1) Solitary thyroid nodules are common and usually detected by palpation or ultrasound. Evaluation is needed to rule out malignancy given the risk of cancer in solitary nodules. 2) Ultrasound and fine needle aspiration biopsy are important diagnostic tools, with ultrasound assessing features suggestive of malignancy and FNAB providing cytology results. 3) Treatment depends on FNAB and risk factor results, ranging from observation for benign nodules to surgery for malignant or suspicious nodules. Surgery type depends on cancer risk and includes lobectomy or total thyroidectomy.

1. Solitary Thyroid Nodule Prepared by: Dr. Aisha M. Al-Zuhair Supervised by: Dr. NaifAwad KFHU – Khobar – Saudi Arabia Jan 20, 2010 1

2. Introduction 2

3. In the general population, thyroid nodules are discovered by palpation in 3% to 7%, and by US in 20% to 76% More common in women than men Prevalence increases linearly with age, exposure to ionizing radiation, and iodine deficiency 3 Hegedus L.: Clinical practice: the thyroid nodule. N Engl J Med 351. (17): 1764-1771.2004

4. History and Physical Most patients present with an asymptomatic mass discovered by a physician on routine neck palpation or by the patient during self-examination. Newly diagnosed thyroid nodules should be evaleuated primarily to role out malignancy. 4

5. When to suspect malignancy 5

6. History of childhood head/neck irradiation Family history of PTC, MTC, or MEN2 Age <20 or >70 years Male sex Enlarging nodule Abnormal cervical adenopathy Fixed nodule 6 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

7. Exposure to Radiation The risk is maximum 20 to 30 years after exposure. Most thyroid carcinomas following radiation exposure are papillary (PTC). There is a 40% chance that patients presenting with a thyroid nodule and a history of radiation to have thyroid cancer. 7

8. Common causes of thyroid nodules 8

9. Benign Colloid nodule Hashimoto’s thyroiditis Simple or hemorrhagic cyst Follicular adenoma Subacutethyroiditis 9 Ross D.M.: Diagnostic approach to and treatment of thyroid nodules. I. In: Rose B.D., ed. UpToDateWellesley (MA)2005

10. Malignant – Primary Follicular cell-derived carcinoma: PTC, FTC, anaplastic thyroid carcinoma C-cell–derived carcinoma: MTC Thyroid lymphoma Malignant – Secondary Metastatic carcinoma 10 Ross D.M.: Diagnostic approach to and treatment of thyroid nodules. I. In: Rose B.D., ed. UpToDateWellesley (MA)2005

11. Management:Diagnostic workup 11

12. Imaging 12

13. Ultrasonography Most sensitive test to detect lesions in the thyroid It is recommended that all patients who have a nodular thyroid, with a palpable solitary nodule or a multinodulargoiter,be evaluated by US Not indicated as screening test in general population 13

14. Ultrasonography Indicated in: Palpable nodule History of radiation to the neck Age<20 & >70 Family history of MTC, MEN2, or PTC Presence of cervical lymphadenopathy 14

15. US prediction of malignancy Solitary versus multiple nodules Size Extracapsular growth Complex or cystic lesions Nodule shape Suspicious cervical adenopathy 15

16. Solitary vs multiple nodules The risk of cancer is not significantly higher for solitary nodules than for glands with several nodules 16

17. Size Cancer is not less frequent in small nodules (diameter <10 mm) 17

18. Extracapsular Growth Hypoechoic nodules with irregular borders, Extension beyond the thyroid capsule, Invasion into perithyroid muscles, and Infiltration of the recurrent laryngeal nerve Are sonographic features suggestive of malignancy 18

19. Complex or Cystic nodule Complex thyroid nodules have solid and cystic components. These are often benign. Some PTCs may be cystic. 19

20. NoduleShape A rounded appearance A more tall than wide shape of the nodule A marked hypoechogenicity of a solid lesion  are newly described US patterns suggestive of malignancy 20

21. Cervical L.N. Enlarged rounded cervical L.N. No hilus Cystic changes Microcalcification Chaotic hypervacularity 21

22. Ultrasonography The sensitivity of each feature is around 85% The predictive value of these US features for cancer is in part diminished by their low sensitivity No US sign by itself can reliably predict malignancy 22

23. 23 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

24. 24 Transverse ultrasonographic view of the right thyroid lobe showing a 1.2-cm hypoechoic nodule (N), which was benign by fine-needle aspiration biopsy. C, carotid artery; T, trachea.

