L.D.R. Thompson Overall Objectives What is the current management of papillary carcinoma? WHOse New in WHOse New in What are the trends and what can we do Thyroid Pathology Thyroid Pathology differently? Supporting data Recommendations Lester D. R. Thompson www.lester-thompson.com 2 Thyroid Neoplasms: General Considerations Thyroid carcinoma is most common endocrine malignancy (3.8% of all new US cancers; 9 th most common cancer type) Incidence = 62,980 /year Death rate = 1,890 (annual) (0.3% all deaths) Age = 45 – 54 years old Sex = F > M (3:1) 14.7 /100,000 population /year 1.1% will develop thyroid cancer during lifetime 97.8% 5-year survival for all thyroid cancers 3 4 WHO Histological Classification of Current Management Thyroid Tumours Thyroid adenoma Thyroid carcinomas Lobectomy or Thyroidectomy Follicular adenoma 8330/0 Papillary carcinoma 8260/3 Hyalinizing trabecular tumour 8336/0 Follicular carcinoma 8330/3 Pre-op FNA dependent Poorly differentiated carcinoma Other thyroid tumours Completion thyroidectomy if any of following: Undifferentiated (anaplastic) carcinoma Teratoma 9080/1 8020/3 Primary lymphoma and plasmacytoma Known distant metastases Squamous cell carcinoma 8070/3 Ectopic thymoma 8580/1 Mucoepidermoid carcinoma 8430/3 Angiosarcoma 9120/3 Extrathyroidal extension Sclerosing mucoepidermoid carcinoma Smooth muscle tumours with eosinophilia 8430/3 Tumor >4 cm Peripheral nerve sheath tumours Mucinous carcinoma 8480/3 Paraganglioma 8693/1 Confirmed cervical lymph node metastasis Medullary carcinoma 8345/3 Solitary fibrous tumour 8815/0 Mixed medullary and follicular cell Follicular dendritic cell tumour 9758/3 Positive margins carcinomas 8346/3 Langerhans cell histiocytosis 9751/1 Spindle cell tumour with thymus-like Secondary tumours Macroscopic multifocal disease (not microscopic) differentiation 8588/3 Carcinoma showing thymus-like Lymphovascular invasion differentiation 8589/3 Poorly differentiated histology Version 1, 2016 (07/2016): NCCN Clinical Practice Guidelines 5 6 WHOse New in Thyroid Gland Pathology 1
L.D.R. Thompson Current Management NO completion thyroidectomy only if all are present: Age between 15 – 45 years No prior radiation No lymphovascular invasion No distant metastases No cervical metastases (suspicious lymph node) No extrathyroidal extension Tumor 1-4 cm Negative resection margins No contralateral lesion No aggressive variant Tall, columnar, diffuse sclerosing, poorly differentiated Version 1, 2016 (07/2016): NCCN Clinical Practice Guidelines 7 10 Thyroid Papillary Carcinoma: Thyroid Papillary Carcinoma: Classic Histologic Types Clinical Features Usual or Conventional types Most common malignant thyroid tumor Occult, incidental, microcarcinoma, Sex: F >> M (4:1) microscopic 3 rd – 5 th decades (majority) Age: Follicular Ethnicity: White > Black Macrofollicular Oncocytic or oxyphilic Symptoms: Clear cell Asymptomatic, palpable mass “Biologically Aggressive” Variants Solitary nodule: 28x fold increased risk of tumor Diffuse sclerosing Lateral neck mass (mets in up to 30%) Tall cell Columnar cell Insular or Poorly differentiated 11 12 WHOse New in Thyroid Gland Pathology 2
L.D.R. Thompson Thyroid Papillary Carcinoma: Thyroid Papillary Carcinoma: Classic Pathology Classic Morphologic Features Architectural Cytomorphologic/Nuclear Macroscopic Vascular or capsular Enlarged cells (compared to Majority are solid and solitary normal thyroid) invasion High nuclear to cytoplasmic Variable growth patterns May be cystic ratio Elongated and/or twisted Nuclear overlapping, Encapsulated versus overt invasion follicles crowding Calcospherites Adjacent tissues or extrathyroidal extension Irregular placement around (psammoma bodies) follicle (pT3) Intratumoral fibrosis Nuclear grooving/folding Fibrosis and calcification may be present Tincture of colloid (bright