Thyroid Nodule. N. Rojanapithayakorn P. Prasarttong-Osoth

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1 Thyroid Nodule N. Rojanapithayakorn P. Prasarttong-Osoth

2 A Brief History of the Thyroid

3 A Brief History of the Thyroid Fabricius Wharton Von Haller

4 A Brief History of the Thyroid Kendall Enrico Fermi

5 A Brief History of the Thyroid Hiroshima,1945 Chernobyl,1986

6 History of Thyroid Surgery

7 History of Thyroid Surgery Billroth

8 History of Thyroid Surgery Kocher

9 Embryology

10 Anatomy

11 Anatomy

12 Superior laryngeal N. Recurrent laryngeal N.

13 Anatomy Lymphatic drainage Level 6 Level 4,3 Level 5

14 Histology

15 Physiology

16 Physiology

17 Thyroid hormone T4-80 ug/d d produced by the thyroid gland T ug/d;80% by peripheral conversion T % bound & T399.0% albumin & pre-albumin Half-life: T4 5-7 days T3 1 day 99.0% bound to TBG,

18 Epidemiology Nodule Framingham study : ages Women 6.4 % Men 1.5 % Mayo study : autopsy series ( no thyroid hx ) 21% had 1 nodules by direct palpation Overall, fewer than 5% of nodules are malignant

19 Benign Thyroid Nodules Colloid nodule Cyst Simple cyst Mixed cystic-solid Thyroid adenoma Non functional or hypofunctional Autonomous Thyroiditis Infection Granulomatous disease Abscess Developmental Unilateral lobe agenesis Cystic hygroma Dermoid

20 Colloid nodules Enlarged follicles containing abundant colloid and benign follicular cells Circumscribed, no fibrous capsule Related to iodine deficiency Endemic area : more than 10 % of children aged 6-12

21 Thyroid Cysts % of all thyroid nodules Simple cysts, hemorrhagic colloid nodules, or cystic parathyroid tumors 30 % are hemorrhagic adenomas 15 % are necrotic papillary cancers Often yield insufficient numbers of cells for Dx

22 Follicular Adenomas Monoclonal tumors arising from follicular epithelium Single lesions with well-developed fibrous capsules Uniform histologic structure distinct from the normal surrounding thyroid

23 Follicular Adenomas Histologic classification Normofollicular (simple) Macrofollicular Microfollicular (fetal) Trabecular and solid (embryonal) Oxyphilic cell type (Hürtle cell)

24 Multinodular goiter Most often caused by iodine deficiency More autonomous with increasing age Should focus on the dominant nodule or nodules that have a different consistency

25 Toxic nodular goiter (Plummer s s disease) Toxic adenoma / Toxic multinodular goiter Autonomously functioning thyroid nodule hypersecreting T3 and T4 Almost never malignant

26 Hashimoto s Thyroiditis Females yrs. Painless diffuse goiter Lab studies Hypothyroidism Anti TPO antibodies (90%) Anti Thyroglobulin antibodies (20-50%) Acute Hyperthyroidism (5%)

27 Subacute Thyroiditis (De Quervain's thyroiditis) Most common cause of painful thyroiditis Often follows a URI FNA : granulomatous change Course Pain and thyrotoxicosis (3-6 6 weeks) Asymptomatic euthyroidism Hypothyroid period (weeks to months) Recovery (complete in 95% after months)

28 Malignant Thyroid Nodules Well-Differentiated Thyroid Carcinomas Papillary carcinoma Follicular variant Tall cell Diffuse sclerosing Encapsulated Follicular carcinoma Overtly invasive Minimally invasive Hurthle cell carcinoma Anaplastic carcinoma Giant cell Small cell Medullary Carcinoma Miscellaneous Sarcoma Lymphoma Squamous cell carcinoma Mucoepidermoid carcinoma Clear cell tumors Pasma cell tumors Metastatic

29 Papillary Carcinoma 60-80% of all thyroid malignancies Mean age of 35 years 80% survive at 10 years Lymph node involvement is common Major route of metastasis is lymphatic 46%-90% of patients have lymph node involvement

30 Papillary Carcinoma Pathology Gross often multi-focal unencapsulated Histology Follicular variant/tall cell/columnar cell/diffuse sclerosing/encapsulated Psammoma bodies Orphan Annie cells