25. Color Doppler US Evaluates nodule vascularity. Hypervascularity with chaotic arrangement of blood vessels favors malignancy. Peripheral flow indicates a benign nodule. 25

26. 26 US images of a left lobe thyroid nodule. (Lt) The 1.7 1.4-cm solid left lobe thyroid nodule was hypoechoic. (Rt) Color Doppler flow imaging shows hypervascularity. FNA biopsy showed papillary thyroid carcinoma, which was confirmed at surgery.

27. Other imaging tech CT and MRI not as routine. Can asses size, retrosternal extension, position and relation to the surrounding structure. RAI scan: To differentiate hot from cold nodules Malignancy has been shown to occur in 15% to 20% of cold nodules 27

28. 28 Images of a large, asymmetric multinodular goiter. (A) Chest radiography shows marked tracheal deviation to the right (arrow). (B) Chest CT confirmed the presence of a large substernal goiter on the left to the level of tracheal bifurcation.

29. Other imaging tech PET scan: 3-dimensional reconstruction images Use in detecting primary and metastatic thyroid cancer The clinical role of PET in pre-OP investigation of thyroid nodules and in differentiating between benign and malignant lesions is controversial 29 Crippa F, Alessi A, Gerali A, et al: FDG-PET in thyroid cancer. Tumori 2003; 89:540-543 Urhan M - PET Clin - July, 2007; 2(3); 295-304.

30. FNAC 30

31. US guided FNA Indicated if: Palpation-guided FNA nondiagnostic Complex (solid/cystic) nodule Palpable small nodule (<1.5 cm) Impalpable nodule Abnormal cervical nodes Nodule with suspicious US features 31

32. FNAC Specimens 70% Benign, 5% Malignant, 10% Suspicious, and 15% Unsatisfactory 32 Shwartz’s principles of surgery, 8th Ed

33. FNAC results Diagnostic / satisfactory Contains no less than six groups of well-preserved thyroid epithelial cells consisting of at least 10 cells in each group Nondiagnostic / unsatisfactory Inadequate number of cells result from acellular cystic fluid, bloody smears, or poor techniques in preparing slides 33

34. 34 (A) Benign (colloid) nodule. (B) Hashimoto thyroiditis. (C) Papillary thyroid carcinoma. (D) Unsatisfactory (nondiagnostic) smear.

35. Benign (-ve) cytology Most common finding Indicative of: Colloid nodule Macrofollicular adenoma Lymphocysticthyroiditis Granulomatusthyroiditis Benign cyst 35

36. Malignant (+ve) cytology Commonest is PTC: Increased cellularity, Tumor cells arranged in sheets and papillary cell groups Typical nuclear abnormalities, which include intranuclear holes and grooves Others include: MTC, anaplastic carcinoma, and high-grade metastatic cancers 36

37. Suspecious cytology Diagnosis cannot be made Inculdes: Follicular neoplasms, Hürthle cell neoplasms, Atypical PTC, or Lymphoma 37

38. Suspecious cytology Follicular neoplasms are most common: Hypercellular with microfollicular arrangement and Decreased or absent colloid Hürthle cell neoplasm: Almost exclusively Hürthle cells Absent or scanty colloid lacking a lymphoid cell population 38

39. 39 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

40. Occasionally associated with a minor hematoma No serious adverse effect of the FNA No seeding of tumor cells in the needle tract has been reported Because of 5% false –ve, repeat of biopsy is recommended in some situations 40 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

41. Indications for repeat biopsy Follow-up of benign nodule Enlarging nodule Recurrent cyst Nodule >4 cm Initial FNA nondiagnostic No nodule shrinkage after T4 therapy 41 Castro M.R., Gharib H.: Thyroid fine-needle aspiration biopsy: progress, practice, and pitfalls. EndocrPract 9. (2): 128-136.2003

42. Tg of FNA of cervical L.N. Thyroglobulin (Tg) can be measured in lymph node or nodule aspirates. FNA-Tg levels were markedly elevated in metastatic lymph nodes FNA-Tg sensitivity was 84.0% The combination of cytology plus FNA-Tg increased FNA sensitivity from 76% to 92.0%. 42 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

43. Immunohistochemical markers Several molecular markers and assays HBME-1 monoclonal antibody stains papillary cancer positively but does not stain benign follicular tumors Galectin-3 acts as a cell-death suppressor distinguish benign from malignant thyroid follicular tumors 43

