Thyroid Nodules: Understanding FNA Cytology (The Bethesda System for Reporting of Thyroid Cytopathology) Shamlal Mangray, MB, BS
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1 Thyroid Nodules: Understanding FNA Cytology (The Bethesda System for Reporting of Thyroid Cytopathology) Shamlal Mangray, MB, BS Attending Pathologist Rhode Island Hospital, Providence, RI
2 DISCLOSURE: No conflicts of interest to declare or at least that I can recall
3 Outline Introduction Review The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)- The Pathologist s Perspective Individual categories with case examples Emphasis on the Indeterminate Category and Potential Options The dawn of Non-invasive follicular thyroid neoplasm with papillary-like nuclei (NIFT-P) The updated Bethesda System 2017
4 KOREA S THYROID CANCER EPIDEMIC -SCREENING AND OVERDIAGNOSIS* Thyroid CA 15x as high in 2011 as in 1993 in S Korea. Thyroid cancer incidence tripled between 1975 and 2009 in US. *Ahn et al. N Engl J Med 2014; 371: 1765
5 SOUTH KOREA S THYROID-CANCER EPIDEMIC TURNING THE TIDE* *Ahn and Welch. N Engl J Med 2015; 373: 2389
6 . SPECTRUM OF THYROID CANCER Fagin and Wells. N Engl J Med 2016: 375:1954
7 Thyroid Cytopathology FNA technique including needle size, technique and the nature of the thyroid gland Cytologic preparation & sample distribution
8 Evaluation of a Thyroid FNA Adequacy of the sample Interpretation of epithelial structures - Monolayered sheets - Syncytial epithelial aggregates - Epithelial structures with transgressing vessels - Micro-follicular structures - Papillary structures Colloid Nuclear changes FNA terminology & reporting: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) Boerner & Asa. Biopsy Interpretation of the Thyroid 2017
9 The Bethesda System for Reporting Thyroid Cytopathology Non-diagnostic (unsatisfactory) Benign (colloid nodule, nodular goiter, hyperplastic nodule, chronic lymphocytic thyroiditis) Atypia of Undetermined Significance (AUS)- alternatively Follicular lesion of undetermined significance Follicular Neoplasm - Follicular neoplasm or suspicious for follicular neoplasm - Hurthle cell neoplasm or suspicious for follicular neoplasm Suspicious for malignancy (Specify) Malignant (Specify)
10 TBSRTC, Implied Risk of Malignancy & Recommended Clinical Management Wong & Baloch Adv Anat Pathol 2012;19:
11 Benign Nodule on Conventional Preparation: Colloid >> cells
12
13 Benign Nodule on ThinPrep
14
15 Benign (Colloid Nodule) Few cells, more colloid Honeycomb sheets (macrofollicles) Degenerative changes Hemorrhage and macrophages DeMay The Art & Science of Cytopathology 2012
16 Suspicious for follicular neoplasm:
17
18
19 Variable morphology even after resection
20
21 Follicular Neoplasm High cellularity/scant colloid Microfollicular pattern Uniform coarse chromatin sometimes nucleoli Most common in cytopathology and assessment is based on capsular and/or vascular space invasion on the resection specimen DeMay The Art & Science of Cytopathology 2012
22 Suspicious for Malignancy
23
24
25 Suspicious for Malignancy: Follicular Carcinoma
26
27 Suspicious for Follicular Carcinoma Marked architectural abnormalities- crowded, 3D groups, irregular follicles, increased single cells Marked cytologic atypia- nuclear enlargement, abnormal chromatin, prominent or multiple nucleoli, atypical mitotic figures, necrosis Much less common finding than follicular neoplasm DeMay The Art & Science of Cytopathology 2012
28 Anaplastic Carcinoma- pleomorphic nuclei
29 Anaplastic Carcinoma- spindle cells
30 Papillary Thyroid Carcinoma (PTC)
31
32 Papillary Thyroid Carcinoma
33 PAPILLARY THYROID CARCINOMA 33
34 CONVENTIONAL PTC WITH RARE FOLLICLES 34
35 Papillary Thyroid Carcinoma Architecture: 3D papillae with cores, monolayered sheets Cytoplasm- squamoid or vacuoles Nucleus- grooves, nuclear pseudoinclusions, fine pale chromatin, marginated nucleoli Background- psammoma bodies, giant cells, gummy colloid DeMay The Art & Science of Cytopathology 2012
36 More Aggressive than Cytopathology
37 More Aggressive than Cytopathology- Sampling
38
39
40
41 Follicular Variant of Papillary Thyroid Carcinoma
42 Follicular Variant of Papillary Thyroid Carcinoma Architectural features of follicular neoplasm but nuclear features of papillary thyroid carcinoma
43 Atypia of Undetermined Significance (AUS)
44 Variable morphology with atypia but low cellularity AUS
45
46
47
48 Follicular lesion of undetermined significance (FLUS) Low cellularity composed of micro-follicles and no colloid
49 Follicular lesion of undetermined significance (FLUS) Low cellularity composed of micro-follicles and no colloid
50
51
52 AUS/FLUS- Nuclear versus Architectural Atypia Gan et al. Cancer Cytopathol 2017;125:245-56
53 AUS/FLUS- Nuclear versus Architectural Atypia Gan et al. Cancer Cytopathol 2017;125:245-56
54 Undetermined Significance/Follicular Lesion of Undetermined Significance Category Using the Bethesda System for Reporting Thyroid Cytology When Reviewing Slides from Different Institutions: A Study of InterObserver Variability among Cytopathologists Padmanabhan Diagn. Cytopathol. 2017;45:
55 Comparison of Molecular Testing Platforms for Indeterminate Thyroid FNA Results Test Objective Testing Substrate Testing Target ThyroSeq ThyroSeq v2 Afirma ThyGenX/ThyraMIR Prove Malig DNA 4 point mut & 3 gene fus Prove Malig DNA 13 point mut & 42 gene fus Exclud malig mrna 167 gene expression Sample Pres. Fresh-frozen Fresh-frozen 1 or 2 passes fresh frozen in proprietary AUS Sensitivity Specificity NPV PPV Follicular Neoplasm Sensitivity Specificity NPV PPV Suspicious for Malig. Sensitivity Specificity NPV PPV 63% 99% 84% 88% 57% 97% 86% 83% 68% 96% 72% 95% 91% (74-98) 92% (86-98) 77% (71-93) 97% (79-100) 90% (80-99) 93% (88-98) 96% (92-95) 83% (23-52) 90% (74-98) 53% (43-63) 95% (85-98) 38% (27-50) 90% (68-99) 49% (36-62) 94% (79-99) 37% (23-52) 94% (80-99) 52% (30-74) 85% (55-98) 76% (61-88) Prove Malig DNA/microRNA ThyrGenX-4 point mut & 3 gene fusion 1 pass into proprietary at room temp 94% (73-100) 80% (64-91) 97% (84-100) 68% (46-85) 82% (57-96) 91% (76-98) 91% (76-98) 82% (57-96) Boerner & Asa. Biopsy Interpretation of the Thyroid 2017
56 Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclei (NIFTP)
57 Cibas & Ali. Thyroid 2017; 11:doi: /thy
58 Cibas & Ali. Thyroid 2017; 11:doi: /thy
59 SUMMARY TBSRTC is a guideline so as to develop uniformity in reporting for the Pathology Community Guidelines from the respective Clinical Societies Ultimately individualization of management based on clinical, imaging and patient factors
60 Thank you for your attention Special thanks to Kim Quimby and Corinthia Dupuis QUESTIONS?
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