Building On The Best A Review and Update on Bethesda Thyroid 2017 Syed Z. Ali, MD, FRCPath, FIAC Professor of Pathology and Radiology The Johns Hopkins Hospital, Baltimore, Maryland USA TBSRTC Diagnostic Categories Nondiagnostic or Unsatisfactory* Benign Atypia of Undetermined Significance (AUS) or FLUS* Suspicious for a Follicular Neoplasm or FN* Suspicious for Malignancy Malignant TBSRTC 2017 - Probabilistic Approach and Relationship to Clinical Algorithms ROM (%) Management Nondiagnostic (1-4) 5-10 Repeat FNA with U/S Benign (0-3) Follow-up AUS/FLUS (10-15) 10-30 Repeat FNA, molec testing or lobectomy SFN/FN (15-30) 25-40 Molec testing, lobectomy SFM (60-75) 50-75 Near-total thyroidectomy or lobectomy Malignant (97-99) Near-total thyroidectomy or lobectomy* ATA 2015, Recommendation 35B For patients with thyroid cancer >1 cm and <4 cm without extra thyroidal extension, and without clinical evidence of any lymph node metastases (cn0), the initial surgical procedure can be either a bilateral procedure (near- total or total thyroidectomy) or a unilateral procedure (lobectomy). Thyroid lobectomy alone may be sufficient initial treatment for low-risk papillary and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow- up based upon disease features and/or patient preferences. 1
Nondiagnostic ROM 5-10% Incidence: 2-20% (<10%) Adequacy criterion At least 6 groups, each with at least 10 benign-appearing, wellvisualized follicular cells (LBP? same adequacy criteria) Should we relax the adequacy criteria? fewer repeat FNAs ~ 95% of ND are benign < 3% FN Rate Exceptions Chronic lymphocytic thyroiditis Abundant colloid Any atypia Reaspirate at 3mo with U/S Shorter interval? Macrophages - Cyst Fluid Only The CFO Dilemma Rule Out PTC, Cystic Variant 2
Hypervacuolization Benign ROM 0-3% Incidence: 60-65% Included entities: Hyperplastic / Adenomatoid nodule Colloid nodule Chronic lymphocytic thyroiditis Graves Disease F/U by clinical and possibly US examination 3
4
AUS*/FLUS - Birth Of An Entity Benign SFN or SFM Cytologic Atypia 5
AUS/FLUS ROM 10-30% 2017 new subcategorization (descriptive) Cytologic atypia Architectural atypia Cytologic and architectural atypia Hurthle cell AUS/FLUS Atypia, NOS A single diagnosis carries a low risk Avoid overuse of this category (new benchmark 10%) Impact of molecular tests Suspicious for a Follicular Neoplasm or Follicular Neoplasm ROM 25-40% Incidence: 7-18% Significant architectural atypia - a predominance of microfollicles and/or trabecula 2017 - slight modification of the criteria (due to NIFTP) follicular patterned lesions with mild nuclear changes are included (but NOTINCIs or papillae) optional note- cannot r/o NIFTP Distinction between follicular adenoma and CA Surgery (usually lobectomy) is needed for definitive diagnosis Macrofollicles Vs. Microfollicles 6
Needle washout for PTH 7
Indeterminate Thyroid Nodule Commercial Molecular Diagnostic Tests Increase pre-operative diagnostic accuracy FNA specimens excellent source for molecular testing Very expensive Indeterminate Thyroid Nodule Commercial Molecular Diagnostic Tests The Rule Out Test Afirma Gene Expression Classifier (Veracyte) Analyze expression of 142 genes multidimensional algorithm MTC and PT markers included Results Benign (53%), Suspicious (38%), Indeterminate NPV-94%, PPV- ~50% Afirma Genomic Sequencing Classifier NPV-96% Significant improvement in Hürthle cell classification Afirma Xpression Atlas RNA-sequencing-based Test Extensive genomic info in potentially malignant nodules for Rx decisions The Rule In + Rule Out Test ThyroSeq Genomic Classifier (V 3.0) UPMC and CBL Path Next generation DNA and RNA sequencing panel MTC and PT markers included NPV-96%, PPV-83% TAT 2 weeks, Cost ($) - >4k 8
The Rule Out Test Rosetta GX Reveal (Thyroid mirna Classifier) Rosetta Genomics Performed on stained FNA smears Single smear, Imaged and archived, One week TAT, Variety of stain types, NPV-91%, PPV-59% TAT and Cost? Suspicious for Malignancy PPV 65-75% Suspicious for Papillary Carcinoma 2017 some cases may need an optional note (FVPTC/NIFTP) suggesting lobectomy Suspicious for Medullary Carcinoma Serum calcitonin level Suspicious for Malignant Lymphoma Recommendation to repeat FNA with flow cytometry Suspicious for Metastatic Cancer Follicular-patterned lesions with focal nuclear features Think of NIFTP 9
Malignant PPV 97-99% Papillary carcinoma Variants 2017 (to avoid FPs due to NIFTP) some modification of the definition and criteria (only cases with classical features true papillae, PBs, INCIs) optional note (for all PTC cases), 3-4% NIFTP Medullary carcinoma Poorly differentiated carcinoma Anaplastic carcinoma Lymphoma Metastatic cancers Other 10
11
Needle washout for Calcitonin PAX8 Positivity 76-79% (Courtesy Dr. J Bishop) 12
NIFTP (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) 2015 - Endocrine Pathology Society working group, US-CAP, Boston 2016 Numerous articles (including JAMA) 13
NIFTP (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Endocrine Pathology Society working group in 2015 Cytopathologic diagnostic criteria for NIFTP? Should we be diagnosing NIFTP on FNA? NONE NO NIFTP is a Histopathologic Diagnosis Educate your clinicians Good communication is needed Cyto-histo correlation could be crucial Cytopathology plays a screening role NIFTP Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features * Incidence 22.9% of all PTCs TBSRTC Reporting ND (0.6%) Benign (8.7%) AUS (31.2%) SFN (26.6%) SFM (24.3%) Malignant (8.7%) Clinical Management Repeat FNA or Afirma Better Afirma or Lobectomy Best Near Total Thyroidectomy (or Lobectomy) Near Total Thyroidectomy * Faquin WC, et al. Cancer Cytopathol. 2015 14
TBSRTC Risk of Malignancy (Anticipated changes due to NIFTP) ROM with NIFTP (%) Optional Note Nondiagnostic 5-10 * None (* No significant change) Benign 0-3 * None AUS 10-30 (6-18) None SFN 25-50 (10-40) Yes SFM 50-75 (45-60) Yes Malignant 97-99 (94-96) Yes TBSRTC Optional Notes (Anticipated Changes Due To NIFTP) Suspicious for a follicular neoplasm The histopathologic follow-up of cases diagnosed as such includes follicular adenoma, follicular carcinoma, and follicular variant of papillary thyroid carcinoma, including its recently described indolent counterpart NIFTP. Suspicious for malignancy The cytomorphologic features are suspicious for follicular variant of papillary thyroid carcinoma and its recently described indolent counterpart NIFTP. Malignant A small proportion of cases (~3-4%) diagnosed as malignant compatible with papillary thyroid carcinoma may prove to be NIFTP on histopathologic examination. 15