44. Despite most studies showing markers to have high sensitivity or specificity, no markers have high sensitivity and specificity for correctly diagnosing thyroid cancer 44 Bartolazzi A., Gasbarri A., PapottiM.Thyroid Cancer Study Group, et al: Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357. (9269): 1644-1650.2001; Segev D.L., Clark D.P., Zieger M.A., et al: Beyond the suspicious thyroid fine needle aspirate: a review. ActaCytol 47. (5): 709-722.2003 Castro M.R., Gharib H.: Continuing controversies in the management of thyroid nodules. Ann Intern Med 142. (11): 926-931.2005

45. Laboratory test 45

46. TSH To detect early or subtle thyroid dysfunction. Inc in hashimotothyroiditis and dec in subacutethyroiditis. If TSH levels abnormal, free T3 & T4 should be measured to confirm the diagnosis. 46 American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. EndocrPract 12. (1): 63-102.2006

47. TPOAb Thyroid peroxidase antibody Measured in pt with high TSH. High levels of TPOab suggest autoimmune disease – hashimotothyroiditis 47

48. Serum Tg Correlates with iodine intake and the size of the thyroid gland rather than with the nature or function of the nodule Seldom used in nodule diagnosis Extremely elevated levels of Tg may suggest thyroid metastasis. 48 American Association of Clinical Endocrinologists. EndocrPract 12. (1): 63-102.2006 Schwartz's Principles of Surgery; 8ed

49. Serum Calcitonin Good marker for C-cell disease and correlates well with tumor burden Prevalence of MTC ranging from 0.4% to 1.4% in patients who have nodular thyroid disease Routine calcitonin measurement in all patients who have a nodular thyroid has been recommended by European studies 49 Elisei R., Bottici V., Luchetti F., et al: Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J ClinEndocrinolMetab 89. (1): 163-168.2004

50. Management:Treatment 50

51. 51 Sabiston Textbook of Surgery, 18th ed

52. FNAC +ve Almost always surgical resection If malignancy is secondary, further investigations needed to identify the primary 52

53. Thyroid operations Total thyroidectomy = 2 total lobectomy + isthemusectomy Subtotal thyroidectomy = 2 subtotal lobectomy + isthemusectomy Near-total thyroidectomy = Total lobectomy + subtotal lobectomy + isthemusectomy Lobectomy 53 Baily & love’s short practice of surgery; 24thed

54. Surgical management Lobectomy + isthemusectomy: In pt with low risk factors & Benign nodules Near-total or Total thyroidectomy: In pt with high risk factors & Benign nodules Malignant nodules 54 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

55. Surgical management Total thyroidectomy + cervical clearance: In MTC PTC and FTC with +ve L.N 55 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

56. FNAC -ve Administration of T4 with TSH suppression: shrinking nodule size, arresting further nodule growth, and preventing the appearance of new nodules 56 Castro M.R., Caraballo P.J., Morris J.C.: Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis. J ClinEndocrinolMetab 87. (9): 4154-4159.2002

57. FNAC -ve T4 therapy not recommended for: As routine For postmenopausal women patients with cardiac disease Large nodule or MNG TSH <0.5 mIU/mL 57 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

58. FNAC -ve Most thyroid nodules do not need specific treatment if malignancy and abnormal thyroid function have been excluded Clinical and US follow-up should be performed every 1 to 2 years. 58 Cooper D.S., Doherty G.M., Haugen B.R.The American Thyroid Association Guidelines Taskforce, et al: Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16. 109-142.2006

59. FNAC nondiagnostic Cyst: aspirate and follow up 3 months Recurrent cyst: surgical Large cyst >3-4cm: surgical Benign nodule: surgical 59 Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi

60. Thank you 60

61. References Shwartz’s principles of surgery, 8th Ed Sabiston text book of surgery, 18th Ed Baily & love’s short practice of surgery; 24thed Gharib H - EndocrinolMetabClin North Am - 01-SEP-2007; 36(3): 707-35, vi Cooper D.S., Doherty G.M., Haugen B.R.The American Thyroid Association Guidelines Taskforce, et al: Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16. 109-142.2006 Castro M.R., Caraballo P.J., Morris J.C.: Effectiveness of thyroid hormone suppressive therapy in benign solitary thyroid nodules: a meta-analysis. J ClinEndocrinolMetab 87. (9): 4154-4159.2002 Elisei R., Bottici V., Luchetti F., et al: Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J ClinEndocrinolMetab 89. (1): 163-168.2004 American Association of Clinical Endocrinologists. EndocrPract 12. (1): 63-102.2006 61