1. FNA of the Thyroid Lisa Kendrick BSc., RT Cytology, CT (ASCP) School of Diagnostic Cytology Health Sciences Centre

2. Objectives Describe the anatomy of the thyroid. Describe the histologic features of the thyroid List and describe the normal cytologic features of the thyroid. State the requirement of adequacy for a FNA of the thyroid. List and describe the common benign conditions of the thyroid. List and describe the common malignancies of the thyroid. List and describe the common metastatic malignancies of the thyroid. Discuss the various methods of treatment of malignancies of the thyroid.

3. Anatomy Located below the larynx Consists of two lobes that lie on either side of the trachea Lobes are connected by an ithmus Is an endocrine gland Concepts of Human Anatomy and Physiology, Van de Graff and Fox, page 504, Figure 19.13

4. Histology Consists of spherical sacs – thyroid follicles Lined by simple cuboidal epithelium Contains colloid Wheater’s Functional Histology 3 rd Edition, Burkitt, Young and Heath, page 310, Figure 17.7

5. Thyroid - Histology

6. Cells of the Thyroid

7. Follicular Cells Nucleus – Central – Round/oval – Finely granular chromatin – 1 – 2 nucleoli Cytoplasm – Pale – Indistinct Arrangement – Honeycomb pattern

8. Hurthle Cells AKA Askanazy cells or Oncocytes Large, polygonal cells Nucleus – Round/oval – Eccentric – Finely granular chromatin Cytoplasm – Abundant – Granular – Eosinophilic

10. Colloid Found in the background May stain blue, pink or metachromatic Two states: – WateryThick

11. Satisfactory Specimen 5 or more groups of 10 cells each on a minimum of 2 slides

12. Benign Conditions of the Thyroid

13. Colloid Nodule Most common form of goiter in adolescents and young women Follicular cells cease to proliferate and colloid accumulates within the follicles

14. Colloid Nodule Cytology – Macrofollicular pattern – Variable cellularity – Hurthle cell change may be seen – Scant follicular cells (normal in appearance) – Macrophages – Abundant colloid

15. Cystic Degeneration FNA can cure 20 – 60% of cystic lesions by evacuation Cytology – Few follicular cells – Abundant macrophages

16. Hashimoto’s Thyroiditis AKA chronic thyroiditis An autoimmune disorder Affects women more than men Associated with hyperthyroidism

17. Hashimoto’s Thyroiditis Cytology – Cellular aspirate presenting in small groups, fragments – Groups of Hurthle cells – Follicular cells with Hurthle cell change – Inflammatory cells (lymphocytes and macrophages) – Tingible body macrophages – Little colloid – Possible lymphoma association

18. Malignancies of the Thyroid

19. Follicular Carcinoma Peak onset ages 40 through 60 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.0 cm (3/8 inch) good prognosis] Rarely associated with radiation exposureradiation exposure Spread to lymph nodes is uncommon (~10%) Invasion into vascular structures (veins and arteries) within the thyroid gland is common Distant spread (to lungs or bones) is uncommon, but more common than with papillary cancerpapillary cancer Overall cure rate high (near 95% for small lesions in young patients), decreases with advanced age www.endocrineweb.com/capap.html

20. Follicular Carcinoma Distinction between neoplasm and carcinoma depends on the histology specimen Identification of invasion of either the capsule or blood vessels confirms the diagnosis of carcinoma It is very difficult to differentiate between neoplasm and carcinoma based on morphology alone

21. Follicular Neoplasms The cellularity varies No colloid Cells are arranged in small, loosely cohesive groups Micro follicular pattern is observed Syncytial patterns predominate There may be overlap of some features with a colloid nodule

22. Follicular Neoplasm Nucleus – Round – Smooth membrane – Fine/coarse even chromatin – Macronucleoli Cytoplasm – Pale – Poorly defined

23. Papillary Carcinoma Peak onset ages 30 through 50 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.5 cm (1/2 inch) good prognosis] Accounts for 85% of thyroid cancers due to radiation exposureradiation exposure Spread to lymph nodes of the neck present in more than 50% of cases Distant spread (to lungs or bones) is very uncommon Overall cure rate very high (near 100% for small lesions in young patients) www.endocrineweb.com/capap.html

24. Papillary Carcinoma Highly variable cellularity (very cellular to scant or cystic) Little to no colloid Papillary arrangements or monolayered fragments Syncytia may be present Enlarged polygonal cells

25. Papillary Carcinoma Nucleus – Central – Overlapping – Round/oval/pleomorphic/ angulated – Finely granular (powdery) chromatin – Micro or macro nucleoli – Folds and creases (grooves) – Cytoplasmic nuclear inclusions Abundant cytoplasm Psammoma bodies may be present Multinucleated macrophages

28. Hurthle Cell Neoplasm Cellularity varies Little to no colloid Cells are dispersed or arranged in loose monolayers May be follicular growth pattern Monomorphic population of Hurthle cells – May have red macronucleoli – May demonstrate binucleation – May demonstrate nuclear grooving

29. Hurthle Cell Neoplasm There is no clear separation between adenomas and carcinoma However if the following features are present a carcinoma may be suspected: – Hypercellularity – Syncytia – Increased N:C – Nuclear pleomorphism – Multinucleoli

