Thyroid Pathology: It starts and ends with the gross Jennifer L. Hunt, MD, MEd Aubrey J. Hough Jr, MD, Endowed Professor of Pathology Chair of Pathology and Laboratory Medicine University of Arkansas for Medical Sciences jhunt2@uams.edu 1 Causes of Thyrophobia Diagnostic ambiguity Indeterminate FNAs Deferred frozen sections Lack of diagnostic assays High inter-observer variation Treatment/prognosis disconnect Aggressive Rx for indolent disease Fear of de-differentiation 2 Agenda Thyroid tumor management Frozen sections Grossing thyroids Papillary carcinoma Follicular carcinoma 3 1
Follicle-derived >95% Well-differentiated <5% Poorly differentiated 80% Papillary Carcinoma <5% Follicular carcinomas Hurthle Insular Anaplastic C-cell-derived Medullary carcinoma Follicle-derived Well-differentiated Poorly Differentiated Undifferentiated (Anaplastic) Papillary carcinoma Follicular Derived Follicular carcinoma Hurthle cell carcinoma 5 5 Thyroid Facts Up to 70% of the population will have a thyroid nodule on ultrasound Most of these are incidental and benign Cytology and fine needle aspiration revolutionized the management of thyroid nodules. 6 2
Simplistic View of Cytology DX Diagnostic test result Malignant Papillary carcinoma Medullary carcinoma Benign Screening test result ( indeterminate ) Follicular lesion Follicular lesion of uncertain significance (FLUS) Atypical Suspicious for malignancy 8 Benign Indeterminate Malignant 3
Management Follicular lesion Fine needle aspiration Lobectomy Frozen Section Atypical Benign Papillary carcinoma Adenoma Carcinoma Follow clinically Completion thyroidectomy Follow Total thyroidectomy 10 Frozen Sections Advantages Rapid diagnosis Immediate impact for decision making Disadvantages Artifacts Tissue wasting Sampling Preliminary diagnosis 11 Frozen sections >80% of thyroid frozens are non-diagnostic Lack of nuclear detail Incomplete sectioning 12 4
Diagnosis Frozen Sections Follicular variant papillary carcinoma Minimally invasive follicular carcinoma FNA Sensitivity 25% 29% XX 17% Papillary carcinoma 74% 87% Frozen Sensitivity Lin HS, Laryngoscope, 110:1431, 2000 Leteurtre, AJCP 115:370, 2001 13 14 15 5
Tips and Tricks Intraoperative gross on goiter Grossly no specific nodule to freeze Encapsulated lesion Freeze as little as possible Freeze mostly capsule Always perform smears Scrap preps Assess nuclei, not cellularity 16 Hyperplastic nodule, Scrape Follicular Adenoma, Scrape 6
Papillary caricinoma, Scrape Papillary caricinoma, Scrape Frozen section Pitfalls Follicular variant Papillary hyperplastic nodule My favorite frozen diagnosis Defer 21 7
Thyroid Frozens Avoid frozens FNA with papillary carcinoma FNA follicular lesion FNA Hürthle cell lesion Gross nodular goiter Do a frozen when FNA atypical or suspicious 22 Grossing Thyroids Common questions Should I ink the thyroid? How should I section the thyroid? How much of the thyroid should I put in? When there is no nodule When there is a follicular nodule 23 Inking the Thyroid Why do we ink To demonstrate margins at the histological level To identify landmarks or regions of interest 24 8
Margins in Thyroid Tumors Thyroid cancer treatment Surgical resection of the entire gland Lobectomy is followed by completion thyroidectomy Radio-active active iodine therapy To treat small residual foci and potential metastatic disease Radio-active iodine scanning for recurrence 25 To Ink or Not to Ink 26 Grossing Thyroids Common questions Should I ink the thyroid? How should I section the thyroid? How much of the thyroid should I put in? When there is no nodule When there is a follicular nodule 27 9
S08-1234 A1 Grossing Thyroids Common questions Should I ink the thyroid? How should I section the thyroid? How much of the thyroid should I put in? When there is no nodule When there is a follicular nodule 30 10
