoma). Conclusions: The malignancy rate for the diagnostic categories of malignant and suspicious for malignancy is comparable to rates found elsewhere in the literature. However, in regards to the category of suspicious for follicular neoplasm our data shows a significantly lower rate of malignancy (5% compared to the published 15-30%). Our results highlight the diagnostic challenges in this category and the need for further research. Correlation of FNA thyroid cytology to surgical pathology
19 (30)
1 (5) Follicular Adenoma (n Z 1)
95% (18 / 19)
PTC: Papillary thyroid carcinoma
180 The Utility of the Atypia of Undetermined Significance: Malignant (AUS:M) Ratio as a Performance Measure in The Bethesda System for Reporting Thyroid Cytopathology Maria Cecilia D. Reyes, MD1, Jeffrey F. Krane, MD, PhD2 1 Barnabas Health, Middletown, New Jersey; 2Brigham & Women's Hospital, Boston, Massachusetts Introduction: The AUS:M (atypia of undetermined significance: malignant) ratio was previously proposed as a performance measure in The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) to monitor appropriate use of the AUS category by cytology laboratories and individual cytopathologists. This study aims to compare AUS:M ratio and AUS rate data over a 6 year period at a single institution to assess the potential utility of these quality measures for practitioners of BSRTC. Materials and Methods: A retrospective review was performed of all thyroid fine needle aspiration (FNA) results at Brigham and Women’s Hospital from 2007-2012. The laboratory uses BSRTC terminology and used essentially identical terminology prior to BSRTC. Results were tabulated for 5 board certified cytopathologists in active service throughout the study period. The AUS:M ratio and AUS rate were determined by year for individual pathologists and for the entire laboratory. Results: A total of 7,630 specimens were analyzed. Overall laboratory AUS and malignancy rates were 10.3 and 4.5% respectively (AUS:M ratio 2.25). Laboratory and individual pathologist annual data are shown in Figure 1 for AUS:M ratios and Figure 2 for AUS rate alone. The annual laboratory AUS:M ratio ranged between 1.6 and 2.9, remaining below the recommended upper limit of 3 throughout the 6 year period. Individual pathologists had more variable annual AUS:M ratios ranging from 0.4 to 9 with annual AUS rates ranging from 2.6% to 14.6%. Conclusions: The AUS:M ratio complements the AUS rate as a performance measure for thyroid FNAs interpreted with BSRTC. The AUS:M ratio is more susceptible than AUS rate alone to large fluctuations with low volume laboratories and/or individual practitioners. Nevertheless, both the AUS:M ratio and AUS rate may be useful tools to monitor
S78
Abstracts
physician and laboratory performance over time, to highlight potential outlying practitioners, and to provide feedback to encourage practice modification.
10
Pathologists
9 8 7 Lab
AUS:M Ratio
6
Patholo gist 1 Patholo gist 2
5 4
material was inadequate. The average length of procedure was 126 minutes in OR compared to 43 minutes in ENDO. Hospital billing for OR procedures was approximately 10 times that of ENDO procedures. Professional billing for OR was approximately 2 times that of ENDO secondary to anesthesiologist charges. Conclusions: EBUS-FNA is relatively non-invasive and effective, providing highly accurate final diagnoses, but the procedure is operatordependent. As shown in this study, there was no overall advantage of an initial OR EBUS-FNA if immediate conversion to mediastinoscopy was not intended. Careful consideration should be made when selecting the setting for EBUS-FNA, given the added length and cost of OR procedures. Table 1 Cytologic Diagnosis by Operator
3
Non-diagnostics Benign Atypical Suspicious Malignant Total ND rate (ND)
2 1 0 2007
2008
2009
2010
2011
2012
Year
Figure 1
Annual AUS:M Ratio By Entire Lab and Individual Pathologists
PULM1 7 PULM2 12 PULM3 5 CT1 23 CT2 4 CT3 5 CT4 3
28 19 14 20 5 4 2
4 2 1 1 1 1 0
2 0 4 1 1 0 0
51 18 25 37 8 6 4
92 51 49 82 19 16 9
8% 24% 10% 28% 21% 31% 33%
16
182
14
BIOMED-2 is a Reliable Test for Lymphoma in Cytopathological Samples
12
