The Bethesda System For Reporting Thyroid Cytopathology Towards a Uniform Terminology With Management Guidelines NCI Thyroid FNA State of the Science Conference Bethesda, MD October 22-23, 2007 154 registrants Pathologists, surgeons, endocrinologists, radiologists Syed Z. Ali, M.D. The Johns Hopkins Hospital, Baltimore, Maryland Terminology The Bethesda System General agreement on need for defined categories Clarity of communication Exchange of data across institutions Discussion focused on number of categories and names Nondiagnostic Benign Atypia of Undetermined Significance (AUS) Suspicious for a Follicular Neo /Follicular Neoplasm Suspicious for Malignancy Malignant 1
ND. Specimen processed and examined, but unsatisfactory for evaluation Macrophages (cyst fluid) only Adequacy criterion At least 6 groups, each with at least 10 benign- appearing, well-visualized follicular cells Exceptions Thyroiditis (=Benign) Abundant colloid (=Benign) Any atypia Cyst Fluid Only Should cyst fluid with only macrophages (< 6 groups of follicular cells) be diagnosed as benign or nondiagnostic? In favor of Benign : Great majority prove to be benign cysts In favor of Benign : Great majority prove to be benign cysts In favor of Nondiagnostic : Can t exclude Cystic Papillary Carcinoma if solid portion of nodule not sampled Dedicated Cyst Fluid Only category Endocrinologist can correlate result with ultrasound findings to determine if the result is representative of the lesion 2
Benign 1. Very low risk of malignancy (0-3%, most recent studies <1%) 2. This category includes Hyperplastic / Adenomatoid nodule Hyperplastic / Adenomatoid nodule Colloid nodule Chronic lymphocytic thyroiditis Graves Disease 3. Patients with a benign nodule are followed by clinical and possibly US examination 3
Suspicious for a Follicular Neoplasm / Follicular Neoplasm To be used for those cases that show significant architectural atypia (a predominance of microfollicles and/or crowded groups). Such cases raise the possibility of follicular carcinoma The distinction between follicular adenoma and carcinoma is not possible by FNA. Surgery (usually lobectomy) is needed for definitive diagnosis 4
Macrofollicles Vs. Microfollicles Macrofollicles Vs. Microfollicles AN 5
Suspicious for a FN / FN - Predictive Value for Malignancy Author Year n % of cases called (S)FN % Malignant* Gharib et al, 1993 731 7 15 Baloch et al, 2002 184 18 30 Yang et al, 2007 326 12 32 Yassa et al, 2007 268 8 28 *of resected nodules only Suspicious for a Follicular Neoplasm, Hurthle Cell Type / Follicular Neoplasm, Hurthle Cell Type Composed exclusively of Hurthle cells DDx includes medullary CA others DDx includes medullary CA, others Distinction between Hurthle cell adenoma and carcinoma not possible by FNA Surgery (usually lobectomy) required for definitive diagnosis What to call this category? Suspicious for a follicular neoplasm, Hurthle cell type Follicular neoplasm, Hurthle cell type 6
Suspicious for a Follicular Neoplasm, Hurthle Cell Type/ Follicular Neoplasm, Hurthle Cell Type Predictive Value for Malignancy Author Year n % of cases % Malignant* called (S)HCN Gharib et al, 1993 378 7 15 Giorgadze et al, 2004 206? 45 Pu et al, 2006 87 2 31 HCN *of resected nodules only 7
Suspicious for Malignancy Suspicious for Papillary Carcinoma Suspicious for Medullary Carcinoma Serum calcitonin level Suspicious for Malignant Lymphoma May include recommendation to repeat FNA with flow cytometry. Suspicious for Metastatic Cancer Suspicious for Papillary Carcinoma - Predictive Value for Malignancy Authors Year n % of cases called Sus for PC % Malignant (PPV)* Gharib et al, 1993 288 3 60 Logani et al, 2000 52? 77 Yang et al, 2007 84 3 76 Yassa et al, 2007 314 9 60 *resected nodules only 8
Malignant Papillary carcinoma Variants Medullary carcinoma Poorly differentiated carcinoma Anaplastic carcinoma Lymphoma Secondary Neoplasms Other 9
Paraganglioma-like thyroid adenoma 10
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Anaplastic Thyroid Carcinoma 12
Atypia of Undetermined Significance (AUS) / Follicular Lesion Of Undetermined Significance The I don t know category. Cases that do not fit easily into Benign, Follicular Neoplasm, Suspicious for CA, or Malignant categories. Examples: Sparsely cellular sample, but pred. microfollicles Atypical cyst lining cells Compromised specimen (obscuring blood, etc.) Recommended management: repeat FNA Surgery considered for repeat atypicals 13
AUS - Benign Cyst AUS - PTC AUS - Adenomatoid Nodule AUS - Follicular Neoplasm Atypia of Undetermined Significance (AUS) / Follicular Lesion Of Undetermined Significance Authors Atypical rate (%) % of Atypicals that remain atypical on repeat FNA Yassa et al, 2007 6 20 Yang et al, 2007 3 4 14
Atypia of Undetermined Significance (AUS) / Follicular Lesion Of Undetermined Significance Authors Yassa et al, 2007 Yang et al, 2007 Malignancy rate (after repeated atypicals) 25% 20% Malignancy rate of a single atypical probably ~ 5-10% Atypia of Undetermined Significance (AUS) / Follicular Lesion Of Undetermined Significance Most atypicals (80-96%) resolve into benign or suspicious/malignant results after repeat FNA. Malignancy rate (~ 5-10%) not sufficient to justify immediate surgery Avoid overuse of this category Benchmarks useful to guide laboratories in tracking their atypical rate (< 7%) The Bethesda System- A Probabilistic Approach to Thyroid FNA Reporting Diagnostic Category Risk of Malig (%) ND 1-4 Benign <1 AUS ~5-10 Sus for a Follicular Neo (FN) 15-30 Sus for a Follic Neo, Hurthle Cell Type 15-45 Sus for Malignancy 60-75 Malignant 97-99 * 25% for repeated atypicals Question Should we explicitly state the risk of malignancy associated with the interpretation we are rendering in the body of the report? Conclusion Relative risk of malignancy is implicit in the proposed probabilistic classification Reporting malignancy probability values (either published literature or individual lab) on the report: Optional Can be communicated verbally to the clinician 15
The Bethesda System- Relationship to Clinical Algorithms Category Risk of Malignancy (%) Management ND 1-4 Repeat FNA w/ US Benign <1 Follow AUS ~5-10 Repeat FNA Sus for a Follic Neo - (FN) 15-30 Lobectomy Sus for a Follic Neo, HCT - (Follic Neo, HCT) 15-45 Lobectomy Sus for Malignancy 60-75 Lobectomy or total thyroidectomy Malignant 97-99 Total thyroidectomy The Bethesda System Final Version Nondiagnostic Benign Atypiaof i f Undetermined d Significance ifi (AUS) Suspicious for a Follicular Neo /Follicular Neoplasm Suspicious for Malignancy Malignant Similar in size and format to book Definitions, criteria, explanatory notes Over 40 contributing authors 200 pages 200 color images $40 16