Intranuclear cytoplasmic and rich) & scalloping inclusions Size varies: Pale chromatin with Crystals or giant cells in chromatin Occult, incidental, minute, microscopic the colloid margination/condensation and clearing < 1.0 cm by WHO definition Orphan Annie Nuclei Large: > 5 cm 13 14 Thyroid Papillary Carcinoma: Classic Morphologic Features Architectural Vascular or capsular invasion Variable growth patterns Elongated and/or twisted follicles Calcospherites (psammoma bodies) Intratumoral fibrosis Tincture of colloid (bright and rich) & scalloping Crystals or giant cells in the colloid 15 16 17 18 WHOse New in Thyroid Gland Pathology 3
L.D.R. Thompson 19 20 21 22 23 24 WHOse New in Thyroid Gland Pathology 4
L.D.R. Thompson Thyroid Papillary Carcinoma: Thyroid Papillary Carcinoma: Classic Morphologic Features Classic Morphologic Features Architectural Cytomorphologic/Nuclear Cytomorphologic/Nuclear Vascular or capsular Enlarged cells (compared to normal thyroid) Enlarged cells (compared to normal thyroid) invasion High nuclear to cytoplasmic Variable growth patterns High nuclear to cytoplasmic ratio ratio Elongated and/or twisted Nuclear overlapping, follicles Nuclear overlapping, crowding crowding Calcospherites Irregular placement around Irregular placement around follicle (psammoma bodies) follicle Intratumoral fibrosis Nuclear grooving/folding/irregular contour Nuclear grooving/folding Tincture of colloid (bright Intranuclear cytoplasmic Intranuclear cytoplasmic inclusions and rich) & scalloping inclusions Pale chromatin with Pale chromatin with chromatin Crystals or giant cells in chromatin the colloid margination/condensation and clearing margination/condensation and clearing Orphan Annie Nuclei Orphan Annie Nuclei 25 26 27 28 29 30 WHOse New in Thyroid Gland Pathology 5
L.D.R. Thompson 31 32 NIFTP: Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclei Accepted term at March, 2015 The Endocrine Pathology Society Conference for Re-Examination of the Encapsulated Follicular Variant of Thyroid Papillary Carcinoma in Boston 33 Materials Reviewed All thyroid surgeries performed in 2002 A minimum of 10 years of follow-up 721 cases reviewed All histology slides reviewed 7,977 primary slides 2,022 additional intraoperative, IHC, levels, specials, deepers Follow-up obtained from EMR or direct communication 35 36 WHOse New in Thyroid Gland Pathology 6
L.D.R. Thompson Papillary carcinoma: Type/Variant Breakdown % of all # of Diagnosis (= 324) papillary Cases cases Classical 106 32.7 Microscopic 98 29.6 Follicular variant 94 29.0 Tall cell 19 5.9 Diffuse sclerosing 4 1.2 37 38 Study Design Study Materials A total of 268 tumors diagnosed as EFVPTC based International, multi-disciplinary study of 138 on current criteria were contributed by working patients with Noninvasive EFVPTC followed for 10- group pathologists from 13 institutions 26 years and 130 patients with invasive EFVPTC Potential cases for Group 1 included Noninvasive followed for 1-18 years collected at 13 sites in 5 EFVPTC with no radioiodine (RAI) treatment and countries. Review of digitalized histologic slides by at least 10 years of follow-up (n=138). Potential cases for Group 2 included EFVPTC with vascular 24 thyroid pathologists from 7 countries. invasion and/or tumor capsule invasion and ≥ 1 Two endocrinologists, one surgeon, and one year of follow-up (n=130). psychiatrist. In addition, a molecular pathologist, a 8 week series of weekly teleconferences aimed to biostatistician, and a thyroid cancer survivor/patient refine groups 1 and 2 and to achieve consensus advocate participated in the study. http://image.upmc.edu:8080/NikiForov%20EFV%2 0Study/view.apml 39 40 Mutations in Papillary Carcinoma and Phenotypical Associations 41 42 WHOse New in Thyroid Gland Pathology 7
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