Zhongren Zhou, MD, PhD, Brooke Koltz, MD, Mark E. Costaldi, MD, Jessica W. Tuffley, CT(ASCP), Todd S. Laughlin, BS, Paul G. Rothberg, PhD University of Rochester Medical Center, Rochester, Minnesota
10
AUS Rate
Lab Patholo gist 1 Patholo gist 2
8 6 4 2 0 2007
2008
2009
2010
2011
2012
Year
Figure 2
Annual AUS Rate By Entire Lab and Individual Pathologists
181 Endobronchial Ultrasound-Guided Fine Needle Aspiration (EBUSFNA): A Retrospective Study Assessing Diagnostic Accuracy, Specimen Adequacy, Procedure Length, and Maximal Cost-effectiveness Jeremy Hart, MD, Dava West, MD, Yolanda M. Brill, MD University of Kentucky, Lexington, Kentucky Introduction: Mediastinal staging by EBUS-FNA with immediate cytologic evaluation is performed by both pulmonologists (PULM) in the endoscopy (ENDO) suite and cardiothoracic surgeons (CT) in the operating room (OR) with the option of converting to mediastinoscopy. Our objective was to compare overall performance and relative costs and length of procedure between ENDO and OR. Materials and Methods: We reviewed 318 EBUS-FNAs over a 3 year period, 192 by PULM and 126 by CT. Cytologic diagnoses were categorized as non-diagnostic, benign, atypical, suspicious, or malignant. Cases with cytologic/histologic discrepancies were re-assessed for diagnostic accuracy. Adequacy for requested ancillary testing was addressed. Procedure time was compared on select cases. Cost analysis from randomly selected ENDO and OR cases was also performed. Results: Cytologic diagnoses by operator are shown in Table 1. Of 66 cases performed in OR with either non-diagnostic or benign findings, only 18 (27%) were converted to immediate mediastinoscopy. Histologic followup was available for 83 cases (26%) with only one discrepancy between cytologic and histologic diagnosis, attributed to sampling error by FNA. Molecular studies were requested in 12 cases with only one case in which
Introduction: The BIOMED-2 polymerase chain reaction(PCR)based immunoglobulin gene (IG) rearrangement assays are commonly used for the detection of B-cell clonality. Although the BIOMED-2 standardized protocols allow detection of clonality in nearly 100% of non-Hodgkin B cell lymphomas when using non-microdissected, formalin-fixed, paraffinembedded (FFPE) tissue, the reliability of these assays in cytopathological specimens has not been widely validated. Our aim was to assess the BIOMED-2 protocol on cytological samples in comparison with concurrent FFPE samples for lymphoma diagnosis. Materials and Methods: 136 cases that were positive for B-cell clonality using the BIOMED-2 protocol were identified retrospectively from our surgical pathological database from January 2009 to December 2012. 29 of these cases also had available cytological specimens including fine needle aspirates (FNA), pleural, peritoneal, pelvic or cerebrospinal fluids (CSF). Two cytology cases, including one reactive lymph node and one Hodgkin lymphoma case, were also studied as control cases. The PAP or Diff-Quick stained smears from all cytopathological samples were used to extract DNA for BIOMED-2 IGH and IGK PCR. Results: A total of 31 cytopathological specimens were tested by BIOMED-2 PCR. Only 2 of 31 (7%) samples gave uninterpretable results. Both specimens had scant cellularity in their smears and a low yield of DNA. Of the 29 evaluable specimens, 27 (93%) cytopathological specimens were PCR positive for clonality, which was concordant with clonality studies on an excisional biopsy and/or the final diagnosis. Of the two cases with a polyclonal result one was a reactive lymphoproliferation and one was a Hodgkin lymphoma. Conclusions: The evaluation of cytopathological specimens using the BIOMED-2 IG PCR can be reliably used to aid in the diagnosis of lymphoma. 183 A Comparison of Megafunnel and Cytospin Cytocentrifugation Methods on Body Cavity Fluids: Quality of Staining and Diagnostic Cell Recovery Benjamin Witt, MD University of Utah/ARUP Laboratories, Salt Lake City, Utah Introduction: Many cytology laboratories use a cytocentrifugation method as the primary specimen preparation type for body cavity fluids. There are
S77
among individuals, we propose that review of atypical cases to reach a consensus may be a good exercise to improve the intrainstitutional reporting of thyroid FNAs.
