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Cytopathology of Follicular Cell Nodules

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Cytopathology of Follicular Cell Nodules 104th Annual USCAP Meeting Boston, March 21-27, 2015 Endocrine Pathology Society. March 21, 2015 Follicular cell-derived tumors of the thyroid gland, a practical update CYTOPATHOLOGY OF FOLLICULAR CELL NODULES Philippe Vielh MD, PhD, FIAC Gustave Roussy Cancer Campus, Villejuif, France President of the International Academy of Cytology Conflict of interest: no disclosure Pierre MASSON (1880-1959) « Of all cancers thyroid carcinomas are those giving to the histopathologists the highest lessons of humility. No classification is more difficult to establish than that of thyroid carcinomas. Their pleomorphism is the rule and very few are adapted to a precise classification » In Tumeurs Humaines. Histologie. Diagnostics et Techniques. 1956, 2ème édition, page 488. OUTLINE Thyroid fine-needle aspiration (FNA) diagnostic and screening capacities the PSC initiative and the NCI meeting Challenges for morphologists Today & tomorrow Conclusions THYROID FNA Most widely used method for the preoperative diagnosis and screening of thyroid nodules Recommended by national and international societies / associations American Thyroid Association (revised) recommendations Cooper DS, et al. Thyroid 2009;19:1167-1214 THYROID FNA Diagnostic method for tumors with clearly defined cytologic features (benign lesions, classical papillary, medullary, and anaplastic ca…) Screening method for follicular carcinomas and other carcinomas with less distinct nuclear features THYROID FNA Great success the majority of thyroid FNAC can be classified as benign (>450,000 annually in the USA) Big shortcoming 15-30% of FNAC are difficult to be classified and have a variable risk of malignancy, while being mostly benign on histology. THYROID FNA Before 2007 Huge variability in reporting and classifying (4-6tier) as well as in defining some thyroid lesions (« grey zone ») before the Papanicolaou Society of Cytopathology (PSC) initiative Interobserver variability Stelow EB, et al. Am J Clin Pathol 2005;124:239-244 PSC initiative started in 2006 NCI Thyroid Fine-Needle Aspiration State of the Science Conference (2007) The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): standardization THYROID FNA The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): terminology and criteria Baloch ZW, et al. Diagn Cytopathol 2008;36(6):427-437 THYROID FNA TBSRTC: diagnostic categories Cibas ES & Ali SZ. Am J Clin Pathol 2009;132:658-665 THYROID FNA TBSRTC: images THYROID FNA TBSRTC : risk & management Cibas ES & Ali SZ. Am J Clin Pathol 2009;132:658-665 Bongiovanni M , et al. Acta Cytol 2012;56(4):333-339 THYROID FNA TBSRTC : 28 members from 14 European countries Kocjan G, et al. Cytopathology 2010;21:86-92 THYROID FNA Spectrum of follicular nuclear size and amount of colloid in follicular lesions of the thyroid. (modified from Cervino JM, Paseyro P, Grosso O, et al. La exploracion citologica de la glandula tirodes y sus correlaciones anatomoclinicas. In, Thyroid Cytopathology: an atlas and text. Kini SR, 2008. THYROID FNA : benign THYROID FNA : benign Thyroid FNA demonstrating a macrofollicular group of cells in a background of abundant watery colloid. These features are typical of a benign thyroid nodule. (Papanicolaou stain) Faquin WC. Head & Neck Pathol 2009;3:82–5 THYROID FNA : malignant CHALLENGES TBSRTC: 3 categories (“grey” zone, indeterminate) Atypia/follicular lesion of undetermined significance (AUS/FLUS) Suspicious for a follicular neoplasm/ follicular neoplasm (SFN/FN) Suspicious for malignancy (SM): typically papillary carcinoma CHALLENGES Nondiagnostic/unsatisfactory ? Fewer than 6 groups of well-preserved, well-stained follicular cell groups with 10 cells each AUS / FLUS ? CHALLENGES Ali SZ & Cibas ES book CHALLENGES: AUS/FLUS (1) Nondiagnostic/unsatisfactory Fewer than 6 groups of well-preserved, well- stained follicular cell groups with 10 cells each Follicular variant of papillary carcinoma CHALLENGES: AUS/FLUS (1) A case diagnosed as FLUS/AUS on initial FNA due to the presence of focal microfollicle formation A) Diff-Quik stained air-dried smear, X20 B) Papanicolaou stained alcohol- fixed smear, X40. A repeat FNA showing monolayer sheet of benign appearing follicular cells and macrophages was diagnosed as hyperplastic nodule C and D) Papanicolaou stained alcohol-fixed smears, X40). Surgical pathology follow-up showing a hyperplastic / adenomatoid nodule E and F) H&E, X40). Faquin WC, et al. Diagn Cytopathol 2010;38:731-9 A case diagnosed as FLUS/AUS on initial FNA The majority of the specimen showed features of nodular goiter (A: Pap stained alcohol-fixed smear, X10) However, one group of follicular cells displayed nuclear elongation with