31 Follicular Carcinoma 20% of all thyroid malignancies Mean age of 39 years 60% survive to 10 years Metastasis : angioinvasion and hematogenous 15% - distant metastases to bone and lung Lymphatic involvement is seen in 13%

32 Follicular Carcinoma Pathology Gross - encapsulated, solitary Histology very well-differentiated vascular and capsular invasion FNA and frozen section cannot accurately distinquish between benign and malignant

33 Hurthle Cell Carcinoma Variant of follicular carcinoma 4-10% of all thyroid malignancies Lymphatic spread seen in 30% of patients Distant metastases to bone and lung is seen in 15% at the time of presentation

34 Hurthle Cell Carcinoma Pathology large, polygonal, eosinophilic follicular cells abundant granular cytoplasm and numerous mitochondria vascular and capsular invasion

35 Medullary Thyroid Carcinoma 10% of all thyroid malignancies Arises from the parafollicular cell or C-cells ( from neural crest cells of the branchial arches ) secrete calcitonin RET proto-oncogene oncogene (chromosome 10)

36 Medullary Thyroid Carcinoma Developes in 4 clinical settings: Sporadic MTC Familial MTC MEN IIa MEN IIb AD

38 Anaplastic Carcinoma 1-10% 10% of all thyroid malignancies Mean age of 60 years Highly lethal Median survival <8 months 53% have previous benign thyroid disease 47% have previous history of WDTC

39 Anaplastic Carcinoma Pathology Classified as large cell or small cell Large cell is more common and has a worse prognosis Histology - sheets of very poorly differentiated cells

40 Thyroid Mets Breast Lung Renal GI Melanoma

41 Evaluation

42 History Age & Gender 4x more prevalent in women than in men among pts with nodules, rate of carcinoma 2x as high in men as in women (8% vs. 4%) higher rate of cancer in extreme age group ( < 20, > 60 yrs )

43 History Hyper- / Hypo- thyroidism Rapid change in size With pain may indicate hemorrhage into nodule Without pain may be bad sign

44 History Exposure to Radiation childhood : large thymus, acne, enlarged tonsils, cervical adenitis, sinusitis, malignancies 30%-50% chance to be malignant Mostly papillary carcinoma

45 Family history Medullary Thyroid Carcinoma Gardner Syndrome (familial adenomatous polyposis) Cowden Syndrome Mucocutaneous hamartomas, keratoses,fibrocystic breast changes & GI polyps Other thyroid carcinoma

46 History History suggestive of malignancy: Age < 20 or > 60 years Male sex Exposure to ionizing radiation Familly history of thyroid cancer Progressive enlargement Hoarseness Dysphagia, Dyspnea

47 Physical Examination Sign of hyperthyroidism Multinodular vs. Solitary nodule multinodular 4.7% chance of malignancy solitary nodule 4.1% chance of malignancy Indirect or fiberoptic laryngoscopy Cervical lymphadenopathy Pemberton s sign

48 Physical Examination Physical findings suggestive of malignancy: Cervical lymphadenopathy Vocal cord paralysis Very firm nodule Rapid tumor growth Fixation to adjacent structures

49 Investigation

50 Serum Testing TSH first-line serum test Identifies subclinical thyrotoxicosis T4, T3 Thyroglobulin Post-treatment treatment good to detect recurrence Calcitonin only in cases of medullary Antibodies Hashimoto s RET proto-oncogene oncogene

51 Plain Films

52 Ultrasonography Thyroid vs. non-thyroid Solitary nodule vs. multinodular goiter Cystic vs. solid Localization for FNA or injection Serial exam of nodule size LN enlargement and calcifications Noninvasive and inexpensive

53 Ultrasonography Findings suggestive of malignancy: Presence of halo Irregular border Presence of cystic components Presence of calcifications Heterogeneous echo pattern Extrathyroidal extension No findings are definitive

54 Ultrasonography When to use Ultrasonography..? Evaluation of a thyroid nodule: when a nodule is difficult to palpate or is deep- seated screening : familial thyroid cancer, childhood cervical irradiation Long term follow-up

55 Technetium 99m Thyroid scan cost-effective, readily available short half-life life trapped but not organified by the thyroid Radioactive iodine radioactive iodine (I-131, I-125, I I-123) I trapped and organified can determine functionality of a thyroid nodule

56 Thyroid scan When to use thyroid scanning..? Thyroid nodule with suppressed TSH Large MNG, esp. with substernal extension In search of ectopic thyroid tissue Immediately postop for localization of residual cancer or thyroid tissue Follow-up for tumor recurrence or metastasis

57 Thyroid scan Study : 4457 patients with nodules Cold 84% 15-25% cancer Warm 10% 9% cancer Hot 5.5% 1-44 % cancer

58 Other Imaging Modalities CT / MRI Evaluate local invasion Extension to substernal region Thyroid/non-thyroid nodule Recurrent or persistent thyroid tumor / scar Iodine contrast!