30. Medullary Carcinoma Occurs in 4 clinical settings and can be associated with other endocrine tumors Females more common than males (except for inherited cancers) Regional metastases (spread to neck lymph nodes) occurs early in the disease Spread to distant organs (metastasis) occurs late and can be to the liver, bone, brain, and adrenal medullaadrenal medulla Not associated with radiation exposureradiation exposure Usually originates in the upper central lobe of the thyroid Poor prognostic factors include age >50, male, distant spread (metastases), and when seen in patients with other endocrine tumors due to MEN II-B syndrome. Residual disease (following surgery) or recurrence can be detected by measuring calcitonin (a hormone that should be measured every 4 months for the first few years and then every 6 months for ever). www.endocrineweb.com/capap.html

31. 4 Variants Sporadic MEN II-A (Sipple Syndrome) MEN II-B Inherited Medullary Carcinoma

32. Medullary Carcinoma Not a common malignancy Can be multifocal (in which the clinician may remove the entire thyroid) Lymph node involvement is common

33. Medullary Carcinoma Cellularity varies Cell morphology varies Plasmacytoid Round Polygonal Spindle Arranged in loose groups Single cells are common Amyloid may be present in the background

34. Medullary Carcinoma Nuclei – Oval/pleomorphic – Coarse salt and pepper chromatin pattern – Central or eccentrically located – Indistinct nucleoli – Binucleation may be seen Intranuclear inclusions may be seen Cytoplasm is finely granular

37. Anaplastic Carcinoma Very rare Diagnosis is often suggested by clinical findings

38. Peak onset age 65 and older Very rare in young patients Females more common than in males Typically presents as rapidly growing neck mass Can occur many years after radiation exposureradiation exposure Spread to lymph nodes of the neck present in more than 90% of cases Distant spread (to lungs or bones) is very common even when first diagnosed Overall cure rate very low Typically requires a very aggressive treatment plan with surgery, radiation and sometimes even chemotherapy. Often requires the patient to get a tracheostomy to maintain their airway. www.endocrineweb.com/capap.html

39. Anaplastic Carcinoma Giant or mixed forms Variable cellularity Inflammatory cells and necrotic debris are found in the background Variable cell morphology – Squamoid – Giant cell – Spindle cell

40. Anaplastic Carcinoma Nucleus – Pleomorphic in shape – Irregular membrane – Coarse, irregularly distributed chromatin – Prominent nucleoli – Atypical mitosis – Multinucleation Cytoplasm – Densely granular

42. Metastatic Malignancies

43. Thyroid is a common site for metastases Common metastatic tumors include: – Adenocarcinoma of the breast – Renal cell carcinoma – Squamous cell carcinoma from elsewhere – Melanoma – Lymphoma

44. Metastatic Melanoma Cells are very pleomorphic Pigment is often not present Clinical history is very important Immunohistochemistry aids in the diagnosis (S100, HMB45)

45. Lymphoma Non-Hodgkin’s Hodgkin’s – monotonous population- Lymphoid cells and of lymphoid cells Reed-Sternberg cells

46. Treatment Methods

47. Surgery Two types – 1. Lobectomy The entire thyroid is removed. – 2. Hemithyroidectomy (lobectomy): The surgeon removes the entire lobe on the side of the thyroid where the growth or cancer is found. If a biopsy of the growth confirms cancer, the surgeon may also remove the other lobe.

48. Radiation Therapy Three types of radiation therapy: – 1. External beam radiation therapy - In external beam radiation therapy, radiation is directed at the cancer and surrounding tissue from a machine outside the body. It is used to treat most types of cancer. – 2. Brachytherapy - treats the cancer with a high total dose of radiation in a concentrated area in a short period of time. Sealed radioactive sources are placed in the body, in or near the cancer. A sealed radioactive source is often called an implant. – 3. Systemic radiation therapy - the radiation source is given as a liquid (either as a drink or in capsules that are swallowed) or by injecting it into a vein (an intravenous injection). The radiation source travels throughout the body.

49. Radioactive Iodine Therapy (RAI) Radioactive iodine (also called iodine-131 or I-131) is commonly used to treat thyroid cancer. It is given either as a drink or as a capsule. Thyroid cells and cancer cells absorb the radioactive iodine. It destroys any cancer cells and normal thyroid cells that may still be in the body after surgery. After radioactive iodine therapy, thyroid hormone replacement therapy is required to replace the hormone that was made by the thyroid cells.

50. Thyroid Hormone Treatment Thyroid hormone therapy is sometimes used to treat papillary or follicular thyroid cancer. It is given as pills. The hormone thyroxine (T4) slows the growth of thyroid cancer cells that may be left in the body after surgery.

51. Classification and Staging

52. TMN Classification (T – tumor, N = node, M = metastases T1 < 1cm, limited to thyroid T2 > 1cm, < 4cm, limited to thyroid T3 > 4cm, limited to thyroid T4 extension beyond capsule N1a - Ipsilateral cervical N1b – Bilateral/midline/contralateral/cervical/mediastinal M0 – no metastases M1 - metastases

53. Stage Grouping – Under 45 years STI – T any, N any, M0 STII – T any, N any, M1

54. Stage Grouping – 45 years and older Stage IA – T0, N any, M0 Stage IB – T1, N any, M0 Stage II – T2, N any, M0 Stage III - T3, N any, M0 Stage IV – T any, N any, M1

55. Questions?