Small Papillary Carcinomas Terminology for small tumors Incidental papillary carcinoma Occult papillary carcinoma Papillary micro-tumor Extremely common Papillary carcinoma: 6-36% autopsy studies 31 Small Papillary Carcinomas Terminology for small tumors Incidental papillary carcinoma Occult papillary carcinoma Papillary micro-tumor Extremely common Papillary carcinoma: 6-36% autopsy studies 32 Occult Papillary Carcinoma John Beach Hazard (1905-1994) Barney Crile, Jr (1907-1992) 1 st FNA Studies 1 st DNA Studies 1950 1960 1970 1990 2000 33 11
Microscopic Papillary Carcinoma 34 Microscopic Papillary Carcinoma 25% 20% 23% N = 5305 microscopic tumors 15% 13% 10% 5% 0% Multifocal LN mets 0.17% Distant mets 3.40% Recurrence 0.40% Death From: Park (2009), Noguchi (2008), Lo (2006), Pelizzo (2006), Ito (2003), Yamashita (1999) 35 Microscopic Papillary Carcinomas No difference in risk factors <0.5 cm 0.5 1.0 cm 1.0 1.5 cm 36 12
Bottom Line: No Consensus I like my thyroids to fit into one tray* Small thyroid: Submit all (5-10 slides) Goiter: 1 per cm, 5-10 slides per side *there is no scientific validity to that statement 37 Survey of Practice Patterns 167 responses (21% response rate) Practice type 38% academic, 54% private practice 73% >10 years experience Sub-specialization 47% general practice 32% head and neck and/or endocrine specialty 22% other type of specialty Kolman, O (In Preparation) 39 13
Capsular Sampling Percent re 60% 40% spondents (%)80% 20% 0% Under 1 cm 1-2 cm 2.1 to 4 cm 4.1 to 6 cm Greater than 6 cm Entire Capsule 10 and under Over 10 No standard number Kolman, O (In Preparation) 40 Submitting Entire Tumor Capsule 100% spondents (%) Percent re 80% 60% 40% 20% 0% Under 1 cm 1-2 cm 2.1 to 4 cm 4.1 to 6 cm Greater than 6 cm Non-specialist Specialist 41 Thyroid Tumor Histology 42 14
My Approach to Follicular Nodules Is it encapsulated? Is there invasion? Are there nuclear features? 43 Thin capsule Thick capsule 15
46 Thin capsule Intermediate capsule Thick capsule Follicular carcinoma, NOS Minimally Invasive Widely Invasive Minimally Invasive Encapsulated Angio-invasive My Approach to Follicular Nodules Is it encapsulated? Is there invasion? Are there nuclear features? 48 16
Thyroid Tumor Invasion Confusing terminology Extrathyroidal extension Tumor capsular invasion 49 Extrathyroidal Extension Tumor that goes beyond the thyroid gland into the perithyroidal soft tissues Prognostic indicators Age Metastasis Extrathyroidal extension Size of tumor 50 Extrathyroidal Extension 51 17
Extrathyroidal Extension 52 Tumor Capsule Invasion Capsular invasion Vascular invasion 53 18
Not Capsular Invasion 55 Capsular Invasion Capsular Invasion 19
Capsular Invasion Diagnostic Clues: FNA track Diagnostic Clues: FNA track 20
Not Vascular Invasion Vascular Invasion 21
Vascular Invasion 64 Vascular Invasion Mortality in Follicular Tumors Capsular invasion Vascular invasion Widely invasive Measured Disease specific Van 0% 28% N/A mortality Heerden (1992) D Avanzo 2% 20% 62% 5-year mortality (2004) Van Heerden, Surgery 112:1130, 1992 D Avanzo, Cancer 100:1123, 2004 66 22
Follicular carcinoma Minimally Invasive, encapsulated By definition: Capsular invasion Diagnostic Clues Thick capsule Dystrophic calcifications Avoid FNA track pitfall 67 Follicular carcinoma Angio-invasive, encapsulated By definition: Vascular invasion At or beyond level of tumor capsule Medium to large sized vessels Reaction around tumor thrombus Endothelialization Fibrin deposition Capsular invasion may be present Diagnostic clues Tumor present within capsule 68 Follicular carcinoma Widely invasive Multifocal invasion throughout thyroid Invasion outside of the thyroid 69 23
Widely invasive carcinoma 71 Widely invasive carcinoma 72 24
My Approach to Follicular Nodules Is it encapsulated? Is there invasion? Are there nuclear features? 73 Papillary Carcinoma: Histology Papillae Psammoma body Nuclear features Chromatin clearing Overlapping Elongation Grooves Inclusions 74 75 25
Papillary Carcinoma: Clinical Excellent survival Prognostic features Algorithms Age of patient Metastases t Extrathyroidal spread Size of tumor Variants (tall cell, columnar cell) 76 Follicular Variant Histology: Definition Pure follicular architecture Papillary carcinoma nuclei Growth Pattern Invasive and infiltrative Encapsulated 77 Follicular variant PTC 26
Follicular variant PTC 27