Table 1 Non diagnostic Benign AUS/FLUS Suspicious for follicular neoplasm (SFFN) Suspicious for malignancy(SM) Malignant
C1
C2
C3
6.6% 70% 11.4% 4.4% 1.8% 5.14%
3.9% 66.3% 15.8% 4.9% 2.4% 6.67%
1.9% 68% 16.8% 1.9% 6.4% 5.09%
Table Correlation of FNA thyroid nodule cytology to surgical pathology specimens Ultrasound FNA Cytology Diagnosis
No. (n Z 63) (%)
Surgical Pathology Specimens Benign (%)
Malignant (%)
Malignancy Rate (%)
Suspicious for Follicular Neoplasm
25 (40)
24 (96) Multinodular hyperplasia (n Z 2) Adenomatoid nodule (n Z 2) Follicular adenoma (n Z13) Adenomatoid hyperplasia (n Z7) 7 (37) Hyperplastic Nodule (n Z 3) Follicular Adenoma (n Z 4)
1 (25) Hurthle cell carcinoma (n Z 1)
4% (1 / 25)
12 (63) PTC (n Z 9) PTC Follicular Variant (n Z 2) Anaplastic Carcinoma (n Z 1) 18 (95) PTC (n Z 17) Medullary Carcinoma (n Z 1)
63% (12 / 19)
Table 2 Artifact (blood, clot) Architectural atypia Cellular atypia (a, b) some features of PTC (papillary thyroid carcinoma)
C1
C2
C3
19.3% 35.5% a-25.8% b-3.2% 16%
20% 46.6% a-15.5% b-6.5% 19.3%
0% 4% a-4% b-0% 92%
19 (30) Suspicious for Papillary Carcinoma
Malignant
179 Correlation of Thyroid Nodule Fine Needle Aspiration with Thyroidectomy Histology: An Institutional Experience at the University of Florida Jennifer Loch, DO, Larry J. Fowler, MD, Michael Black, MD University of Florida, Gainesville, Florida Introduction: Thyroid nodules are a common clinical finding and appropriate management relies heavily on fine-needle aspiration (FNA). The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has standardized the diagnostic terminology for thyroid FNA, allowing appropriate triage of those patients at risk for malignancy. This study correlates these ultrasound-guided FNA diagnoses with the subsequent thyroidectomy or lobectomy specimens in order to analyze the appropriate triage for these patients. Materials and Methods: A retrospective quality assurance review of ultrasound-guided FNA cases performed between July 2009 to January 2013 at Shands Hospital. Only the cytology cases diagnosed as suspicious for follicular neoplasm, suspicious for malignancy, or malignant were selected. Moreover, only those cases which had subsequent thyroidectomy or lobectomy available for review were chosen. Results: The distribution of specimens over the three thyroid FNA categories examined were as follows: suspicious for follicular neoplasm, 25 (40%), suspicious for papillary carcinoma, 19 (30%), and malignant 19 (30%). The subsequent malignant histology for these three FNA categories ranged as follows: suspicious for follicular neoplasm, 1 (4%), suspicious for papillary carcinoma, 12 (63%), and malignant 18 (95%). In regards to the diagnostic category of suspicious for follicular adenoma; 52% and 44% proved to be a follicular adenoma or hyperplastic nodule respectively. And only one case out of twenty-five cytology cases diagnosed as suspicious for follicular neoplasms (4%), was shown to be malignant (Hurthle Cell Carcinoma). Conclusions: The malignancy rate for the diagnostic categories of malignant and suspicious for malignancy is comparable to rates found elsewhere in the literature. However, in regards to the category of suspicious for follicular neoplasm our data shows a significantly lower rate of malignancy (5% compared to the published 15-30%). Our results highlight the diagnostic challenges in this category and the need for further research. Correlation of FNA thyroid cytology to surgical pathology
19 (30)
1 (5) Follicular Adenoma (n Z 1)
95% (18 / 19)
PTC: Papillary thyroid carcinoma