59 Fine-Needle Aspiration Biopsy Safe, efficacious, cost-effective Results comparable to large-needle biopsy, less complications Allow preop.. diagnosis and planning Sensitivity 70-98% Specificity %

60 Fine-Needle Aspiration Biopsy Technique: No gauge needle multiple passes ideally from periphery of lesion reaspirate after fluid drawn smeared and fixed in 95% alcohol

61 Fine-Needle Aspiration Biopsy Results Benign Malignant : papillary,medullary,anaplastic Suspicious/Indeterminate : follicular neoplasms, Hürthle cell neoplasms, papillary cancer, or lymphoma. Insufficient/Inadequate

62 (A) Benign epithelial cells, typical of a "colloid nodule". (B) Epithelial cells in a follicular arrangement (C) Epithelial cells in a pappilary formation from a papillary thyroid carcinoma. Nuclear grooves are also apparent.

63 Management

65 Management Benign Thyroid Nodule Thyroid suppressive therapy several reports - shrinkage of thyroid nodules clinically significant decrease in nodule volume in only 20% effect in larger nodules is probably smaller

66 Management Benign Thyroid Nodule Thyroid suppressive therapy Adverse Effects. decrease in bone density in postmenopausal women 3-fold increase in atrial fibrillation and increased mortality attributable to cardiovascular diseases

67 Management Benign Thyroid Nodule Thyroid suppressive therapy Should be avoided in patients with large thyroid nodules or long-standing goiters, TSH < 1µIU/mL postmenopausal women or men > 60 years patients with osteoporosis, cardiovascular disease, or systemic illnesses.

68 Management Benign Thyroid Nodule Surgical Indications. Compressive symptoms Suspicious malignancy Associated Hyperthyroidism. Cosmetic STN : Unilateral thyroid lobectomy MNG : Bilateral subtotal thyroidectomy

69 Management Benign Thyroid Nodule Radioiodine Therapy gradual decrease in thyroid volume radiation-induced thyroid dysfunction (hyperthyroidism in 5%, hypothyroidism in 20-30%) risk of induction of carcinoma alternative to surgery in elderly patients and those with cardiopulmonary disease

70 Management Benign Thyroid Nodule Percutaneous Ethanol Injection recurrent cystic nodules AFTN with a large fluid component before radioiodine treatment small AFTN with incomplete inhibition of the surrounding parenchyma should not be performed in solid, cold nodules, unless surgical treatment is contraindicated

71 Management Toxic nodular goiter overt hyperthyroidism:rx is always indicated subclinical hyperthyroidism : Rx in elderly patients and in younger ones who are at risk for cardiac disease or osteoporosis

72 Management Toxic nodular goiter Antithyroid-Drug Therapy hyperthyroidism is reversible, but always recurs after discontinued indicated before thyroid surgery before and sometimes after radioiodine treatment in elderly patients and those with other health problems

73 Management Toxic nodular goiter Surgery Uninodular : Lobectomy simple and effective recurrences after surgery are rare hypothyroidism develops in 10-20% recommended in children and adolescents; may be preferred in patients with large nodules

74 Management Toxic nodular goiter Surgery Multinodular :Bilateral subtotal thyroidectomy incidence of persistent and recurrent hyperthyroidism should be less than 10-20% widely varying rates of post-treatment hypothyroidism recommended in patients with large goiters

75 Management Toxic nodular goiter Radioiodine Therapy as effective as surgery more gradual than that after surgery hypothyroidism : less than 20% in most studies, in a large follow-up study, the risk of thyroid carcinoma was not increased attractive option for the majority of patients

76 Management Toxic nodular goiter Percutaneous Ethanol Injection alternative to radioiodine therapy and surgery for patients with uninodular goiter especially for patients with small nodules

77 Management Cystic Lesions Almost half such nodules disappear permanently after one or more aspirations Surgery : recurrence : usually >4 cm aspiration tends to yield bloody fluid but insufficient material for diagnosis Thyroxine therapy is ineffective