chromatin clearing and intranuclear grooves (B: Pap-stained alcohol-fixed smear, X40) Repeat FNA demonstrated monotonous population of follicular cells arranged in cohesive groups (C: Diff-Quik stained air-dried smear, X20) showing diagnostic nuclear features of papillary thyroid carcinoma (D: ThinPrep-Papanicolaou stain, X40. Surgical pathology follow-up showed an encapsulated follicular patterned lesion (E: H&E, X10) exhibiting diagnostic nuclear cytology of papillary carcinoma (F: H&E, X40. Faquin WC, et al. Diagn Cytopathol 2010;38:731-9 A case diagnosed as FLUS/AUS due to the presence of oncocytic follicular cells with nuclear pleomorphism Notice the lymphocytic infiltrate indicating an element of chronic lymphocytic thyroiditis A) Papanicolaou stained alcohol- fixed smear, X10; B) ThinPrep-Papanicolaou stain, X60; C and D) ThinPrep, Papanicolaou stain, X40). Surgical excision was performed without repeat FNA which showed an oncocytic follicular nodule with marked random nuclear atypia arising in chronic lymphocytic thyroiditis E) H&E, X20; F) H&E, X40). Faquin WC et al. Diagn Cytopathol 2010;38:731-9 CHALLENGES : SFN/FN (2) Follicular adenoma Follicular carcinoma CAPSULAR INVASION (CI) Schematic drawing for the interpretation of the presence or absence of CI. The diagram depicts a follicular neoplasm (orange) surrounded by a fibrous capsule (green). a) bosselation on the inner aspect of the capsule does not represent CI; b) sharp tumor bud invades into but not through the capsule suggesting invasion requiring deeper sections to exclude; c) tumor totally transgresses the capsule invading beyond the outer contour of the capsule qualifying as CI; d) tumor clothed by thin (probably new) fibrous capsule but already extending beyond an imaginary (dotted) line drawn through the outer contour of the capsule qualifying as CI; e) satellite tumor nodule with similar features (architecture, cytomorphology) to the main tumor lying outside the capsule qualifying as CI; f) Follicles aligned perpendicular to the capsule suggesting invasion requiring deeper sections to exclude g) follicles aligned parallel to the capsule do not represent CI; h) mushroom-shaped tumor with total transgression of the capsule qualifies as CI; i) mushroom-shaped tumor within but not through the capsule suggests invasion requiring deeper sections to exclude; j) neoplastic follicles in the fibrous capsule with a degenerated appearance accompanied by lymphocytes and siderophages does not represent CI but rather capsular rupture related to prior fine needle aspiration. Ghossein R. Head & Neck Pathol 2009;3:86–93 VASCULAR INVASION (VI) Schematic drawing for the interpretation of the presence or absence of VI. The diagram depicts a follicular neoplasm (green) surrounded by a fibrous capsule (blue) a) Bulging of tumor into vessels within the tumor proper does not constitute VI. b) Tumor thrombus covered by endothelial cells in intracapsular vessel qualifies as VI. c) Tumor thrombus in intracapsular vessel considered as VI since it is attached to the vessel wall. d) Although not endothelialized, this tumor thrombus qualifies for VI because it is accompanied by a fibrin thrombus. e) Endothelialized tumor thrombus in vessel outside the tumor capsule represents VI. f) Artefactual dislodgement of tumor manifesting as irregular tumor fragments into vascular lumen unaccompanied by endothelial covering or fibrin thrombus. Ghossein R. Head & Neck Pathol 2009;3:86–93 CHALLENGES: SFN/FN (2) microfollicles trabeculae Ali SZ & Cibas ES book CHALLENGES : SFN/FN (2) CHALLENGES : SFN/FN (2) Follicular adenoma / carcinoma Follicular variant of papillary carcinoma CHALLENGES: SFN/FN (2) CHALLENGES : SFN/FN (2) Follicular carcinoma Follicular variant of papillary carcinoma Poorly differentiated carcinoma CHALLENGES : SFN/FN (2) Oncocytic (Hürthle) cell neoplasms CHALLENGES: SFN/FN (2) Ali SZ & Cibas ES book CHALLENGES: SFN/FN (2) + Ali SZ & Cibas ES book CHALLENGES : SFN/FN (2) Benign lesion Mix of benign follicular cells + Hürthle cells CHALLENGES : SFN/FN (2) Benign lesion Mix of benign follicular cells + Hürthle cells Hashimoto thyroiditis CHALLENGES : SFN/FN (2) CHALLENGES : SFN/FN (2) Benign lesion Mix of benign follicular cells + Hürthle cells Hashimoto thyroiditis Oncocytic tumor (benign/malignant) Auger M. Cancer (Cancer Cytopathology) 2014;122:241-249 CHALLENGES : SFN/FN (2) CHALLENGES: SM (3) Ali SZ & Cibas ES book CHALLENGES: SM (3) Ali SZ & Cibas ES book CHALLENGES: other (4) Acute inflammation vs undifferentiated (anaplastic) carcinoma Papillary thyroid carcinoma + Hashimoto thyroiditis CHALLENGES: other (4) CHALLENGES: general (5) Intra- and interobserver variability in thyroid cyto- and histopathology Stelow EB, et al. Am J Clin Pathol 2005;124:239-244 Elsheikh TM, et al. Am J Clin Pathol
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