180 The Utility of the Atypia of Undetermined Significance: Malignant (AUS:M) Ratio as a Performance Measure in The Bethesda System for Reporting Thyroid Cytopathology Maria Cecilia D. Reyes, MD1, Jeffrey F. Krane, MD, PhD2 1 Barnabas Health, Middletown, New Jersey; 2Brigham & Women's Hospital, Boston, Massachusetts Introduction: The AUS:M (atypia of undetermined significance: malignant) ratio was previously proposed as a performance measure in The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) to monitor appropriate use of the AUS category by cytology laboratories and individual cytopathologists. This study aims to compare AUS:M ratio and AUS rate data over a 6 year period at a single institution to assess the potential utility of these quality measures for practitioners of BSRTC. Materials and Methods: A retrospective review was performed of all thyroid fine needle aspiration (FNA) results at Brigham and Women’s Hospital from 2007-2012. The laboratory uses BSRTC terminology and used essentially identical terminology prior to BSRTC. Results were tabulated for 5 board certified cytopathologists in active service throughout the study period. The AUS:M ratio and AUS rate were determined by year for individual pathologists and for the entire laboratory. Results: A total of 7,630 specimens were analyzed. Overall laboratory AUS and malignancy rates were 10.3 and 4.5% respectively (AUS:M ratio 2.25). Laboratory and individual pathologist annual data are shown in Figure 1 for AUS:M ratios and Figure 2 for AUS rate alone. The annual laboratory AUS:M ratio ranged between 1.6 and 2.9, remaining below the recommended upper limit of 3 throughout the 6 year period. Individual pathologists had more variable annual AUS:M ratios ranging from 0.4 to 9 with annual AUS rates ranging from 2.6% to 14.6%. Conclusions: The AUS:M ratio complements the AUS rate as a performance measure for thyroid FNAs interpreted with BSRTC. The AUS:M ratio is more susceptible than AUS rate alone to large fluctuations with low volume laboratories and/or individual practitioners. Nevertheless, both the AUS:M ratio and AUS rate may be useful tools to monitor
S78
Abstracts
physician and laboratory performance over time, to highlight potential outlying practitioners, and to provide feedback to encourage practice modification.
10
Pathologists
9 8 7 Lab
AUS:M Ratio
6
Patholo gist 1 Patholo gist 2
5 4
material was inadequate. The average length of procedure was 126 minutes in OR compared to 43 minutes in ENDO. Hospital billing for OR procedures was approximately 10 times that of ENDO procedures. Professional billing for OR was approximately 2 times that of ENDO secondary to anesthesiologist charges. Conclusions: EBUS-FNA is relatively non-invasive and effective, providing highly accurate final diagnoses, but the procedure is operatordependent. As shown in this study, there was no overall advantage of an initial OR EBUS-FNA if immediate conversion to mediastinoscopy was not intended. Careful consideration should be made when selecting the setting for EBUS-FNA, given the added length and cost of OR procedures. Table 1 Cytologic Diagnosis by Operator
3
Non-diagnostics Benign Atypical Suspicious Malignant Total ND rate (ND)
2 1 0 2007
2008
2009
2010
2011
2012
Year
Figure 1
Annual AUS:M Ratio By Entire Lab and Individual Pathologists
PULM1 7 PULM2 12 PULM3 5 CT1 23 CT2 4 CT3 5 CT4 3
28 19 14 20 5 4 2
4 2 1 1 1 1 0
2 0 4 1 1 0 0
51 18 25 37 8 6 4
92 51 49 82 19 16 9
8% 24% 10% 28% 21% 31% 33%
16
182
14
BIOMED-2 is a Reliable Test for Lymphoma in Cytopathological Samples
12
Zhongren Zhou, MD, PhD, Brooke Koltz, MD, Mark E. Costaldi, MD, Jessica W. Tuffley, CT(ASCP), Todd S. Laughlin, BS, Paul G. Rothberg, PhD University of Rochester Medical Center, Rochester, Minnesota
10
AUS Rate
Lab Patholo gist 1 Patholo gist 2
8 6 4 2 0 2007
2008
2009
2010
2011
2012
Year
Figure 2
Annual AUS Rate By Entire Lab and Individual Pathologists