78 Management Hashimoto s Thyroiditis Thyroid suppression (levothyroxine( levothyroxine) Triiodothyronine (for myxedema coma) Surgery for compression or pain Subacute Thyroiditis NSAID s and salicylates. Oral steroids in severe cases Beta blockers for symptoms of hyperthyroidism

79 Management Suspicious Thyroid Nodule by FNA 20% are found to be malignant lesions Recommend surgical excision Lobectomy and isthmectomy Total thyroidectomy in : history of irradiation multiple thyroid nodules

80 Management Nondiagnostic Cytologic Specimen Usually results from a cystic nodule US-FNA directed is indicated 5% of thyroid nodules remain nondiagnostic. such nodules should be surgically excised

81 Management Indications for reaspiration Follow-up of benign nodule Enlarging nodule Recurrent cyst Thyroid nodule > 4 cm Initial nondiagnostic FNA biopsy No shrinkage of nodule after T4 therapy

82 Management Thyroid Nodules in Children Infections and developmental abnormalities are more common than in adults Incidence of cancer : 30% (14 61% ) FNA has not been used in very young children, surgery may be used to identify the cause

83 Management Thyroid incedentalomas Cancer < 5%, mostly papillary FNA in Familly history of thyroid cancer, childhood history of radiation U/S finding : size > 1.5 cm,hypoechoic, pattern, irregular margin,internal microcalcification

84 Management of thyroid cancer

85 Management Surgery is the definitive management of thyroid cancer, excluding most cases of ATC and lymphoma Types of operations: lobectomy with isthmectomy total thyroidectomy subtotal thyroidectomy

86 Management (WDTC) : Papillary and Follicular Lobectomy vs. Total thyroidectomy

87 Management (WDTC) : Papillary and Follicular Rationale for total thyroidectomy 30%-87.5% of PTC involve opposite lobe 7%-10% recurrence in the contralateral lobe Lower recurrence rates, some studies show increased survival Facilitates earlier detection & Rx for recurrent or metastatic carcinoma with iodine Potential to differentiate to ATC

88 Management (WDTC) : Papillary and Follicular Rationale for lobectomy Lower incidence of complications Hypoparathyroidism (1%-29%) Recurrent laryngeal nerve injury (1%-2%) Superior laryngeal nerve injury Long term prognosis is not improved by total thyroidectomy

89 Management (WDTC) : Papillary and Follicular Prognostic factors AMES (Lahey Clinic, Burlington, MA) AGES GAMES Grade (Mayo Clinic, Rochester, MN) (Memorial Sloan Kettering Cancer Center, NY) Age ( > 45 yrs ) Metastases of the tumor (other than Neck LN) Extent of primary tumor ( Extraglandular ) Size of tumor (> 4 cm)

90 Management (WDTC) : Papillary and Follicular Indications for total thyroidectomy Age < 15 y or > 45 yrs Radiation history Known distant metastases Bilateral nodularity Extrathyroidal extension Tumor > 4 cm in diameter Cervical lymph node metastases Aggressive variant

91 Management (WDTC) : Papillary and Follicular Managing lymphatic involvement If any cervical nodes are clinically palpable or identified by MR or CT imaging as being suspicious, a neck dissection should be done Elective neck dissections are not done

92 Management (WDTC) : Hurthle Cell Carcinoma Total thyroidectomy is recommended because: Lesions are often Multifocal They are more aggressive than WDTCs Most do not concentrate iodine

93 Management Medullary Carcinoma Recommended surgical management total thyroidectomy central lymph node dissection lateral jugular sampling Prophylactic thyroidectomy recommended age 2-62 If patient has MEN syndrome remove pheochromocytoma before thyroid surgery

94 Management Anaplastic Carcinoma Most have extensive extrathyroidal involvement at the time of diagnosis surgery is limited to biopsy and tracheostomy Radiotherapy and Chemotherapy

95 attention Thanks for your attention

Thyroid Nodule. Disclosure. Learning Objectives P A P A P A 3/18/2014. Nothing to disclose.

Thyroid Nodule. Disclosure. Learning Objectives P A P A P A 3/18/2014. Nothing to disclose. Thyroid Nodule Evaluating the patient with a thyroid nodule and some management options. Miguel V. Valdez PA C Disclosure Nothing to disclose. Learning Objectives Examination of thyroid gland Options for