181 Endobronchial Ultrasound-Guided Fine Needle Aspiration (EBUSFNA): A Retrospective Study Assessing Diagnostic Accuracy, Specimen Adequacy, Procedure Length, and Maximal Cost-effectiveness Jeremy Hart, MD, Dava West, MD, Yolanda M. Brill, MD University of Kentucky, Lexington, Kentucky Introduction: Mediastinal staging by EBUS-FNA with immediate cytologic evaluation is performed by both pulmonologists (PULM) in the endoscopy (ENDO) suite and cardiothoracic surgeons (CT) in the operating room (OR) with the option of converting to mediastinoscopy. Our objective was to compare overall performance and relative costs and length of procedure between ENDO and OR. Materials and Methods: We reviewed 318 EBUS-FNAs over a 3 year period, 192 by PULM and 126 by CT. Cytologic diagnoses were categorized as non-diagnostic, benign, atypical, suspicious, or malignant. Cases with cytologic/histologic discrepancies were re-assessed for diagnostic accuracy. Adequacy for requested ancillary testing was addressed. Procedure time was compared on select cases. Cost analysis from randomly selected ENDO and OR cases was also performed. Results: Cytologic diagnoses by operator are shown in Table 1. Of 66 cases performed in OR with either non-diagnostic or benign findings, only 18 (27%) were converted to immediate mediastinoscopy. Histologic followup was available for 83 cases (26%) with only one discrepancy between cytologic and histologic diagnosis, attributed to sampling error by FNA. Molecular studies were requested in 12 cases with only one case in which
Introduction: The BIOMED-2 polymerase chain reaction(PCR)based immunoglobulin gene (IG) rearrangement assays are commonly used for the detection of B-cell clonality. Although the BIOMED-2 standardized protocols allow detection of clonality in nearly 100% of non-Hodgkin B cell lymphomas when using non-microdissected, formalin-fixed, paraffinembedded (FFPE) tissue, the reliability of these assays in cytopathological specimens has not been widely validated. Our aim was to assess the BIOMED-2 protocol on cytological samples in comparison with concurrent FFPE samples for lymphoma diagnosis. Materials and Methods: 136 cases that were positive for B-cell clonality using the BIOMED-2 protocol were identified retrospectively from our surgical pathological database from January 2009 to December 2012. 29 of these cases also had available cytological specimens including fine needle aspirates (FNA), pleural, peritoneal, pelvic or cerebrospinal fluids (CSF). Two cytology cases, including one reactive lymph node and one Hodgkin lymphoma case, were also studied as control cases. The PAP or Diff-Quick stained smears from all cytopathological samples were used to extract DNA for BIOMED-2 IGH and IGK PCR. Results: A total of 31 cytopathological specimens were tested by BIOMED-2 PCR. Only 2 of 31 (7%) samples gave uninterpretable results. Both specimens had scant cellularity in their smears and a low yield of DNA. Of the 29 evaluable specimens, 27 (93%) cytopathological specimens were PCR positive for clonality, which was concordant with clonality studies on an excisional biopsy and/or the final diagnosis. Of the two cases with a polyclonal result one was a reactive lymphoproliferation and one was a Hodgkin lymphoma. Conclusions: The evaluation of cytopathological specimens using the BIOMED-2 IG PCR can be reliably used to aid in the diagnosis of lymphoma. 183 A Comparison of Megafunnel and Cytospin Cytocentrifugation Methods on Body Cavity Fluids: Quality of Staining and Diagnostic Cell Recovery Benjamin Witt, MD University of Utah/ARUP Laboratories, Salt Lake City, Utah Introduction: Many cytology laboratories use a cytocentrifugation method as the primary specimen preparation type for body cavity fluids. There are